Sample records for aaas philip hauge

  1. Lifetime achievement

    NASA Astrophysics Data System (ADS)

    Carlowicz, Michael

    The American Association for the Advancement of Science (AAAS) is accepting nominations for the 1996 Philip Hauge Abelson Prize. The prize is awarded annually to either a public servant who has made sustained contributions to the advancement of science or to scientists who have distinguished themselves for both the quality of their work and their leadership in the scientific community.

  2. Risk of abdominal aortic aneurysm (AAA) among male and female relatives of AAA patients.

    PubMed

    van de Luijtgaarden, Koen M; Rouwet, Ellen V; Hoeks, Sanne E; Stolker, Robert J; Verhagen, Hence Jm; Majoor-Krakauer, Danielle

    2017-04-01

    Sex affects the presentation, treatment, and outcomes of abdominal aortic aneurysm (AAA). Although AAAs are less prevalent in women, at least in the general population, women with an AAA have a poorer prognosis in comparison to men. Sex differences in the genetic predisposition for aneurysm disease remain to be established. In this study we investigated the familial risk of AAA for women compared to men. All living AAA patients included in a 2004-2012 prospective database were invited to the multidisciplinary vascular/genetics outpatient clinic between 2009 and 2012 for assessment of family history using detailed questionnaires. AAA risk for male and female relatives was calculated separately and stratified by sex of the AAA patients. Families of 568 AAA patients were investigated and 22.5% of the patients had at least one affected relative. Female relatives had a 2.8-fold and male relatives had a 1.7-fold higher risk than the estimated sex-specific population risk. Relatives of female AAA patients had a higher aneurysm risk than relatives of male patients (9.0 vs 5.9%, p = 0.022), corresponding to 5.5- and 2.0-fold increases in aneurysm risk in the female and male relatives, respectively. The risk for aortic aneurysm in relatives of AAA patients is higher than expected from population risk. The excess risk is highest for the female relatives of AAA patients and for the relatives of female AAA patients. These findings endorse targeted AAA family screening for female and male relatives of all AAA patients.

  3. AAA Foundation for Traffic Safety

    MedlinePlus

    ... of Top Deadly Mistakes Made by Teen Drivers -- AAA AAA: Road debris causes avoidable crashes, deaths Save the ... and 500 deaths! Foundation News Stay Tuned New AAA Foundation for Traffic Safety website coming Fall 2017 ...

  4. AAA-ATPases in Protein Degradation

    PubMed Central

    Yedidi, Ravikiran S.; Wendler, Petra; Enenkel, Cordula

    2017-01-01

    Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea. PMID:28676851

  5. AAA-ATPases in Protein Degradation.

    PubMed

    Yedidi, Ravikiran S; Wendler, Petra; Enenkel, Cordula

    2017-01-01

    Proteolytic machineries containing multisubunit protease complexes and AAA-ATPases play a key role in protein quality control and the regulation of protein homeostasis. In these protein degradation machineries, the proteolytically active sites are formed by either threonines or serines which are buried inside interior cavities of cylinder-shaped complexes. In eukaryotic cells, the proteasome is the most prominent protease complex harboring AAA-ATPases. To degrade protein substrates, the gates of the axial entry ports of the protease need to be open. Gate opening is accomplished by AAA-ATPases, which form a hexameric ring flanking the entry ports of the protease. Protein substrates with unstructured domains can loop into the entry ports without the assistance of AAA-ATPases. However, folded proteins require the action of AAA-ATPases to unveil an unstructured terminus or domain. Cycles of ATP binding/hydrolysis fuel the unfolding of protein substrates which are gripped by loops lining up the central pore of the AAA-ATPase ring. The AAA-ATPases pull on the unfolded polypeptide chain for translocation into the proteolytic cavity of the protease. Conformational changes within the AAA-ATPase ring and the adjacent protease chamber create a peristaltic movement for substrate degradation. The review focuses on new technologies toward the understanding of the function and structure of AAA-ATPases to achieve substrate recognition, unfolding and translocation into proteasomes in yeast and mammalian cells and into proteasome-equivalent proteases in bacteria and archaea.

  6. LMIP/AAA: Local Authentication, Authorization and Accounting (AAA) Protocol for Mobile IP

    NASA Astrophysics Data System (ADS)

    Chenait, Manel

    Mobile IP represents a simple and scalable global mobility solution. However, it inhibits various vulnerabilities to malicious attacks and, therefore, requires the integration of appropriate security services. In this paper, we discuss two authentication schemes suggested for Mobile IP: standard authentication and Mobile IP/AAA authentication. In order to provide Mobile IP roaming services including identity verication, we propose an improvement to Mobile/AAA authentication scheme by applying a local politic key management in each domain, hence we reduce hando latency by avoiding the involvement of AAA infrastructure during mobile node roaming.

  7. NASA Airborne Astronomy Ambassadors (AAA)

    NASA Astrophysics Data System (ADS)

    Backman, D. E.; Harman, P. K.; Clark, C.

    2016-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) is a three-part professional development (PD) program for high school physics and astronomy teachers. The AAA experience consists of: (1) blended-learning professional development composed of webinars, asynchronous content learning, and a series of hands-on workshops (2) a STEM immersion experience at NASA Armstrong Flight Research Center's B703 science research aircraft facility in Palmdale, California, and (3) ongoing participation in the AAA community of practice (CoP) connecting participants with astrophysics and planetary science Subject Matter Experts (SMEs). The SETI Institute (SI) is partnering with school districts in Santa Clara and Los Angeles Counties during the AAA program's "incubation" period, calendar years 2016 through 2018. AAAs will be selected by the school districts based on criteria developed during spring 2016 focus group meetings led by the program's external evaluator, WestEd.. Teachers with 3+ years teaching experience who are assigned to teach at least 2 sections in any combination of the high school courses Physics (non-AP), Physics of the Universe (California integrated model), Astronomy, or Earth & Space Sciences are eligible. Partner districts will select at least 48 eligible applicants with SI oversight. WestEd will randomly assign selected AAAs to group A or group B. Group A will complete PD in January - June of 2017 and then participate in SOFIA science flights during fall 2017 (SOFIA Cycle 5). Group B will act as a control during the 2017-18 school year. Group B will then complete PD in January - June of 2018 and participate in SOFIA science flights in fall 2018 (Cycle 6). Under the current plan, opportunities for additional districts to seek AAA partnerships with SI will be offered in 2018 or 2019. A nominal two-week AAA curriculum component will be developed by SI for classroom delivery that will be aligned with selected California Draft Science Framework Disciplinary Core Ideas

  8. Multifunctional Mitochondrial AAA Proteases

    PubMed Central

    Glynn, Steven E.

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle. PMID:28589125

  9. Multifunctional Mitochondrial AAA Proteases.

    PubMed

    Glynn, Steven E

    2017-01-01

    Mitochondria perform numerous functions necessary for the survival of eukaryotic cells. These activities are coordinated by a diverse complement of proteins encoded in both the nuclear and mitochondrial genomes that must be properly organized and maintained. Misregulation of mitochondrial proteostasis impairs organellar function and can result in the development of severe human diseases. ATP-driven AAA+ proteins play crucial roles in preserving mitochondrial activity by removing and remodeling protein molecules in accordance with the needs of the cell. Two mitochondrial AAA proteases, i-AAA and m-AAA, are anchored to either face of the mitochondrial inner membrane, where they engage and process an array of substrates to impact protein biogenesis, quality control, and the regulation of key metabolic pathways. The functionality of these proteases is extended through multiple substrate-dependent modes of action, including complete degradation, partial processing, or dislocation from the membrane without proteolysis. This review discusses recent advances made toward elucidating the mechanisms of substrate recognition, handling, and degradation that allow these versatile proteases to control diverse activities in this multifunctional organelle.

  10. 78 FR 61390 - Philips Lighting, Including Workers Whose Wages Were Paid Under Philips Lightolier, Genlyte Group...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-82,244] Philips Lighting, Including Workers Whose Wages Were Paid Under Philips Lightolier, Genlyte Group, and Genlyte Thomas Group LLC, and Including On-Site Leased Workers From Adecco, Wilmington, Massachusetts; Amended Certification Regarding Eligibility To Apply for Worker...

  11. Pathophysiology of AAA: heredity vs environment.

    PubMed

    Björck, Martin; Wanhainen, Anders

    2013-01-01

    Abdominal aortic aneurysm (AAA) has a complex pathophysiology, in which both environmental and genetic factors play important roles, the most important being smoking. The recently reported falling prevalence rates of AAA in northern Europe and Australia/New Zeeland are largely explained by healthier smoking habits. Dietary factors and obesity, in particular abdominal obesity, are also of importance. A family history of AAA among first-degree relatives is present in approximately 13% of incident cases. The probability that a monozygotic twin of a person with an AAA has the disease is 24%, 71 times higher than that for a monozygotic twin of a person without AAA. Approximately 1000 SNPs in 100 candidate genes have been studied, and three genome-wide association studies were published, identifying different diverse weak associations. An example of interaction between environmental and genetic factors is the effect of cholesterol, where genetic and dietary factors affect levels of both HDL and LDL. True epigenetic studies have not yet been published. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Genetic analysis of abdominal aortic aneurysms (AAA)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    St. Jean, P.L.; Hart, B.K.; Zhang, X.C.

    1994-09-01

    The association between AAA and gender, smoking (SM), hypertension (HTN) and inguinal herniation (IH) was examined in 141 AAA probands and 139 of their 1st degree relatives with aortic exam (36 affected, 103 unaffected). There was no significant difference between age at diagnosis of affecteds and age at exam of unaffecteds. Of 181 males, 142 had AAA; of 99 females, 35 had AAA. Using log-linear modeling AAA was significantly associated at the 5% level with gender, SM and HTN but not IH. The association of AAA with SM and HTN held when males and females were analyzed separately. HTN wasmore » -1.5 times more common in both affected males and females, while SM was 1.5 and 2 times more common in affected males and females, respectively. Tests of association and linkage analyses were performed with relevant candidate genes: 3 COL3A1 polymorphisms (C/T, ALA/THR, AvaII), 2 ELN polymorphisms (SER/GLY, (CA)n), FBN1(TAAA)n, 2 APOB polymorphisms (Xbal,Ins/Del), CLB4B (CA)n, PI and markers D1S243 (CA)n, HPR (CA)n and MFD23(CA)n. The loci were genotyped in > 100 AAA probands and > 95 normal controls. No statistically significant evidence of association at the 5% level was obtained for any of the loci using chi-square test of association. 28 families with 2 or more affecteds were analyzed using the affected pedigree member method (APM) and lod-score analyses. There was no evidence for linkage with any loci using APM. Lod-score analysis under an autosomal recessive model resulted in excluding linkage (lod score < -2) of all loci to AAA at {theta}=0.0. Under an autosomal dominant model, linkage was excluded at {theta}=0.0 to ELN, APOB, CLG4B, D1S243, HPR and MFD23. The various genes previously proposed in AAA pathogenesis are neither associated nor casually related in our study population.« less

  13. 78 FR 73751 - Proposed Amendment of Class E Airspace; Philip, SD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-09

    ...-0916; Airspace Docket No. 13-AGL-30] Proposed Amendment of Class E Airspace; Philip, SD AGENCY: Federal... proposes to amend Class E airspace at Philip, SD. Additional controlled airspace is necessary to... the surface to accommodate new standard instrument approach procedures at Philip Airport, Philip, SD...

  14. Structural Elements Regulating AAA+ Protein Quality Control Machines.

    PubMed

    Chang, Chiung-Wen; Lee, Sukyeong; Tsai, Francis T F

    2017-01-01

    Members of the ATPases Associated with various cellular Activities (AAA+) superfamily participate in essential and diverse cellular pathways in all kingdoms of life by harnessing the energy of ATP binding and hydrolysis to drive their biological functions. Although most AAA+ proteins share a ring-shaped architecture, AAA+ proteins have evolved distinct structural elements that are fine-tuned to their specific functions. A central question in the field is how ATP binding and hydrolysis are coupled to substrate translocation through the central channel of ring-forming AAA+ proteins. In this mini-review, we will discuss structural elements present in AAA+ proteins involved in protein quality control, drawing similarities to their known role in substrate interaction by AAA+ proteins involved in DNA translocation. Elements to be discussed include the pore loop-1, the Inter-Subunit Signaling (ISS) motif, and the Pre-Sensor I insert (PS-I) motif. Lastly, we will summarize our current understanding on the inter-relationship of those structural elements and propose a model how ATP binding and hydrolysis might be coupled to polypeptide translocation in protein quality control machines.

  15. Philip, South Dakota geothermal district heating systems

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lund, J.W.

    1997-12-01

    The geothermal heating project in Philip, South Dakota which uses the waste water from the Haakon School has now been in operation for 15 years. This project was one of the 23 cost shared by the U.S. DOE starting in 1978, of which 15 became operational. This article describes the geothermal heating system for eight buildings in downtown Philip.

  16. Protein quality control in organelles - AAA/FtsH story.

    PubMed

    Janska, Hanna; Kwasniak, Malgorzata; Szczepanowska, Joanna

    2013-02-01

    This review focuses on organellar AAA/FtsH proteases, whose proteolytic and chaperone-like activity is a crucial component of the protein quality control systems of mitochondrial and chloroplast membranes. We compare the AAA/FtsH proteases from yeast, mammals and plants. The nature of the complexes formed by AAA/FtsH proteases and the current view on their involvement in degradation of non-native organellar proteins or assembly of membrane complexes are discussed. Additional functions of AAA proteases not directly connected with protein quality control found in yeast and mammals but not yet in plants are also described shortly. Following an overview of the molecular functions of the AAA/FtsH proteases we discuss physiological consequences of their inactivation in yeast, mammals and plants. The molecular basis of phenotypes associated with inactivation of the AAA/FtsH proteases is not fully understood yet, with the notable exception of those observed in m-AAA protease-deficient yeast cells, which are caused by impaired maturation of mitochondrial ribosomal protein. Finally, examples of cytosolic events affecting protein quality control in mitochondria and chloroplasts are given. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Updates on AAA screening and surveillance

    PubMed

    Theivendran, Mayo; Chuen, Jason

    2018-05-01

    Screening and diagnostic surveillance of latent conditions have a profound impact on public healthcare expenditure and clinical outcomes. Abdominal aortic aneurysm (AAA) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. This article is the second of two that will outline current areas of controversy and research in AAA disease in order to support a more detailed understanding of issues in managing patients with this condition, and inform the development of Australasian clinical guidelines and health policy. Screening and surveillance of AAA should be evidence-based and follow clinical guidelines; however, advances in treatment technology and epidemiological data have influenced results. Goals of care and cost‑effectiveness should play central parts in screening and surveillance strategies.

  18. Philip Morrison--A Profile.

    ERIC Educational Resources Information Center

    Eisenberg, Anne

    1982-01-01

    Highlights the career and accomplishments of Philip Morrison, one of the most thoughtful advocates of arms control, valued for his scientific contributions to the Manhattan Project, theoretical physics, astrophysics, and the public understanding of science. (Author/JN)

  19. Philip Morris' new scientific initiative: an analysis

    PubMed Central

    HIRSCHHORN, N.; BIALOUS, S. A.; SHATENSTEIN, S.

    2001-01-01

    In the fall of 2000, Philip Morris re-initiated an external research grants programme ("Philip Morris External Research Program", or PMERP), the first since the dissolution of the Council for Tobacco Research (CTR) and the Center for Indoor Air Research (CIAR). The ostensible purpose of the programme is to help develop cigarette designs "that might reduce the health risk of smoking". Internal company documents also indicate that Philip Morris urgently seeks to restore its scientific "credibility", as part of a "new openness" in relation to the external community. The structure of the review panel—a cohort of external peer reviewers, a science advisory board, and an internal, anonymous review and approvals committee—is nearly identical to that of the CIAR. The majority of the named reviewers have had previous affiliation with the tobacco industry either as reviewers or grantees, but only a minority have done research directly on tobacco or smoking. The programmatic substance of the PMERP could be interpreted as soliciting exculpatory evidence with respect to smoking and exposure to smoke. We remain sceptical about the scientific integrity of PMERP.


Keywords: Philip Morris; scientific credibility; tobacco industry PMID:11544389

  20. m-AAA and i-AAA complexes coordinate to regulate OMA1, the stress-activated supervisor of mitochondrial dynamics.

    PubMed

    Consolato, Francesco; Maltecca, Francesca; Tulli, Susanna; Sambri, Irene; Casari, Giorgio

    2018-04-09

    The proteolytic processing of dynamin-like GTPase OPA1, mediated by the activity of both YME1L1 [intermembrane (i)-AAA protease complex] and OMA1, is a crucial step in the regulation of mitochondrial dynamics. OMA1 is a zinc metallopeptidase of the inner mitochondrial membrane that undergoes pre-activating proteolytic and auto-proteolytic cleavage after mitochondrial import. Here, we identify AFG3L2 [matrix (m) - AAA complex] as the major protease mediating this event, which acts by maturing the 60 kDa pre-pro-OMA1 to the 40 kDa pro-OMA1 form by severing the N-terminal portion without recognizing a specific consensus sequence. Therefore, m - AAA and i - AAA complexes coordinately regulate OMA1 processing and turnover, and consequently control which OPA1 isoforms are present, thus adding new information on the molecular mechanisms of mitochondrial dynamics and neurodegenerative diseases affected by these phenomena.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

  1. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein

    PubMed Central

    Gleave, Emma S.; Schmidt, Helgo; Carter, Andrew P.

    2014-01-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. PMID:24680784

  2. NASA Airborne Astronomy Ambassadors (AAA) Professional Development and NASA Connections

    NASA Astrophysics Data System (ADS)

    Backman, D. E.; Clark, C.; Harman, P. K.

    2017-12-01

    NASA's Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content learning, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong's B703 science research aircraft facility in Palmdale, California, and (3) ongoing opportunities for connection with NASA astrophysics and planetary science Subject Matter Experts (SMEs). AAA implementation in 2016-18 involves partnerships between the SETI Institute and seven school districts in northern and southern California. AAAs in the current cohort were selected by the school districts based on criteria developed by AAA program staff working with WestEd evaluation consultants. The selected teachers were then randomly assigned by WestEd to a Group A or B to support controlled testing of student learning. Group A completed their PD during January - August 2017, then participated in NASA SOFIA science flights during fall 2017. Group B will act as a control during the 2017-18 school year, then will complete their professional development and SOFIA flights during 2018. A two-week AAA electromagnetic spectrum and multi-wavelength astronomy curriculum aligned with the Science Framework for California Public Schools and Next Generation Science Standards was developed by program staff for classroom delivery. The curriculum (as well as the AAA's pre-flight PD) capitalizes on NASA content by using "science snapshot" case studies regarding astronomy research conducted by SOFIA. AAAs also interact with NASA SMEs during flight weeks and will translate that interaction into classroom content. The AAA program will make controlled measurements of student gains in standards-based learning plus changes in student attitudes towards STEM, and observe & record the AAAs' implementation of curricular changes. Funded by NASA: NNX16AC51

  3. Young adults' opinions of Philip Morris and its television advertising.

    PubMed

    Henriksen, L; Fortmann, S P

    2002-09-01

    To determine what young people think about the tobacco company Philip Morris and how it affects their evaluations of the company's new television advertising. Data were gathered in the context of a controlled experiment in which participants saw four Philip Morris ads about youth smoking prevention, four Philip Morris ads about charitable works, or four Anheuser-Busch ads about preventing underage drinking (the control group). Knowledge and opinion of Philip Morris were measured before ad exposure. A California state university in the San Francisco Bay area. A convenience sample of undergraduates (n = 218) aged 18-25 years. Advertising evaluation measured by 12 semantic differential scales. A little more than half of the students knew that Philip Morris is a tobacco company. Neither this knowledge nor students' smoking status was related to their opinion of the company. Philip Morris ads were rated less favourably by students who were aware that the sponsor is a tobacco company than by students who were unaware. Advertisements designed to discredit the tobacco industry typically avoid references to specific companies. This study suggests that such counter-advertising would benefit from teaching audiences about the industry's corporate identities.

  4. Understanding Philip Morris's pursuit of US government regulation of tobacco.

    PubMed

    McDaniel, P A; Malone, R E

    2005-06-01

    To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Internal Philip Morris documents released as part of the Master Settlement Agreement. Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted.

  5. A structural analysis of the AAA+ domains in Saccharomyces cerevisiae cytoplasmic dynein.

    PubMed

    Gleave, Emma S; Schmidt, Helgo; Carter, Andrew P

    2014-06-01

    Dyneins are large protein complexes that act as microtubule based molecular motors. The dynein heavy chain contains a motor domain which is a member of the AAA+ protein family (ATPases Associated with diverse cellular Activities). Proteins of the AAA+ family show a diverse range of functionalities, but share a related core AAA+ domain, which often assembles into hexameric rings. Dynein is unusual because it has all six AAA+ domains linked together, in one long polypeptide. The dynein motor domain generates movement by coupling ATP driven conformational changes in the AAA+ ring to the swing of a motile element called the linker. Dynein binds to its microtubule track via a long antiparallel coiled-coil stalk that emanates from the AAA+ ring. Recently the first high resolution structures of the dynein motor domain were published. Here we provide a detailed structural analysis of the six AAA+ domains using our Saccharomycescerevisiae crystal structure. We describe how structural similarities in the dynein AAA+ domains suggest they share a common evolutionary origin. We analyse how the different AAA+ domains have diverged from each other. We discuss how this is related to the function of dynein as a motor protein and how the AAA+ domains of dynein compare to those of other AAA+ proteins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

    PubMed

    Meecham, Lewis; Summerour, Virginia; Hobbs, Simon; Newman, Jeremy; Wall, Michael L

    2018-05-01

    The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Young adults' opinions of Philip Morris and its television advertising

    PubMed Central

    Henriksen, L; Fortmann, S

    2002-01-01

    Objective: To determine what young people think about the tobacco company Philip Morris and how it affects their evaluations of the company's new television advertising. Design: Data were gathered in the context of a controlled experiment in which participants saw four Philip Morris ads about youth smoking prevention, four Philip Morris ads about charitable works, or four Anheuser-Busch ads about preventing underage drinking (the control group). Knowledge and opinion of Philip Morris were measured before ad exposure. Setting: A California state university in the San Francisco Bay area. Subjects: A convenience sample of undergraduates (n = 218) aged 18–25 years. Main outcome measures: Advertising evaluation measured by 12 semantic differential scales. Results: A little more than half of the students knew that Philip Morris is a tobacco company. Neither this knowledge nor students' smoking status was related to their opinion of the company. Philip Morris ads were rated less favourably by students who were aware that the sponsor is a tobacco company than by students who were unaware. Conclusions: Advertisements designed to discredit the tobacco industry typically avoid references to specific companies. This study suggests that such counter-advertising would benefit from teaching audiences about the industry's corporate identities. PMID:12198275

  8. Fundamental Characteristics of AAA+ Protein Family Structure and Function

    PubMed Central

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins. PMID:27703410

  9. Fundamental Characteristics of AAA+ Protein Family Structure and Function.

    PubMed

    Miller, Justin M; Enemark, Eric J

    2016-01-01

    Many complex cellular events depend on multiprotein complexes known as molecular machines to efficiently couple the energy derived from adenosine triphosphate hydrolysis to the generation of mechanical force. Members of the AAA+ ATPase superfamily (ATPases Associated with various cellular Activities) are critical components of many molecular machines. AAA+ proteins are defined by conserved modules that precisely position the active site elements of two adjacent subunits to catalyze ATP hydrolysis. In many cases, AAA+ proteins form a ring structure that translocates a polymeric substrate through the central channel using specialized loops that project into the central channel. We discuss the major features of AAA+ protein structure and function with an emphasis on pivotal aspects elucidated with archaeal proteins.

  10. Understanding Philip Morris's pursuit of US government regulation of tobacco

    PubMed Central

    McDaniel, P; Malone, R

    2005-01-01

    Objective: To investigate Philip Morris's support of US Food and Drug Administration (FDA) regulation of tobacco products and analyse its relationship to the company's image enhancement strategies. Data sources: Internal Philip Morris documents released as part of the Master Settlement Agreement. Methods: Searches of the Legacy Tobacco Documents Library (http://legacy.library.ucsf.edu) beginning with such terms as "FDA" and "regulatory strategy" and expanding to include relevant new terms. Results: Philip Morris's support for government regulation of tobacco is part of a broader effort to address its negative public image, which has a damaging impact on the company's stock price, political influence, and employee morale. Through regulation, the company seeks to enhance its legitimacy, redefine itself as socially responsible, and alter the litigation environment. Whereas health advocates frame tobacco use as a public health policy issue, Philip Morris's regulatory efforts focus on framing tobacco use as an individual choice by informed adults to use a risky product. This framing allows Philip Morris to portray itself as a reasonable and responsible manufacturer and marketer of risky products. Conclusions: Philip Morris's ability to improve its image through support of FDA regulation may undermine tobacco control efforts aimed at delegitimising the tobacco industry. It may also create the impression that Philip Morris's products are being made safer and ultimately protect the company from litigation. While strong regulation of tobacco products and promotion remain critical public health goals, previous experiences with tobacco regulation show that caution may be warranted. PMID:15923470

  11. AAA-DDD triple hydrogen bond complexes.

    PubMed

    Blight, Barry A; Camara-Campos, Amaya; Djurdjevic, Smilja; Kaller, Martin; Leigh, David A; McMillan, Fiona M; McNab, Hamish; Slawin, Alexandra M Z

    2009-10-07

    Experiment and theory both suggest that the AAA-DDD pattern of hydrogen bond acceptors (A) and donors (D) is the arrangement of three contiguous hydrogen bonding centers that results in the strongest association between two species. Murray and Zimmerman prepared the first example of such a system (complex 3*2) and determined the lower limit of its association constant (K(a)) in CDCl(3) to be 10(5) M(-1) by (1)H NMR spectroscopy (Murray, T. J. and Zimmerman, S. C. J. Am. Chem. Soc. 1992, 114, 4010-4011). The first cationic AAA-DDD pair (3*4(+)) was described by Bell and Anslyn (Bell, D. A. and Anslyn, E. A. Tetrahedron 1995, 51, 7161-7172), with a K(a) > 5 x 10(5) M(-1) in CH(2)Cl(2) as determined by UV-vis spectroscopy. We were recently able to quantify the strength of a neutral AAA-DDD arrangement using a more chemically stable AAA-DDD system, 6*2, which has an association constant of 2 x 10(7) M(-1) in CH(2)Cl(2) (Djurdjevic, S., Leigh, D. A., McNab, H., Parsons, S., Teobaldi, G. and Zerbetto, F. J. Am. Chem. Soc. 2007, 129, 476-477). Here we report on further AA(A) and DDD partners, together with the first precise measurement of the association constant of a cationic AAA-DDD species. Complex 6*10(+)[B(3,5-(CF(3))(2)C(6)H(3))(4)(-)] has a K(a) = 3 x 10(10) M(-1) at RT in CH(2)Cl(2), by far the most strongly bound triple hydrogen bonded system measured to date. The X-ray crystal structure of 6*10(+) with a BPh(4)(-) counteranion shows a planar array of three short (NH...N distances 1.95-2.15 A), parallel (but staggered rather than strictly linear; N-H...N angles 165.4-168.8 degrees), primary hydrogen bonds. These are apparently reinforced, as theory predicts, by close electrostatic interactions (NH-*-N distances 2.78-3.29 A) between each proton and the acceptor atoms of the adjacent primary hydrogen bonds.

  12. Assessing heterogeneity in oligomeric AAA+ machines.

    PubMed

    Sysoeva, Tatyana A

    2017-03-01

    ATPases Associated with various cellular Activities (AAA+ ATPases) are molecular motors that use the energy of ATP binding and hydrolysis to remodel their target macromolecules. The majority of these ATPases form ring-shaped hexamers in which the active sites are located at the interfaces between neighboring subunits. Structural changes initiate in an active site and propagate to distant motor parts that interface and reshape the target macromolecules, thereby performing mechanical work. During the functioning cycle, the AAA+ motor transits through multiple distinct states. Ring architecture and placement of the catalytic sites at the intersubunit interfaces allow for a unique level of coordination among subunits of the motor. This in turn results in conformational differences among subunits and overall asymmetry of the motor ring as it functions. To date, a large amount of structural information has been gathered for different AAA+ motors, but even for the most characterized of them only a few structural states are known and the full mechanistic cycle cannot be yet reconstructed. Therefore, the first part of this work will provide a broad overview of what arrangements of AAA+ subunits have been structurally observed focusing on diversity of ATPase oligomeric ensembles and heterogeneity within the ensembles. The second part of this review will concentrate on methods that assess structural and functional heterogeneity among subunits of AAA+ motors, thus bringing us closer to understanding the mechanism of these fascinating molecular motors.

  13. Thinking the "unthinkable": why Philip Morris considered quitting.

    PubMed

    Smith, E A; Malone, R E

    2003-06-01

    To investigate the genesis and development of tobacco company Philip Morris's recent image enhancement strategies and analyse their significance. Internal Philip Morris documents, made available by the terms of the Master Settlement Agreement between the tobacco companies and the attorneys general of 46 states, and secondary newspaper sources. Searches of the Philip Morris documents website (www.pmdocs.com) beginning with terms such as "image management" and "identity" and expanding as relevant new terms (consultant names, project names, and dates), were identified, using a "snowball" sampling strategy. In the early 1990s, Philip Morris, faced with increasing pressures generated both externally, from the non-smokers' rights and public health communities, and internally, from the conflicts among its varied operating companies, seriously considered leaving the tobacco business. Discussions of this option, which occurred at the highest levels of management, focused on the changing social climate regarding tobacco and smoking that the tobacco control movement had effected. However, this option was rejected in favour of the image enhancement strategy that culminated with the recent "Altria" name change. This analysis suggests that advocacy efforts have the potential to significantly denormalise tobacco as a corporate enterprise.

  14. Biomarkers for AAA: Encouraging steps but clinical relevance still to be delivered.

    PubMed

    Htun, Nay Min; Peter, Karlheinz

    2014-10-01

    Potential biomarkers have been investigated using proteomic studies in a variety of diseases. Some biomarkers have central roles in both diagnosis and monitoring of various disorders in clinical medicine, such as troponins, brain natriuretic peptide, and C-reactive protein. Although several biomarkers have been suggested in human abdominal aortic aneurysm (AAA), reliable markers have been lacking. In this issue, Moxon et al. [Proteomics Clin Appl. 2014, 8, 762-772] undertook a broad and systematic proteomic approach toward identification of biomarkers in a commonly used AAA mouse model (AAA created by angiotensin-II infusion). In this mouse model, apolipoprotein C1 and matrix metalloproteinase-9 were identified as novel biomarkers of stable AAA. This finding represents an important step forward, toward a clinically relevant role of biomarkers in AAA. This also encourages for further studies toward the identification of biomarkers (or their combinations) that can predict AAA progression and rupture, which would represent a major progress in AAA management and would establish an AAA biomarker as a much anticipated clinical tool. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. AAAS: Politics. . . and Science

    ERIC Educational Resources Information Center

    Science News, 1978

    1978-01-01

    Reviews topics discussed during the American Association for the Advancement of Science (AAAS) meeting held in Washington, D.C. Topics included: the equal rights amendment, laetrile, nuclear radiation hazards, sociobiology, and various science topics. (SL)

  16. Electron cryomicroscopy structure of a membrane-anchored mitochondrial AAA protease.

    PubMed

    Lee, Sukyeong; Augustin, Steffen; Tatsuta, Takashi; Gerdes, Florian; Langer, Thomas; Tsai, Francis T F

    2011-02-11

    FtsH-related AAA proteases are conserved membrane-anchored, ATP-dependent molecular machines, which mediate the processing and turnover of soluble and membrane-embedded proteins in eubacteria, mitochondria, and chloroplasts. Homo- and hetero-oligomeric proteolytic complexes exist, which are composed of homologous subunits harboring an ATPase domain of the AAA family and an H41 metallopeptidase domain. Mutations in subunits of mitochondrial m-AAA proteases have been associated with different neurodegenerative disorders in human, raising questions on the functional differences between homo- and hetero-oligomeric AAA proteases. Here, we have analyzed the hetero-oligomeric yeast m-AAA protease composed of homologous Yta10 and Yta12 subunits. We combined genetic and structural approaches to define the molecular determinants for oligomer assembly and to assess functional similarities between Yta10 and Yta12. We demonstrate that replacement of only two amino acid residues within the metallopeptidase domain of Yta12 allows its assembly into homo-oligomeric complexes. To provide a molecular explanation, we determined the 12 Å resolution structure of the intact yeast m-AAA protease with its transmembrane domains by electron cryomicroscopy (cryo-EM) and atomic structure fitting. The full-length m-AAA protease has a bipartite structure and is a hexamer in solution. We found that residues in Yta12, which facilitate homo-oligomerization when mutated, are located at the interface between neighboring protomers in the hexamer ring. Notably, the transmembrane and intermembrane space domains are separated from the main body, creating a passage on the matrix side, which is wide enough to accommodate unfolded but not folded polypeptides. These results suggest a mechanism regarding how proteins are recognized and degraded by m-AAA proteases.

  17. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration

    PubMed Central

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-01-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders. PMID:29451229

  18. m-AAA proteases, mitochondrial calcium homeostasis and neurodegeneration.

    PubMed

    Patron, Maria; Sprenger, Hans-Georg; Langer, Thomas

    2018-03-01

    The function of mitochondria depends on ubiquitously expressed and evolutionary conserved m-AAA proteases in the inner membrane. These ATP-dependent peptidases form hexameric complexes built up of homologous subunits. AFG3L2 subunits assemble either into homo-oligomeric isoenzymes or with SPG7 (paraplegin) subunits into hetero-oligomeric proteolytic complexes. Mutations in AFG3L2 are associated with dominant spinocerebellar ataxia (SCA28) characterized by the loss of Purkinje cells, whereas mutations in SPG7 cause a recessive form of hereditary spastic paraplegia (HSP7) with motor neurons of the cortico-spinal tract being predominantly affected. Pleiotropic functions have been assigned to m-AAA proteases, which act as quality control and regulatory enzymes in mitochondria. Loss of m-AAA proteases affects mitochondrial protein synthesis and respiration and leads to mitochondrial fragmentation and deficiencies in the axonal transport of mitochondria. Moreover m-AAA proteases regulate the assembly of the mitochondrial calcium uniporter (MCU) complex. Impaired degradation of the MCU subunit EMRE in AFG3L2-deficient mitochondria results in the formation of deregulated MCU complexes, increased mitochondrial calcium uptake and increased vulnerability of neurons for calcium-induced cell death. A reduction of calcium influx into the cytosol of Purkinje cells rescues ataxia in an AFG3L2-deficient mouse model. In this review, we discuss the relationship between the m-AAA protease and mitochondrial calcium homeostasis and its relevance for neurodegeneration and describe a novel mouse model lacking MCU specifically in Purkinje cells. Our results pledge for a novel view on m-AAA proteases that integrates their pleiotropic functions in mitochondria to explain the pathogenesis of associated neurodegenerative disorders.

  19. Mitochondrial AAA proteases--towards a molecular understanding of membrane-bound proteolytic machines.

    PubMed

    Gerdes, Florian; Tatsuta, Takashi; Langer, Thomas

    2012-01-01

    Mitochondrial AAA proteases play an important role in the maintenance of mitochondrial proteostasis. They regulate and promote biogenesis of mitochondrial proteins by acting as processing enzymes and ensuring the selective turnover of misfolded proteins. Impairment of AAA proteases causes pleiotropic defects in various organisms including neurodegeneration in humans. AAA proteases comprise ring-like hexameric complexes in the mitochondrial inner membrane and are functionally conserved from yeast to man, but variations are evident in the subunit composition of orthologous enzymes. Recent structural and biochemical studies revealed how AAA proteases degrade their substrates in an ATP dependent manner. Intersubunit coordination of the ATP hydrolysis leads to an ordered ATP hydrolysis within the AAA ring, which ensures efficient substrate dislocation from the membrane and translocation to the proteolytic chamber. In this review, we summarize recent findings on the molecular mechanisms underlying the versatile functions of mitochondrial AAA proteases and their relevance to those of the other AAA+ machines. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Thinking the "unthinkable": why Philip Morris considered quitting

    PubMed Central

    Smith, E; Malone, R

    2003-01-01

    Objective: To investigate the genesis and development of tobacco company Philip Morris's recent image enhancement strategies and analyse their significance. Data sources: Internal Philip Morris documents, made available by the terms of the Master Settlement Agreement between the tobacco companies and the attorneys general of 46 states, and secondary newspaper sources. Study selection: Searches of the Philip Morris documents website (www.pmdocs.com) beginning with terms such as "image management" and "identity" and expanding as relevant new terms (consultant names, project names, and dates), were identified, using a "snowball" sampling strategy. Findings and conclusions: In the early 1990s, Philip Morris, faced with increasing pressures generated both externally, from the non-smokers' rights and public health communities, and internally, from the conflicts among its varied operating companies, seriously considered leaving the tobacco business. Discussions of this option, which occurred at the highest levels of management, focused on the changing social climate regarding tobacco and smoking that the tobacco control movement had effected. However, this option was rejected in favour of the image enhancement strategy that culminated with the recent "Altria" name change. This analysis suggests that advocacy efforts have the potential to significantly denormalise tobacco as a corporate enterprise. PMID:12773733

  1. Meiotic Clade AAA ATPases: Protein Polymer Disassembly Machines.

    PubMed

    Monroe, Nicole; Hill, Christopher P

    2016-05-08

    Meiotic clade AAA ATPases (ATPases associated with diverse cellular activities), which were initially grouped on the basis of phylogenetic classification of their AAA ATPase cassette, include four relatively well characterized family members, Vps4, spastin, katanin and fidgetin. These enzymes all function to disassemble specific polymeric protein structures, with Vps4 disassembling the ESCRT-III polymers that are central to the many membrane-remodeling activities of the ESCRT (endosomal sorting complexes required for transport) pathway and spastin, katanin p60 and fidgetin affecting multiple aspects of cellular dynamics by severing microtubules. They share a common domain architecture that features an N-terminal MIT (microtubule interacting and trafficking) domain followed by a single AAA ATPase cassette. Meiotic clade AAA ATPases function as hexamers that can cycle between the active assembly and inactive monomers/dimers in a regulated process, and they appear to disassemble their polymeric substrates by translocating subunits through the central pore of their hexameric ring. Recent studies with Vps4 have shown that nucleotide-induced asymmetry is a requirement for substrate binding to the pore loops and that recruitment to the protein lattice via MIT domains also relieves autoinhibition and primes the AAA ATPase cassettes for substrate binding. The most striking, unifying feature of meiotic clade AAA ATPases may be their MIT domain, which is a module that is found in a wide variety of proteins that localize to ESCRT-III polymers. Spastin also displays an adjacent microtubule binding sequence, and the presence of both ESCRT-III and microtubule binding elements may underlie the recent findings that the ESCRT-III disassembly function of Vps4 and the microtubule-severing function of spastin, as well as potentially katanin and fidgetin, are highly coordinated. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning

    PubMed Central

    D’Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research. PMID:29038607

  3. Advanced, Analytic, Automated (AAA) Measurement of Engagement During Learning.

    PubMed

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in embodied theories of cognition and affect, which advocate a close coupling between thought and action. It uses machine-learned computational models to automatically infer mental states associated with engagement (e.g., interest, flow) from machine-readable behavioral and physiological signals (e.g., facial expressions, eye tracking, click-stream data) and from aspects of the environmental context. We present15 case studies that illustrate the potential of the AAA approach for measuring engagement in digital learning environments. We discuss strengths and weaknesses of the AAA approach, concluding that it has significant promise to catalyze engagement research.

  4. Altria means tobacco: Philip Morris's identity crisis.

    PubMed

    Smith, Elizabeth A; Malone, Ruth E

    2003-04-01

    Philip Morris Companies, the world's largest and most profitable tobacco seller, has changed its corporate name to The Altria Group. The company has also embarked on a plan to improve its corporate image. Examination of internal company documents reveals that these changes have been planned for over a decade and that the company expects to reap specific and substantial rewards from them. Tobacco control advocates should be alert to the threat Philip Morris's plans pose to industry focused tobacco control campaigns. Company documents also suggest what the vulnerabilities of those plans are and how advocates might best exploit them.

  5. The Weekend Effect in AAA Repair.

    PubMed

    O'Donnell, Thomas F X; Li, Chun; Swerdlow, Nicholas J; Liang, Patric; Pothof, Alexander B; Patel, Virendra I; Giles, Kristina A; Malas, Mahmoud B; Schermerhorn, Marc L

    2018-04-18

    Conflicting reports exist regarding whether patients undergoing surgery on the weekend or later in the week experience worse outcomes. We identified patients undergoing abdominal aortic aneurysm (AAA) repair in the Vascular Quality Initiative between 2009 and 2017 [n = 38,498; 30,537 endovascular aneurysm repair (EVAR) and 7961 open repair]. We utilized mixed effects logistic regression to compare adjusted rates of perioperative mortality based on the day of repair. Tuesday was the most common day for elective repair (22%), Friday for symptomatic repairs (20%), and ruptured aneurysms were evenly distributed. Patients with ruptured aneurysms experienced similar adjusted mortality whether they underwent repair during the week or on weekends. Transfers of ruptured AAA were more common over the weekend. However, patients transferred on the weekend experienced higher adjusted mortality than those transferred during the week (28% vs 21%, P = 0.02), despite the fact that during the week, transferred patients actually experienced lower adjusted mortality than patients treated at the index hospital (21% vs 31%, P < 0.01). Among symptomatic patients, adjusted mortality was higher for those undergoing repair over the weekend than those whose surgeries were delayed until a weekday (7.9% vs 3.1%, P = 0.02). Adjusted mortality in elective cases did not vary across the days of the week. Results were consistent between open and EVAR patients. We found no evidence of a weekend effect for ruptured or symptomatic AAA repair. However, patients with ruptured AAA transferred on the weekend experienced higher mortality than those transferred during the week, suggesting a need for improvement in weekend transfer processes.

  6. The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying.

    PubMed

    Wang, Shuaiyu; Jacquemyn, Julie; Murru, Sara; Martinelli, Paola; Barth, Esther; Langer, Thomas; Niessen, Carien M; Rugarli, Elena I

    2016-12-01

    The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency.

  7. APC-PCI complex levels for screening of AAA in patients with peripheral atherosclerosis.

    PubMed

    Zarrouk, Moncef; Keshavarz, Kave; Lindblad, Bengt; Gottsäter, Anders

    2013-11-01

    To evaluate the use of activated protein C-protein C inhibitor (APC-PCI) complex levels for detection of abdominal aortic aneurysm (AAA) in patients with peripheral atherosclerotic disease (PAD). APC-PCI levels and aortic diameter evaluated in 511 PAD patients without previously known AAA followed-up concerning survival for 4.8(0.5) years. AAA was found in 13% of patients. Aortic diameter correlated (r = 0.138; p = 0.002) with APC-PCI levels which were higher (0.40[0.45] vs. 0.30[0.49] μg/l; p = 0.004) in patients with AAA. This difference persisted in multivariate analysis (p = 0.029). A threshold value of APC-PCI ≥0.15 μg/L showed a specificity of 11%, a sensitivity of 97% and a negative predictive value of 96% for an AAA diagnosis. APC-PCI levels were higher in patients with AAA, and showed high sensitivity but low specificity for the diagnosis and can therefore not be considered as a screening tool in PAD patients. An AAA prevalence of 13% in patients with PAD indicates a need for AAA screening within this population.

  8. Inhibition of early AAA formation by aortic intraluminal pentagalloyl glucose (PGG) infusion in a novel porcine AAA model.

    PubMed

    Kloster, Brian O; Lund, Lars; Lindholt, Jes S

    2016-05-01

    The vast majority of abdominal aortic aneurysms found in screening programs are small, and as no effective treatment exits, many will expand until surgery is indicated. Therefore, it remains intriguing to develop a safe and low cost treatment of these small aneurysms, that is able to prevent or delay their expansion. In this study, we investigated whether intraluminal delivered pentagalloyl glucose (PGG) can impair the early AAA development in a porcine model. The infrarenal aorta was exposed in thirty pigs. Twenty underwent an elastase based AAA inducing procedure and ten of these received an additional intraluminal PGG infusion. The final 10 were sham operated and served as controls. All pigs who only had an elastase infusion developed macroscopically expanding AAAs. In pigs treated with an additional PGG infusion the growth rate of the AP-diameter rapidly returned to physiological values as seen in the control group. In the elastase group, histology revealed more or less complete resolution of the elastic lamellae in the media while they were more abundant, coherent and structurally organized in the PGG group. The control group displayed normal physiological growth and histology. In our model, intraluminal delivered PGG is able to penetrate the aortic wall from the inside and impair the early AAA development by stabilizing the elastic lamellae and preserving their integrity. The principle holds a high clinical potential if it can be translated to human conditions, since it, if so, potentially could represent a new drug for stabilizing small abdominal aneurysms.

  9. Characterization of the modular design of the autolysin/adhesin Aaa from Staphylococcus aureus.

    PubMed

    Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

    2012-01-01

    Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus colonization of host extracellular matrix and tissue, suggesting a role for

  10. Talks With Great Teachers: Philip Morrison.

    ERIC Educational Resources Information Center

    Roberts, Dana

    1982-01-01

    Presents excerpts of an interview with Philip Morrison, Institute Professor of Physics at M.I.T., who has made significant contributions to areas ranging from high-energy astrophysics to elementary school science education. (Author/SK)

  11. AAA (2010) CAPD clinical practice guidelines: need for an update.

    PubMed

    DeBonis, David A

    2017-09-01

    Review and critique of the clinical value of the AAA CAPD guidance document in light of criteria for credible and useful guidance documents, as discussed by Field and Lohr. A qualitative review of the of the AAA CAPD guidelines using a framework by Field and Lohr to assess their relative value in supporting the assessment and management of CAPD referrals. Relevant literature available through electronic search tools and published texts were used along with the AAA CAPD guidance document and the chapter by Field and Lohr. The AAA document does not meet many of the key requirements discussed by Field and Lohr. It does not reflect the current literature, fails to help clinicians understand for whom auditory processing testing and intervention would be most useful, includes contradictory suggestions which reduce clarity and appears to avoid conclusions that might cast the CAPD construct in a negative light. It also does not include input from diverse affected groups. All of these reduce the document's credibility. The AAA CAPD guidance document will need to be updated and re-conceptualised in order to provide meaningful guidance for clinicians.

  12. Advanced, Analytic, Automated (AAA) Measurement of Engagement during Learning

    ERIC Educational Resources Information Center

    D'Mello, Sidney; Dieterle, Ed; Duckworth, Angela

    2017-01-01

    It is generally acknowledged that engagement plays a critical role in learning. Unfortunately, the study of engagement has been stymied by a lack of valid and efficient measures. We introduce the advanced, analytic, and automated (AAA) approach to measure engagement at fine-grained temporal resolutions. The AAA measurement approach is grounded in…

  13. Molecularly Defined Nanostructures Based on a Novel AAA-DDD Triple Hydrogen-Bonding Motif.

    PubMed

    Papmeyer, Marcus; Vuilleumier, Clément A; Pavan, Giovanni M; Zhurov, Konstantin O; Severin, Kay

    2016-01-26

    A facile and flexible method for the synthesis of a new AAA-DDD triple hydrogen-bonding motif is described. Polytopic supramolecular building blocks with precisely oriented AAA and DDD groups are thus accessible in few steps. These building blocks were used for the assembly of large macrocycles featuring four AAA-DDD interactions and a macrobicyclic complex with a total of six AAA-DDD interactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. The m-AAA Protease Associated with Neurodegeneration Limits MCU Activity in Mitochondria.

    PubMed

    König, Tim; Tröder, Simon E; Bakka, Kavya; Korwitz, Anne; Richter-Dennerlein, Ricarda; Lampe, Philipp A; Patron, Maria; Mühlmeister, Mareike; Guerrero-Castillo, Sergio; Brandt, Ulrich; Decker, Thorsten; Lauria, Ines; Paggio, Angela; Rizzuto, Rosario; Rugarli, Elena I; De Stefani, Diego; Langer, Thomas

    2016-10-06

    Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca 2+ uniporter MCU. While MAIP1 assists biogenesis of the MCU subunit EMRE, the m-AAA protease degrades non-assembled EMRE and ensures efficient assembly of gatekeeper subunits with MCU. Loss of the m-AAA protease results in accumulation of constitutively active MCU-EMRE channels lacking gatekeeper subunits in neuronal mitochondria and facilitates mitochondrial Ca 2+ overload, mitochondrial permeability transition pore opening, and neuronal death. Together, our results explain neuronal loss in m-AAA protease deficiency by deregulated mitochondrial Ca 2+ homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. An AAA-DDD triply hydrogen-bonded complex easily accessible for supramolecular polymers.

    PubMed

    Han, Yi-Fei; Chen, Wen-Qiang; Wang, Hong-Bo; Yuan, Ying-Xue; Wu, Na-Na; Song, Xiang-Zhi; Yang, Lan

    2014-12-15

    For a complementary hydrogen-bonded complex, when every hydrogen-bond acceptor is on one side and every hydrogen-bond donor is on the other, all secondary interactions are attractive and the complex is highly stable. AAA-DDD (A=acceptor, D=donor) is considered to be the most stable among triply hydrogen-bonded sequences. The easily synthesized and further derivatized AAA-DDD system is very desirable for hydrogen-bonded functional materials. In this case, AAA and DDD, starting from 4-methoxybenzaldehyde, were synthesized with the Hantzsch pyridine synthesis and Friedländer annulation reaction. The association constant determined by fluorescence titration in chloroform at room temperature is 2.09×10(7)  M(-1) . The AAA and DDD components are not coplanar, but form a V shape in the solid state. Supramolecular polymers based on AAA-DDD triply hydrogen bonded have also been developed. This work may make AAA-DDD triply hydrogen-bonded sequences easily accessible for stimuli-responsive materials. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Characterization of the Modular Design of the Autolysin/Adhesin Aaa from Staphylococcus Aureus

    PubMed Central

    Hirschhausen, Nina; Schlesier, Tim; Peters, Georg; Heilmann, Christine

    2012-01-01

    Background Staphylococcus aureus is a frequent cause of serious and life-threatening infections, such as endocarditis, osteomyelitis, pneumonia, and sepsis. Its adherence to various host structures is crucial for the establishment of diseases. Adherence may be mediated by a variety of adhesins, among them the autolysin/adhesins Atl and Aaa. Aaa is composed of three N-terminal repeated sequences homologous to a lysin motif (LysM) that can confer cell wall attachment and a C-terminally located cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain having bacteriolytic activity in many proteins. Methodology/Principal Findings Here, we show by surface plasmon resonance that the LysM domain binds to fibrinogen, fibronectin, and vitronectin respresenting a novel adhesive function for this domain. Moreover, we demonstrated that the CHAP domain not only mediates the bacteriolytic activity, but also adherence to fibrinogen, fibronectin, and vitronectin, thus demonstrating for the first time an adhesive function for this domain. Adherence of an S. aureus aaa mutant and the complemented aaa mutant is slightly decreased and increased, respectively, to vitronectin, but not to fibrinogen and fibronectin, which might at least in part result from an increased expression of atl in the aaa mutant. Furthermore, an S. aureus atl mutant that showed enhanced adherence to fibrinogen, fibronectin, and endothelial cells also demonstrated increased aaa expression and production of Aaa. Thus, the redundant functions of Aaa and Atl might at least in part be interchangeable. Lastly, RT-PCR and zymographic analysis revealed that aaa is negatively regulated by the global virulence gene regulators agr and SarA. Conclusions/Significance We identified novel functions for two widely distributed protein domains, LysM and CHAP, i.e. the adherence to the extracellular matrix proteins fibrinogen, fibronectin, and vitronectin. The adhesive properties of Aaa might promote S. aureus

  17. Role of AAA(+)-proteins in peroxisome biogenesis and function.

    PubMed

    Grimm, Immanuel; Erdmann, Ralf; Girzalsky, Wolfgang

    2016-05-01

    Mutations in the PEX1 gene, which encodes a protein required for peroxisome biogenesis, are the most common cause of the Zellweger spectrum diseases. The recognition that Pex1p shares a conserved ATP-binding domain with p97 and NSF led to the discovery of the extended family of AAA+-type ATPases. So far, four AAA+-type ATPases are related to peroxisome function. Pex6p functions together with Pex1p in peroxisome biogenesis, ATAD1/Msp1p plays a role in membrane protein targeting and a member of the Lon-family of proteases is associated with peroxisomal quality control. This review summarizes the current knowledge on the AAA+-proteins involved in peroxisome biogenesis and function.

  18. A methodology for developing anisotropic AAA phantoms via additive manufacturing.

    PubMed

    Ruiz de Galarreta, Sergio; Antón, Raúl; Cazón, Aitor; Finol, Ender A

    2017-05-24

    An Abdominal Aortic Aneurysm (AAA) is a permanent focal dilatation of the abdominal aorta at least 1.5 times its normal diameter. The criterion of maximum diameter is still used in clinical practice, although numerical studies have demonstrated the importance of biomechanical factors for rupture risk assessment. AAA phantoms could be used for experimental validation of the numerical studies and for pre-intervention testing of endovascular grafts. We have applied multi-material 3D printing technology to manufacture idealized AAA phantoms with anisotropic mechanical behavior. Different composites were fabricated and the phantom specimens were characterized by biaxial tensile tests while using a constitutive model to fit the experimental data. One composite was chosen to manufacture the phantom based on having the same mechanical properties as those reported in the literature for human AAA tissue; the strain energy and anisotropic index were compared to make this choice. The materials for the matrix and fibers of the selected composite are, respectively, the digital materials FLX9940 and FLX9960 developed by Stratasys. The fiber proportion for the composite is equal to 0.15. The differences between the composite behavior and the AAA tissue are small, with a small difference in the strain energy (0.4%) and a maximum difference of 12.4% in the peak Green strain ratio. This work represents a step forward in the application of 3D printing technology for the manufacturing of AAA phantoms with anisotropic mechanical behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Loss of Drosophila i-AAA protease, dYME1L, causes abnormal mitochondria and apoptotic degeneration.

    PubMed

    Qi, Y; Liu, H; Daniels, M P; Zhang, G; Xu, H

    2016-02-01

    Mitochondrial AAA (ATPases Associated with diverse cellular Activities) proteases i-AAA (intermembrane space-AAA) and m-AAA (matrix-AAA) are closely related and have major roles in inner membrane protein homeostasis. Mutations of m-AAA proteases are associated with neuromuscular disorders in humans. However, the role of i-AAA in metazoans is poorly understood. We generated a deletion affecting Drosophila i-AAA, dYME1L (dYME1L(del)). Mutant flies exhibited premature aging, progressive locomotor deficiency and neurodegeneration that resemble some key features of m-AAA diseases. dYME1L(del) flies displayed elevated mitochondrial unfolded protein stress and irregular cristae. Aged dYME1L(del) flies had reduced complex I (NADH/ubiquinone oxidoreductase) activity, increased level of reactive oxygen species (ROS), severely disorganized mitochondrial membranes and increased apoptosis. Furthermore, inhibiting apoptosis by targeting dOmi (Drosophila Htra2/Omi) or DIAP1, or reducing ROS accumulation suppressed retinal degeneration. Our results suggest that i-AAA is essential for removing unfolded proteins and maintaining mitochondrial membrane architecture. Loss of i-AAA leads to the accumulation of oxidative damage and progressive deterioration of membrane integrity, which might contribute to apoptosis upon the release of proapoptotic molecules such as dOmi. Containing ROS level could be a potential strategy to manage mitochondrial AAA protease deficiency.

  20. "The Big WHY": Philip Morris's failed search for corporate social value.

    PubMed

    McDaniel, Patricia A; Malone, Ruth E

    2012-10-01

    We examined Philip Morris USA's exploration of corporate social responsibility practices and principles and its outcome. We analyzed archival internal tobacco industry documents, generated in 2000 to 2002, related to discussions of corporate social responsibility among a Corporate Responsibility Taskforce and senior management at Philip Morris. In exploring corporate social responsibility, Philip Morris executives sought to identify the company's social value-its positive contribution to society. Struggling to find an answer, they considered dramatically changing the way the company marketed its products, apologizing for past actions, and committing the company to providing benefits for future generations. These ideas were eventually abandoned. Despite an initial call to distinguish between social and economic value, Philip Morris ultimately equated social value with providing shareholder returns. When even tobacco executives struggle to define their company's social value, it signals an opening to advocate for endgame scenarios that would encourage supply-side changes appropriate to the scale of the tobacco disease epidemic and consistent with authentic social value.

  1. Altria Means Tobacco: Philip Morris’s Identity Crisis

    PubMed Central

    Smith, Elizabeth A.; Malone, Ruth E.

    2003-01-01

    Philip Morris Companies, the world’s largest and most profitable tobacco seller, has changed its corporate name to The Altria Group. The company has also embarked on a plan to improve its corporate image. Examination of internal company documents reveals that these changes have been planned for over a decade and that the company expects to reap specific and substantial rewards from them. Tobacco control advocates should be alert to the threat Philip Morris’s plans pose to industryfocused tobacco control campaigns. Company documents also suggest what the vulnerabilities of those plans are and how advocates might best exploit them. PMID:12660196

  2. Multi-Centre Study on Cardiovascular Risk Management on Patients Undergoing AAA Surveillance.

    PubMed

    Saratzis, A; Dattani, N; Brown, A; Shalhoub, J; Bosanquet, D; Sidloff, D; Stather, P

    2017-07-01

    The risk of cardiovascular events and death in patients with abdominal aortic aneurysms (AAA) is high. Screening has been introduced to reduce AAA related mortality; however, after AAA diagnosis, cardiovascular modification may be as important to patient outcomes as surveillance. The aim of this study was to assess cardiovascular risk reduction in patients with small AAA. Institutional approval was granted for The Vascular and Endovascular Research Network (VERN) to retrospectively collect data pertaining to cardiovascular risk reduction from four tertiary vascular units in England. Patients with small AAA (January 2013-December 2015) were included. Demographic details, postcode, current medications, and smoking status were recorded using a bespoke electronic database and analysed. In a secondary analysis VERN contacted all AAA screening units in England and Wales to assess their current protocols relating to CV protection. In total, 1053 patients were included (mean age 74 ± 9 years, all men). Of these, 745 patients (70.8%) had been prescribed an antiplatelet agent and 787 (74.7%) a statin. Overall, only 666 patients (63.2%) were prescribed both a statin and antiplatelet. Two hundred and sixty eight patients (32.1%) were current smokers and the proportion of patients who continued to smoke decreased with age. Overall, only 401 patients (48.1%) were prescribed a statin, antiplatelet, and had stopped smoking. In the secondary analysis 38 AAA screening units (84% national coverage) replied. Thirty-one units (82%) suggest changes to the patient's prescription; however, none monitor compliance with these recommendations or assess whether the general practitioner has been made aware of the AAA diagnosis or prescription advice. Many patients with small AAA are not prescribed an antiplatelet/statin, and still smoke cigarettes, and therefore remain at high risk of cardiovascular morbidity and mortality. National guidance to ensure this high risk group of patients is

  3. Combination of endovascular graft exclusion and drug therapy in AAA with hypertension or hyperglycemia.

    PubMed

    Wang, Dile; Qu, Bihui; He, Tao

    2017-08-01

    The objective of the present study was to evaluate the efficacy of combination of endovascular graft exclusion and drugs for hypertension/hyperglycemia for the treatment of abdominal aortic aneurysm (AAA). We analyzed 156 patients with AAA. Eighty-four patients were hypertensive and 72 were hyperglycemic. After endovascular graft exclusion, hypertensive patients were divided into four groups and treated with cyclopenthiazide, reserpine, propranolol, and placebo respectively. Hyperglycemic patients were divided into three groups and treated with metformin, insulin, and placebo respectively. Body temperature and peripheral blood leukocytes were measured at day 1, 2, 7, and 14 after endovascular graft exclusion. Size of AAAs, blood pressure, and blood sugar were measured again after 1 year. In hypertensive patients, the size of AAAs reduced after endovascular graft exclusion, while the combined treatments with cyclopenthiazide, reserpine, or propranolol helped to reduce blood pressure (blood pressure decrease <10 mmHg (18/21), <10 mmHg (12/21), <10 mmHg (8/21), and <10 mmHg (10/21) in the control group, cyclopenthiazide group, reserpine group, and propranolol group, respectively. AAA size decreased in the control group (P<0.001) and in the other three groups (P<0.0001). Similar results were obtained in hyperglycemic patients. The size of AAAs reduced after endovascular graft exclusion. Combined treatment with Metformin and Insulin reduced blood sugar (control, blood sugar >7.8 mmol/L (22/24), AAA size (P<0.001); metformin, blood sugar >7.8 mmol/L (14/24), AAA size (P<0.0001); insulin, blood sugar >7.8 mmol/L (11/24), AAA size (P<0.0001). Combination of endovascular graft exclusion with medicine is more effective than the former treatment alone for AAA therapy.

  4. Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

    PubMed

    Tong, Feng; Linares-Mendez, Iamnica J; Han, Yi-Fei; Wisner, James A; Wang, Hong-Bo

    2018-04-25

    Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.

  5. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders

    PubMed Central

    Law, Kelsey B.; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O.; Moser, Ann; Brumell, John H.; Braverman, Nancy

    2017-01-01

    ABSTRACT Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs. PMID:28521612

  6. The peroxisomal AAA ATPase complex prevents pexophagy and development of peroxisome biogenesis disorders.

    PubMed

    Law, Kelsey B; Bronte-Tinkew, Dana; Di Pietro, Erminia; Snowden, Ann; Jones, Richard O; Moser, Ann; Brumell, John H; Braverman, Nancy; Kim, Peter K

    2017-05-04

    Peroxisome biogenesis disorders (PBDs) are metabolic disorders caused by the loss of peroxisomes. The majority of PBDs result from mutation in one of 3 genes that encode for the peroxisomal AAA ATPase complex (AAA-complex) required for cycling PEX5 for peroxisomal matrix protein import. Mutations in these genes are thought to result in a defect in peroxisome assembly by preventing the import of matrix proteins. However, we show here that loss of the AAA-complex does not prevent matrix protein import, but instead causes an upregulation of peroxisome degradation by macroautophagy, or pexophagy. The loss of AAA-complex function in cells results in the accumulation of ubiquitinated PEX5 on the peroxisomal membrane that signals pexophagy. Inhibiting autophagy by genetic or pharmacological approaches rescues peroxisome number, protein import and function. Our findings suggest that the peroxisomal AAA-complex is required for peroxisome quality control, whereas its absence results in the selective degradation of the peroxisome. Thus the loss of peroxisomes in PBD patients with mutations in their peroxisomal AAA-complex is a result of increased pexophagy. Our study also provides a framework for the development of novel therapeutic treatments for PBDs.

  7. Roles of conserved arginines in ATP-binding domains of AAA+ chaperone ClpB from Thermus thermophilus.

    PubMed

    Yamasaki, Takashi; Nakazaki, Yosuke; Yoshida, Masasuke; Watanabe, Yo-hei

    2011-07-01

    ClpB, a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA+), forms a ring-shaped hexamer and cooperates with the DnaK chaperone system to reactivate aggregated proteins in an ATP-dependent manner. The ClpB protomer consists of an N-terminal domain, an AAA+ module (AAA-1), a middle domain, and a second AAA+ module (AAA-2). Each AAA+ module contains highly conserved WalkerA and WalkerB motifs, and two arginines (AAA-1) or one arginine (AAA-2). Here, we investigated the roles of these arginines (Arg322, Arg323, and Arg747) of ClpB from Thermus thermophilus in the ATPase cycle and chaperone function by alanine substitution. These mutations did not affect nucleotide binding, but did inhibit the hydrolysis of the bound ATP and slow the threading of the denatured protein through the central pore of the T. thermophilus ClpB ring, which severely impaired the chaperone functions. Previously, it was demonstrated that ATP binding to the AAA-1 module induced motion of the middle domain and stabilized the ClpB hexamer. However, the arginine mutations of the AAA-1 module destabilized the ClpB hexamer, even though ATP-induced motion of the middle domain was not affected. These results indicated that the three arginines are crucial for ATP hydrolysis and chaperone activity, but not for ATP binding. In addition, the two arginines in AAA-1 and the ATP-induced motion of the middle domain independently contribute to the stabilization of the hexamer. © 2011 The Authors Journal compilation © 2011 FEBS.

  8. Regionalization of Emergent Vascular Surgery for Patients With Ruptured AAA Improves Outcomes.

    PubMed

    Warner, Courtney J; Roddy, Sean P; Chang, Benjamin B; Kreienberg, Paul B; Sternbach, Yaron; Taggert, John B; Ozsvath, Kathleen J; Stain, Steven C; Darling, R Clement

    2016-09-01

    Safe and efficient endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (r-AAA) requires advanced infrastructure and surgical expertise not available at all US hospitals. The objective was to assess the impact of regionalizing r-AAA care to centers equipped for both open surgical repair (r-OSR) and EVAR (r-EVAR) by vascular surgeons. A retrospective review of all patients with r-AAA undergoing open or endovascular repair in a 12-hospital region. Patient demographics, transfer status, type of repair, and intraoperative variables were recorded. Outcomes included perioperative morbidity and mortality. Four hundred fifty-one patients with r-AAA were treated from 2002 to 2015. Three hundred twenty-one patients (71%) presented initially to community hospitals (CHs) and 130 (29%) presented to the tertiary medical center (MC). Of the 321 patients presenting to CH, 133 (41%) were treated locally (131 OSR; 2 EVAR) and 188 (59%) were transferred to the MC. In total, 318 patients were treated at the MC (122 OSR; 196 EVAR). At the MC, r-EVAR was associated with a lower mortality rate than r-OSR (20% vs 37%, P = 0.001). Transfer did not influence r-EVAR mortality (20% in r-EVAR presenting to MC vs 20% in r-EVAR transferred, P > 0.2). Overall, r-AAA mortality at the MC was 20% lower than CH (27% vs 46%, P < 0.001). Regionalization of r-AAA repair to centers equipped for both r-EVAR and r-OSR decreased mortality by approximately 20%. Transfer did not impact the mortality of r-EVAR at the tertiary center. Care of r-AAA in the US should be centralized to centers equipped with available technology and vascular surgeons.

  9. On the Impact of Intraluminal Thrombus Mechanical Behavior in AAA Passive Mechanics.

    PubMed

    Riveros, Fabián; Martufi, Giampaolo; Gasser, T Christian; Rodriguez-Matas, Jose F

    2015-09-01

    Intraluminal thrombus (ILT) is a pseudo-tissue that develops from coagulated blood, and is found in most abdominal aortic aneurysms (AAAs) of clinically relevant size. A number of studies have suggested that ILT mechanical characteristics may be related to AAA risk of rupture, even though there is still great controversy in this regard. ILT is isotropic and inhomogeneous and may appear as a soft (single-layered) or stiff (multilayered fibrotic) tissue. This paper aims to investigate how ILT constitution and topology influence the magnitude and location of peak wall stress (PWS). In total 21 patient-specific AAAs (diameter 4.2-5.4 cm) were reconstructed from computer tomography images and biomechanically analyzed using state-of-the-art modeling assumptions. Results indicated that PWS correlated stronger with ILT volume (ρ = 0.44, p = 0.05) and minimum thickness of ILT layer (ρ = 0.73, p = 0.001) than with maximum AAA diameter (ρ = 0.05, p = 0.82). On average PWS was 20% (SD 12%) higher for FE models that used soft instead of stiff ILT models (p < 0.001). PWS location strongly correlated with sites of minimum ILT thickness in the section of maximum AAA diameter and was independent from ILT stiffness. In addition, ILT heterogeneity, i.e., the spatial composition of soft and stiff thrombus tissue, can considerably influence stress in the AAA wall. The present study is limited to identification of influential biomechanical factors, and how its findings translate to an AAA rupture risk assessment remains to be explored by clinical studies.

  10. "Clockwork": Philip Pullman's Posthuman Fairy Tale

    ERIC Educational Resources Information Center

    Gooding, Richard

    2011-01-01

    This article examines the connections between posthumanism and narrative form in Philip Pullman's "Clockwork." Beginning with an account of Pullman's materialism, it argues that the novel represents consciousness and agency as emergent properties of matter, a position that manifests itself first in the tale's figurative language and later in the…

  11. Identifying patients with AAA with the highest risk following endovascular repair.

    PubMed

    Cadili, Ali; Turnbull, Robert; Hervas-Malo, Marilou; Ghosh, Sunita; Chyczij, Harold

    2012-08-01

    It has been demonstrated that endovascular repair of arterial disease results in reduced perioperative morbidity and mortality compared to open surgical repair. The rates of complications and need for reinterventions, however, have been found to be higher than that in open repair. The purpose of this study was to identify the predictors of endograft complications and mortality in patients undergoing endovascular abdominal aortic aneurysm (AAA) repair; specifically, our aim was to identify a subset of patients with AAA whose risk of periprocedure mortality was so high that they should not be offered endovascular repair. We undertook a prospective review of patients with AAA receiving endovascular therapy at a single institution. Collected variables included age, gender, date of procedure, indication for procedure, size of aneurysm (where applicable), type of endograft used, presence of rupture, American Society of Anesthesiologists (ASA) class, major medical comorbidities, type of anesthesia (general, epidural, or local), length of intensive care unit (ICU) stay, and length of hospital stay. These factors were correlated with the study outcomes (overall mortality, graft complications, morbidity, and reintervention) using univariate and multivariate logistic regression. A total of 199 patients underwent endovascular AAA repair during the study period. The ICU stay, again, was significantly correlated with the primary outcomes (death and graft complications). In addition, length of hospital stay greater than 3 days, also emerged as a statistically significant predictor of graft complications in this subgroup (P = .024). Survival analysis for patients with AAA revealed that age over 85 years and ICU stay were predictive of decreased survival. Statistical analysis for other subgroups of patients (inflammatory AAA or dissection) was not performed due to the small numbers in these subgroups. Patients with AAA greater than 85 years of age are at a greater risk of mortality

  12. Public versus internal conceptions of addiction: An analysis of internal Philip Morris documents.

    PubMed

    Elias, Jesse; Hendlin, Yogi Hale; Ling, Pamela M

    2018-05-01

    Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine's pharmacology and the user's biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine's addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement. We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris's move from public denial to public affirmation of nicotine's addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government's filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine's (IoM's) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris's public statements reinforce the idea that nicotine's pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis. Philip Morris's research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine's pharmacology, the industry's continued aggressive advertising, lobbying, and

  13. Assessment of the accuracy of AortaScan for detection of abdominal aortic aneurysm (AAA).

    PubMed

    Abbas, A; Smith, A; Cecelja, M; Waltham, M

    2012-02-01

    AortaScan AMI 9700 is a portable 3D ultrasound device that automatically measures the maximum diameter of the abdominal aorta without the need for a trained sonographer. It is designed to rapidly diagnose or exclude an AAA and may have particular use in screening programs. Our objective was to determine its accuracy to detect AAA. Subjects from our AAA screening and surveillance programs were examined. The aorta was scanned using the AortaScan and computed tomography (CT). Ninety-one subjects underwent imaging (44 AAA on conventional ultrasound surveillance and 47 controls). The largest measurement obtained by AortaScan was compared against the CT-aortic measurement. The mean aortic diameter was 2.8 cm. The CT scan confirmed the diagnosis of AAA in 43 subjects. There was one false positive measurement on conventional ultrasound. AortaScan missed the diagnosis of AAA in eight subjects. There were thirteen false positive measurements. The sensitivity, specificity, positive and negative predictive values were 81%, 72%, 72% and 81% respectively. A device to detect AAA without the need for a trained operator would have potential in a community-based screening programme. The AortaScan, however, lacks adequate sensitivity and significant technical improvement is necessary before it could be considered a replacement for trained screening personnel. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  14. From adversary to target market: the ACT-UP boycott of Philip Morris.

    PubMed

    Offen, N; Smith, E A; Malone, R E

    2003-06-01

    In 1990, the AIDS Coalition to Unleash Power (ACT-UP) sparked a year long boycott of Philip Morris's Marlboro cigarettes and Miller beer. The boycott protested the company's support of Senator Jesse Helms (R-North Carolina), a leading opponent of AIDS funding and civil rights for lesbian, gay, bisexual and transgender (LGBT) people. ACT-UP demanded that Philip Morris sever its ties with Helms and acknowledge its responsibility to the LGBT community and to people with AIDS. To assess the impact of the boycott on the LGBT community, the tobacco industry, and the tobacco control movement; and to determine what lessons tobacco control advocates can extract from this case. Internal tobacco industry documents and newspaper archives. Search of tobacco industry documents websites using "boycott", "ACT-UP", "gay", and other terms. Philip Morris used the boycott to its own advantage. It exploited differences within the community and settled the boycott by pledging large donations to combat AIDS. Through corporate philanthropy, Philip Morris gained entrée to the LGBT market without appearing gay friendly. Many LGBT organisations, thirsty for recognition and funding from mainstream corporations, welcomed Philip Morris's overtures without considering the health hazards of tobacco. Unless the goal of a boycott is to convince the tobacco industry to abandon tobacco altogether, such actions invite the industry to expand its marketing under the guise of philanthropy. Tobacco control advocates should be clear about goals and acceptable settlement terms before participating in a boycott of a tobacco company.

  15. Dosimetric comparison of peripheral NSCLC SBRT using Acuros XB and AAA calculation algorithms.

    PubMed

    Ong, Chloe C H; Ang, Khong Wei; Soh, Roger C X; Tin, Kah Ming; Yap, Jerome H H; Lee, James C L; Bragg, Christopher M

    2017-01-01

    There is a concern for dose calculation in highly heterogenous environments such as the thorax region. This study compares the quality of treatment plans of peripheral non-small cell lung cancer (NSCLC) stereotactic body radiation therapy (SBRT) using 2 calculation algorithms, namely, Eclipse Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB), for 3-dimensional conformal radiation therapy (3DCRT) and volumetric-modulated arc therapy (VMAT). Four-dimensional computed tomography (4DCT) data from 20 anonymized patients were studied using Varian Eclipse planning system, AXB, and AAA version 10.0.28. A 3DCRT plan and a VMAT plan were generated using AAA and AXB with constant plan parameters for each patient. The prescription and dose constraints were benchmarked against Radiation Therapy Oncology Group (RTOG) 0915 protocol. Planning parameters of the plan were compared statistically using Mann-Whitney U tests. Results showed that 3DCRT and VMAT plans have a lower target coverage up to 8% when calculated using AXB as compared with AAA. The conformity index (CI) for AXB plans was 4.7% lower than AAA plans, but was closer to unity, which indicated better target conformity. AXB produced plans with global maximum doses which were, on average, 2% hotter than AAA plans. Both 3DCRT and VMAT plans were able to achieve D95%. VMAT plans were shown to be more conformal (CI = 1.01) and were at least 3.2% and 1.5% lower in terms of PTV maximum and mean dose, respectively. There was no statistically significant difference for doses received by organs at risk (OARs) regardless of calculation algorithms and treatment techniques. In general, the difference in tissue modeling for AXB and AAA algorithm is responsible for the dose distribution between the AXB and the AAA algorithms. The AXB VMAT plans could be used to benefit patients receiving peripheral NSCLC SBRT. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights

  16. Public versus internal conceptions of addiction: An analysis of internal Philip Morris documents

    PubMed Central

    2018-01-01

    Background Tobacco addiction is a complex, multicomponent phenomenon stemming from nicotine’s pharmacology and the user’s biology, psychology, sociology, and environment. After decades of public denial, the tobacco industry now agrees with public health authorities that nicotine is addictive. In 2000, Philip Morris became the first major tobacco company to admit nicotine’s addictiveness. Evolving definitions of addiction have historically affected subsequent policymaking. This article examines how Philip Morris internally conceptualized addiction immediately before and after this announcement. Methods and findings We analyzed previously secret, internal Philip Morris documents made available as a result of litigation against the tobacco industry. We compared these documents to public company statements and found that Philip Morris’s move from public denial to public affirmation of nicotine’s addictiveness coincided with pressure on the industry from poor public approval ratings, the Master Settlement Agreement (MSA), the United States government’s filing of the Racketeer Influenced and Corrupt Organizations (RICO) suit, and the Institute of Medicine’s (IoM’s) endorsement of potentially reduced risk products. Philip Morris continued to research the causes of addiction through the 2000s in order to create successful potentially reduced exposure products (PREPs). While Philip Morris’s public statements reinforce the idea that nicotine’s pharmacology principally drives smoking addiction, company scientists framed addiction as the result of interconnected biological, social, psychological, and environmental determinants, with nicotine as but one component. Due to the fragmentary nature of the industry document database, we may have missed relevant information that could have affected our analysis. Conclusions Philip Morris’s research suggests that tobacco industry activity influences addiction treatment outcomes. Beyond nicotine’s pharmacology

  17. AAA+ Machines of Protein Destruction in Mycobacteria.

    PubMed

    Alhuwaider, Adnan Ali H; Dougan, David A

    2017-01-01

    The bacterial cytosol is a complex mixture of macromolecules (proteins, DNA, and RNA), which collectively are responsible for an enormous array of cellular tasks. Proteins are central to most, if not all, of these tasks and as such their maintenance (commonly referred to as protein homeostasis or proteostasis) is vital for cell survival during normal and stressful conditions. The two key aspects of protein homeostasis are, (i) the correct folding and assembly of proteins (coupled with their delivery to the correct cellular location) and (ii) the timely removal of unwanted or damaged proteins from the cell, which are performed by molecular chaperones and proteases, respectively. A major class of proteins that contribute to both of these tasks are the AAA+ (ATPases associated with a variety of cellular activities) protein superfamily. Although much is known about the structure of these machines and how they function in the model Gram-negative bacterium Escherichia coli , we are only just beginning to discover the molecular details of these machines and how they function in mycobacteria. Here we review the different AAA+ machines, that contribute to proteostasis in mycobacteria. Primarily we will focus on the recent advances in the structure and function of AAA+ proteases, the substrates they recognize and the cellular pathways they control. Finally, we will discuss the recent developments related to these machines as novel drug targets.

  18. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis

    PubMed Central

    Elsholz, Alexander K. W.; Birk, Marlene S.; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis. We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics. PMID:28748186

  19. Functional Diversity of AAA+ Protease Complexes in Bacillus subtilis.

    PubMed

    Elsholz, Alexander K W; Birk, Marlene S; Charpentier, Emmanuelle; Turgay, Kürşad

    2017-01-01

    Here, we review the diverse roles and functions of AAA+ protease complexes in protein homeostasis, control of stress response and cellular development pathways by regulatory and general proteolysis in the Gram-positive model organism Bacillus subtilis . We discuss in detail the intricate involvement of AAA+ protein complexes in controlling sporulation, the heat shock response and the role of adaptor proteins in these processes. The investigation of these protein complexes and their adaptor proteins has revealed their relevance for Gram-positive pathogens and their potential as targets for new antibiotics.

  20. Structural basis for the ATP-independent proteolytic activity of LonB proteases and reclassification of their AAA+ modules.

    PubMed

    An, Young Jun; Na, Jung-Hyun; Kim, Myung-Il; Cha, Sun-Shin

    2015-10-01

    Lon proteases degrade defective or denature proteins as well as some folded proteins for the control of cellular protein quality. There are two types of Lon proteases, LonA and LonB. Each consists of two functional components: a protease component and an ATPase associated with various cellular activities (AAA+ module). Here, we report the 2.03 -resolution crystal structure of the isolated AAA+ module (iAAA+ module) of LonB from Thermococcus onnurineus NA1 (TonLonB). The iAAA+ module, having no bound nucleotide, adopts a conformation virtually identical to the ADP-bound conformation of AAA+ modules in the hexameric structure of TonLonB; this provides insights into the ATP-independent proteolytic activity observed in a LonB protease. Structural comparison of AAA+ modules between LonA and LonB revealed that the AAA+ modules of Lon proteases are separated into two distinct clades depending on their structural features. The AAA+ module of LonB belongs to the -H2 & Ins1 insert clade (HINS clade)- defined for the first time in this study, while the AAA+ module of LonA is a member of the HCLR clade.

  1. The AAA protein spastin possesses two levels of basal ATPase activity.

    PubMed

    Fan, Xiangyu; Lin, Zhijie; Fan, Guanghui; Lu, Jing; Hou, Yongfei; Habai, Gulijiazi; Sun, Linyue; Yu, Pengpeng; Shen, Yuequan; Wen, Maorong; Wang, Chunguang

    2018-05-01

    The AAA ATPase spastin is a microtubule-severing enzyme that plays important roles in various cellular events including axon regeneration. Herein, we found that the basal ATPase activity of spastin is negatively regulated by spastin concentration. By determining a spastin crystal structure, we demonstrate the necessity of intersubunit interactions between spastin AAA domains. Neutralization of the positive charges in the microtubule-binding domain (MTBD) of spastin dramatically decreases the ATPase activity at low concentration, although the ATP-hydrolyzing potential is not affected. These results demonstrate that, in addition to the AAA domain, the MTBD region of spastin is also involved in regulating ATPase activity, making interactions between spastin protomers more complicated than expected. © 2018 Federation of European Biochemical Societies.

  2. A conserved inter-domain communication mechanism regulates the ATPase activity of the AAA-protein Drg1.

    PubMed

    Prattes, Michael; Loibl, Mathias; Zisser, Gertrude; Luschnig, Daniel; Kappel, Lisa; Rössler, Ingrid; Grassegger, Manuela; Hromic, Altijana; Krieger, Elmar; Gruber, Karl; Pertschy, Brigitte; Bergler, Helmut

    2017-03-17

    AAA-ATPases fulfil essential roles in different cellular pathways and often act in form of hexameric complexes. Interaction with pathway-specific substrate and adaptor proteins recruits them to their targets and modulates their catalytic activity. This substrate dependent regulation of ATP hydrolysis in the AAA-domains is mediated by a non-catalytic N-terminal domain. The exact mechanisms that transmit the signal from the N-domain and coordinate the individual AAA-domains in the hexameric complex are still the topic of intensive research. Here, we present the characterization of a novel mutant variant of the eukaryotic AAA-ATPase Drg1 that shows dysregulation of ATPase activity and altered interaction with Rlp24, its substrate in ribosome biogenesis. This defective regulation is the consequence of amino acid exchanges at the interface between the regulatory N-domain and the adjacent D1 AAA-domain. The effects caused by these mutations strongly resemble those of pathological mutations of the AAA-ATPase p97 which cause the hereditary proteinopathy IBMPFD (inclusion body myopathy associated with Paget's disease of the bone and frontotemporal dementia). Our results therefore suggest well conserved mechanisms of regulation between structurally, but not functionally related members of the AAA-family.

  3. From adversary to target market: the ACT-UP boycott of Philip Morris

    PubMed Central

    Offen, N; Smith, E; Malone, R

    2003-01-01

    Background: In 1990, the AIDS Coalition to Unleash Power (ACT-UP) sparked a year long boycott of Philip Morris's Marlboro cigarettes and Miller beer. The boycott protested the company's support of Senator Jesse Helms (R-North Carolina), a leading opponent of AIDS funding and civil rights for lesbian, gay, bisexual and transgender (LGBT) people. ACT-UP demanded that Philip Morris sever its ties with Helms and acknowledge its responsibility to the LGBT community and to people with AIDS. Objective: To assess the impact of the boycott on the LGBT community, the tobacco industry, and the tobacco control movement; and to determine what lessons tobacco control advocates can extract from this case. Data sources: Internal tobacco industry documents and newspaper archives. Methods: Search of tobacco industry documents websites using "boycott", "ACT-UP", "gay", and other terms. Results: Philip Morris used the boycott to its own advantage. It exploited differences within the community and settled the boycott by pledging large donations to combat AIDS. Through corporate philanthropy, Philip Morris gained entrée to the LGBT market without appearing gay friendly. Many LGBT organisations, thirsty for recognition and funding from mainstream corporations, welcomed Philip Morris's overtures without considering the health hazards of tobacco. Conclusions: Unless the goal of a boycott is to convince the tobacco industry to abandon tobacco altogether, such actions invite the industry to expand its marketing under the guise of philanthropy. Tobacco control advocates should be clear about goals and acceptable settlement terms before participating in a boycott of a tobacco company. PMID:12773732

  4. Stress Testing of the Philips 60W Replacement Lamp L Prize Entry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Poplawski, Michael E.; Ledbetter, Marc R.; Smith, Mark

    2012-04-24

    The Pacific Northwest National Laboratory, operated by Battelle for the U.S. Department of Energy, worked with Intertek to develop a procedure for stress testing medium screw-base light sources. This procedure, composed of alternating stress cycles and performance evaluation, was used to qualitatively compare and contrast the durability and reliability of the Philips 60W replacement lamp L Prize entry with market-proven compact fluorescent lamps (CFLs) with comparable light output and functionality. The stress cycles applied simultaneous combinations of electrical, thermal, vibration, and humidity stresses of increasing magnitude. Performance evaluations measured relative illuminance, x chromaticity and y chromaticity shifts after each stressmore » cycle. The Philips L Prize entry lamps appear to be appreciably more durable than the incumbent energy-efficient technology, as represented by the evaluated CFLs, and with respect to the applied stresses. Through the course of testing, all 15 CFL samples permanently ceased to function as a result of the applied stresses, while only 1 Philips L Prize entry lamp exhibited a failure, the nature of which was minor, non-destructive, and a consequence of a known (and resolved) subcontractor issue. Given that current CFL technology appears to be moderately mature and no Philips L Prize entry failures could be produced within the stress envelope causing 100 percent failure of the benchmark CFLs, it seems that, in this particular implementation, light-emitting diode (LED) technology would be much more durable in the field than current CFL technology. However, the Philips L Prize entry lamps used for testing were carefully designed and built for the competition, while the benchmark CFLs were mass produced for retail sale—a distinction that should be taken into consideration. Further reliability testing on final production samples would be necessary to judge the extent to which the results of this analysis apply to production

  5. Pictorial account and landscape evolution of the crevasses near Fort St. Philip, Louisiana

    USGS Publications Warehouse

    Suir, Glenn M.; Jones, William R.; Garber, Adrienne L.; Barras, John A.

    2014-01-01

    Quantifying the effects of active natural and constructed crevasses is critical to the planning and success of future ecosystem restoration activities. This document provides a historical overview of landscape changes within the vicinity of the natural crevasses near Fort St. Philip, Louisiana. A significant event influencing landscape change within the Fort St. Philip study area was the breaching of the eastern levee of the Mississippi River. Initially, the river water that was diverted through these crevasse channels physically removed significant marsh areas within the study area. These initial direct impacts were succeeded by several decades of larger regional loss patterns driven by subsidence and other episodic events (e.g, hurricanes and floods), and recent localized land gains. These increases in land area are potentially the long-term results of the Fort St. Philip crevasses, and the short-term impacts of delta management activities. However, for the majority of the 1956-2008 period of analysis, the crevassing of the eastern bank of the Mississippi River levee was a loss accelerant in the Fort St. Philip area.

  6. “The Big WHY”: Philip Morris’s Failed Search for Corporate Social Value

    PubMed Central

    Malone, Ruth E.

    2012-01-01

    Objectives. We examined Philip Morris USA’s exploration of corporate social responsibility practices and principles and its outcome. Methods. We analyzed archival internal tobacco industry documents, generated in 2000 to 2002, related to discussions of corporate social responsibility among a Corporate Responsibility Taskforce and senior management at Philip Morris. Results. In exploring corporate social responsibility, Philip Morris executives sought to identify the company’s social value—its positive contribution to society. Struggling to find an answer, they considered dramatically changing the way the company marketed its products, apologizing for past actions, and committing the company to providing benefits for future generations. These ideas were eventually abandoned. Despite an initial call to distinguish between social and economic value, Philip Morris ultimately equated social value with providing shareholder returns. Conclusions. When even tobacco executives struggle to define their company’s social value, it signals an opening to advocate for endgame scenarios that would encourage supply-side changes appropriate to the scale of the tobacco disease epidemic and consistent with authentic social value. PMID:22897536

  7. Abdominal aorta aneurysm (AAA): Is there a role for prevention and therapy using antioxidants?

    PubMed

    Pincemail, Joël; Defraigne, Jean-Olivier; Courtois, Audrey; Albert, Adelin; Cheramy-Bien, Jean-Paul; Sakalihasan, Natzi

    2017-09-18

    Abdominal aortic aneurysm (AAA) is a degenerative disease that cause mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seems to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. Reducing oxidative stress by antioxidants has been shown to be a potential strategy for limiting AAA development. Human studies confirmed that oxidative stress and endothelial dysfunction are well associated with AAA development. Unfortunately, there is currently no evidence showing that strategies using low molecular weight antioxidants (vitamins C and E, β-carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function but also their capacity to stimulate enzymatic antioxidants trough activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. Clinical studies are therefore urgently necessary to confirm such a suggestion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. A. Philip Randolph: Integration in the Workplace.

    ERIC Educational Resources Information Center

    Wright, Sarah

    This biography for younger readers describes the life of A. Philip Randolph, the civil rights activist who organized the labor union for Pullman car porters, the Brotherhood of Sleeping Car Porters. The book presents an overview of the civil rights movement in the United States while documenting the part Randolph played as advocate for African…

  9. Campaign to counter a deteriorating consumer market: Philip Morris's Project Sunrise.

    PubMed

    Givel, M

    2013-02-01

    From 1997 to 2000, Philip Morris implemented Project Sunrise. This paper discusses the impact of this project on national and Philip Morris's cigarette unit sales, public opinion about smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use. A qualitative archival content analysis of Project Sunrise from 1997 to 2000, and a descriptive statistical analysis of cigarette unit sales and operating profits, acceptability of smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use from 1996 to 2006. Qualitative data sources related to Project Sunrise found on WebCat, Pubmed.com, LexisNexis Academic and Philip Morris's website, and archived tobacco industry documents were analysed using NVivo Version 9.0. A descriptive statistical analysis of cigarette unit sales, public opinion about smoking and secondhand tobacco smoke, and national prevalence trends for tobacco use was undertaken. Project Sunrise was a high-level strategic corporate plan to maintain profits that included four possible scenarios resulting in seven interwoven strategies. However, national prevalence rates for tobacco use declined, sales of national and Philip Morris cigarettes declined, operating profits remained at substantially lower levels after 2000 from 2001 to 2006, and a large majority of Americans agreed that there were significant health dangers associated with smoking and secondhand tobacco smoke. The impact of Project Sunrise, including countering the anti-tobacco movement, was less than successful in the USA. Copyright © 2012 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  10. Contributions of Philip Teitelbaum to affective neuroscience.

    PubMed

    Berridge, Kent C

    2012-06-01

    As part of a festschrift issue for Philip Teitelbaum, I offer here the thesis that Teitelbaum deserves to be viewed as an important forefather to the contemporary field of affective neuroscience (which studies motivation, emotion and affect in the brain). Teitelbaum's groundbreaking analyses of motivation deficits induced by lateral hypothalamic damage, of roles of food palatability in revealing residual function, and of recovery of 'lost' functions helped shape modern understanding of how motivation circuits operate within the brain. His redefinition of the minimum requirement for identifying motivation raised the conceptual bar for thinking about the topic among behavioral neuroscientists. His meticulous analyses of patterned stages induced by brain manipulations, life development and clinical disorders added new dimensions to our appreciation of how brain systems work. His steadfast highlighting of integrative functions and behavioral complexity helped provide a healthy functionalist counterbalance to reductionist trends in science of the late 20th century. In short, Philip Teitelbaum can be seen to have made remarkable contributions to several domains of psychology and neuroscience, including affective neuroscience. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Contributions of Philip Teitelbaum to affective neuroscience

    PubMed Central

    Berridge, Kent C.

    2011-01-01

    As part of a festschrift issue for Philip Teitelbaum, I offer here the thesis that Teitelbaum deserves to be viewed as an important forefather to the contemporary field of affective neuroscience (which studies motivation, emotion and affect in the brain). Teitelbaum’s groundbreaking analyses of motivation deficits induced by lateral hypothalamic damage, of roles of food palatability in revealing residual function, and of recovery of ‘lost’ functions helped shape modern understanding of how motivation circuits operate within the brain. His redefinition of the minimum requirement for identifying motivation raised the conceptual bar for thinking about the topic among behavioral neuroscientists. His meticulous analyses of patterned stages induced by brain manipulations, life development and clinical disorders added new dimensions to our appreciation of how brain systems work. His steadfast highlighting of integrative functions and behavioral complexity helped provide a healthy functionalist counterbalance to reductionist trends in science of the late 20th century. In short, Philip Teitelbaum can be seen to have made remarkable contributions to several domains of psychology and neuroscience, including affective neuroscience. PMID:22051942

  12. Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak.

    PubMed

    Mascoli, C; Freyrie, A; Gargiulo, M; Gallitto, E; Pini, R; Faggioli, G; Serra, C; De Molo, C; Stella, A

    2016-05-01

    The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra-procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02-0.35; p < .001). No differences in median AAA sac

  13. The Airborne Astronomy Ambassadors (AAA) Program and NASA Astrophysics Connections

    NASA Astrophysics Data System (ADS)

    Backman, Dana Edward; Clark, Coral; Harman, Pamela

    2018-01-01

    The NASA Airborne Astronomy Ambassadors (AAA) program is a three-part professional development (PD) experience for high school physics, astronomy, and earth science teachers. AAA PD consists of: (1) blended learning via webinars, asynchronous content delivery, and in-person workshops, (2) a STEM immersion experience at NASA Armstrong’s B703 science research aircraft facility in Palmdale, California, including interactions with NASA astrophysics & planetary science Subject Matter Experts (SMEs) during science flights on SOFIA, and (3) continuing post-flight opportunities for teacher & student connections with SMEs.

  14. Did King Philip II of Ancient Macedonia Suffer a Zygomatico-Orbital Fracture? A Maxillofacial Surgeon's Approach.

    PubMed

    Stathopoulos, Panagiotis

    2017-09-01

    Philip II, father of Alexander the Great, succeeded his brother, Perdiccas III, to the throne of Macedonia in 360 BC. He has been described by historians as a generous king and military genius who managed to achieve his ambitious plans by expanding the Macedonian city-state over the whole Greek territory and the greater part of the Balkan Peninsula. The aim of our study was to present the evidence with regard to the facial injury of King Philip II of Macedonia and discuss the treatment of the wound by his famous physician, Critobulos. We reviewed the literature for historical, archaeological, and paleopathological evidence of King Philip's facial injury. We include a modern reconstruction of Philip's face based on the evidence of his injury by a team of anatomists and archaeologists from the Universities of Bristol and Manchester. In the light of the archaeological findings by Professor Andronikos and the paleopathological evidence by Musgrave, it can be claimed with confidence that King Philip II suffered a significant injury of his zygomaticomaxillary complex and supraorbital rim caused by an arrow as can be confirmed in many historical sources. To the best of our knowledge, this is the first attempt to present the trauma of King Philip II from a maxillofacial surgeon's point of view.

  15. Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

    2006-03-01

    The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

  16. Improved Resident Adherence to AAA Screening Guidelines via an Electronic Reminder.

    PubMed

    Sypert, David; Van Dyke, Kenneth; Dhillon, Namrata; Elliott, John O; Jordan, Kim

    The 2014 United States Preventive Services Task Force systematic review found abdominal aortic aneurysm (AAA) screening decreased related mortality by close to half. Despite the simplicity of screening, research suggests poor adherence to the recommended AAA screening guidelines. Using the quality improvement plan-study-do-act cycle, we retrospectively established poor adherence to AAA screening and poor documentation of smoking history in our resident clinic. An electronic reminder was prospectively implemented into our electronic medical record (EMR) with the goal of improving screening rates. After 1 year, a retrospective chart review was conducted. Comparisons of the pre- and post-electronic reminder intervention data were made using chi-square tests and odds ratios (OR). The purposeful AAA screening rate improved 27.8% during the intervention, 40.3% (95% confidence interval [CI]: 28.6-52.0%) versus 12.5% (95% CI: 3.1-21.9%), p = .002, suggesting patients were more likely to be screened as a result of the electronic reminder, OR = 4.73 (95% CI: 1.77-12.65). This improvement translates to a large effect size, Cohen's d = 0.86 (95% CI: 0.31-1.40). Electronic reminders are a simple EMR addition that can provide evidence-based education while improving adherence rates with preventive health screening measures.

  17. Persistent type II endoleak after EVAR: the predictive value of the AAA thrombus volume.

    PubMed

    Gallitto, Enrico; Gargiulo, Mauro; Mascoli, Chiara; Freyrie, Antonio; DE Matteis, Massimo; Serra, Carla; Bianchini Massoni, Claudio; Faggioli, Gianluca; Stella, Andrea

    2018-02-01

    Persistent type II endoleaks (ELIIp, ≥6 months) after an endovascular aneurysm repair (EVAR) can be associated with adverse outcomes. The aims of this study are the evaluation of the incidence of ELIIp, their preoperative morphological predictive features (PMF) and the post-EVAR abdominal aortic aneurysm (AAA) evolution in the presence of ELIIp. Patients underwent EVAR between 2008 and 2010 were prospectively collected. Cases with ELIIp (group A: AG) were identified. A control group without ELIIp (group B: BG), homogeneous for clinical characteristics, follow-up timing and methods (CTA and/or CEUS at 6.12 months and yearly thereafter) was retrospectively selected. The PMF evaluated by computed-tomography-angiography (CTA) were: AAA-diameter, number and diameter of AAA efferent patent vessels (EPV), AAA-total volume (TV), AAA-thrombus volume (THV) and TV/THV rate (%VR). Volumes were calculated by the dedicated vessels analysis software. AG and BG were compared. The primary endpoint was to evaluate the incidence of ELIIp. Secondary endpoints were to analyze the relation between PMF and ELIIp and to assess the post-EVAR AAA-evolution in the presence of ELIIp. Between 2008 and 2010, 200 patients underwent EVAR to treat AAA electively. An ELIIp was detected in 35cases (17.5%) (AG). Twenty-seven patients (13.5%) were included in BG. An overall of 62 patients (GA+GB) were analyzed. The mean pre-operative AAA diameter and EPV were 58±11.6 mm and 5.5±1.8 mm, respectively. The mean TV and THV were 187±111.5 cc and 82±75 cc, respectively. The median %VR was 42.3%. ELIIp was correlated to EPV≥6 (χ2, p=.015) and %VR <40% (logistic regression, P=0.032). The mean follow-up was 22±9 months. Seven (20%) ELIIp spontaneously sealed and 6 (17%) required reinterventions (2 conversions to OR). There were not PMF associated to ELIIp evolution and AAA growth post-EVAR. ELIIp is a not rare complication and it could require re-interventions. Our data suggest that VEP≥6 or %VT<40

  18. Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

    PubMed

    Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

    2014-01-01

    In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

  19. Siemens, Philips megaproject to yield superchip in 5 years

    NASA Astrophysics Data System (ADS)

    1985-02-01

    The development of computer chips using complementary metal oxide semiconductor (CMOS) memory technology is described. The management planning and marketing strategy of the Philips and Siemens corporations with regard to the memory chip are discussed.

  20. Prevalence of abdominal aortic aneurysm (AAA) in a population undergoing computed tomography colonography in Canterbury, New Zealand.

    PubMed

    Khashram, M; Jones, G T; Roake, J A

    2015-08-01

    There is compelling level 1 evidence in support of screening men for abdominal aortic aneurysm (AAA) to reduce AAA mortality. However, New Zealand (NZ) lacks data on AAA prevalence, and national screening has not been implemented. The aim of this study was to determine the prevalence of AAA in a population undergoing a computed tomography colonography (CTC) for gastrointestinal symptoms. This was an observational study; all consecutive CTCs performed in three regions of the South Island of NZ over a 4 year period were reviewed. Data on abdominal and thoracic aorta diameters ≥30 mm, and iliac and femoral aneurysms ≥20 mm were recorded. Previous aortic surgical grafts or endovascular stents were also documented. Demographics, survival, and AAA related outcomes were collected and used for analysis. Included were 4,893 scans on 4,644 patients (1,933 men [41.6%], 2,711 women [58.4%]) with a median age of 69.3 years (range 17.0-97.0 years). There were 309 scans on 289 patients (75.4% men) who had either an aneurysm or a previous aortic graft with a median age of 79.6 years (range 57.0-96.0 years). Of these, 223 had a native AAA ≥30 mm. The prevalence of AAA rose with age from 1.3% in men aged 55-64 years, to 9.1% in 65-74 year olds, 16.8% in 75-84 year olds, and 22.0% in ≥85 year olds. The corresponding figures in women were 0.4%, 2%, 3.9%, and 6.2%, respectively. In this observational study, the prevalence of AAA was high and warrants further evaluation. The results acquired help to define a population that may benefit from a national AAA screening programme. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  1. Peak AAA fatty acid homolog contaminants present in the dietary supplement l-Tryptophan associated with the onset of eosinophilia-myalgia syndrome.

    PubMed

    Klarskov, Klaus; Gagnon, Hugo; Racine, Mathieu; Boudreault, Pierre-Luc; Normandin, Chad; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-05-22

    The eosinophilia-myalgia syndrome (EMS) outbreak that occurred in the USA and elsewhere in 1989 was caused by the ingestion of Showa Denko K.K. (SD) L-tryptophan (L-Trp). "Six compounds" detected in the L-Trp were reported as case-associated contaminants. Recently the final and most statistically significant contaminant, "Peak AAA" was structurally characterized. The "compound" was actually shown to be two structural isomers resulting from condensation reactions of L-Trp with fatty acids derived from the bacterial cell membrane. They were identified as the indole C-2 anteiso (AAA 1 -343) and linear (AAA 2 -343) aliphatic chain isomers. Based on those findings, we utilized a combination of on-line HPLC-electrospray ionization mass spectrometry (LC-MS), as well as both precursor and product ion tandem mass spectrometry (MS/MS) to facilitate identification of a homologous family of condensation products related to AAA 1 -343 and AAA 2 -343. We structurally characterized eight new AAA 1 -XXX/AAA 2 -XXX contaminants, where XXX represents the integer molecular ions of all the related homologs, differing by aliphatic chain length and isomer configuration. The contaminants were derived from the following fatty acids of the bacterial cell membrane, 5-methylheptanoic acid (anteiso-C8:0) for AAA 1 -315; n-octanoic acid (n-C8:0) for AAA 2 -315; 6-methyloctanoic acid (anteiso-C9:0) for AAA 1 -329; n-nonanoic acid (n-C9:0) for AAA 2 -329; 10-methyldodecanoic acid (anteiso-C13:0) for AAA 1 -385; n-tridecanoic acid (n-C13:0) for AAA 2 -385; 11-methyltridecanoic acid (anteiso-C14:0) for AAA 1 -399; and n-tetradecanoic acid (n-C14:0) for AAA 2 -399. The concentration levels for these contaminants were estimated to be 0.1-7.9 μg / 500 mg of an individual SD L-Trp tablet or capsule The structural similarity of these homologs to case-related contaminants of Spanish Toxic Oil Syndrome (TOS) is discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Multibands tunneling in AAA-stacked trilayer graphene

    NASA Astrophysics Data System (ADS)

    Redouani, Ilham; Jellal, Ahmed; Bahaoui, Abdelhadi; Bahlouli, Hocine

    2018-04-01

    We study the electronic transport through np and npn junctions for AAA-stacked trilayer graphene. Two kinds of gates are considered where the first is a single gate and the second is a double gate. After obtaining the solutions for the energy spectrum, we use the transfer matrix method to determine the three transmission probabilities for each individual cone τ = 0 , ± 1 . We show that the quasiparticles in AAA-stacked trilayer graphene are not only chiral but also labeled by an additional cone index τ. The obtained bands are composed of three Dirac cones that depend on the chirality indexes. We show that there is perfect transmission for normal or near normal incidence, which is a manifestation of the Klein tunneling effect. We analyze also the corresponding total conductance, which is defined as the sum of the conductance channels in each individual cone. Our results are numerically discussed and compared with those obtained for ABA- and ABC-stacked trilayer graphene.

  3. SU-E-T-538: Evaluation of IMRT Dose Calculation Based on Pencil-Beam and AAA Algorithms.

    PubMed

    Yuan, Y; Duan, J; Popple, R; Brezovich, I

    2012-06-01

    To evaluate the accuracy of dose calculation for intensity modulated radiation therapy (IMRT) based on Pencil Beam (PB) and Analytical Anisotropic Algorithm (AAA) computation algorithms. IMRT plans of twelve patients with different treatment sites, including head/neck, lung and pelvis, were investigated. For each patient, dose calculation with PB and AAA algorithms using dose grid sizes of 0.5 mm, 0.25 mm, and 0.125 mm, were compared with composite-beam ion chamber and film measurements in patient specific QA. Discrepancies between the calculation and the measurement were evaluated by percentage error for ion chamber dose and γ〉l failure rate in gamma analysis (3%/3mm) for film dosimetry. For 9 patients, ion chamber dose calculated with AAA-algorithms is closer to ion chamber measurement than that calculated with PB algorithm with grid size of 2.5 mm, though all calculated ion chamber doses are within 3% of the measurements. For head/neck patients and other patients with large treatment volumes, γ〉l failure rate is significantly reduced (within 5%) with AAA-based treatment planning compared to generally more than 10% with PB-based treatment planning (grid size=2.5 mm). For lung and brain cancer patients with medium and small treatment volumes, γ〉l failure rates are typically within 5% for both AAA and PB-based treatment planning (grid size=2.5 mm). For both PB and AAA-based treatment planning, improvements of dose calculation accuracy with finer dose grids were observed in film dosimetry of 11 patients and in ion chamber measurements for 3 patients. AAA-based treatment planning provides more accurate dose calculation for head/neck patients and other patients with large treatment volumes. Compared with film dosimetry, a γ〉l failure rate within 5% can be achieved for AAA-based treatment planning. © 2012 American Association of Physicists in Medicine.

  4. Structural Insights into the Allosteric Operation of the Lon AAA+ Protease.

    PubMed

    Lin, Chien-Chu; Su, Shih-Chieh; Su, Ming-Yuan; Liang, Pi-Hui; Feng, Chia-Cheng; Wu, Shih-Hsiung; Chang, Chung-I

    2016-05-03

    The Lon AAA+ protease (LonA) is an evolutionarily conserved protease that couples the ATPase cycle into motion to drive substrate translocation and degradation. A hallmark feature shared by AAA+ proteases is the stimulation of ATPase activity by substrates. Here we report the structure of LonA bound to three ADPs, revealing the first AAA+ protease assembly where the six protomers are arranged alternately in nucleotide-free and bound states. Nucleotide binding induces large coordinated movements of conserved pore loops from two pairs of three non-adjacent protomers and shuttling of the proteolytic groove between the ATPase site and a previously unknown Arg paddle. Structural and biochemical evidence supports the roles of the substrate-bound proteolytic groove in allosteric stimulation of ATPase activity and the conserved Arg paddle in driving substrate degradation. Altogether, this work provides a molecular framework for understanding how ATP-dependent chemomechanical movements drive allosteric processes for substrate degradation in a major protein-destruction machine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A pull-back algorithm to determine the unloaded vascular geometry in anisotropic hyperelastic AAA passive mechanics.

    PubMed

    Riveros, Fabián; Chandra, Santanu; Finol, Ender A; Gasser, T Christian; Rodriguez, Jose F

    2013-04-01

    Biomechanical studies on abdominal aortic aneurysms (AAA) seek to provide for better decision criteria to undergo surgical intervention for AAA repair. More accurate results can be obtained by using appropriate material models for the tissues along with accurate geometric models and more realistic boundary conditions for the lesion. However, patient-specific AAA models are generated from gated medical images in which the artery is under pressure. Therefore, identification of the AAA zero pressure geometry would allow for a more realistic estimate of the aneurysmal wall mechanics. This study proposes a novel iterative algorithm to find the zero pressure geometry of patient-specific AAA models. The methodology allows considering the anisotropic hyperelastic behavior of the aortic wall, its thickness and accounts for the presence of the intraluminal thrombus. Results on 12 patient-specific AAA geometric models indicate that the procedure is computational tractable and efficient, and preserves the global volume of the model. In addition, a comparison of the peak wall stress computed with the zero pressure and CT-based geometries during systole indicates that computations using CT-based geometric models underestimate the peak wall stress by 59 ± 64 and 47 ± 64 kPa for the isotropic and anisotropic material models of the arterial wall, respectively.

  6. Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair

    PubMed Central

    Bhat, Javaid Y.; Thieulin-Pardo, Gabriel; Hartl, F. Ulrich; Hayer-Hartl, Manajit

    2017-01-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO2 molecule and binding of a Mg2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are “misfire” products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins. PMID:28443288

  7. Rubisco Activases: AAA+ Chaperones Adapted to Enzyme Repair.

    PubMed

    Bhat, Javaid Y; Thieulin-Pardo, Gabriel; Hartl, F Ulrich; Hayer-Hartl, Manajit

    2017-01-01

    Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), the key enzyme of the Calvin-Benson-Bassham cycle of photosynthesis, requires conformational repair by Rubisco activase for efficient function. Rubisco mediates the fixation of atmospheric CO 2 by catalyzing the carboxylation of the five-carbon sugar ribulose-1,5-bisphosphate (RuBP). It is a remarkably inefficient enzyme, and efforts to increase crop yields by bioengineering Rubisco remain unsuccessful. This is due in part to the complex cellular machinery required for Rubisco biogenesis and metabolic maintenance. To function, Rubisco must undergo an activation process that involves carboxylation of an active site lysine by a non-substrate CO 2 molecule and binding of a Mg 2+ ion. Premature binding of the substrate RuBP results in an inactive enzyme. Moreover, Rubisco can also be inhibited by a range of sugar phosphates, some of which are "misfire" products of its multistep catalytic reaction. The release of the inhibitory sugar molecule is mediated by the AAA+ protein Rubisco activase (Rca), which couples hydrolysis of ATP to the structural remodeling of Rubisco. Rca enzymes are found in the vast majority of photosynthetic organisms, from bacteria to higher plants. They share a canonical AAA+ domain architecture and form six-membered ring complexes but are diverse in sequence and mechanism, suggesting their convergent evolution. In this review, we discuss recent advances in understanding the structure and function of this important group of client-specific AAA+ proteins.

  8. Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue.

    PubMed

    O'Leary, Siobhan A; Mulvihill, John J; Barrett, Hilary E; Kavanagh, Eamon G; Walsh, Michael T; McGloughlin, Tim M; Doyle, Barry J

    2015-02-01

    Varying degrees of calcification are present in most abdominal aortic aneurysms (AAAs). However, their impact on AAA failure properties and AAA rupture risk is unclear. The aim of this work is evaluate and compare the failure properties of partially calcified and predominantly fibrous AAA tissue and investigate the potential reasons for failure. Uniaxial mechanical testing was performed on AAA samples harvested from 31 patients undergoing open surgical repair. Individual tensile samples were divided into two groups: fibrous (n=31) and partially calcified (n=38). The presence of calcification was confirmed by fourier transform infrared spectroscopy (FTIR). A total of 69 mechanical tests were performed and the failure stretch (λf), failure stress (σf) and failure tension (Tf) were recorded for each test. Following mechanical testing, the failure sites of a subset of both tissue types were examined using scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) to investigate the potential reasons for failure. It has been shown that the failure properties of partially calcified tissue are significantly reduced compared to fibrous tissue and SEM and EDS results suggest that the junction between a calcification deposit and the fibrous matrix is highly susceptible to failure. This study implicates the presence of calcification as a key player in AAA rupture risk and provides further motivation for the development of non-invasive methods of measuring calcification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Chasing Ernst L Wynder: 40 years of Philip Morris' efforts to influence a leading scientist

    PubMed Central

    Fields, N; Chapman, S

    2003-01-01

    Study objective: To highlight strategies used by the Philip Morris tobacco company to try to manipulate the eminent scientist, Dr Ernst Wynder between 1955 and 1995. Methods: Systematic keyword and opportunistic searching of www.pmdocs.com for formerly internal tobacco industry documents concerning Philip Morris executives and Wynder. Available materials included reports, budget reviews, and correspondence. Main results: The emergence of smoking as a priority issue on the American public health agenda can be largely attributed to Wynder's research and publicity efforts. Philip Morris viewed Wynder as a prestigious scientist whose commitment to the pursuit of reduced harm cigarettes could lend legitimacy to its desire to position itself as a responsible company intent on addressing consumer concerns. Philip Morris courted Wynder with large equipment loans and grants for more than 30 years, and used its public relations agency to sanitise press releases to remove material unacceptable to the company. Wynder consistently failed to acknowledge industry support while routinely acknowledging other funding from the National Cancer Institute and the American Cancer Society. In retrospect, Wynder realised the insidious effect of tobacco industry research support but failed to acknowledge this may have applied to his own association with the industry. Conclusions: Industry documents reveal a deliberate attempt by Philip Morris to pursue and manipulate Dr Wynder to legitimise their company positions. PMID:12883059

  10. National dosimetric audit network finds discrepancies in AAA lung inhomogeneity corrections.

    PubMed

    Dunn, Leon; Lehmann, Joerg; Lye, Jessica; Kenny, John; Kron, Tomas; Alves, Andrew; Cole, Andrew; Zifodya, Jackson; Williams, Ivan

    2015-07-01

    This work presents the Australian Clinical Dosimetry Service's (ACDS) findings of an investigation of systematic discrepancies between treatment planning system (TPS) calculated and measured audit doses. Specifically, a comparison between the Anisotropic Analytic Algorithm (AAA) and other common dose-calculation algorithms in regions downstream (≥2cm) from low-density material in anthropomorphic and slab phantom geometries is presented. Two measurement setups involving rectilinear slab-phantoms (ACDS Level II audit) and anthropomorphic geometries (ACDS Level III audit) were used in conjunction with ion chamber (planar 2D array and Farmer-type) measurements. Measured doses were compared to calculated doses for a variety of cases, with and without the presence of inhomogeneities and beam-modifiers in 71 audits. Results demonstrate a systematic AAA underdose with an average discrepancy of 2.9 ± 1.2% when the AAA algorithm is implemented in regions distal from lung-tissue interfaces, when lateral beams are used with anthropomorphic phantoms. This systemic discrepancy was found for all Level III audits of facilities using the AAA algorithm. This discrepancy is not seen when identical measurements are compared for other common dose-calculation algorithms (average discrepancy -0.4 ± 1.7%), including the Acuros XB algorithm also available with the Eclipse TPS. For slab phantom geometries (Level II audits), with similar measurement points downstream from inhomogeneities this discrepancy is also not seen. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. Adipocytes and abdominal aortic aneurysm: Putative potential role of adipocytes in the process of AAA development.

    PubMed

    Kugo, Hirona; Moriyama, Tatsuya; Zaima, Nobuhiro

    2018-01-15

    Background Adipose tissue plays a role in the storage of excess energy as triglycerides (TGs). Excess fat accumulation causes various metabolic and cardiovascular diseases. It has been reported that ectopic fat deposition and excess TG accumulation in non-adipose tissue might be important predictors of cardiometabolic and vascular risk. For example, ectopic fat in perivascular tissue promotes atherosclerotic plaque formation in the arterial wall. Objective Recently, it has been reported that ectopic fat (adipocyte) in the vascular wall of an abdominal aortic aneurysm (AAA) is present in both human and experimental animal models. The pathological significance of adipocytes in the AAA wall has not been fully understood. In this review, we summarized the functions of adipocytes and discussed potential new drugs that target vascular adipocytes for AAA treatment. Result Previous studies suggest that adipocytes in vascular wall play an important role in the development of AAA. Conclusion Adipocytes in the vascular wall could be novel targets for the development of AAA therapeutic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Analysis of a Typical Chinese High School Biology Textbook Using the AAAS Textbook Standards

    ERIC Educational Resources Information Center

    Liang, Ye; Cobern, William W.

    2013-01-01

    The purpose of this study was to evaluate a typical Chinese high school biology textbook using the textbook standards of the American Association for the Advancement of Science (AAAS). The data were composed of three chapters selected from the textbook. Each chapter was analyzed and rated using the AAAS textbook standards. Pearson correlations…

  13. Risky Subjectivities in Philip Pullman's "Northern Lights"

    ERIC Educational Resources Information Center

    Mahon, Áine; O'Brien, Elizabeth

    2018-01-01

    This paper engages the philosophical concepts of subjectification and acknowledgment in conversation with Philip Pullman's young adult novel, "Northern Lights". Our particular focus is Lyra Belacqua, Pullman's central character. Precarious in her vulnerability and in her unknown significance, we read Lyra as usefully negotiating the…

  14. SOFIA Technology: The NASA Airborne Astronomy Ambassador (AAA) Experience and Online Resources

    NASA Astrophysics Data System (ADS)

    Clark, C.; Harman, P. K.; Backman, D. E.

    2016-12-01

    SOFIA, an 80/20 partnership of NASA and the German Aerospace Center (DLR), consists of a modified Boeing 747SP carrying a reflecting telescope with an effective diameter of 2.5 meters. SOFIA is the largest airborne observatory in the world, capable of observations impossible for even the largest and highest ground-based telescopes. The SOFIA Program Office is at NASA ARC, Moffett Field, CA; the aircraft is based in Palmdale, CA. During its planned 20-year lifetime, SOFIA will foster development of new scientific instrumentation and inspire the education of young scientists and engineers. Astrophysicists are awarded time on SOFIA to study many kinds of astronomical objects and phenomena. Among the most interesting are: Star birth, evolution, and death Formation of new planetary systems Chemistry of complex molecules in space Planet and exoplanet atmospheres Galactic gas & dust "ecosystems" Environments around supermassive black holes SOFIA currently has eight instruments, five US-made and three German. The instruments — cameras, spectrometers, and a photometer,— operate at near-, mid- and far-infrared wavelengths, each spectral range being best suited to studying particular celestial phenomena. NASA's Airborne Astronomy Ambassadors' (AAAs) experience includes a STEM immersion component. AAAs are onboard during two overnight SOFIA flights that provide insight into the acquisition of scientific data as well as the interfaces between the telescope, instrument, & aircraft. AAAs monitor system performance and view observation targets from their dedicated workstation during flights. Future opportunities for school district partnerships leading to selection of future AAA cohorts will be offered in 2018-19. AAAs may access public archive data via the SOFIA Data Cycle System (DCS) https://dcs.sofia.usra.edu/. Additional SOFIA science and other resources are available at: www.sofia.usra.edu, including lessons that use photovoltaic circuits, and other technology for the

  15. Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

    PubMed

    Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

    2017-07-24

    This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

  16. Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

    PubMed

    Guebert, Alexandra; Conroy, Leigh; Weppler, Sarah; Alghamdi, Majed; Conway, Jessica; Harper, Lindsay; Phan, Tien; Olivotto, Ivo A; Smith, Wendy L; Quirk, Sarah

    2018-05-01

    Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMC CTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breast CTV V 95% , was <2.5%. For IMC CTV , the median differences V 95% , and V 80% were <5% and 0%, respectively; indicating IMC CTV coverage only decreased when marginally covered. Mean superficial dose increased by a median of 3.2 Gy. In the subvolume analysis, the medial subvolumes were "hotter" when recalculated with AXB and the lateral subvolumes "cooler" with AXB; however, all differences were within 2 Gy. We observed minimal difference in magnitude and spatial distribution of dose when comparing the two algorithms. The largest observable differences occurred in superficial dose regions. Therefore, clinical implementation of AXB from AAA for breast radiotherapy is not expected to result in changes in clinical

  17. Engineering Silicone Rubbers for In vitro Studies: Creating AAA Models and ILT Analogues with Physiological Properties

    PubMed Central

    Corbett, T.J.; Doyle, B.J.; Callanan, A.; Walsh, M.T.; McGloughlin, T.M

    2010-01-01

    Background In vitro studies of abdominal aortic aneurysm (AAA) have been widely reported. Frequently mock artery models with intraluminal thrombus (ILT) analogues are used to mimic the AAA in vivo. While the models used may be physiological, their properties are frequently either not reported or investigated. Method of Approach This study is concerned with the testing and characterisation of previously used vessel analogue materials and the development of new materials for the manufacture of AAA models. These materials were used in conjunction with a previously validated injection moulding technique to manufacture AAA models of ideal geometry. To determine the model properties (stiffness (β) and compliance) the diameter change of each AAA model was investigated under incrementally increasing internal pressures and compared to published in vivo studies to determine if the models behaved physiologically. A FEA study was implemented to determine if the pressure – diameter change behaviour of the models could be predicted numerically. ILT analogues were also manufactured and characterised. Ideal models were manufactured with ILT analogue internal to the aneurysm region and the effect of the ILT analogue on the model compliance and stiffness was investigated. Results The wall materials had similar properties to aortic tissue at physiological pressures (Einit 2.22MPa and 1.57MPa (aortic tissue: 1.8MPa)). ILT analogues had similar Young’s modulus to the medial layer of ILT (0.24 and 0.33MPa (ILT: 0.28MPa)). All models had aneurysm sac compliance in the physiological range (2.62 – 8.01×10-4/mmHg (AAA in vivo: 1.8 – 9.4×10-4/mmHg)). The necks of our AAA models had similar stiffness to healthy aortas (20.44 – 29.83 (healthy aortas in vivo: 17.5±5.5)). Good agreement was seen between the diameter changes due to pressurisation in the experimental and FEA wall models with a maximum error of 7.3% at 120mmHg. It was also determined that the inclusion of ILT analogue

  18. Introducing AAA-MS, a rapid and sensitive method for amino acid analysis using isotope dilution and high-resolution mass spectrometry.

    PubMed

    Louwagie, Mathilde; Kieffer-Jaquinod, Sylvie; Dupierris, Véronique; Couté, Yohann; Bruley, Christophe; Garin, Jérôme; Dupuis, Alain; Jaquinod, Michel; Brun, Virginie

    2012-07-06

    Accurate quantification of pure peptides and proteins is essential for biotechnology, clinical chemistry, proteomics, and systems biology. The reference method to quantify peptides and proteins is amino acid analysis (AAA). This consists of an acidic hydrolysis followed by chromatographic separation and spectrophotometric detection of amino acids. Although widely used, this method displays some limitations, in particular the need for large amounts of starting material. Driven by the need to quantify isotope-dilution standards used for absolute quantitative proteomics, particularly stable isotope-labeled (SIL) peptides and PSAQ proteins, we developed a new AAA assay (AAA-MS). This method requires neither derivatization nor chromatographic separation of amino acids. It is based on rapid microwave-assisted acidic hydrolysis followed by high-resolution mass spectrometry analysis of amino acids. Quantification is performed by comparing MS signals from labeled amino acids (SIL peptide- and PSAQ-derived) with those of unlabeled amino acids originating from co-hydrolyzed NIST standard reference materials. For both SIL peptides and PSAQ standards, AAA-MS quantification results were consistent with classical AAA measurements. Compared to AAA assay, AAA-MS was much faster and was 100-fold more sensitive for peptide and protein quantification. Finally, thanks to the development of a labeled protein standard, we also extended AAA-MS analysis to the quantification of unlabeled proteins.

  19. Philip Morris changes its name, but not its harmful practices.

    PubMed

    Myers, M L

    2002-09-01

    After spending more than $250 million on an advertising campaign to improve its name and reputation, Philip Morris has abruptly shifted course and decided instead to change its corporate name-to The Altria Group, Inc.

  20. Validation of a Piezoelectric Sensor Array-Based Device for Measurement of Carotid-Femoral Pulse Wave Velocity: The Philips Prototype.

    PubMed

    Xu, Shao-Kun; Hong, Xiang-Fei; Cheng, Yi-Bang; Liu, Chang-Yuan; Li, Yan; Yin, Bin; Wang, Ji-Guang

    2018-03-01

    Multiple piezoelectric pressure mechanotransducers topologized into an array might improve efficiency and accuracy in collecting arterial pressure waveforms for measurement of pulse wave velocity (PWV). In the present study, we validated a piezoelectric sensor array-based prototype (Philips) against the validated and clinically widely used Complior device (Alam Medical). We recruited 33 subjects with a wide distribution of PWV. For the validation, PWV was measured sequentially with the Complior device (four times) and the Philips prototype (three times). With the 99 paired PWV values, we investigated the agreement between the Philips prototype and the Complior device using Pearson correlation analysis and Bland-Altman plot. We also performed analysis on the determinants and reproducibility of PWV measured with both devices. The correlation coefficient for PWV measured with the two devices was 0.92 ( p < 0.0001). Compared with the Complior device, the Philips prototype slightly overestimated PWV by 0.24 (± 2 standard deviations, ± 1.91) m/s, especially when PWV was high. The correlation coefficient between the difference and the average of the Philips and Complior measurements was 0.21 ( p = 0.035). Nonetheless, they had similar determinants. Age, mean arterial pressure, and sex altogether explained 81.6 and 83.9% of the variance of PWV values measured with the Philips prototype and Complior device, respectively. When the two extremes of the three PWV values measured with the Philips prototype and the Complior device were investigated, the coefficients of variation were 8.26 and 3.26%, respectively. Compared with the Complior device, the Philips prototype had similar accuracy, determinants, and reproducibility in measuring PWV.

  1. Molecular insights into the m-AAA protease-mediated dislocation of transmembrane helices in the mitochondrial inner membrane.

    PubMed

    Lee, Seoeun; Lee, Hunsang; Yoo, Suji; Kim, Hyun

    2017-12-08

    Protein complexes involved in respiration, ATP synthesis, and protein import reside in the mitochondrial inner membrane; thus, proper regulation of these proteins is essential for cell viability. The m -AAA protease, a conserved hetero-hexameric AAA (ATPase associated with diverse cellular activities) protease, composed of the Yta10 and Yta12 proteins, regulates mitochondrial proteostasis by mediating protein maturation and degradation. It also recognizes and mediates the dislocation of membrane-embedded substrates, including foreign transmembrane (TM) segments, but the molecular mechanism involved in these processes remains elusive. This study investigated the role of the TM domains in the m -AAA protease by systematic replacement of one TM domain at a time in yeast. Our data indicated that replacement of the Yta10 TM2 domain abolishes membrane dislocation for only a subset of substrates, whereas replacement of the Yta12 TM2 domain impairs membrane dislocation for all tested substrates, suggesting different roles of the TM domains in each m -AAA protease subunit. Furthermore, m -AAA protease-mediated membrane dislocation was impaired in the presence of a large downstream hydrophilic moiety in a membrane substrate. This finding suggested that the m -AAA protease cannot dislocate large hydrophilic domains across the membrane, indicating that the membrane dislocation probably occurs in a lipid environment. In summary, this study highlights previously underappreciated biological roles of TM domains of the m -AAA proteases in mediating the recognition and dislocation of membrane-embedded substrates. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. SU-F-T-609: Impact of Dosimetric Variation for Prescription Dose Using Analytical Anisotropic Algorithm (AAA) in Lung SBRT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kawai, D; Takahashi, R; Kamima, T

    Purpose: Actual irradiated prescription dose to patients cannot be verified. Thus, independent dose verification and second treatment planning system are used as the secondary check. AAA dose calculation engine has contributed to lung SBRT. We conducted a multi-institutional study to assess variation of prescription dose for lung SBRT when using AAA in reference to using Acuros XB and Clarkson algorithm. Methods: Six institutes in Japan participated in this study. All SBRT treatments were planed using AAA in Eclipse and Adaptive Convolve (AC) in Pinnacle3. All of the institutes used a same independent dose verification software program (Simple MU Analysis: SMU,more » Triangle Product, Ishikawa, Japan), which implemented a Clarkson-based dose calculation algorithm using CT image dataset. A retrospective analysis for lung SBRT plans (73 patients) was performed to compute the confidence limit (CL, Average±2SD) in dose between the AAA and the SMU. In one of the institutes, a additional analysis was conducted to evaluate the variations between the AAA and the Acuros XB (AXB). Results: The CL for SMU shows larger systematic and random errors of 8.7±9.9 % for AAA than the errors of 5.7±4.2 % for AC. The variations of AAA correlated with the mean CT values in the voxels of PTV (a correlation coefficient : −0.7) . The comparison of AXB vs. AAA shows smaller systematic and random errors of −0.7±1.7%. The correlation between dose variations for AXB and the mean CT values in PTV was weak (0.4). However, there were several plans with more than 2% deviation of AAPM TG114 (Maximum: −3.3 %). Conclusion: In comparison for AC, prescription dose calculated by AAA may be more variable in lung SBRT patient. Even AXB comparison shows unexpected variation. Care should be taken for the use of AAA in lung SBRT. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

  3. Electromagnetic interference may cause false asystole alarms in certain Philips IntelliVue monitoring products.

    PubMed

    2011-09-01

    Electromagnetic interference (EMI) may cause some Philips Healthcare IntelliVue MMS, MP2, MP5, and X2 patient monitoring products to incorrectly display a flat electrocardiogram (ECG) waveform and generate a false asystole alarm. This occurs while the devices' pace pulse rejection feature is enabled. Facilities that suspect such behavior in their inventories should contact Philips to discuss whether installation of firmware version D.02.05 will help address the problem.

  4. Increased galectin-3 levels are associated with abdominal aortic aneurysm progression and inhibition of galectin-3 decreases elastase-induced AAA development.

    PubMed

    Fernandez-García, Carlos-Ernesto; Tarin, Carlos; Roldan-Montero, Raquel; Martinez-Lopez, Diego; Torres-Fonseca, Monica; Lindhot, Jes S; Vega de Ceniga, Melina; Egido, Jesus; Lopez-Andres, Natalia; Blanco-Colio, Luis-Miguel; Martín-Ventura, Jose-Luis

    2017-11-15

    Abdominal aortic aneurysm (AAA) evolution is unpredictable and no specific treatment exists for AAA, except surgery to prevent aortic rupture. Galectin-3 has been previously associated with CVD, but its potential role in AAA has not been addressed. Galectin-3 levels were increased in the plasma of AAA patients ( n =225) compared with the control group ( n =100). In addition, galectin-3 concentrations were associated with the need for surgical repair, independently of potential confounding factors. Galectin-3 mRNA and protein expression were increased in human AAA samples compared with healthy aortas. Experimental AAA in mice was induced via aortic elastase perfusion. Mice were treated intravenously with the galectin-3 inhibitor modified citrus pectin (MCP, 10 mg/kg, every other day) or saline. Similar to humans, galectin-3 serum and aortic mRNA levels were also increased in elastase-induced AAA mice compared with control mice. Mice treated with MCP showed decreased aortic dilation, as well as elastin degradation, vascular smooth muscle cell (VSMC) loss, and macrophage content at day 14 postelastase perfusion compared with control mice. The underlying mechanism(s) of the protective effect of MCP was associated with a decrease in galectin-3 and cytokine (mainly CCL5) mRNA and protein expression. Interestingly, galectin-3 induced CCL5 expression by a mechanism involving STAT3 activation in VSMC. Accordingly, MCP treatment decreased STAT3 phosphorylation in elastase-induced AAA. In conclusion, increased galectin-3 levels are associated with AAA progression, while galectin-3 inhibition decreased experimental AAA development. Our data suggest the potential role of galectin-3 as a therapeutic target in AAA. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  5. Prevalence of previously undiagnosed abdominal aortic aneurysms in the area of Como: the ComoCuore "looking for AAA" ultrasonography screening.

    PubMed

    Corrado, Giovanni; Durante, Alessandro; Genchi, Vincenzo; Trabattoni, Loris; Beretta, Sandro; Rovelli, Enza; Foglia-Manzillo, Giovanni; Ferrari, Giovanni

    2016-08-01

    The prognosis for abdominal aortic aneurysm (AAA) rupture is poor. Long-term follow-up of population-based randomized trials has demonstrated that ultrasound (US) screening for abdominal aortic aneurysms (AAAs) measuring 3 cm or greater decreases AAA-related mortality rates and is cost-effective. We though to prospectively perform during a 26-month period a limited US examination of the infrarenal aorta in volunteers of both gender aged 60-85 years without history of AAA living in the area of Como, Italy. From September 2010 to November 2013 ComoCuore, a no-profit nongovernmental association, enrolled 1555 people (aged 68.8 ± 6.8 years; 48.6 % males). Clinical data and a US imaging of the aorta were collected for each participant. AAA was found in 22 volunteers (1.4 %) mainly males (2.5 % in males vs. 0.4 % in females p = 0.005). Overall, the prevalence of cardiovascular risk factors was higher in patients with vs. without AAA (mean 2.9 ± 3.0 vs. 1.4 ± 1.0 respectively, p < 0.0001). Independent predictors of AAA on multivariate analysis were age (OR 1.14, 1.06-1.22; p < 0.0001), male gender (OR 8.23, 1.79-37.91; p = 0.007), and both current (OR 4.98, 1.57-15.79; p = 0.007) and previous smoking (OR 2.76, 1.12-8.94; p = 0.03). Our study confirms the feasibility of one time US screening for AAA in a large cohort of asymptomatic people. Independent predictors of AAA were male sex, older age and a history of smoking. Accordingly to recent data the prevalence of AAA seems to be declining, maybe due to a reduction of smoking in Italy.

  6. SU-F-T-413: Calculation Accuracy of AAA and Acuros Using Cerrobend Blocks for TBI at 400cm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lamichhane, N; Studenski, M

    2016-06-15

    Purpose: It is essential to assess the lung dose during TBI to reduce toxicity. Here we characterize the accuracy of the AAA and Acuros algorithms when using cerrobend lung shielding blocks at an extended distance for TBI. Methods: We positioned a 30×30×30 cm3 solid water slab phantom at 400 cm SSD and measured PDDs (Exradin A12 and PTW parallel plate ion chambers). A 2 cm thick, 10×10 cm2 cerrobend block was hung 2 cm in front of the phantom. This geometry was reproduced in the planning system for both AAA and Acuros. In AAA, the mass density of the cerrobendmore » block was forced to 9.38 g/cm3 and in Acuros it was forced to 8.0 g/cm3 (limited to selecting stainless steel). Three different relative electron densities (RED) were tested for each algorithm; 4.97, 6.97, and 8.97. Results: PDDs from both Acuros and AAA underestimated the delivered dose. AAA calculated that depth dose was higher for RED of 4.97 as compared to 6.97 and 8.97 but still lower than measured. There was no change in the percent depth dose with changing relative electron densities for Acuros. Conclusion: Care should be taken before using AAA or Acuros with cerrobend blocks as the planning system underestimates dose. Acuros limits the ability to modify RED when compared to AAA.« less

  7. 3. Historic American Buildings Survey Philip E. Gardner, Photographer April ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. Historic American Buildings Survey Philip E. Gardner, Photographer April 1958 FRONT THRESHOLD FROM N. BEFORE OLD BRICK CAPPED BY NEW - Fort Frederica, Captain John Mackay House (Ruins), Lot No. 6, North Ward, Saint Simons Island, Glynn County, GA

  8. Structural Insights into the Unusually Strong ATPase Activity of the AAA Domain of the Caenorhabditis elegans Fidgetin-like 1 (FIGL-1) Protein*

    PubMed Central

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-01-01

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function. PMID:23979136

  9. Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

    PubMed

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-10-11

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

  10. Crystal Structure and Biochemical Characterization of a Mycobacterium smegmatis AAA-Type Nucleoside Triphosphatase Phosphohydrolase (Msm0858).

    PubMed

    Unciuleac, Mihaela-Carmen; Smith, Paul C; Shuman, Stewart

    2016-05-15

    AAA proteins (ATPases associated with various cellular activities) use the energy of ATP hydrolysis to drive conformational changes in diverse macromolecular targets. Here, we report the biochemical characterization and 2.5-Å crystal structure of a Mycobacterium smegmatis AAA protein Msm0858, the ortholog of Mycobacterium tuberculosis Rv0435c. Msm0858 is a magnesium-dependent ATPase and is active with all nucleoside triphosphates (NTPs) and deoxynucleoside triphosphates (dNTPs) as substrates. The Msm0858 structure comprises (i) an N-terminal domain (amino acids [aa] 17 to 201) composed of two β-barrel modules and (ii) two AAA domains, D1 (aa 212 to 473) and D2 (aa 476 to 744), each of which has ADP in the active site. Msm0858-ADP is a monomer in solution and in crystallized form. Msm0858 domains are structurally homologous to the corresponding modules of mammalian p97. However, the position of the N-domain modules relative to the AAA domains in the Msm0858-ADP tertiary structure is different and would impede the formation of a p97-like hexameric quaternary structure. Mutational analysis of the A-box and B-box motifs indicated that the D1 and D2 AAA domains are both capable of ATP hydrolysis. Simultaneous mutations of the D1 and D2 active-site motifs were required to abolish ATPase activity. ATPase activity was effaced by mutation of the putative D2 arginine finger, suggesting that Msm0858 might oligomerize during the ATPase reaction cycle. A truncated variant Msm0858 (aa 212 to 745) that lacks the N domain was characterized as a catalytically active homodimer. Recent studies have underscored the importance of AAA proteins (ATPases associated with various cellular activities) in the physiology of mycobacteria. This study reports the ATPase activity and crystal structure of a previously uncharacterized mycobacterial AAA protein, Msm0858. Msm0858 consists of an N-terminal β-barrel domain and two AAA domains, each with ADP bound in the active site. Msm0858 is a

  11. The two faces of hydrogen-bond strength on triple AAA-DDD arrays.

    PubMed

    Lopez, Alfredo Henrique Duarte; Caramori, Giovanni Finoto; Coimbra, Daniel Fernando; Parreira, Renato Luis Tame; da Silva, Éder Henrique

    2013-12-02

    Systems that are connected through multiple hydrogen bonds are the cornerstone of molecular recognition processes in biology, and they are increasingly being employed in supramolecular chemistry, specifically in molecular self-assembly processes. For this reason, the effects of different substituents (NO2, CN, F, Cl, Br, OCH3 and NH2) on the electronic structure, and consequently on the magnitude of hydrogen bonds in triple AAA-DDD arrays (A=acceptor, D=donor) were evaluated in the light of topological [electron localization function (ELF) and quantum theory of atoms in molecules (QTAIM)], energetic [Su-Li energy-decomposition analysis (EDA) and natural bond orbital analysis (NBO)], and geometrical analysis. The results based on local H-bond descriptors (geometries, QTAIM, ELF, and NBO) indicate that substitutions with electron-withdrawing groups on the AAA module tend to strengthen, whereas electron-donating substituents tend to weaken the covalent character of the AAA-DDD intermolecular H-bonds, and also indicate that the magnitude of the effect is dependent on the position of substitution. In contrast, Su-Li EDA results show an opposite behavior when compared to local H-bond descriptors, indicating that electron-donating substituents tend to increase the magnitude of H-bonds in AAA-DDD arrays, and thus suggesting that the use of local H-bond descriptors describes the nature of H bonds only partially, not providing enough insight about the strength of such H bonds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Effects of doping and bias voltage on the screening in AAA-stacked trilayer graphene

    NASA Astrophysics Data System (ADS)

    Mohammadi, Yawar; Moradian, Rostam; Shirzadi Tabar, Farzad

    2014-09-01

    We calculate the static polarization of AAA-stacked trilayer graphene (TLG) and study its screening properties within the random phase approximation (RPA) in all undoped, doped and biased regimes. We find that the static polarization of undoped AAA-stacked TLG is a combination of the doped and undoped single-layer graphene static polarization. This leads to an enhancement of the dielectric background constant along a Thomas-Fermi screening with the Thomas-Fermi wave vector which is independent of carrier concentrations and a 1/r3 power law decay for the long-distance behavior of the screened Coulomb potential. We show that effects of a bias voltage can be taken into account by a renormalization of the interlayer hopping energy to a new bias-voltage-dependent value, indicating screening properties of AAA-stacked TLG can be tuned electrically. We also find that screening properties of doped AAA-stacked TLG, when μ exceeds √{2}γ, are similar to that of doped SLG only depending on doping. While for μ<√{2}γ, its screening properties are combination of SLG and AA-stacked bilayer graphene screening properties and they are determined by doping and the interlayer hopping energy.

  13. Asymmetric processing of a substrate protein in sequential allosteric cycles of AAA+ nanomachines

    NASA Astrophysics Data System (ADS)

    Kravats, Andrea N.; Tonddast-Navaei, Sam; Bucher, Ryan J.; Stan, George

    2013-09-01

    Essential protein quality control includes mechanisms of substrate protein (SP) unfolding and translocation performed by powerful ring-shaped AAA+ (ATPases associated with various cellular activities) nanomachines. These SP remodeling actions are effected by mechanical forces imparted by AAA+ loops that protrude into the central channel. Sequential intra-ring allosteric motions, which underlie repetitive SP-loop interactions, have been proposed to comprise clockwise (CW), counterclockwise (CCW), or random (R) conformational transitions of individual AAA+ subunits. To probe the effect of these allosteric mechanisms on unfoldase and translocase functions, we perform Langevin dynamics simulations of a coarse-grained model of an all-alpha SP processed by the single-ring ClpY ATPase or by the double-ring p97 ATPase. We find that, in all three allosteric mechanisms, the SP undergoes conformational transitions along a common set of pathways, which reveals that the active work provided by the ClpY machine involves single loop-SP interactions. Nevertheless, the rates and yields of SP unfolding and translocation are controlled by mechanism-dependent loop-SP binding events, as illustrated by faster timescales of SP processing in CW allostery compared with CCW and R allostery. The distinct efficacy of allosteric mechanisms is due to the asymmetric collaboration of adjacent subunits, which involves CW-biased structural motions of AAA+ loops and results in CW-compatible torque applied onto the SP. Additional simulations of mutant ClpY rings, which render a subset of subunits catalytically-defective or reduce their SP binding affinity, reveal that subunit-based conformational transitions play the major role in SP remodeling. Based on these results we predict that the minimally functional AAA+ ring includes three active subunits, only two of which are adjacent.

  14. Dosimetric comparison of Acuros XB, AAA, and XVMC in stereotactic body radiotherapy for lung cancer.

    PubMed

    Tsuruta, Yusuke; Nakata, Manabu; Nakamura, Mitsuhiro; Matsuo, Yukinori; Higashimura, Kyoji; Monzen, Hajime; Mizowaki, Takashi; Hiraoka, Masahiro

    2014-08-01

    To compare the dosimetric performance of Acuros XB (AXB), anisotropic analytical algorithm (AAA), and x-ray voxel Monte Carlo (XVMC) in heterogeneous phantoms and lung stereotactic body radiotherapy (SBRT) plans. Water- and lung-equivalent phantoms were combined to evaluate the percentage depth dose and dose profile. The radiation treatment machine Novalis (BrainLab AG, Feldkirchen, Germany) with an x-ray beam energy of 6 MV was used to calculate the doses in the composite phantom at a source-to-surface distance of 100 cm with a gantry angle of 0°. Subsequently, the clinical lung SBRT plans for the 26 consecutive patients were transferred from the iPlan (ver. 4.1; BrainLab AG) to the Eclipse treatment planning systems (ver. 11.0.3; Varian Medical Systems, Palo Alto, CA). The doses were then recalculated with AXB and AAA while maintaining the XVMC-calculated monitor units and beam arrangement. Then the dose-volumetric data obtained using the three different radiation dose calculation algorithms were compared. The results from AXB and XVMC agreed with measurements within ± 3.0% for the lung-equivalent phantom with a 6 × 6 cm(2) field size, whereas AAA values were higher than measurements in the heterogeneous zone and near the boundary, with the greatest difference being 4.1%. AXB and XVMC agreed well with measurements in terms of the profile shape at the boundary of the heterogeneous zone. For the lung SBRT plans, AXB yielded lower values than XVMC in terms of the maximum doses of ITV and PTV; however, the differences were within ± 3.0%. In addition to the dose-volumetric data, the dose distribution analysis showed that AXB yielded dose distribution calculations that were closer to those with XVMC than did AAA. Means ± standard deviation of the computation time was 221.6 ± 53.1 s (range, 124-358 s), 66.1 ± 16.0 s (range, 42-94 s), and 6.7 ± 1.1 s (range, 5-9 s) for XVMC, AXB, and AAA, respectively. In the phantom evaluations, AXB and XVMC agreed better with

  15. Structure determination of disease associated peak AAA from l-Tryptophan implicated in the eosinophilia-myalgia syndrome.

    PubMed

    Klarskov, Klaus; Gagnon, Hugo; Boudreault, Pierre-Luc; Normandin, Chad; Plancq, Baptiste; Marsault, Eric; Gleich, Gerald J; Naylor, Stephen

    2018-01-05

    The eosinophilia-myalgia syndrome (EMS) outbreak of 1989 that occurred in the USA and elsewhere was caused by the ingestion of l-Tryptophan (L-Trp) solely manufactured by the Japanese company Showa Denko K.K. (SD). Six compounds present in the SD L-Trp were reported to be case-associated contaminants. However, "one" of these compounds, Peak AAA has remained structurally uncharacterized, despite the fact that it was described as "the only statistically significant (p=0.0014) contaminant". Here, we employ on-line microcapillary-high performance liquid chromatography-electrospray ionization mass spectrometry (LC-MS), and tandem mass spectrometry (MS/MS) to determine that Peak AAA is in fact two structurally related isomers. Peak AAA 1 and Peak AAA 2 differed in LC retention times, and were determined by accurate mass-LC-MS to both have a protonated molecular ion (MH +) of mass 343.239Da (Da), corresponding to a molecular formula of C 21 H 30 N 2 O 2, and possessing eight degrees of unsaturation (DoU) for the non-protonated molecule. By comparing the LC-MS and LC-MS-MS retention times and spectra with authentic synthetic standards, Peak AAA 1 was identified as the intermolecular condensation product of L-Trp with anteiso 7-methylnonanoic acid, to afford (S)-2-amino-3-(2-((S,E)-7-methylnon-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Peak AAA 2 was determined to be a condensation product of L-Trp with decanoic acid, which produced (S)-2-amino-3-(2-((E)-dec-1-en-1-yl)-1H-indol-3-yl)propanoic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Structural dynamics of the MecA-ClpC complex: a type II AAA+ protein unfolding machine.

    PubMed

    Liu, Jing; Mei, Ziqing; Li, Ningning; Qi, Yutao; Xu, Yanji; Shi, Yigong; Wang, Feng; Lei, Jianlin; Gao, Ning

    2013-06-14

    The MecA-ClpC complex is a bacterial type II AAA(+) molecular machine responsible for regulated unfolding of substrates, such as transcription factors ComK and ComS, and targeting them to ClpP for degradation. The six subunits of the MecA-ClpC complex form a closed barrel-like structure, featured with three stacked rings and a hollow passage, where substrates are threaded and translocated through successive pores. Although the general concepts of how polypeptides are unfolded and translocated by internal pore loops of AAA(+) proteins have long been conceived, the detailed mechanistic model remains elusive. With cryoelectron microscopy, we captured four different structures of the MecA-ClpC complexes. These complexes differ in the nucleotide binding states of the two AAA(+) rings and therefore might presumably reflect distinctive, representative snapshots from a dynamic unfolding cycle of this hexameric complex. Structural analysis reveals that nucleotide binding and hydrolysis modulate the hexameric complex in a number of ways, including the opening of the N-terminal ring, the axial and radial positions of pore loops, the compactness of the C-terminal ring, as well as the relative rotation between the two nucleotide-binding domain rings. More importantly, our structural and biochemical data indicate there is an active allosteric communication between the two AAA(+) rings and suggest that concerted actions of the two AAA(+) rings are required for the efficiency of the substrate unfolding and translocation. These findings provide important mechanistic insights into the dynamic cycle of the MecA-ClpC unfoldase and especially lay a foundation toward the complete understanding of the structural dynamics of the general type II AAA(+) hexamers.

  17. Structure and evolution of N-domains in AAA metalloproteases.

    PubMed

    Scharfenberg, Franka; Serek-Heuberger, Justyna; Coles, Murray; Hartmann, Marcus D; Habeck, Michael; Martin, Jörg; Lupas, Andrei N; Alva, Vikram

    2015-02-27

    Metalloproteases of the AAA (ATPases associated with various cellular activities) family play a crucial role in protein quality control within the cytoplasmic membrane of bacteria and the inner membrane of eukaryotic organelles. These membrane-anchored hexameric enzymes are composed of an N-terminal domain with one or two transmembrane helices, a central AAA ATPase module, and a C-terminal Zn(2+)-dependent protease. While the latter two domains have been well studied, so far, little is known about the N-terminal regions. Here, in an extensive bioinformatic and structural analysis, we identified three major, non-homologous groups of N-domains in AAA metalloproteases. By far, the largest one is the FtsH-like group of bacteria and eukaryotic organelles. The other two groups are specific to Yme1: one found in plants, fungi, and basal metazoans and the other one found exclusively in animals. Using NMR and crystallography, we determined the subunit structure and hexameric assembly of Escherichia coli FtsH-N, exhibiting an unusual α+β fold, and the conserved part of fungal Yme1-N from Saccharomyces cerevisiae, revealing a tetratricopeptide repeat fold. Our bioinformatic analysis showed that, uniquely among these proteins, the N-domain of Yme1 from the cnidarian Hydra vulgaris contains both the tetratricopeptide repeat region seen in basal metazoans and a region of homology to the N-domains of animals. Thus, it is a modern-day representative of an intermediate in the evolution of animal Yme1 from basal eukaryotic precursors. Copyright © 2015. Published by Elsevier Ltd.

  18. Structure and Function of p97 and Pex1/6 Type II AAA+ Complexes.

    PubMed

    Saffert, Paul; Enenkel, Cordula; Wendler, Petra

    2017-01-01

    Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria. Tremendous efforts have been undertaken to understand the conformational dynamics of protein remodeling type II AAA+ complexes. A uniform mode of action has not been derived from these works. This review focuses on p97/VCP and the Pex1/6 complex, which both structurally remodel ubiquitinated substrate proteins. P97/VCP plays a role in many processes, including ER- associated protein degradation, and the Pex1/Pex6 complex dislocates and recycles the transport receptor Pex5 from the peroxisomal membrane during peroxisomal protein import. We give an introduction into existing knowledge about the biochemical and cellular activities of the complexes before discussing structural information. We particularly emphasize recent electron microscopy structures of the two AAA+ complexes and summarize their structural differences.

  19. SMYD2 promoter DNA methylation is associated with abdominal aortic aneurysm (AAA) and SMYD2 expression in vascular smooth muscle cells.

    PubMed

    Toghill, Bradley J; Saratzis, Athanasios; Freeman, Peter J; Sylvius, Nicolas; Bown, Matthew J

    2018-01-01

    Abdominal aortic aneurysm (AAA) is a deadly cardiovascular disease characterised by the gradual, irreversible dilation of the abdominal aorta. AAA is a complex genetic disease but little is known about the role of epigenetics. Our objective was to determine if global DNA methylation and CpG-specific methylation at known AAA risk loci is associated with AAA, and the functional effects of methylation changes. We assessed global methylation in peripheral blood mononuclear cell DNA from 92 individuals with AAA and 93 controls using enzyme-linked immunosorbent assays, identifying hyper-methylation in those with large AAA and a positive linear association with AAA diameter ( P  < 0.0001, R 2  = 0.3175).We then determined CpG methylation status of regulatory regions in genes located at AAA risk loci identified in genome-wide association studies, using bisulphite next-generation sequencing (NGS) in vascular smooth muscle cells (VSMCs) taken from aortic tissues of 44 individuals (24 AAAs and 20 controls). In IL6R , 2 CpGs were hyper-methylated ( P  = 0.0145); in ERG , 13 CpGs were hyper-methylated ( P  = 0.0005); in SERPINB9 , 6 CpGs were hypo-methylated ( P  = 0.0037) and 1 CpG was hyper-methylated ( P  = 0.0098); and in SMYD2 , 4 CpGs were hypo-methylated ( P  = 0.0012).RT-qPCR was performed for each differentially methylated gene on mRNA from the same VSMCs and compared with methylation. This analysis revealed downregulation of SMYD2 and SERPINB9 in AAA, and a direct linear relationship between SMYD2 promoter methylation and SMYD2 expression ( P  = 0.038). Furthermore, downregulation of SMYD2 at the site of aneurysm in the aortic wall was further corroborated in 6 of the same samples used for methylation and gene expression analysis with immunohistochemistry. This study is the first to assess DNA methylation in VSMCs from individuals with AAA using NGS, and provides further evidence there is an epigenetic basis to AAA. Our study shows that

  20. The Adult Asperger Assessment (AAA): A Diagnostic Method

    ERIC Educational Resources Information Center

    Baron-Cohen, Simon; Wheelwright, Sally; Robinson, Janine; Woodbury-Smith, Marc

    2005-01-01

    At the present time there are a large number of adults who have "suspected" Asperger syndrome (AS). In this paper we describe a new instrument, the Adult Asperger Assessment (AAA), developed in our clinic for adults with AS. The need for a new instrument relevant to the diagnosis of AS in adulthood arises because existing instruments are designed…

  1. A Curious Reality: Exploring the Paintings of Philip C. Curtis

    ERIC Educational Resources Information Center

    Stephens, Pamela; Walkup, Nancy

    2011-01-01

    Many of the paintings of 20th-century American artist Philip C. Curtis defy clear classification. Curtis's artworks often show dreamlike and fantastical qualities and are therefore frequently pigeonholed as Surrealistic. While this classification is not completely erroneous, it fails to acknowledge some subtle differences between Curtis's artwork…

  2. Characterization of the binding specificity of Anguilla anguilla agglutinin (AAA) in comparison to Ulex europaeus agglutinin I (UEA-I).

    PubMed

    Baldus, S E; Thiele, J; Park, Y O; Hanisch, F G; Bara, J; Fischer, R

    1996-08-01

    Using immunochemical and immunohistochemical methods, the binding site of Anguilla anguilla agglutinin (AAA) was characterized and compared with the related fucose-specific lectin from Ulex europaeus (UEA-I). In solid-phase enzyme-linked immunoassays, the two lectins recognized Fuc alpha 1-2Gal beta-HSA. AAA additionally cross-reacted with neoglycolipids bearing lacto-N-fucopentaose (LNFP) I [H type 1] and II [Le(a)] and lactodifucotetraose (LDFT) as glycan moieties. UEA-I, on the other hand, bound to a LDFT-derived neoglycolipid but not to the other neoglycolipids tested. Binding of AAA to gastric mucin was competitively neutralized by Le(a)-specific monoclonal antibodies. UEA-I binding, on the other hand, was reduced after co-incubation with H type 2- and Le(y)-specific monoclonal antibodies. According to our results, AAA reacts with fucosylated type 1 chain antigens, whereas UEA-I binds only to the alpha 1-2-fucosylated LDFT-derived neoglycolipid. In immunohistochemical studies, the reactivity of AAA and UEA-I in normal pyloric mucosa from individuals with known Lewis and secretor status was analysed. AAA showed a broad reaction in the superficial pyloric mucosa from secretors and non-secretors, but AAA reactivity was more pronounced in Le(a+b-) individuals. On the other hand, UEA-I stained the superficial pyloric mucosa only from secretor individuals. A staining of deep mucous glands by the lectins was found in all specimens. Both reacted with most human carcinomas of different origin. Slight differences in their binding pattern were observed and may be explained by the different fine-specificities of the lectins.

  3. Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liège AAA Family Study

    PubMed Central

    Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T.; Tromp, Gerard; Kuivaniemi, Helena

    2014-01-01

    Background The objectives were to answer the following questions using a well-characterized population in Liège, Belgium: 1) what percentage of abdominal aortic aneurysm (AAA) patients have a positive family history for AAA, 2) what is the prevalence of AAAs among relatives of AAA patients; and 3) do familial and sporadic AAA cases differ in clinical characteristics. Methods and Results Unrelated AAA patients diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. In the initial interview 62 (10%) of the 618 AAA patients reported a positive family history for AAA. We divided the 618 patients into two study groups: Group I: 296 AAA patients (268; 91% males) were followed up with computerized tomography combined with positron emission tomography, and Group II: 322 AAA patients (295; 92% males) whose families were invited to ultrasonography screening. Ultrasonography screening identified 24 new AAAs among 186 relatives (≥ 50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonography screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P<0.0001). Conclusions The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis and provide rationale for targeted screening of relatives of AAA patients. PMID:24365082

  4. Family members of patients with abdominal aortic aneurysms are at increased risk for aneurysms: analysis of 618 probands and their families from the Liège AAA Family Study.

    PubMed

    Sakalihasan, Natzi; Defraigne, Jean-Olivier; Kerstenne, Marie-Ange; Cheramy-Bien, Jean-Paul; Smelser, Diane T; Tromp, Gerard; Kuivaniemi, Helena

    2014-05-01

    The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Substituent effects in double-helical hydrogen-bonded AAA-DDD complexes.

    PubMed

    Wang, Hong-Bo; Mudraboyina, Bhanu P; Wisner, James A

    2012-01-27

    Two series of DDD and AAA hydrogen-bond arrays were synthesized that form triply-hydrogen-bonded double-helical complexes when combined in CDCl(3) solution. Derivatization of the DDD arrays with electron-withdrawing groups increases the complex association constants by up to a factor of 30 in those arrays examined. Derivatization of the AAA arrays with electron donating substituents reveals a similar magnitude effect on the complex stabilities. The effect of substitution on both types of arrays are modeled quite satisfactorily (R(2) > 0.96 in all cases) as free energy relationships with respect to the sums of their Hammett substituent constants. In all, the complex stabilities can be manipulated over more than three orders of magnitude (>20 kJ mol(-1)) using this type of modification. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Inflammatory cell phenotypes in AAAs: their role and potential as targets for therapy.

    PubMed

    Dale, Matthew A; Ruhlman, Melissa K; Baxter, B Timothy

    2015-08-01

    Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused ≈15 000 deaths annually in the United States. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4(+) T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Proinflammatory CD4(+) T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to proinflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the proinflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. © 2015 American Heart Association, Inc.

  7. Revisiting the Vocational School Fallacy: A Tribute to Philip Foster

    ERIC Educational Resources Information Center

    Lauglo, Jon

    2010-01-01

    More than four decades ago, Philip J. Foster (1927-2008) published an essay on the "The vocational school fallacy in development planning," drawing on research on schools in Ghana. That essay has been reprinted in numerous texts and remains frequently quoted in recent research literature. What were his main general insights about vocational…

  8. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  9. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  10. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  11. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAX (CONTINUED) INCOME TAXES Small Business Corporations and Their Shareholders § 1.1368-2 Accumulated... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  12. 26 CFR 1.1368-2 - Accumulated adjustments account (AAA).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TAX (CONTINUED) INCOME TAXES (CONTINUED) Small Business Corporations and Their Shareholders § 1.1368-2... earnings and profits or previously taxed income pursuant to an election made under section 1368(e)(3) and... AAA for redemptions and distributions in the year of a redemption. (c) Distribution of money and loss...

  13. Creating the "desired mindset": Philip Morris's efforts to improve its corporate image among women.

    PubMed

    McDaniel, Patricia A; Malone, Ruth E

    2009-01-01

    Through analysis of tobacco company documents, we explored how and why Philip Morris sought to enhance its corporate image among American women. Philip Morris regarded women as an influential political group. To improve its image among women, while keeping tobacco off their organizational agendas, the company sponsored women's groups and programs. It also sought to appeal to women it defined as "active moms" by advertising its commitment to domestic violence victims. It was more successful in securing women's organizations as allies than active moms. Increasing tobacco's visibility as a global women's health issue may require addressing industry influence.

  14. Working to make an image: an analysis of three Philip Morris corporate image media campaigns

    PubMed Central

    Szczypka, Glen; Wakefield, Melanie A; Emery, Sherry; Terry‐McElrath, Yvonne M; Flay, Brian R; Chaloupka, Frank J

    2007-01-01

    Objective To describe the nature and timing of, and population exposure to, Philip Morris USA's three explicit corporate image television advertising campaigns and explore the motivations behind each campaign. Methods : Analysis of television ratings from the largest 75 media markets in the United States, which measure the reach and frequency of population exposure to advertising; copies of all televised commercials produced by Philip Morris; and tobacco industry documents, which provide insights into the specific goals of each campaign. Findings Household exposure to the “Working to Make a Difference: the People of Philip Morris” averaged 5.37 ads/month for 27 months from 1999–2001; the “Tobacco Settlement” campaign averaged 10.05 ads/month for three months in 2000; and “PMUSA” averaged 3.11 ads/month for the last six months in 2003. The percentage of advertising exposure that was purchased in news programming in order to reach opinion leaders increased over the three campaigns from 20%, 39% and 60%, respectively. These public relations campaigns were designed to counter negative images, increase brand recognition, and improve the financial viability of the company. Conclusions Only one early media campaign focused on issues other than tobacco, whereas subsequent campaigns have been specifically concerned with tobacco issues, and more targeted to opinion leaders. The size and timing of the advertising buys appeared to be strategically crafted to maximise advertising exposure for these population subgroups during critical threats to Philip Morris's public image. PMID:17897994

  15. Working to make an image: an analysis of three Philip Morris corporate image media campaigns.

    PubMed

    Szczypka, Glen; Wakefield, Melanie A; Emery, Sherry; Terry-McElrath, Yvonne M; Flay, Brian R; Chaloupka, Frank J

    2007-10-01

    To describe the nature and timing of, and population exposure to, Philip Morris USA's three explicit corporate image television advertising campaigns and explore the motivations behind each campaign. Analysis of television ratings from the largest 75 media markets in the United States, which measure the reach and frequency of population exposure to advertising; copies of all televised commercials produced by Philip Morris; and tobacco industry documents, which provide insights into the specific goals of each campaign. Household exposure to the "Working to Make a Difference: the People of Philip Morris" averaged 5.37 ads/month for 27 months from 1999-2001; the "Tobacco Settlement" campaign averaged 10.05 ads/month for three months in 2000; and "PMUSA" averaged 3.11 ads/month for the last six months in 2003. The percentage of advertising exposure that was purchased in news programming in order to reach opinion leaders increased over the three campaigns from 20%, 39% and 60%, respectively. These public relations campaigns were designed to counter negative images, increase brand recognition, and improve the financial viability of the company. Only one early media campaign focused on issues other than tobacco, whereas subsequent campaigns have been specifically concerned with tobacco issues, and more targeted to opinion leaders. The size and timing of the advertising buys appeared to be strategically crafted to maximise advertising exposure for these population subgroups during critical threats to Philip Morris's public image.

  16. AAAS: Automated Affirmative Action System. General Description, Phase 1.

    ERIC Educational Resources Information Center

    Institute for Services to Education, Inc., Washington, DC. TACTICS Management Information Systems Directorate.

    This document describes phase 1 of the Automated Affirmative Action System (AAAS) of the Tuskegee Institute, which was designed to organize an inventory of any patterns of job classification and assignment identifiable by sex or minority group; any job classification or organizational unit where women and minorities are not employed or are…

  17. Philip Morris's website and television commercials use new language to mislead the public into believing it has changed its stance on smoking and disease

    PubMed Central

    Friedman, Lissy C

    2007-01-01

    Objectives This paper analyses Philip Morris's evolving website and the legal strategies employed in its creation and dissemination. Methods Internal tobacco documents were searched and examined and their substance verified and triangulated using media accounts, legal and public health research papers, and visits to Philip Morris's website. Various drafts of website language, as well as informal discussion of the website's creation, were located in internal Philip Morris documents. I compared website statements pertaining to Philip Morris's stance on cigarette smoking and disease with statements made in tobacco trials. Results Philip Morris created and disseminated its website's message that it agreed that smoking causes disease and is addictive in an effort to sway public opinion, while maintaining in a litigation setting its former position that it cannot be proved that smoking causes disease or is addictive. Conclusions Philip Morris has not changed its position on smoking and health or addiction in the one arena where it has the most to lose—in the courtroom, under oath. PMID:18048599

  18. Endothelial MMP-9 drives the inflammatory response in abdominal aortic aneurysm (AAA).

    PubMed

    Ramella, Martina; Boccafoschi, Francesca; Bellofatto, Kevin; Md, Antonia Follenzi; Fusaro, Luca; Boldorini, Renzo; Casella, Francesco; Porta, Carla; Settembrini, Piergiorgio; Cannas, Mario

    2017-01-01

    Progression of abdominal aortic aneurysm (AAA) is typified by chronic inflammation and extracellular matrix (ECM) degradation of the aortic wall. Vascular inflammation involves complex interactions among inflammatory cells, endothelial cells (ECs), vascular smooth muscle cells (vSMCs), and ECM. Although vascular endothelium and medial neoangiogenesis play a key role in AAA, the molecular mechanisms underlying their involvement are only partially understood. In AAA biopsies, we found increased MMP-9, IL-6, and monocyte chemoattractant protein-1 (MCP-1), which correlated with massive medial neo-angiogenesis (C4d positive staining). In this study, we developed an in vitro model in order to characterize the role of endothelial matrix metalloproteinase-9 (e-MMP-9) as a potential trigger of medial disruption and in the inflammatory response bridging between ECs and vSMC. Lentiviral-mediated silencing of e-MMP-9 through RNA interference inhibited TNF-alpha-mediated activation of NF-κB in EA.hy926 human endothelial cells. In addition, EA.hy926 cells void of MMP-9 failed to migrate in a 3D matrix. Moreover, silenced EA.hy926 affected vSMC behavior in terms of matrix remodeling. In fact, also MMP-9 in vSMC resulted inhibited when endothelial MMP-9 was suppressed.

  19. Hepatorenal revascularization enables EVAR repair on a patient with AAA and an ectopic right renal artery.

    PubMed

    Lazaris, A M; Moulakakis, K; Mantas, G; Poulou, K; Alexiou, E; Vasdekis, S; Geroulakos, G

    2018-06-07

    The last thirty years the endovascular repair (EVAR) has become the standard method of treatment of abdominal aortic aneurysms (AAA). Nevertheless, the method has limitations based mainly on the anatomic characteristics of the specific aneurysm. In these cases a combination of endovascular and open techniques can be used. We describe a case of a patient with an infrarenal AAA and an ectopic right renal artery emerging from within the aneurysm sac. The patient was treated with a combination of endovascular and open techniques. In particular, he underwent a hepatorenal revascularization followed by a standard EVAR procedure, with a successful final outcome. For the treatment of AAA disease, the combination of open and endovascular procedures can overcome difficulties where a standard EVAR cannot be an option. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

    PubMed

    Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

    2011-10-01

    Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

  1. How Philip Morris built Marlboro into a global brand for young adults: implications for international tobacco control.

    PubMed

    Hafez, N; Ling, P M

    2005-08-01

    To describe Philip Morris' global market research and international promotional strategies targeting young adults. Analysis of previously secret tobacco industry documents. Philip Morris pursued standardised market research and strategic marketing plans in different regions throughout the world using research on young adults with three principle foci: lifestyle/psychographic research, brand studies, and advertising/communication effectiveness. Philip Morris identified core similarities in the lifestyles and needs of young consumers worldwide, such as independence, hedonism, freedom, and comfort. In the early 1990s Philip Morris adopted standardised global marketing efforts, creating a central advertising production bank and guidelines for brand images and promotions, but allowing regional managers to create regionally appropriate individual advertisements. Values and lifestyles play a central role in the global marketing of tobacco to young adults. Worldwide counter marketing initiatives, coupled with strong, coherent global marketing policies such as the Framework Convention on Tobacco Control, are needed to break associations between young adult values and tobacco brands. As globalisation promotes the homogenisation of values and lifestyles, tobacco control messages that resonate with young adults in one part of the world may appeal to young adults in other countries. Successful tobacco control messages that appeal to young people, such as industry denormalisation, may be expanded globally with appropriate tailoring to appeal to regional values.

  2. Mechanism of Enzyme Repair by the AAA+ Chaperone Rubisco Activase.

    PubMed

    Bhat, Javaid Y; Miličić, Goran; Thieulin-Pardo, Gabriel; Bracher, Andreas; Maxwell, Andrew; Ciniawsky, Susanne; Mueller-Cajar, Oliver; Engen, John R; Hartl, F Ulrich; Wendler, Petra; Hayer-Hartl, Manajit

    2017-09-07

    How AAA+ chaperones conformationally remodel specific target proteins in an ATP-dependent manner is not well understood. Here, we investigated the mechanism of the AAA+ protein Rubisco activase (Rca) in metabolic repair of the photosynthetic enzyme Rubisco, a complex of eight large (RbcL) and eight small (RbcS) subunits containing eight catalytic sites. Rubisco is prone to inhibition by tight-binding sugar phosphates, whose removal is catalyzed by Rca. We engineered a stable Rca hexamer ring and analyzed its functional interaction with Rubisco. Hydrogen/deuterium exchange and chemical crosslinking showed that Rca structurally destabilizes elements of the Rubisco active site with remarkable selectivity. Cryo-electron microscopy revealed that Rca docks onto Rubisco over one active site at a time, positioning the C-terminal strand of RbcL, which stabilizes the catalytic center, for access to the Rca hexamer pore. The pulling force of Rca is fine-tuned to avoid global destabilization and allow for precise enzyme repair. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Identification of a Degradation Signal Sequence within Substrates of the Mitochondrial i-AAA Protease.

    PubMed

    Rampello, Anthony J; Glynn, Steven E

    2017-03-24

    The i-AAA protease is a component of the mitochondrial quality control machinery that regulates respiration, mitochondrial dynamics, and protein import. The protease is required to select specific substrates for degradation from among the diverse complement of proteins present in mitochondria, yet the rules that govern this selection are unclear. Here, we reconstruct the yeast i-AAA protease, Yme1p, to examine the in vitro degradation of two intermembrane space chaperone subunits, Tim9 and Tim10. Yme1p degrades Tim10 more rapidly than Tim9 despite high sequence and structural similarity, and loss of Tim10 is accelerated by the disruption of conserved disulfide bonds within the substrate. An unstructured N-terminal region of Tim10 is necessary and sufficient to target the substrate to the protease through recognition of a short phenylalanine-rich motif, and the presence of similar motifs in other small Tim proteins predicts robust degradation by the protease. Together, these results identify the first specific degron sequence within a native i-AAA protease substrate. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. What Is Wrong with Religious Education? A Response to Philip Barnes

    ERIC Educational Resources Information Center

    Whately, Hugo

    2008-01-01

    This article reviews Philip Barnes' account of problems with religious education (RE), and explores the practical implications of his position. Acknowledging his compelling logic--that RE is premised on an acceptance of all religions as equally theologically true--this article argues for optimism: with controversy and ambiguity moving to centre…

  5. Role of mitochondrial processing peptidase and AAA proteases in processing of the yeast acetohydroxyacid synthase precursor.

    PubMed

    Dasari, Suvarna; Kölling, Ralf

    2016-07-01

    We studied presequence processing of the mitochondrial-matrix targeted acetohydroxyacid synthase (Ilv2). C-terminal 3HA-tagging altered the cleavage pattern from a single step to sequential two-step cleavage, giving rise to two Ilv2-3HA forms (A and B). Both cleavage events were dependent on the mitochondrial processing peptidase (MPP). We present evidence for the involvement of three AAA ATPases, m- and i-AAA proteases, and Mcx1, in Ilv2-3HA processing. Both, precursor to A-form and A-form to B-form cleavage were strongly affected in a ∆yme1 mutant. These defects could be suppressed by overexpression of MPP, suggesting that MPP activity is limiting in the ∆yme1 mutant. Our data suggest that for some substrates AAA ATPases could play an active role in the translocation of matrix-targeted proteins.

  6. A Non-Competitive Inhibitor of VCP/p97 and VPS4 Reveals Conserved Allosteric Circuits in Type I and II AAA ATPases.

    PubMed

    Pöhler, Robert; Krahn, Jan H; van den Boom, Johannes; Dobrynin, Grzegorz; Kaschani, Farnusch; Eggenweiler, Hans-Michael; Zenke, Frank T; Kaiser, Markus; Meyer, Hemmo

    2018-02-05

    AAA ATPases have pivotal functions in diverse cellular processes essential for survival and proliferation. Revealing strategies for chemical inhibition of this class of enzymes is therefore of great interest for the development of novel chemotherapies or chemical tools. Here, we characterize the compound MSC1094308 as a reversible, allosteric inhibitor of the type II AAA ATPase human ubiquitin-directed unfoldase (VCP)/p97 and the type I AAA ATPase VPS4B. Subsequent proteomic, genetic and biochemical studies indicate that MSC1094308 binds to a previously characterized drugable hotspot of p97, thereby inhibiting the D2 ATPase activity. Our results furthermore indicate that a similar allosteric site exists in VPS4B, suggesting conserved allosteric circuits and drugable sites in both type I and II AAA ATPases. Our results may thus guide future chemical tool and drug discovery efforts for the biomedically relevant AAA ATPases. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. [Incidence and risk factors of ischemic colitis after AAA repair in our cohort of patients from 2005 through 2009].

    PubMed

    Biros, E; Staffa, R

    2011-12-01

    Using retrospective analysis, we sought to investigate the incidence, risk factors and therapeutic outcomes of ischemic colitis in patients after surgical and endovascular repair of abdominal aortic aneurysms (AAA). The complete inpatient and outpatient medical records of all patients undergoing surgical or endovascular AAA repair in our Department from January 2005 to December 2009 were retrospectively reviewed. We selected all patients who had developed an acute or chronic form of postoperative large or small bowel ischemia. We carried out data analysis and focused on determining the incidence and risk factors of this complication and the outcomes of its treatment. Two hundred and seven AAA repairs were performed in the 2nd Department of Surgery of St. Anne's University Hospital in Brno and the Faculty of Medicine of Masaryk University in Brno during the studied period. This number includes endovascular AAA repairs (13 patients; 6.3%) as well as one robot-assisted operation, and also the whole clinical spectrum of AAA manifestations, from non-symptomatic forms to ruptured aneurysm forms. The rest of the patients underwent open operation. Bowel ischemia developed in a total of 11 patients (5.3 %), who all underwent open AAA repair. Six of these patients presented with non-ruptured AAA and the remaining 5 with ruptured AAA. In 3 patients, bowel ischemia was diagnosed with a delay of several months from the original revascularization operation in the clinical form of postischemic stricture of the large bowel (2 patients) or postischemic colitis (1 patient). 8 patients were diagnosed with acute ischemic colitis affecting an isolated segment of the small bowel in one patient, extended segments of the large bowel (descending colon + sigmoid colon + rectum) in 2 patients, and typically the descending and sigmoid colon in 5 patients. None of the three patients with late manifestation of ischemic colitis died. Of the 8 patients with acute presentation, resection of the

  8. SU-E-T-122: Anisotropic Analytical Algorithm (AAA) Vs. Acuros XB (AXB) in Stereotactic Treatment Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mynampati, D; Scripes, P Godoy; Kuo, H

    2015-06-15

    Purpose: To evaluate dosimetric differences between superposition beam model (AAA) and determinant photon transport solver (AXB) in lung SBRT and Cranial SRS dose computations. Methods: Ten Cranial SRS and ten Lung SBRT plans using Varian, AAA -11.0 were re-planned using Acuros -XB-11.0 with fixed MU. 6MV photon Beam model with HD120-MLC used for dose calculations. Four non-coplanar conformal arcs used to deliver 21Gy or 18Gy to SRS targets (0.4 to 6.2cc). 54Gy (3Fractions) or 50Gy (5Fractions) was planned for SBRT targets (7.3 to 13.9cc) using two VAMT non-coplanar arcs. Plan comparison parameters were dose to 1% PTV volume (D1), dosemore » to 99% PTV volume( D99), Target mean (Dmean), Conformity index (ratio of prescription isodose volume to PTV), Homogeneity Index [ (D2%-D98%)/Dmean] and R50 (ratio of 50% of prescription isodose volume to PTV). OAR parameters were Brain volume receiving 12Gy dose (V12Gy) and maximum dose (D0.03) to Brainstem for SRS. For lung SBRT, maximum dose to Heart and Cord, Mean lung dose (MLD) and volume of lung receiving 20Gy (V20Gy) were computed. PTV parameters compared by percentage difference between AXB and AAA parameters. OAR parameters and HI compared by absolute difference between two calculations. For analysis, paired t-test performed over the parameters. Results: Compared to AAA, AXB SRS plans have on average 3.2% lower D99, 6.5% lower CI and 3cc less Brain-V12. However, AXB SBRT plans have higher D1, R50 and Dmean by 3.15%, 1.63% and 2.5%. For SRS and SBRT, AXB plans have average HI 2 % and 4.4% higher than AAA plans. In both techniques, all other parameters vary within 1% or 1Gy. In both sets only two parameters have P>0.05. Conclusion: Even though t-test results signify difference between AXB and AAA plans, dose differences in dose estimations by both algorithms are clinically insignificant.« less

  9. How Philip Morris built Marlboro into a global brand for young adults: implications for international tobacco control

    PubMed Central

    Hafez, N; Ling, P

    2005-01-01

    Objective: To describe Philip Morris' global market research and international promotional strategies targeting young adults. Methods: : Analysis of previously secret tobacco industry documents. Results: Philip Morris pursued standardised market research and strategic marketing plans in different regions throughout the world using research on young adults with three principle foci: lifestyle/psychographic research, brand studies, and advertising/communication effectiveness. Philip Morris identified core similarities in the lifestyles and needs of young consumers worldwide, such as independence, hedonism, freedom, and comfort. In the early 1990s Philip Morris adopted standardised global marketing efforts, creating a central advertising production bank and guidelines for brand images and promotions, but allowing regional managers to create regionally appropriate individual advertisements. Conclusions: Values and lifestyles play a central role in the global marketing of tobacco to young adults. Worldwide counter marketing initiatives, coupled with strong, coherent global marketing policies such as the Framework Convention on Tobacco Control, are needed to break associations between young adult values and tobacco brands. As globalisation promotes the homogenisation of values and lifestyles, tobacco control messages that resonate with young adults in one part of the world may appeal to young adults in other countries. Successful tobacco control messages that appeal to young people, such as industry denormalisation, may be expanded globally with appropriate tailoring to appeal to regional values. PMID:16046690

  10. Coordinated gripping of substrate by subunits of a AAA+ proteolytic machine

    PubMed Central

    Iosefson, Ohad; Nager, Andrew R.; Baker, Tania A.; Sauer, Robert T.

    2014-01-01

    Hexameric AAA+ unfoldases of ATP-dependent proteases and protein-remodeling machines use conserved loops that line the axial pore to apply force to substrates during the mechanical processes of protein unfolding and translocation. Whether loops from multiple subunits act independently or coordinately in these processes is a critical aspect of mechanism but is currently unknown for any AAA+ machine. By studying covalently linked hexamers of the E. coli ClpX unfoldase bearing different numbers and configurations of wild-type and mutant pore loops, we show that loops function synergistically, with the number of wild-type loops required for efficient degradation depending upon the stability of the protein substrate. Our results support a mechanism in which a power stroke initiated in one subunit of the ClpX hexamer results in the concurrent movement of all six pore loops, which coordinately grip and apply force to the substrate. PMID:25599533

  11. From AAA to Acuros XB-clinical implications of selecting either Acuros XB dose-to-water or dose-to-medium.

    PubMed

    Zifodya, Jackson M; Challens, Cameron H C; Hsieh, Wen-Long

    2016-06-01

    When implementing Acuros XB (AXB) as a substitute for anisotropic analytic algorithm (AAA) in the Eclipse Treatment Planning System, one is faced with a dilemma of reporting either dose to medium, AXB-Dm or dose to water, AXB-Dw. To assist with decision making on selecting either AXB-Dm or AXB-Dw for dose reporting, a retrospective study of treated patients for head & neck (H&N), prostate, breast and lung is presented. Ten patients, previously treated using AAA plans, were selected for each site and re-planned with AXB-Dm and AXB-Dw. Re-planning was done with fixed monitor units (MU) as well as non-fixed MUs. Dose volume histograms (DVH) of targets and organs at risk (OAR), were analyzed in conjunction with ICRU-83 recommended dose reporting metrics. Additionally, comparisons of plan homogeneity indices (HI) and MUs were done to further highlight the differences between the algorithms. Results showed that, on average AAA overestimated dose to the target volume and OARs by less than 2.0 %. Comparisons between AXB-Dw and AXB-Dm, for all sites, also showed overall dose differences to be small (<1.5 %). However, in non-water biological media, dose differences between AXB-Dw and AXB-Dm, as large as 4.6 % were observed. AXB-Dw also tended to have unexpectedly high 3D maximum dose values (>135 % of prescription dose) for target volumes with high density materials. Homogeneity indices showed that AAA planning and optimization templates would need to be adjusted only for the H&N and Lung sites. MU comparison showed insignificant differences between AXB-Dw relative to AAA and between AXB-Dw relative to AXB-Dm. However AXB-Dm MUs relative to AAA, showed an average difference of about 1.3 % signifying an underdosage by AAA. In conclusion, when dose is reported as AXB-Dw, the effect that high density structures in the PTV has on the dose distribution should be carefully considered. As the results show overall small dose differences between the algorithms, when

  12. SU-E-T-516: Dosimetric Validation of AcurosXB Algorithm in Comparison with AAA & CCC Algorithms for VMAT Technique.

    PubMed

    Kathirvel, M; Subramanian, V Sai; Arun, G; Thirumalaiswamy, S; Ramalingam, K; Kumar, S Ashok; Jagadeesh, K

    2012-06-01

    To dosimetrically validate AcurosXB algorithm for Volumetric Modulated Arc Therapy (VMAT) in comparison with standard clinical Anisotropic Analytic Algorithm(AAA) and Collapsed Cone Convolution(CCC) dose calculation algorithms. AcurosXB dose calculation algorithm is available with Varian Eclipse treatment planning system (V10). It uses grid-based Boltzmann equation solver to predict dose precisely in lesser time. This study was made to realize algorithms ability to predict dose accurately as its delivery for which five clinical cases each of Brain, Head&Neck, Thoracic, Pelvic and SBRT were taken. Verification plans were created on multicube phantom with iMatrixx-2D detector array and then dose prediction was done with AcurosXB, AAA & CCC (COMPASS System) algorithm and the same were delivered onto CLINAC-iX treatment machine. Delivered dose was captured in iMatrixx plane for all 25 plans. Measured dose was taken as reference to quantify the agreement between AcurosXB calculation algorithm against previously validated AAA and CCC algorithm. Gamma evaluation was performed with clinical criteria distance-to-agreement 3&2mm and dose difference 3&2% in omnipro-I'MRT software. Plans were evaluated in terms of correlation coefficient, quantitative area gamma and average gamma. Study shows good agreement between mean correlation 0.9979±0.0012, 0.9984±0.0009 & 0.9979±0.0011 for AAA, CCC & Acuros respectively. Mean area gamma for criteria 3mm/3% was found to be 98.80±1.04, 98.14±2.31, 98.08±2.01 and 2mm/2% was found to be 93.94±3.83, 87.17±10.54 & 92.36±5.46 for AAA, CCC & Acuros respectively. Mean average gamma for 3mm/3% was 0.26±0.07, 0.42±0.08, 0.28±0.09 and 2mm/2% was found to be 0.39±0.10, 0.64±0.11, 0.42±0.13 for AAA, CCC & Acuros respectively. This study demonstrated that the AcurosXB algorithm had a good agreement with the AAA & CCC in terms of dose prediction. In conclusion AcurosXB algorithm provides a valid, accurate and speedy alternative to AAA

  13. Analysis of the cooperative ATPase cycle of the AAA+ chaperone ClpB from Thermus thermophilus by using ordered heterohexamers with an alternating subunit arrangement.

    PubMed

    Yamasaki, Takashi; Oohata, Yukiko; Nakamura, Toshiki; Watanabe, Yo-hei

    2015-04-10

    The ClpB/Hsp104 chaperone solubilizes and reactivates protein aggregates in cooperation with DnaK/Hsp70 and its cofactors. The ClpB/Hsp104 protomer has two AAA+ modules, AAA-1 and AAA-2, and forms a homohexamer. In the hexamer, these modules form a two-tiered ring in which each tier consists of homotypic AAA+ modules. By ATP binding and its hydrolysis at these AAA+ modules, ClpB/Hsp104 exerts the mechanical power required for protein disaggregation. Although ATPase cycle of this chaperone has been studied by several groups, an integrated understanding of this cycle has not been obtained because of the complexity of the mechanism and differences between species. To improve our understanding of the ATPase cycle, we prepared many ordered heterohexamers of ClpB from Thermus thermophilus, in which two subunits having different mutations were cross-linked to each other and arranged alternately and measured their nucleotide binding, ATP hydrolysis, and disaggregation abilities. The results indicated that the ATPase cycle of ClpB proceeded as follows: (i) the 12 AAA+ modules randomly bound ATP, (ii) the binding of four or more ATP to one AAA+ ring was sensed by a conserved Arg residue and converted another AAA+ ring into the ATPase-active form, and (iii) ATP hydrolysis occurred cooperatively in each ring. We also found that cooperative ATP hydrolysis in at least one ring was needed for the disaggregation activity of ClpB. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.

    PubMed

    Esaki, Masatoshi; Islam, Md Tanvir; Tani, Naoki; Ogura, Teru

    2017-07-14

    Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.

  15. The Genocidal Mentality: Philip II of Spain and Sultan Abdul Hamid II.

    ERIC Educational Resources Information Center

    Kuttner, Robert E.

    1986-01-01

    Historical comparison of Sultan Abdul Hamid of Turkey and King Philip II of Spain with Adolph Hitler revealed similar personality traits, possibly characteristic determinants of individuals prone to undertake genocidal measures. Commitment to bureaucratic detail coupled with opportunistic belief in Messianic destiny are key factors in these…

  16. m-AAA Complexes Are Not Crucial for the Survival of Arabidopsis Under Optimal Growth Conditions Despite Their Importance for Mitochondrial Translation.

    PubMed

    Kolodziejczak, Marta; Skibior-Blaszczyk, Renata; Janska, Hanna

    2018-05-01

    For optimal mitochondrial activity, the mitochondrial proteome must be properly maintained or altered in response to developmental and environmental stimuli. Based on studies of yeast and humans, one of the key players in this control are m-AAA proteases, mitochondrial inner membrane-bound ATP-dependent metalloenzymes. This study focuses on the importance of m-AAA proteases in plant mitochondria, providing their first experimentally proven physiological substrate. We found that the Arabidopsis m- AAA complexes composed of AtFTSH3 and/or AtFTSH10 are involved in the proteolytic maturation of ribosomal subunit L32. Consequently, in the double Arabidopsis ftsh3/10 mutant, mitoribosome biogenesis, mitochondrial translation and functionality of OXPHOS (oxidative phosphorylation) complexes are impaired. However, in contrast to their mammalian or yeast counterparts, plant m-AAA complexes are not critical for the survival of Arabidopsis under optimal conditions; ftsh3/10 plants are only slightly smaller in size at the early developmental stage compared with plants containing m-AAA complexes. Our data suggest that a lack of significant visible morphological alterations under optimal growth conditions involves mechanisms which rely on existing functional redundancy and induced functional compensation in Arabidopsis mitochondria.

  17. ARTIST (Asian regional tobacco industry scientist team): Philip Morris' attempt to exert a scientific and regulatory agenda on Asia

    PubMed Central

    Tong, E; Glantz, S

    2004-01-01

    Objective: To describe how the transnational tobacco industry has collaborated with local Asian tobacco monopolies and companies to promote a scientific and regulatory agenda. Methods: Analysis of previously secret tobacco industry documents. Results: Transnational tobacco companies began aggressively entering the Asia market in the 1980s, and the current tobacco industry in Asia is a mix of transnational and local monopolies or private companies. Tobacco industry documents demonstrate that, in 1996, Philip Morris led an organisation of scientific representatives from different tobacco companies called the Asian Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia. ARTIST was initially a vehicle for PM's strategies against anticipated calls for global smoke-free areas from a World Health Organization secondhand smoke study. ARTIST evolved through 2001 into a forum to present scientific and regulatory issues faced primarily by Philip Morris and other transnational tobacco companies. Philip Morris' goal for the organisation became to reach the external scientific and public health community and regulators in Asia. Conclusion: The Asian tobacco industry has changed from an environment of invasion by transnational tobacco companies to an environment of participation with Philip Morris' initiated activities. With this participation, tobacco control efforts in Asia face new challenges as Philip Morris promotes and integrates its scientific and regulatory agenda into the local Asian tobacco industry. As the local Asian tobacco monopolies and companies can have direct links with their governments, future implementation of effective tobacco control may be at odds with national priorities. PMID:15564214

  18. ARTIST (Asian regional tobacco industry scientist team): Philip Morris' attempt to exert a scientific and regulatory agenda on Asia.

    PubMed

    Tong, E K; Glantz, S A

    2004-12-01

    To describe how the transnational tobacco industry has collaborated with local Asian tobacco monopolies and companies to promote a scientific and regulatory agenda. Analysis of previously secret tobacco industry documents. Transnational tobacco companies began aggressively entering the Asia market in the 1980s, and the current tobacco industry in Asia is a mix of transnational and local monopolies or private companies. Tobacco industry documents demonstrate that, in 1996, Philip Morris led an organisation of scientific representatives from different tobacco companies called the Asian Regional Tobacco Industry Science Team (ARTIST), whose membership grew to include monopolies from Korea, China, Thailand, and Taiwan and a company from Indonesia. ARTIST was initially a vehicle for PM's strategies against anticipated calls for global smoke-free areas from a World Health Organization secondhand smoke study. ARTIST evolved through 2001 into a forum to present scientific and regulatory issues faced primarily by Philip Morris and other transnational tobacco companies. Philip Morris' goal for the organisation became to reach the external scientific and public health community and regulators in Asia. The Asian tobacco industry has changed from an environment of invasion by transnational tobacco companies to an environment of participation with Philip Morris' initiated activities. With this participation, tobacco control efforts in Asia face new challenges as Philip Morris promotes and integrates its scientific and regulatory agenda into the local Asian tobacco industry. As the local Asian tobacco monopolies and companies can have direct links with their governments, future implementation of effective tobacco control may be at odds with national priorities.

  19. The plant i-AAA protease controls the turnover of an essential mitochondrial protein import component.

    PubMed

    Opalińska, Magdalena; Parys, Katarzyna; Murcha, Monika W; Jańska, Hanna

    2018-01-29

    Mitochondria are multifunctional organelles that play a central role in energy metabolism. Owing to the life-essential functions of these organelles, mitochondrial content, quality and dynamics are tightly controlled. Across the species, highly conserved ATP-dependent proteases prevent malfunction of mitochondria through versatile activities. This study focuses on a molecular function of the plant mitochondrial inner membrane-embedded AAA protease (denoted i -AAA) FTSH4, providing its first bona fide substrate. Here, we report that the abundance of the Tim17-2 protein, an essential component of the TIM17:23 translocase (Tim17-2 together with Tim50 and Tim23), is directly controlled by the proteolytic activity of FTSH4. Plants that are lacking functional FTSH4 protease are characterized by significantly enhanced capacity of preprotein import through the TIM17:23-dependent pathway. Taken together, with the observation that FTSH4 prevents accumulation of Tim17-2, our data point towards the role of this i -AAA protease in the regulation of mitochondrial biogenesis in plants. © 2018. Published by The Company of Biologists Ltd.

  20. Assessment of resistomycin, as an anticancer compound isolated and characterized from Streptomyces aurantiacus AAA5.

    PubMed

    Vijayabharathi, Rajendran; Bruheim, Per; Andreassen, Trygve; Raja, Duraisamy Senthil; Devi, Palanisamy Bruntha; Sathyabama, Sathyaseelan; Priyadarisini, Venkatesan Brindha

    2011-12-01

    A new actinomycete strain, isolated from humus soils in the Western Ghats, was found to be an efficient pigment producer. The strain, designated AAA5, was identified as a putative Streptomyces aurantiacus strain based on cultural properties, morphology, carbon source utilization, and analysis of the 16S rRNA gene. The strain produced a reddish-brown pigmented compound during the secondary metabolites phase. A yellow compound was derived from the extracted pigment and was identified as the quinone-related antibiotic resistomycin based on ultraviolet-visible spectrophotometry, fourier transform infrared spectroscopy, liquid chromatography and mass spectroscopy, and nuclear magnetic resonance analyses. The AAA5 strain was found to produce large quantities of resistomycin (52.5 mg/L). It showed potent cytotoxic activity against cell lines viz. HepG2 (hepatic carcinoma) and HeLa (cervical carcinoma) in vitro, with growth inhibition (GI(50)) of 0.006 and 0.005 μg/ml, respectively. The strain also exhibited broad antimicrobial activities against both Gram-positive and Gram-negative bacteria. Therefore, AAA5 may have great potential as an industrial resistomycin-producing strain.

  1. The Abdominal Aortic Aneurysm Statistically Corrected Operative Risk Evaluation (AAA SCORE) for predicting mortality after open and endovascular interventions.

    PubMed

    Ambler, Graeme K; Gohel, Manjit S; Mitchell, David C; Loftus, Ian M; Boyle, Jonathan R

    2015-01-01

    Accurate adjustment of surgical outcome data for risk is vital in an era of surgeon-level reporting. Current risk prediction models for abdominal aortic aneurysm (AAA) repair are suboptimal. We aimed to develop a reliable risk model for in-hospital mortality after intervention for AAA, using rigorous contemporary statistical techniques to handle missing data. Using data collected during a 15-month period in the United Kingdom National Vascular Database, we applied multiple imputation methodology together with stepwise model selection to generate preoperative and perioperative models of in-hospital mortality after AAA repair, using two thirds of the available data. Model performance was then assessed on the remaining third of the data by receiver operating characteristic curve analysis and compared with existing risk prediction models. Model calibration was assessed by Hosmer-Lemeshow analysis. A total of 8088 AAA repair operations were recorded in the National Vascular Database during the study period, of which 5870 (72.6%) were elective procedures. Both preoperative and perioperative models showed excellent discrimination, with areas under the receiver operating characteristic curve of .89 and .92, respectively. This was significantly better than any of the existing models (area under the receiver operating characteristic curve for best comparator model, .84 and .88; P < .001 and P = .001, respectively). Discrimination remained excellent when only elective procedures were considered. There was no evidence of miscalibration by Hosmer-Lemeshow analysis. We have developed accurate models to assess risk of in-hospital mortality after AAA repair. These models were carefully developed with rigorous statistical methodology and significantly outperform existing methods for both elective cases and overall AAA mortality. These models will be invaluable for both preoperative patient counseling and accurate risk adjustment of published outcome data. Copyright © 2015 Society

  2. In-depth study of single photon time resolution for the Philips digital silicon photomultiplier

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Gundacker, S.; Pizzichemi, M.; Ghezzi, A.; Auffray, E.; Lecoq, P.; Paganoni, M.

    2016-06-01

    The digital silicon photomultiplier (SiPM) has been commercialised by Philips as an innovative technology compared to analog silicon photomultiplier devices. The Philips digital SiPM, has a pair of time to digital converters (TDCs) connected to 12800 single photon avalanche diodes (SPADs). Detailed measurements were performed to understand the low photon time response of the Philips digital SiPM. The single photon time resolution (SPTR) of every single SPAD in a pixel consisting of 3200 SPADs was measured and an average value of 85 ps full width at half maximum (FWHM) was observed. Each SPAD sends the signal to the TDC with different signal propagation time, resulting in a so called trigger network skew. This distribution of the trigger network skew for a pixel (3200 SPADs) has been measured and a variation of 50 ps FWHM was extracted. The SPTR of the whole pixel is the combination of SPAD jitter, trigger network skew, and the SPAD non-uniformity. The SPTR of a complete pixel was 103 ps FWHM at 3.3 V above breakdown voltage. Further, the effect of the crosstalk at a low photon level has been studied, with the two photon time resolution degrading if the events are a combination of detected (true) photons and crosstalk events. Finally, the time response to multiple photons was investigated.

  3. Editor's Choice - Prolonged ICU Length of Stay after AAA Repair: Analysis of Time Trends and Long-term Outcome.

    PubMed

    Gavali, H; Mani, K; Tegler, G; Kawati, R; Covaciu, L; Wanhainen, A

    2017-08-01

    The aim of the study was to investigate the frequency and outcome of prolonged intensive care unit (ICU) length of stay (LOS) after abdominal aortic aneurysm (AAA) repair in the endovascular era. All patients operated on for AAA between 1999 and 2013 at Uppsala University hospital were identified. Data were retrieved from the Swedish Vascular registry, the Swedish Intensive Care registry, the National Population registry, and case records. Prolonged ICU LOS was defined as ≥ 48 h during the primary hospital stay. Patients surviving ≥ 48 h after AAA surgery were included in the analysis. A total of 725 patients were identified, of whom 707 (97.5%) survived ≥ 48 h; 563 (79.6%) underwent intact AAA repair and 144 (20.4%) ruptured AAA repair. A total of 548 patients (77.5%) required < 48 h of intensive care, 115 (16.3%) 2-6 days and 44 (6.2%) ≥ 7 days. The rate of prolonged ICU LOS declined considerably over time, from 41.4% of all AAA repairs in 1999 to 7.3% in 2013 (p < .001) whereas the use of endovascular aortic repair (EVAR) increased from 6.9% in 1999 to 78.0% in 2013 (p < .001). The 30 day survival rate was 98.2% for those with < 48 h ICU stay versus 93.0% for 2-6 days versus 81.8% for ≥ 7 days (p < .001); the corresponding 90 day survival was 97.1% versus 86.1% versus 63.6% (p < .001) respectively. For patients surviving 90 days after repair, there was no difference in long-term survival between the groups. During the period of progressively increasing use of EVAR, a simultaneous significant reduction in frequency of prolonged ICU LOS occurred. Although prolonged ICU LOS was associated with a high short-term mortality, long-term outcome among those surviving the initial 90 days was less affected. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

  4. Stan Bull, Long-Time NREL Leader, Named AAAS Fellow | News | NREL

    Science.gov Websites

    , Named AAAS Fellow January 11, 2011 Stanley R. Bull, former associate director for Science and Technology emeritus researcher. He was cited for "distinguished leadership in creating new programs, development partner with existing energy companies, including the fossil-fuel industry, and to "provide our

  5. Hydrogeochemical and stream sediment reconnaissance basic data for Philip Smith Mountains Quadrangle, Alaska

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Not Available

    1981-05-29

    Field and laboratory data are presented for 1128 water samples from the Philip Smith Mountains Quadrangle, Alaska. The samples were collected by Los Alamos Scientific Laboratory; laboratory analysis and data reporting were performed by the Uranium Resource Evaluation Project at Oak Ridge, Tennessee.

  6. Enhancing the IT Infrastructure at Saint Philip's Hospital: Point-of-Care Solutions

    ERIC Educational Resources Information Center

    Naydenova, Iva; White, Bruce

    2013-01-01

    Healthcare has become a rapidly changing field. With the introduction of value-based purchasing to determine reimbursement of Medicare providers based on the quality of care in addition to outcomes in treatment, the environment is becoming ever more competitive. Saint Philip's Hospital is among the largest non-profit hospitals in the nation…

  7. On 50 Years of Giving Psychology Away: An Interview with Philip Zimbardo

    ERIC Educational Resources Information Center

    Slavich, George M.

    2009-01-01

    This article presents an interview with Philip Zimbardo, emeritus professor of psychology at Stanford University, who is internationally recognized as the voice and face of contemporary American psychology. He earned his PhD in social psychology from Yale University in 1959 and has since received seven honorary doctorates for his contributions to…

  8. The lameness of King Philip II and Royal Tomb I at Vergina, Macedonia

    PubMed Central

    Bartsiokas, Antonis; Arsuaga, Juan-Luis; Santos, Elena; Algaba, Milagros; Gómez-Olivencia, Asier

    2015-01-01

    King Philip II was the father of Alexander the Great. He suffered a notorious penetrating wound by a lance through his leg that was nearly fatal and left him lame in 339 B.C.E. (i.e., 3 y before his assassination in 336 B.C.E.). In 1977 and 1978 two male skeletons were excavated in the Royal Tombs II and I of Vergina, Greece, respectively. Tomb I also contained another adult (likely a female) and a newborn skeleton. The current view is that Philip II was buried in Tomb II. However, the male skeleton of Tomb II bears no lesions to his legs that would indicate lameness. We investigated the skeletal material of Tomb I with modern forensic techniques. The male individual in Tomb I displays a conspicuous case of knee ankylosis that is conclusive evidence of lameness. Right through the overgrowth of the knee, there is a hole. There are no obvious signs that are characteristic of infection and osteomyelitis. This evidence indicates that the injury was likely caused by a severe penetrating wound to the knee, which resulted in an active inflammatory process that stopped years before death. Standard anthropological age-estimation techniques based on dry bone, epiphyseal lines, and tooth analysis gave very wide age ranges for the male, centered around 45 y. The female would be around 18-y-old and the infant would be a newborn. It is concluded that King Philip II, his wife Cleopatra, and their newborn child are the occupants of Tomb I. PMID:26195763

  9. Creating the “desired mindset”: Philip Morris’s efforts to improve its corporate image among women

    PubMed Central

    McDaniel, Patricia A.; Malone, Ruth E.

    2009-01-01

    Through analysis of tobacco company documents, we explored how and why Philip Morris sought to enhance its corporate image among American women. Philip Morris regarded women as an influential group. To improve its image among women, while keeping tobacco off their organizational agendas, the company sponsored women’s groups and programs. It also sought to appeal to women it defined as “active moms” by advertising its commitment to domestic violence victims. It was more successful in securing women’s organizations as allies than active moms. Increasing tobacco’s visibility as a global women’s health issue may require addressing industry influence. PMID:19851947

  10. Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control.

    PubMed

    Carroni, Marta; Franke, Kamila B; Maurer, Michael; Jäger, Jasmin; Hantke, Ingo; Gloge, Felix; Linder, Daniela; Gremer, Sebastian; Turgay, Kürşad; Bukau, Bernd; Mogk, Axel

    2017-11-22

    Ring-forming AAA+ chaperones exert ATP-fueled substrate unfolding by threading through a central pore. This activity is potentially harmful requiring mechanisms for tight repression and substrate-specific activation. The AAA+ chaperone ClpC with the peptidase ClpP forms a bacterial protease essential to virulence and stress resistance. The adaptor MecA activates ClpC by targeting substrates and stimulating ClpC ATPase activity. We show how ClpC is repressed in its ground state by determining ClpC cryo-EM structures with and without MecA. ClpC forms large two-helical assemblies that associate via head-to-head contacts between coiled-coil middle domains (MDs). MecA converts this resting state to an active planar ring structure by binding to MD interaction sites. Loss of ClpC repression in MD mutants causes constitutive activation and severe cellular toxicity. These findings unravel an unexpected regulatory concept executed by coiled-coil MDs to tightly control AAA+ chaperone activity.

  11. AAAS Communicating Science Program: Reflections on Evaluation

    NASA Astrophysics Data System (ADS)

    Braha, J.

    2015-12-01

    The AAAS Center for Public Engagement (Center) with science builds capacity for scientists to engage public audiences by fostering collaboration among natural or physical scientists, communication researchers, and public engagement practitioners. The recently launched Leshner Leadership Institute empowers cohorts of mid-career scientists to lead public engagement by supporting their networks of scientists, researchers, and practitioners. The Center works closely with social scientists whose research addresses science communication and public engagement with science to ensure that the Communicating Science training program builds on empirical evidence to inform best practices. Researchers ( Besley, Dudo, & Storkdieck 2015) have helped Center staff and an external evaluator develop pan instrument that measures progress towards goals that are suggested by the researcher, including internal efficacy (increasing scientists' communication skills and confidence in their ability to engage with the public) and external efficacy (scientists' confidence in engagement methods). Evaluation results from one year of the Communicating Science program suggest that the model of training yields positive results that support scientists in the area that should lead to greater engagement. This talk will explore the model for training, which provides a context for strategic communication, as well as the practical factors, such as time, access to public engagement practitioners, and technical skill, that seems to contribute to increased willingness to engage with public audiences. The evaluation program results suggest willingness by training participants to engage directly or to take preliminary steps towards engagement. In the evaluation results, 38% of trained scientists reported time as a barrier to engagement; 35% reported concern that engagement would distract from their work as a barrier. AAAS works to improve practitioner-researcher-scientist networks to overcome such barriers.

  12. Fan filter cleaning on the CHeCS AAA in the US Lab

    NASA Image and Video Library

    2009-05-05

    ISS019-E-013710 (5 May 2009) --- Japan Aerospace Exploration Agency (JAXA) astronaut Koichi Wakata, Expedition 19/20 flight engineer, cleans a fan filter on the Crew Health Care System Avionics Air Assembly (CHeCS AAA) in the Destiny laboratory of the International Space Station.

  13. Philip Vickers Fithian (1747-1776), a Princeton Tutor on a Virginia Plantation.

    ERIC Educational Resources Information Center

    Parker, Franklin; Parker, Betty J.

    This paper narrates the life of Philip Vickers Fithian, a northern tutor on a southern plantation prior to the American Revolution. Fithian's life is described from the time he was born in 1747, through his years at the College of New Jersey, renamed Princeton College in 1896 and later Princeton University, until he graduated in 1772, and until…

  14. NASA Astrophysics E/PO Impact: NASA SOFIA AAA Program Evaluation Results

    NASA Astrophysics Data System (ADS)

    Harman, Pamela; Backman, Dana E.; Clark, Coral; Inverness Research Sofia Aaa Evaluation Team, Wested Sofia Aaa Evaluation Team

    2015-01-01

    SOFIA is an airborne observatory, studying the universe at infrared wavelengths, capable of making observations that are impossible for even the largest and highest ground-based telescopes. SOFIA also inspires the development of new scientific instrumentation and fosters the education of young scientists and engineers.SOFIA is an 80% - 20% partnership of NASA and the German Aerospace Center (DLR), consisting of an extensively modified Boeing 747SP aircraft carrying a reflecting telescope with an effective diameter of 2.5 meters (100 inches). The SOFIA aircraft is based at NASA Armstrong Flight Research Center, Building 703, in Palmdale, California. The Science Program and Outreach Offices are located at NASA Ames Research center. SOFIA is a program in NASA's Science Mission Directorate, Astrophysics Division.Data will be collected to study many different kinds of astronomical objects and phenomena, including star cycles, solar system formation, identification of complex molecules in space, our solar system, galactic dust, nebulae and ecosystems.Airborne Astronomy Ambassador (AAA) Program:The SOFIA Education and Communications program exploits the unique attributes of airborne astronomy to contribute to national goals for the reform of science, technology, engineering, and math (STEM) education, and to elevate public scientific and technical literacy.The AAA effort is a professional development program aspiring to improve teaching, inspire students, and inform the community. To date, 55 educators from 21 states; Cycles 0, 1 and 2; have completed their astronomy professional development and their SOFIA science flight experience. Evaluation has confirmed the program's positive impact on the teacher participants, on their students, and in their communities. The inspirational experience has positively impacted their practice and career trajectory. AAAs have incorporated content knowledge and specific components of their experience into their curricula, and have given

  15. SFM-FDTD analysis of triangular-lattice AAA structure: Parametric study of the TEM mode

    NASA Astrophysics Data System (ADS)

    Hamidi, M.; Chemrouk, C.; Belkhir, A.; Kebci, Z.; Ndao, A.; Lamrous, O.; Baida, F. I.

    2014-05-01

    This theoretical work reports a parametric study of enhanced transmission through annular aperture array (AAA) structure arranged in a triangular lattice. The effect of the incidence angle in addition to the inner and outer radii values on the evolution of the transmission spectra is carried out. To this end, a 3D Finite-Difference Time-Domain code based on the Split Field Method (SFM) is used to calculate the spectral response of the structure for any angle of incidence. In order to work through an orthogonal unit cell which presents the advantage to reduce time and space of computation, special periodic boundary conditions are implemented. This study provides a new modeling of AAA structures useful for producing tunable ultra-compact devices.

  16. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    NASA Astrophysics Data System (ADS)

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-03-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell.

  17. Moyamoya disease-associated protein mysterin/RNF213 is a novel AAA+ ATPase, which dynamically changes its oligomeric state

    PubMed Central

    Morito, Daisuke; Nishikawa, Kouki; Hoseki, Jun; Kitamura, Akira; Kotani, Yuri; Kiso, Kazumi; Kinjo, Masataka; Fujiyoshi, Yoshinori; Nagata, Kazuhiro

    2014-01-01

    Moyamoya disease is an idiopathic human cerebrovascular disorder that is characterized by progressive stenosis and abnormal collateral vessels. We recently identified mysterin/RNF213 as its first susceptibility gene, which encodes a 591-kDa protein containing enzymatically active P-loop ATPase and ubiquitin ligase domains and is involved in proper vascular development in zebrafish. Here we demonstrate that mysterin further contains two tandem AAA+ ATPase modules and forms huge ring-shaped oligomeric complex. AAA+ ATPases are known to generally mediate various biophysical and mechanical processes with the characteristic ring-shaped structure. Fluorescence correlation spectroscopy and biochemical evaluation suggested that mysterin dynamically changes its oligomeric forms through ATP/ADP binding and hydrolysis cycles. Thus, the moyamoya disease-associated gene product is a unique protein that functions as ubiquitin ligase and AAA+ ATPase, which possibly contributes to vascular development through mechanical processes in the cell. PMID:24658080

  18. The Living Tomorrow Project: how Philip Morris has used a Belgian tourist attraction to promote ventilation approaches to the control of second hand smoke.

    PubMed

    Pilkington, P; Gilmore, A B

    2004-12-01

    To examine the involvement of Philip Morris in Living Tomorrow 2 and determine the rationale behind its involvement. Research was conducted through a web based search of internal tobacco industry documents made publicly available through litigation. For approximately 1,000,000 euros Philip Morris (now Altria) became a co-initiator of Living Tomorrow 2, a tourist complex in Belgium that aims to demonstrate how we will be living in the future. In addition to promoting the company and its grocery products, Philip Morris is using the complex and its website to promote ventilation as a means of accommodating smokers and non-smokers in the indoor environment. Particular emphasis was placed on the bar and restaurant areas. Despite the rationale for its involvement, Philip Morris fails to acknowledge its role as a cigarette manufacturer. As a form of corporate sponsorship Philip Morris thought its involvement could evade any European tobacco advertising ban. Philip Morris is using a tourist attraction to promote its views on control of second hand smoke (SHS) and accommodation of smokers and non-smokers in the indoor environment. However, ventilation does not deal with the health effects of SHS. Policymakers must be cognisant of the devious tactics the industry employs to promote its own agenda, especially in relation to indoor air quality and smoking in public places. Tobacco control legislation should be continually modified and strengthened in response to the changing activities of the tobacco industry as it strives to evade existing legislation and deter the advent of new legislation.

  19. High-intensity interval exercise training before abdominal aortic aneurysm repair (HIT-AAA): protocol for a randomised controlled feasibility trial.

    PubMed

    Tew, Garry A; Weston, Matthew; Kothmann, Elke; Batterham, Alan M; Gray, Joanne; Kerr, Karen; Martin, Denis; Nawaz, Shah; Yates, David; Danjoux, Gerard

    2014-01-10

    In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair. A minimum of 50 patients awaiting elective repair of a 5.5-7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24-48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated. Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and

  20. OGLE16aaa - a signature of a hungry supermassive black hole

    NASA Astrophysics Data System (ADS)

    Wyrzykowski, Łukasz; Zieliński, M.; Kostrzewa-Rutkowska, Z.; Hamanowicz, A.; Jonker, P. G.; Arcavi, I.; Guillochon, J.; Brown, P. J.; Kozłowski, S.; Udalski, A.; Szymański, M. K.; Soszyński, I.; Poleski, R.; Pietrukowicz, P.; Skowron, J.; Mróz, P.; Ulaczyk, K.; Pawlak, M.; Rybicki, K. A.; Greiner, J.; Krühler, T.; Bolmer, J.; Smartt, S. J.; Maguire, K.; Smith, K.

    2017-02-01

    We present the discovery and first three months of follow-up observations of a currently on-going unusual transient detected by the Optical Gravitational Lensing Experiment (OGLE-IV) survey, located in the centre of a galaxy at redshift z = 0.1655. The long rise to absolute magnitude of -20.5 mag, slow decline, very broad He and H spectral features make OGLE16aaa similar to other optical/UV tidal disruption events (TDEs). Weak narrow emission lines in the spectrum and archival photometric observations suggest the host galaxy is a weak-line active galactic nucleus, which has been accreting at higher rate in the past. OGLE16aaa, along with SDSS J0748, seems to form a sub-class of TDEs by weakly or recently active supermassive black holes (SMBHs). This class might bridge the TDEs by quiescent SMBHs and flares observed as `changing-look quasars', if we interpret the latter as TDEs. If this picture is true, the previously applied requirement for identifying a flare as a TDE that it had to come from an inactive nucleus, could be leading to observational bias in TDE selection, thus affecting TDE-rate estimations.

  1. Evaluation of the polarization properties of a Philips-type prism for the construction of imaging polarimeters

    NASA Astrophysics Data System (ADS)

    Fernandez-Borda, R.; Waluschka, E.; Pellicori, S.; Martins, J. V.; Ramos-Izquierdo, L.; Cieslak, J. D.; Thompson, P.

    2009-08-01

    The design and construction of wide FOV imaging polarimeters for use in atmospheric remote sensing requires significant attention to the prevention of artificial polarization induced by the optical elements. Surface, coatings, and angles of incidence throughout the system must be carefully designed in order to minimize these artifacts because the remaining instrumental bias polarization is the main factor which drives the final polarimetric accuracy of the system. In this work, we present a detailed evaluation and analysis to explore the possibility of retrieving the initial polarization state of the light traveling through a generic system that has inherent instrumental polarization. Our case is a wide FOV lens and a splitter device. In particular, we chose as splitter device a Philips-type prism, because it is able to divide the signal in 3 independent channels that could be simultaneously analyze to retrieve the three first elements of the Stoke vector (in atmospheric applications the elliptical polarization can be neglected [1]). The Philips-type configuration is a versatile, compact and robust prism device that is typically used in three color camera systems. It has been used in some commercial polarimetric cameras which do not claim high accuracy polarization measurements [2]. With this work, we address the accuracy of our polarization inversion and measurements made with the Philips-type beam divider.

  2. A. Philip Randolph's Attempt at Equal Economic Opportunity: A Case Study

    ERIC Educational Resources Information Center

    Walker, Joel

    2013-01-01

    A. Philip Randolph, the national president of the Brotherhood of Sleeping Car Porters was one of the driving forces behind the March on Washington Movement in 1941. In frustration over the federal government's lack of support for opportunities in the booming war industries and equality in the military, Randolph had begun to organize the March…

  3. Antibacterial and cytotoxic activity of isoprenylated coumarin mammea A/AA isolated from Mammea africana.

    PubMed

    Canning, Corene; Sun, Shi; Ji, Xiangming; Gupta, Smiti; Zhou, Kequan

    2013-05-02

    The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 μg/ml), Streptococcus pneumoniae (MIC=0.25 μg/ml), and Clostridium difficile (MIC=0.25 μg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. The Philip Morris Information Network: A Library Database on an In-House Timesharing System.

    ERIC Educational Resources Information Center

    DeBardeleben, Marian Z.; And Others

    1983-01-01

    Outlines a database constructed at Philip Morris Research Center Library which encompasses holdings and circulation and acquisitions records for all items in the library. Host computer (DECSYSTEM-2060), software (BASIC), database design, search methodology, cataloging, and accessibility are noted; sample search, circ-in profile, end user profiles,…

  5. Hiding in the Shadows: Philip Morris and the Use of Third Parties to Oppose Ingredient Disclosure Regulations

    PubMed Central

    Velicer, Clayton; Glantz, Stanton A.

    2015-01-01

    Background In 1996 Massachusetts proposed regulations that would require tobacco companies to disclose information about the ingredients in their products on a by-brand basis. This paper examines the strategies employed by Philip Morris to stop these regulations from being implemented. Methods and Finding We used previously secret tobacco industry documents and published literature to examine the activities of the tobacco companies after the regulations were proposed. Philip Morris hired a public relations firm to establish a coalition that was instructed to oppose the regulations by linking them to other industrial sectors (the slippery slope) and stating they would damage the state's economy. Philip Morris also retained a polling firm to test the popularity of specific arguments against ingredient disclosure and developed a strategic plan for opposing similar regulations in Vermont. Conclusion Tobacco companies have historically used third parties to form coalitions to oppose ingredient disclosure regulations. These coalitions have had success preventing regulations from being implemented after they are initially proposed by creating the appearance of local opposition. With countries around the world currently implementing ingredient disclosure regulations in the WHO Framework Convention on Tobacco, governments and regulatory agencies should be aware of the political strategies that the tobacco companies have used to create the impression of popular opposition to these measures. PMID:26717245

  6. Patient and Aneurysm Characteristics Predicting Prolonged Length of Stay After Elective Open AAA Repair in the Endovascular Era.

    PubMed

    Casillas-Berumen, Sergio; Rojas-Miguez, Florencia A; Farber, Alik; Komshian, Sevan; Kalish, Jeffrey A; Rybin, Denis; Doros, Gheorghe; Siracuse, Jeffrey J

    2018-01-01

    Open aortic aneurysm repair (AAA) repair can be resource intensive and associated with a prolonged length of stay (LOS). We sought to examine patient and aneurysm predictors of prolonged LOS to better identify those at risk in the preoperative setting. Patient data were obtained from the targeted AAA American College of Surgery National Surgical Quality Improvement Program database from 2012 to 2014 of patients undergoing open AAA repair. Multivariable logistic regression was used to determine predictors of prolonged postoperative LOS defined as greater than 10 days (75th percentile). There were 1172 open AAA repairs identified. The majority (54%) of patients were older than 70 years and male (74%). Surgical approach was transperitoneal (70.9%) and retroperitoneal (29.1%). Aneurysms were 51.4% infrarenal, 33% juxtarenal, 5.7% pararenal, 7.4% suprarenal, and 2.5% type IV thoracoabdominal. Mean and median LOS were 9.1 ± 7.4 and 7 (0-72) days, respectively. Independently associated with extended LOS factors were visceral revascularization (odds ratio [OR]: 5.32, 95% confidence interval [CI]: 2.77-10.22, P < .001), type IV thoracoabdominal extent (OR: 3.09, 95% CI: 1.01-9.46, P = .048), suprarenal extent (OR: 1.89, 95% CI: 1.07-3.34, P = .029) and juxtarenal (OR: 1.43, 95% CI: 1.01-2.02, P = .004), non-Caucasian race (OR: 2.80, 95% CI: 1.77-4.41, P < .001), chronic obstructive pulmonary disease (OR: 1.76, 95% CI: 1.20-2.59, P = .004), not-from-home admission (OR: 1.91, 95% CI: 1.13-3.24), and age greater than 70 (OR: 1.49, 95% CI: 1.08-2.05, P = .014). We identified patient and aneurysm characteristics independently associated with protracted LOS following open AAA repair. Prospective identification of high-risk patients may allow physicians and hospitals to engage in multidisciplinary collaborations preoperatively to try to improve LOS in this resource-intensive population.

  7. Anti-tobacco advertisements by Massachusetts and Philip Morris: what teenagers think

    PubMed Central

    Biener, L

    2002-01-01

    Design: A 1999 telephone survey of teenagers in households identified during a random digit dial survey of adults conducted during the prior four years. Respondents were asked to describe an ad they had seen in the past 30 days, and then to rate its perceived effectiveness. Participants: Respondents were 733 youth between the ages of 14 and 17 years. Intervention: The most prominent anti-tobacco advertisements broadcast in Massachusetts during the time covered by the survey consisted of those produced by the Massachusetts Tobacco Control Program and those produced by the Philip Morris tobacco company. The ads described by respondents were grouped into four categories based on their sponsor and their approach. Main outcome measures: Perceived effectiveness of anti-tobacco advertisements seen during the month before the survey as measured on an 11 point scale. Results: Ads featuring the serious consequences of smoking were seen as significantly more effective by youth than both Massachusetts ads that did not discuss illness (p < 0.001) and Philip Morris "Think, Don't Smoke" ads (p < 0.001). Conclusion: Youth prevention programmes should not shy away from anti-tobacco ads that feature the serious consequences of smoking. These types of ads are the ones perceived as most effective by teenagers regardless of their smoking status, age, sex or ethnicity. PMID:12034981

  8. Mocking God and Celebrating Satan: Parodies and Profanities in Philip Pullman's "His Dark Materials"

    ERIC Educational Resources Information Center

    Oliver, Chantal

    2012-01-01

    Given its stance against organised religion, it is perhaps not surprising that Philip Pullman's award-winning trilogy "His Dark Materials" has, alongside the plaudits and praise, invited controversy and debate. Jacobs ("The Weekly Standard, 2000"), for instance, views the "anti-Christian" theme in Pullman's work as both misleading and dishonest,…

  9. AAA and AXB algorithms for the treatment of nasopharyngeal carcinoma using IMRT and RapidArc techniques.

    PubMed

    Kamaleldin, Maha; Elsherbini, Nader A; Elshemey, Wael M

    2017-09-27

    The aim of this study is to evaluate the impact of anisotropic analytical algorithm (AAA) and 2 reporting systems (AXB-D m and AXB-D w ) of Acuros XB algorithm (AXB) on clinical plans of nasopharyngeal patients using intensity-modulated radiotherapy (IMRT) and RapidArc (RA) techniques. Six plans of different algorithm-technique combinations are performed for 10 patients to calculate dose-volume histogram (DVH) physical parameters for planning target volumes (PTVs) and organs at risk (OARs). The number of monitor units (MUs) and calculation time are also determined. Good coverage is reported for all algorithm-technique combination plans without exceeding the tolerance for OARs. Regardless of the algorithm, RA plans persistently reported higher D 2% values for PTV-70. All IMRT plans reported higher number of MUs (especially with AXB) than did RA plans. AAA-IMRT produced the minimum calculation time of all plans. Major differences between the investigated algorithm-technique combinations are reported only for the number of MUs and calculation time parameters. In terms of these 2 parameters, it is recommended to employ AXB in calculating RA plans and AAA in calculating IMRT plans to achieve minimum calculation times at reduced number of MUs. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  10. Dystopian Visions of Global Capitalism: Philip Reeve's "Mortal Engines" and M.T Anderson's "Feed"

    ERIC Educational Resources Information Center

    Bullen, Elizabeth; Parsons, Elizabeth

    2007-01-01

    This article examines Philip Reeve's novel for children, "Mortal Engines", and M.T. Anderson's young adult novel, "Feed", by assessing these dystopias as prototypical texts of what Ulrich Beck calls risk society. Through their visions of a fictional future, the two narratives explore the hazards created by contemporary techno-economic progress,…

  11. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters

    PubMed Central

    2013-01-01

    Purpose Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. Methods The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. Results In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC’s ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0

  12. Clinical implications in the use of the PBC algorithm versus the AAA by comparison of different NTCP models/parameters.

    PubMed

    Bufacchi, Antonella; Nardiello, Barbara; Capparella, Roberto; Begnozzi, Luisa

    2013-07-04

    Retrospective analysis of 3D clinical treatment plans to investigate qualitative, possible, clinical consequences of the use of PBC versus AAA. The 3D dose distributions of 80 treatment plans at four different tumour sites, produced using PBC algorithm, were recalculated using AAA and the same number of monitor units provided by PBC and clinically delivered to each patient; the consequences of the difference on the dose-effect relations for normal tissue injury were studied by comparing different NTCP model/parameters extracted from a review of published studies. In this study the AAA dose calculation is considered as benchmark data. The paired Student t-test was used for statistical comparison of all results obtained from the use of the two algorithms. In the prostate plans, the AAA predicted lower NTCP value (NTCPAAA) for the risk of late rectal bleeding for each of the seven combinations of NTCP parameters, the maximum mean decrease was 2.2%. In the head-and-neck treatments, each combination of parameters used for the risk of xerostemia from irradiation of the parotid glands involved lower NTCPAAA, that varied from 12.8% (sd=3.0%) to 57.5% (sd=4.0%), while when the PBC algorithm was used the NTCPPBC's ranging was from 15.2% (sd=2.7%) to 63.8% (sd=3.8%), according the combination of parameters used; the differences were statistically significant. Also NTCPAAA regarding the risk of radiation pneumonitis in the lung treatments was found to be lower than NTCPPBC for each of the eight sets of NTCP parameters; the maximum mean decrease was 4.5%. A mean increase of 4.3% was found when the NTCPAAA was calculated by the parameters evaluated from dose distribution calculated by a convolution-superposition (CS) algorithm. A markedly different pattern was observed for the risk relating to the development of pneumonitis following breast treatments: the AAA predicted higher NTCP value. The mean NTCPAAA varied from 0.2% (sd = 0.1%) to 2.1% (sd = 0.3%), while the mean NTCPPBC

  13. Morphological State as a Predictor for Reintervention and Mortality After EVAR for AAA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohrlander, Tomas; Dencker, Magnus; Acosta, Stefan, E-mail: stefan.acosta@telia.com

    2012-10-15

    Purpose: This study was designed to assess aorto-iliac morphological characteristics in relation to reintervention and all-cause long-term mortality in patients undergoing standard EVAR for infrarenal AAA. Methods: Patients treated with EVAR (Zenith{sup Registered-Sign} Stentgrafts, Cook) between May 1998 and February 2006 were prospectively enrolled in a computerized database where comorbidities and preoperative aneurysm morphology were entered. Reinterventions and mortality were checked until December 1, 2010. Median follow-up time was 68 months. Results: A total of 304 patients were included, of which 86% were men. Median age was 74 years. The reintervention rate was 23.4% (71/304). A greater diameter of themore » common iliac artery (p = 0.037; hazard ratio (HR) 1.037 [1.002-1.073]) was an independent factor for an increased number of reinterventions. The 30-day mortality rate was 3.0% (9/304). Aneurysm-related deaths due to AAA occurred in 4.9% (15/304). Five patients died due to a concomitant ruptured thoracic aortic aneurysm. The mortality until end of follow-up was 54.3% (165/304). The proportion of deaths caused by vascular diseases was 61.6%. The severity of angulation of the iliac arteries (p = 0.014; HR 1.018 [95% confidence interval (CI) 1.004-1.033]) and anemia (p = 0.044; HR 2.79 [95% CI 1.029-7.556]) remained as independent factors associated with all-cause long-term mortality. The crude reintervention-free survival rate at 1, 3, and 5 years was 84.5%, 64.8%, and 51.6%, respectively. Conclusions: The initial aorto-iliac morphological state in patients scheduled for standard EVAR for AAA seems to be strongly related to the need for reinterventions and long-term mortality.« less

  14. Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97.

    PubMed

    Hänzelmann, Petra; Schindelin, Hermann

    2016-01-05

    p97 belongs to the superfamily of AAA+ ATPases and is characterized by a tandem AAA module, an N-terminal domain involved in substrate and cofactor interactions, and a functionally important unstructured C-terminal tail. The ATPase activity is controlled by an intradomain communication within the same protomer and an interdomain communication between neighboring protomers. Here, we present for the first time crystal structures in which the physiologically relevant p97 hexamer constitutes the content of the asymmetric unit, namely in the apo state without nucleotide in either the D1 or D2 module and in the pre-activated state with ATPγS bound to both modules. The structures provide new mechanistic insights into the interdomain communication mediated by conformational changes of the C terminus as well as an intersubunit signaling network, which couples the nucleotide state to the conformation of the central putative substrate binding pore. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Structural basis of protein translocation by the Vps4-Vta1 AAA ATPase

    PubMed Central

    Monroe, Nicole; Han, Han; Shen, Peter S; Sundquist, Wesley I; Hill, Christopher P

    2017-01-01

    Many important cellular membrane fission reactions are driven by ESCRT pathways, which culminate in disassembly of ESCRT-III polymers by the AAA ATPase Vps4. We report a 4.3 Å resolution cryo-EM structure of the active Vps4 hexamer with its cofactor Vta1, ADP·BeFx, and an ESCRT-III substrate peptide. Four Vps4 subunits form a helix whose interfaces are consistent with ATP binding, is stabilized by Vta1, and binds the substrate peptide. The fifth subunit approximately continues this helix but appears to be dissociating. The final Vps4 subunit completes a notched-washer configuration as if transitioning between the ends of the helix. We propose that ATP binding propagates growth at one end of the helix while hydrolysis promotes disassembly at the other end, so that Vps4 ‘walks’ along ESCRT-III until it encounters the ordered N-terminal domain to destabilize the ESCRT-III lattice. This model may be generally applicable to other protein-translocating AAA ATPases. DOI: http://dx.doi.org/10.7554/eLife.24487.001 PMID:28379137

  16. Inflammatory cell phenotypes in AAAs; their role and potential as targets for therapy

    PubMed Central

    Dale, Matthew A; Ruhlman, Melissa K.; Baxter, B. Timothy

    2015-01-01

    Abdominal aortic aneurysms are characterized by chronic inflammatory cell infiltration. AAA is typically an asymptomatic disease and caused approximately 15,000 deaths annually in the U.S. Previous studies have examined both human and murine aortic tissue for the presence of various inflammatory cell types. Studies show that in both human and experimental AAAs, prominent inflammatory cell infiltration, such as CD4+ T cells and macrophages, occurs in the damaged aortic wall. These cells have the ability to undergo phenotypic modulation based on microenvironmental cues, potentially influencing disease progression. Pro-inflammatory CD4+ T cells and classically activated macrophages dominate the landscape of aortic infiltrates. The skew to pro-inflammatory phenotypes alters disease progression and plays a role in causing chronic inflammation. The local cytokine production and presence of inflammatory mediators, such as extracellular matrix breakdown products, influence the uneven balance of the inflammatory infiltrate phenotypes. Understanding and developing new strategies that target the pro-inflammatory phenotype could provide useful therapeutic targets for a disease with no current pharmacological intervention. PMID:26044582

  17. 76 FR 71048 - Sixth Annual Philip S. Chen, Jr. Distinguished Lecture on Innovation and Technology Transfer

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    ..., Jr. Distinguished Lecture on Innovation and Technology Transfer AGENCY: National Institutes of Health... sixth annual Philip S. Chen, Jr., Ph.D. Distinguished Lecture on Innovation and Technology Transfer... present ``Treatment of Cancer with Recombinant Immunotoxins: From Technology Transfer to the Patient.'' Dr...

  18. Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

    PubMed Central

    Zhuang, Lei; Zhang, Jun; Xiang, Xin

    2007-01-01

    Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger ΔnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the ΔnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo. PMID:17237507

  19. Paradise Lost and Found: Obedience, Disobedience, and Storytelling in C.S. Lewis and Philip Pullman.

    ERIC Educational Resources Information Center

    Wood, Naomi

    2001-01-01

    Considers how in the fantasy series "The Chronicles of Narnia" and "His Dark Materials," by C.S. Lewis and Philip Pullman respectively, the authors use symbols and themes from "Paradise Lost." Notes that each author's narrative choice uses his view of cosmic order to persuade readers that obedience should be…

  20. PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

    PubMed

    Osadnik, Hendrik; Schöpfel, Michael; Heidrich, Eyleen; Mehner, Denise; Lilie, Hauke; Parthier, Christoph; Risselada, H Jelger; Grubmüller, Helmut; Stubbs, Milton T; Brüser, Thomas

    2015-11-01

    Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ(54) enhancer-binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ(54) -dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiologic tasks via coiled-coil domains. © 2015 John Wiley & Sons Ltd.

  1. Comparison of Acuros (AXB) and Anisotropic Analytical Algorithm (AAA) for dose calculation in treatment of oesophageal cancer: effects on modelling tumour control probability.

    PubMed

    Padmanaban, Sriram; Warren, Samantha; Walsh, Anthony; Partridge, Mike; Hawkins, Maria A

    2014-12-23

    To investigate systematic changes in dose arising when treatment plans optimised using the Anisotropic Analytical Algorithm (AAA) are recalculated using Acuros XB (AXB) in patients treated with definitive chemoradiotherapy (dCRT) for locally advanced oesophageal cancers. We have compared treatment plans created using AAA with those recalculated using AXB. Although the Anisotropic Analytical Algorithm (AAA) is currently more widely used in clinical routine, Acuros XB (AXB) has been shown to more accurately calculate the dose distribution, particularly in heterogeneous regions. Studies to predict clinical outcome should be based on modelling the dose delivered to the patient as accurately as possible. CT datasets from ten patients were selected for this retrospective study. VMAT (Volumetric modulated arc therapy) plans with 2 arcs, collimator rotation ± 5-10° and dose prescription 50 Gy / 25 fractions were created using Varian Eclipse (v10.0). The initial dose calculation was performed with AAA, and AXB plans were created by re-calculating the dose distribution using the same number of monitor units (MU) and multileaf collimator (MLC) files as the original plan. The difference in calculated dose to organs at risk (OAR) was compared using dose-volume histogram (DVH) statistics and p values were calculated using the Wilcoxon signed rank test. The potential clinical effect of dosimetric differences in the gross tumour volume (GTV) was evaluated using three different TCP models from the literature. PTV Median dose was apparently 0.9 Gy lower (range: 0.5 Gy - 1.3 Gy; p < 0.05) for VMAT AAA plans re-calculated with AXB and GTV mean dose was reduced by on average 1.0 Gy (0.3 Gy -1.5 Gy; p < 0.05). An apparent difference in TCP of between 1.2% and 3.1% was found depending on the choice of TCP model. OAR mean dose was lower in the AXB recalculated plan than the AAA plan (on average, dose reduction: lung 1.7%, heart 2.4%). Similar trends were seen for CRT plans

  2. Preferences of AAA/AAG codon recognition by modified nucleosides, τm5s2U34 and t6A37 present in tRNALys.

    PubMed

    Sonawane, Kailas D; Kamble, Asmita S; Fandilolu, Prayagraj M

    2017-12-27

    Deficiency of 5-taurinomethyl-2-thiouridine, τm 5 s 2 U at the 34th 'wobble' position in tRNA Lys causes MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a neuromuscular disease. This modified nucleoside of mt tRNA Lys , recognizes AAA/AAG codons during protein biosynthesis process. Its preference to identify cognate codons has not been studied at the atomic level. Hence, multiple MD simulations of various molecular models of anticodon stem loop (ASL) of mt tRNA Lys in presence and absence of τm 5 s 2 U 34 and N 6 -threonylcarbamoyl adenosine (t 6 A 37 ) along with AAA and AAG codons have been accomplished. Additional four MD simulations of multiple ASL mt tRNA Lys models in the context of ribosomal A-site residues have also been performed to investigate the role of A-site in recognition of AAA/AAG codons. MD simulation results show that, ASL models in presence of τm 5 s 2 U 34 and t 6 A 37 with codons AAA/AAG are more stable than the ASL lacking these modified bases. MD trajectories suggest that τm 5 s 2 U recognizes the codons initially by 'wobble' hydrogen bonding interactions, and then tRNA Lys might leave the explicit codon by a novel 'single' hydrogen bonding interaction in order to run the protein biosynthesis process smoothly. We propose this model as the 'Foot-Step Model' for codon recognition, in which the single hydrogen bond plays a crucial role. MD simulation results suggest that, tRNA Lys with τm 5 s 2 U and t 6 A recognizes AAA codon more preferably than AAG. Thus, these results reveal the consequences of τm 5 s 2 U and t 6 A in recognition of AAA/AAG codons in mitochondrial disease, MERRF.

  3. SU-F-T-600: Influence of Acuros XB and AAA Dose Calculation Algorithms On Plan Quality Metrics and Normal Lung Doses in Lung SBRT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yaparpalvi, R; Mynampati, D; Kuo, H

    Purpose: To study the influence of superposition-beam model (AAA) and determinant-photon transport-solver (Acuros XB) dose calculation algorithms on the treatment plan quality metrics and on normal lung dose in Lung SBRT. Methods: Treatment plans of 10 Lung SBRT patients were randomly selected. Patients were prescribed to a total dose of 50-54Gy in 3–5 fractions (10?5 or 18?3). Doses were optimized accomplished with 6-MV using 2-arcs (VMAT). Doses were calculated using AAA algorithm with heterogeneity correction. For each plan, plan quality metrics in the categories- coverage, homogeneity, conformity and gradient were quantified. Repeat dosimetry for these AAA treatment plans was performedmore » using AXB algorithm with heterogeneity correction for same beam and MU parameters. Plan quality metrics were again evaluated and compared with AAA plan metrics. For normal lung dose, V{sub 20} and V{sub 5} to (Total lung- GTV) were evaluated. Results: The results are summarized in Supplemental Table 1. PTV volume was mean 11.4 (±3.3) cm{sup 3}. Comparing RTOG 0813 protocol criteria for conformality, AXB plans yielded on average, similar PITV ratio (individual PITV ratio differences varied from −9 to +15%), reduced target coverage (−1.6%) and increased R50% (+2.6%). Comparing normal lung doses, the lung V{sub 20} (+3.1%) and V{sub 5} (+1.5%) were slightly higher for AXB plans compared to AAA plans. High-dose spillage ((V105%PD - PTV)/ PTV) was slightly lower for AXB plans but the % low dose spillage (D2cm) was similar between the two calculation algorithms. Conclusion: AAA algorithm overestimates lung target dose. Routinely adapting to AXB for dose calculations in Lung SBRT planning may improve dose calculation accuracy, as AXB based calculations have been shown to be closer to Monte Carlo based dose predictions in accuracy and with relatively faster computational time. For clinical practice, revisiting dose-fractionation in Lung SBRT to correct for dose

  4. TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

    DOE PAGES

    Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne; ...

    2015-04-28

    The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from amore » signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.« less

  5. Story as a Bridge to Transformation: The Way beyond Death in Philip Pullman's "The Amber Spyglass."

    ERIC Educational Resources Information Center

    Lenz, Millicent

    2003-01-01

    Explains that in "The Amber Spyglass," Philip Pullman extends the psychological depth of literature for young readers by presenting in palpable terms a confrontation with death met by the human capacity for dealing creatively, through story, with personal mortality. Contends that Pullman's portrayal of the power of storytelling is placed within…

  6. Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

    PubMed

    Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

    2018-04-12

    Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright

  7. Morphological Differences in the Aorto-iliac Segment in AAA Patients of Caucasian and Asian Origin.

    PubMed

    Banzic, I; Lu, Q; Zhang, L; Stepak, H; Davidovic, L; Oszkinis, G; Mladenovic, A; Markovic, M; Rancic, Z; Jing, Z; Brankovic, M

    2016-06-01

    The objective was to quantify aorto-iliac morphology differences between AAA patients of Caucasian and Asian origin. Additionally, the impact of patient demographic characteristics was assessed, which could influence the morphological differences. This international multicentre study included two tertiary referral institutions from Europe and one from China. CT scans with 3D reconstruction of 296 patients with infrarenal AAA >5 cm were analysed. Eighteen measurements were recorded from each CT scan and compared between Caucasian and Asian patients. Caucasian patients had longer common iliac arteries (right: 65.0 vs. 33.1 mm, p < .001 left: 65.0 vs. 35.2 mm, p < .001), longer aneurysm neck (33.0 vs. 28.4 mm, p < .001), greater aneurysm to aortic axis angle (153.0° vs. 142.2°, p < .001), and longer combined aorto-iliac length (195.7 vs. 189.2 mm, p < .001). However, Asian patients had a longer infrarenal abdominal aorta (152.0 vs. 130.0 mm, p < .001), longer AAA (126.2 vs. 93.0 mm), and greater linear distance from renal artery to aorto-iliac bifurcation (143.6 vs. 116.0 mm, p < .001). Caucasian patients had a larger inner common iliac artery diameter (right: 16.0 vs. 14.9 mm, p < .001, left: 16.0 vs. 15.2 mm, p < .001), larger inner exernal iliac artery diameter (right: 9.0 vs. 7.5 mm, p < .001 left: 9.0 vs. 7.7 mm, p < .001), and larger inner common femoral artery diameter (right: 10.0 vs. 5.9 mm, p < .001 left: 10.0 vs. 6.1 mm, p < .001). No difference was observed in AAA transverse diameter (62.0 vs. 63.1 mm, p = .492). The results showed that aorto-iliac anatomy in Caucasians differs significantly from Asians, particularly in the length of the common iliac arteries and infrarenal abdominal aorta, and in the transverse diameter of the common, external iliac, and common femoral arteries. Therefore, the exact criteria for stent graft design are dependent on the racial origin of the patient. Copyright © 2015 European

  8. Analytical solution for tension-saturated and unsaturated flow from wicking porous pipes in subsurface irrigation: The Kornev-Philip legacies revisited

    NASA Astrophysics Data System (ADS)

    Kacimov, A. R.; Obnosov, Yu. V.

    2017-03-01

    The Russian engineer Kornev in his 1935 book raised perspectives of subsurface "negative pressure" irrigation, which have been overlooked in modern soil science. Kornev's autoirrigation utilizes wicking of a vacuumed water from a porous pipe into a dry adjacent soil. We link Kornev's technology with a slightly modified Philip (1984)'s analytical solutions for unsaturated flow from a 2-D cylindrical pipe in an infinite domain. Two Darcian flows are considered and connected through continuity of pressure along the pipe-soil contact. The first fragment is a thin porous pipe wall in which water seeps at tension saturation; the hydraulic head is a harmonic function varying purely radially across the wall. The Thiem solution in this fragment gives the boundary condition for azimuthally varying suction pressure in the second fragment, ambient soil, making the exterior of the pipe. The constant head, rather than Philip's isobaricity boundary condition, along the external wall slightly modifies Philip's formulae for the Kirchhoff potential and pressure head in the soil fragment. Flow characteristics (magnitudes of the Darcian velocity, total flow rate, and flow net) are explicitly expressed through series of Macdonald's functions. For a given pipe's external diameter, wall thickness, position of the pipe above a free water datum in the supply tank, saturated conductivities of the wall and soil, and soil's sorptive number, a nonlinear equation with respect to the total discharge from the pipe is obtained and solved by a computer algebra routine. Efficiency of irrigation is evaluated by computation of the moisture content within selected zones surrounding the porous pipe.Plain Language SummarySubsurface irrigation by "automatic" gadgets like pitchers or porous pipes is a water saving technology which minimizes evaporative losses and deep percolation. Moisture is emitted by capillary suction of a relatively dry soil and "thirsty</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12773366','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12773366"><span>The outing of <span class="hlt">Philip</span> Morris: advertising tobacco to gay men.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smith, Elizabeth A; Malone, Ruth E</p> <p>2003-06-01</p> <p>This case study describes the events surrounding the first time a major tobacco company advertised in gay media. We analyzed internal tobacco company documents, mainstream newspapers, and the gay press. <span class="hlt">Philip</span> Morris was unprepared for the attention its entry into the gay market received. The company's reaction to this incident demonstrates that its approach to the gay community both parallels and diverges from industry strategies toward other marginalized communities. The tobacco industry's relationship to the gay community is relatively undeveloped, a fact that may provide tobacco control advocates an opportunity for early intervention. The gay community's particular vulnerabilities to the industry make development of gay tobacco control programs crucial to reducing gay smoking prevalence and industry presence in the community.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27782735','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27782735"><span>Evaluation of the dose calculation accuracy for small fields defined by jaw or MLC for <span class="hlt">AAA</span> and Acuros XB algorithms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fogliata, Antonella; Lobefalo, Francesca; Reggiori, Giacomo; Stravato, Antonella; Tomatis, Stefano; Scorsetti, Marta; Cozzi, Luca</p> <p>2016-10-01</p> <p>Small field measurements are challenging, due to the physical characteristics coming from the lack of charged particle equilibrium, the partial occlusion of the finite radiation source, and to the detector response. These characteristics can be modeled in the dose calculations in the treatment planning systems. Aim of the present work is to evaluate the MU calculation accuracy for small fields, defined by jaw or MLC, for anisotropic analytical algorithm (<span class="hlt">AAA</span>) and Acuros XB algorithms, relative to output measurements on the beam central axis. Single point output factor measurement was acquired with a PTW microDiamond detector for 6 MV, 6 and 10 MV unflattened beams generated by a Varian TrueBeam STx equipped with high definition-MLC. Fields defined by jaw or MLC apertures were set; jaw-defined: 0.6 × 0.6, 0.8 × 0.8, 1 × 1, 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 ; MLC-defined: 0.5 × 0.5 cm 2 to the maximum field defined by the jaw, with 0.5 cm stepping, and jaws set to: 2 × 2, 3 × 3, 4 × 4, 5 × 5, and 10 × 10 cm 2 . MU calculation was obtained with 1 mm grid in a virtual water phantom for the same fields, for <span class="hlt">AAA</span> and Acuros algorithms implemented in the Varian eclipse treatment planning system (version 13.6). Configuration parameters as the effective spot size (ESS) and the dosimetric leaf gap (DLG) were varied to find the best parameter setting. Differences between calculated and measured doses were analyzed. Agreement better than 0.5% was found for field sizes equal to or larger than 2 × 2 cm 2 for both algorithms. A dose overestimation was present for smaller jaw-defined fields, with the best agreement, averaged over all the energies, of 1.6% and 4.6% for a 1 × 1 cm 2 field calculated by <span class="hlt">AAA</span> and Acuros, respectively, for a configuration with ESS = 1 mm for both X and Y directions for <span class="hlt">AAA</span>, and ESS = 1.5 and 0 mm for X and Y directions for Acuros. Conversely, a calculated dose underestimation was found for small MLC-defined fields, with the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22923768','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22923768"><span>Mechanism of the <span class="hlt">AAA</span>+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U Thomas</p> <p>2012-10-01</p> <p>The <span class="hlt">AAA</span>+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these <span class="hlt">AAA</span>+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3446707','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3446707"><span>Mechanism of the <span class="hlt">AAA</span>+ ATPases pontin and reptin in the biogenesis of H/ACA RNPs</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Machado-Pinilla, Rosario; Liger, Dominique; Leulliot, Nicolas; Meier, U. Thomas</p> <p>2012-01-01</p> <p>The <span class="hlt">AAA</span>+ ATPases pontin and reptin function in a staggering array of cellular processes including chromatin remodeling, transcriptional regulation, DNA damage repair, and assembly of macromolecular complexes, such as RNA polymerase II and small nucleolar (sno) RNPs. However, the molecular mechanism for all of these <span class="hlt">AAA</span>+ ATPase associated activities is unknown. Here we document that, during the biogenesis of H/ACA RNPs (including telomerase), the assembly factor SHQ1 holds the pseudouridine synthase NAP57/dyskerin in a viselike grip, and that pontin and reptin (as components of the R2TP complex) are required to pry NAP57 from SHQ1. Significantly, the NAP57 domain captured by SHQ1 harbors most mutations underlying X-linked dyskeratosis congenita (X-DC) implicating the interface between the two proteins as a target of this bone marrow failure syndrome. Homing in on the essential first steps of H/ACA RNP biogenesis, our findings provide the first insight into the mechanism of action of pontin and reptin in the assembly of macromolecular complexes. PMID:22923768</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA256399','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA256399"><span>Three Experts on Quality Management: <span class="hlt">Philip</span> B. Crosby, W. Edwards Deming, Joseph M. Juran</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1992-07-01</p> <p>Department of the Navy Office of the Under Secretary of the Navy Total Quality Leadership Omce THREE EXPERTS ON QUALITY MANAGEMENT : <span class="hlt">PHILIP</span> B. CROSBY W...research, as the "price of nonconformance." To aid managers in statistical theory , statistical thinking, and the application tracking the cost of doing...Quality Management emphasizes that the process must become a way of life in Theory of Systems. "A system is a series of the organization. Continuance is</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1346002-nanomechanical-thermophoretic-analyses-nucleotide-dependent-interactions-between-aaa+-subunits-magnesium-chelatase','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1346002-nanomechanical-thermophoretic-analyses-nucleotide-dependent-interactions-between-aaa+-subunits-magnesium-chelatase"><span>Nanomechanical and thermophoretic analyses of the nucleotide-dependent interactions between the <span class="hlt">AAA</span> + subunits of magnesium chelatase</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Adams, Nathan B. P.; Vasilev, Cvetelin; Brindley, Amanda A.; ...</p> <p>2016-04-30</p> <p>In chlorophyll biosynthesis, the magnesium chelatase enzyme complex catalyzes the insertion of a Mg 2+ ion into protoporphyrin IX. Prior to this event, two of the three subunits, the <span class="hlt">AAA</span> + proteins ChlI and ChlD, form a ChlID–MgATP complex. We used microscale thermophoresis to directly determine dissociation constants for the I-D subunits from Synechocystis, and to show that the formation of a ChlID–MgADP complex, mediated by the arginine finger and the sensor II domain on ChlD, is necessary for the assembly of the catalytically active ChlHID–MgATP complex. The N-terminal <span class="hlt">AAA</span> + domain of ChlD is essential for complex formation, butmore » some stability is preserved in the absence of the C-terminal integrin domain of ChlD, particularly if the intervening polyproline linker region is retained. Single molecule force spectroscopy (SMFS) was used to determine the factors that stabilize formation of the ChlID–MgADP complex at the single molecule level; ChlD was attached to an atomic force microscope (AFM) probe in two different orientations, and the ChlI subunits were tethered to a silica surface; the probability of subunits interacting more than doubled in the presence of MgADP, and we show that the N-terminal <span class="hlt">AAA</span> + domain of ChlD mediates this process, in agreement with the microscale thermophoresis data. Analysis of the unbinding data revealed a most probable interaction force of around 109 pN for formation of single ChlID–MgADP complexes. Finally, these experiments provide a quantitative basis for understanding the assembly and function of the Mg chelatase complex.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-iss012e10817.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-iss012e10817.html"><span>McArthur removes <span class="hlt">AAA</span> clamps and ducts inside the CHeCS Rack during Expedition 12</span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>2005-12-09</p> <p>ISS012-E-10817 (9 December 2005) --- Astronaut William S. (Bill) McArthur Jr., Expedition 12 commander and NASA space station science officer, opens the back panel of the Crew Health Care System (CHeCS) rack and removes the Avionics Air Assembly (<span class="hlt">AAA</span>) air ducts during in-flight maintenance (IFM) in the Destiny laboratory of the International Space Station.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1447881','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1447881"><span>The Outing of <span class="hlt">Philip</span> Morris: Advertising Tobacco to Gay Men</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Smith, Elizabeth A.; Malone, Ruth E.</p> <p>2003-01-01</p> <p>Objectives. This case study describes the events surrounding the first time a major tobacco company advertised in gay media. Methods. We analyzed internal tobacco company documents, mainstream newspapers, and the gay press. Results. <span class="hlt">Philip</span> Morris was unprepared for the attention its entry into the gay market received. The company’s reaction to this incident demonstrates that its approach to the gay community both parallels and diverges from industry strategies toward other marginalized communities. Conclusions. The tobacco industry’s relationship to the gay community is relatively undeveloped, a fact that may provide tobacco control advocates an opportunity for early intervention. The gay community’s particular vulnerabilities to the industry make development of gay tobacco control programs crucial to reducing gay smoking prevalence and industry presence in the community. PMID:12773366</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=aaa&pg=6&id=ED547619','ERIC'); return false;" href="https://eric.ed.gov/?q=aaa&pg=6&id=ED547619"><span>Student-Athlete Perceptions of a Summer Pre-Enrollment Experience at an NCAA Division I-<span class="hlt">AAA</span> Institution</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Dalgety, Michael Franklin</p> <p>2012-01-01</p> <p>The purpose of this exploratory qualitative study was to examine student-athlete perceptions of the role of summer pre-enrollment in their adjustment and transition to college. The study focused on student-athletes who received athletically-related financial aid at a National Collegiate Athletic Association (NCAA) Division I-<span class="hlt">AAA</span> institution. The…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15313097','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15313097"><span>Turning free speech into corporate speech: <span class="hlt">Philip</span> Morris' efforts to influence U.S. and European journalists regarding the U.S. EPA report on secondhand smoke.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Muggli, Monique E; Hurt, Richard D; Becker, Lee B</p> <p>2004-09-01</p> <p>Previously secret internal tobacco company documents show that the tobacco industry launched an extensive multifaceted effort to influence the scientific debate about the harmful effects of secondhand smoke. Integral to the industry's campaign was an effort to derail the Environmental Protection Agency's (EPA) risk assessment on environmental tobacco smoke (ETS) by recruiting a network of journalists to generate news articles supporting the industry's position and pushing its public relations messages regarding the ETS issue. Searches of previously secret internal tobacco industry records were conducted online and at the Minnesota Tobacco Document Depository. In addition, searches on the World Wide Web were conducted for each National Journalism Center alumnus. Lexis-Nexis was used to locate news stories written by the journalists cited in this paper. <span class="hlt">Philip</span> Morris turned to its public relations firm Burson Marsteller to "build considerable reasonable doubt em leader particularly among consumers" about the "scientific weaknesses" of the EPA report. A Washington, DC, media and political consultant Richard Hines was a key player in carrying out Burson Marsteller's media recommendations of "EPA bashing" for <span class="hlt">Philip</span> Morris. In March 1993, <span class="hlt">Philip</span> Morris' vice president of corporate affairs policy and administration reported to Steve Parrish, vice president and general counsel of <span class="hlt">Philip</span> Morris, that their consultant was "responsible for a number of articles that have appeared in em leader major news publications regarding EPA and ETS." In addition to placing favorable stories in the press through its consultant, <span class="hlt">Philip</span> Morris sought to expand its journalist network by financially supporting a U.S. school of journalism; the National Journalism Center (NJC). <span class="hlt">Philip</span> Morris gleaned "about 15 years worth of journalists at print and visual media throughout the country em leader to get across [its] side of the story" resulting in "numerous pieces consistent with our point of</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18845623','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18845623"><span>"Working to shape what society's expectations of us should be": <span class="hlt">Philip</span> Morris' societal alignment strategy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yang, J S; Malone, R E</p> <p>2008-12-01</p> <p>A key element of <span class="hlt">Philip</span> Morris's (PM's) corporate social responsibility initiatives is "societal alignment", defined as "strategies and programs to meet society's expectations of a responsible tobacco company". This study explored the genesis and implementation of <span class="hlt">Philip</span> Morris' (PM) societal alignment efforts. The study retrieved and analysed approximately 375 previously undisclosed PM documents now available electronically. Using an iterative process, the study categorised themes and prepared a case analysis. Beginning in 1999, PM sought to become "societally aligned" by identifying expectations of a responsible tobacco company through public opinion research and developing and publicising programs to meet those expectations. Societal alignment was undertaken within the US and globally to ensure an environment favourable to PM's business objectives. Despite PM's claims to be "changing", however, societal alignment in practice was highly selective. PM responded to public "expectations" largely by retooling existing positions and programs, while entirely ignoring other expectations that might have interfered with its business goals. It also appears that convincing employees of the value and authenticity of societal alignment was difficult. As implementation of the Framework Convention on Tobacco Control proceeds, tobacco control advocates should closely monitor development of such "alignment" initiatives and expose the motivations and contradictions they reveal.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3324763','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3324763"><span>The I domain of the <span class="hlt">AAA</span>+ HslUV protease coordinates substrate binding, ATP hydrolysis, and protein degradation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sundar, Shankar; Baker, Tania A; Sauer, Robert T</p> <p>2012-01-01</p> <p>In the <span class="hlt">AAA</span>+ HslUV protease, substrates are bound and unfolded by a ring hexamer of HslU, before translocation through an axial pore and into the HslV degradation chamber. Here, we show that the N-terminal residues of an Arc substrate initially bind in the HslU axial pore, with key contacts mediated by a pore loop that is highly conserved in all <span class="hlt">AAA</span>+ unfoldases. Disordered loops from the six intermediate domains of the HslU hexamer project into a funnel-shaped cavity above the pore and are positioned to contact protein substrates. Mutations in these I-domain loops increase KM and decrease Vmax for degradation, increase the mobility of bound substrates, and prevent substrate stimulation of ATP hydrolysis. HslU-ΔI has negligible ATPase activity. Thus, the I domain plays an active role in coordinating substrate binding, ATP hydrolysis, and protein degradation by the HslUV proteolytic machine. PMID:22102327</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_10");'>10</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li class="active"><span>12</span></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_12 --> <div id="page_13" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="241"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23464309','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23464309"><span>Experimental verification of the Acuros XB and <span class="hlt">AAA</span> dose calculation adjacent to heterogeneous media for IMRT and RapidArc of nasopharygeal carcinoma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kan, Monica W K; Leung, Lucullus H T; So, Ronald W K; Yu, Peter K N</p> <p>2013-03-01</p> <p>To compare the doses calculated by the Acuros XB (AXB) algorithm and analytical anisotropic algorithm (<span class="hlt">AAA</span>) with experimentally measured data adjacent to and within heterogeneous medium using intensity modulated radiation therapy (IMRT) and RapidArc(®) (RA) volumetric arc therapy plans for nasopharygeal carcinoma (NPC). Two-dimensional dose distribution immediately adjacent to both air and bone inserts of a rectangular tissue equivalent phantom irradiated using IMRT and RA plans for NPC cases were measured with GafChromic(®) EBT3 films. Doses near and within the nasopharygeal (NP) region of an anthropomorphic phantom containing heterogeneous medium were also measured with thermoluminescent dosimeters (TLD) and EBT3 films. The measured data were then compared with the data calculated by <span class="hlt">AAA</span> and AXB. For AXB, dose calculations were performed using both dose-to-medium (AXB_Dm) and dose-to-water (AXB_Dw) options. Furthermore, target dose differences between <span class="hlt">AAA</span> and AXB were analyzed for the corresponding real patients. The comparison of real patient plans was performed by stratifying the targets into components of different densities, including tissue, bone, and air. For the verification of planar dose distribution adjacent to air and bone using the rectangular phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 98.7%, 99.5%, and 97.7% on the axial plane for <span class="hlt">AAA</span>, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans, while they were 97.6%, 98.2%, and 97.7%, respectively, on the coronal plane. For the verification of planar dose distribution within the NP region of the anthropomorphic phantom, the percentages of pixels that passed the gamma analysis with the ± 3%/3mm criteria were 95.1%, 91.3%, and 99.0% for <span class="hlt">AAA</span>, AXB_Dm, and AXB_Dw, respectively, averaged over all IMRT and RA plans. Within the NP region where air and bone were present, the film measurements represented the dose close to unit density water</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22649032-su-dose-calculation-accuracy-ct-images-reconstructed-artifact-reduction-algorithm','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22649032-su-dose-calculation-accuracy-ct-images-reconstructed-artifact-reduction-algorithm"><span>SU-F-T-441: Dose Calculation Accuracy in CT Images Reconstructed with Artifact Reduction Algorithm</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ng, C; Chan, S; Lee, F</p> <p></p> <p>Purpose: Accuracy of radiotherapy dose calculation in patients with surgical implants is complicated by two factors. First is the accuracy of CT number, second is the dose calculation accuracy. We compared measured dose with dose calculated on CT images reconstructed with FBP and an artifact reduction algorithm (OMAR, <span class="hlt">Philips</span>) for a phantom with high density inserts. Dose calculation were done with Varian <span class="hlt">AAA</span> and AcurosXB. Methods: A phantom was constructed with solid water in which 2 titanium or stainless steel rods could be inserted. The phantom was scanned with the <span class="hlt">Philips</span> Brillance Big Bore CT. Image reconstruction was done withmore » FBP and OMAR. Two 6 MV single field photon plans were constructed for each phantom. Radiochromic films were placed at different locations to measure the dose deposited. One plan has normal incidence on the titanium/steel rods. In the second plan, the beam is at almost glancing incidence on the metal rods. Measurements were then compared with dose calculated with <span class="hlt">AAA</span> and AcurosXB. Results: The use of OMAR images slightly improved the dose calculation accuracy. The agreement between measured and calculated dose was best with AXB and image reconstructed with OMAR. Dose calculated on titanium phantom has better agreement with measurement. Large discrepancies were seen at points directly above and below the high density inserts. Both <span class="hlt">AAA</span> and AXB underestimated the dose directly above the metal surface, while overestimated the dose below the metal surface. Doses measured downstream of metal were all within 3% of calculated values. Conclusion: When doing treatment planning for patients with metal implants, care must be taken to acquire correct CT images to improve dose calculation accuracy. Moreover, great discrepancies in measured and calculated dose were observed at metal/tissue interface. Care must be taken in estimating the dose in critical structures that come into contact with metals.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Multiverse&id=EJ905243','ERIC'); return false;" href="https://eric.ed.gov/?q=Multiverse&id=EJ905243"><span>"Nothing like Pretend": Difference, Disorder, and Dystopia in the Multiple World Spaces of <span class="hlt">Philip</span> Pullman's "His Dark Materials"</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Cantrell, Sarah K.</p> <p>2010-01-01</p> <p>This article examines the multiple worlds in <span class="hlt">Philip</span> Pullman's "His Dark Materials" trilogy in light Pierre Bourdieu's "space of possibles" and the combination of chance and choice that impact Lyra and Will's decisions. Rather than viewing chance or destiny as disempowering, this article considers how the protagonists' choices also encourage…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27402735','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27402735"><span>Unfolding the mechanism of the <span class="hlt">AAA</span>+ unfoldase VAT by a combined cryo-EM, solution NMR study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huang, Rui; Ripstein, Zev A; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E; Rubinstein, John L</p> <p>2016-07-19</p> <p>The <span class="hlt">AAA</span>+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous <span class="hlt">AAA</span>+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28844860','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28844860"><span>An <span class="hlt">AAA</span> Motor-Driven Mechanical Switch in Rpn11 Controls Deubiquitination at the 26S Proteasome.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Worden, Evan J; Dong, Ken C; Martin, Andreas</p> <p>2017-09-07</p> <p>Poly-ubiquitin chains direct protein substrates to the 26S proteasome, where they are removed by the deubiquitinase Rpn11 during ATP-dependent substrate degradation. Rapid deubiquitination is required for efficient degradation but must be restricted to committed substrates that are engaged with the ATPase motor to prevent premature ubiquitin chain removal and substrate escape. Here we reveal the ubiquitin-bound structure of Rpn11 from S. cerevisiae and the mechanisms for mechanochemical coupling of substrate degradation and deubiquitination. Ubiquitin binding induces a conformational switch of Rpn11's Insert-1 loop from an inactive closed state to an active β hairpin. This switch is rate-limiting for deubiquitination and strongly accelerated by mechanical substrate translocation into the <span class="hlt">AAA</span>+ motor. Deubiquitination by Rpn11 and ubiquitin unfolding by the ATPases are in direct competition. The <span class="hlt">AAA</span>+ motor-driven acceleration of Rpn11 is therefore important to ensure that poly-ubiquitin chains are removed only from committed substrates and fast enough to prevent their co-degradation. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28215061','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28215061"><span>The INNOVATION Trial: four-year safety and effectiveness of the INCRAFT® <span class="hlt">AAA</span> Stent-Graft System for endovascular repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pratesi, Giovanni; Pratesi, Carlo; Chiesa, Roberto; Coppi, Gioacchino; Scheinert, Dierk; Brunkwall, Jan S; van der Meulen, Stefaan; Torsello, Giovanni</p> <p>2017-10-01</p> <p>This paper reports the 4-year safety and effectiveness of the INCRAFT® <span class="hlt">AAA</span> Stent-Graft System (Cordis Corp., Milpitas, CA, USA), an ultra-low-profile device for the treatment of abdominal aortic aneurysms. The INNOVATION Trial is the prospective, first-in-human, multicenter trial to evaluate the safety and effectiveness of the INCRAFT® System. Patients underwent annual clinical and computed tomography angiography examination as part of the study protocol. The INCRAFT® <span class="hlt">AAA</span> Stent-Graft System is a customizable tri-modular design, with an ultra-low profile (14-Fr) delivery system. Patient were treated under approved protocol, the prescribed clinical and imaging follow-up at annually through 5 years. Results analyzed and adjudicated by a clinical events committee, independent core laboratory, and a data safety and monitoring board. This manuscript reports results through 4 years of follow-up. A total of 60 patients were enrolled in the trial, all of whom were successfully treated. Follow-up rates at 1 and 4 years were 93% (56/60) and 85% (51/60), respectively. All-cause mortality at 4 years was 17.6% and no death was <span class="hlt">AAA</span>-, device-, or procedure-related. The secondary reintervention rate at 1 year was 4.6%, primarily the result of stent thrombosis. In total, 10 patients required 13 post-procedure interventions within 4-years of follow-up (2 to repair a type I endoleak, 4 to repair a type II endoleak, 1 for stent thrombosis, 1 for renal stenosis, 1 for aneurysm enlargement, 2 for limb migration and 2 for prosthesis stenosis or occlusion). There were 4 cases (10%) of aneurysm enlargement reported at the 4 year follow-up. At 4 years, 38 out of 39 patients were free from type I and III endoleaks. There were no proximal type I or type III endoleaks at 4-year follow-up. Core laboratory evaluation of the postoperative imaging studies indicated absence of endograft migration while a single fracture was demonstrated without any clinical sequelae. The INCRAFT® <span class="hlt">AAA</span> Stent</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1747921','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1747921"><span>How <span class="hlt">Philip</span> Morris unlocked the Japanese cigarette market: lessons for global tobacco control</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lambert, A; Sargent, J; Glantz, S; Ling, P</p> <p>2004-01-01</p> <p>Background: The Framework Convention on Tobacco Control includes tobacco advertising restrictions that are strongly opposed by the tobacco industry. Marketing strategies used by transnational tobacco companies to open the Japanese market in the absence of such restrictions are described. Methods: Analysis of internal company documents. Findings: Between 1982 and 1987 transnational tobacco companies influenced the Japanese government through the US Trade Representative to open distribution networks and eliminate advertising restrictions. US cigarette exports to Japan increased 10-fold between 1985 and 1996. Television advertising was central to opening the market by projecting a popular image (despite a small actual market share) to attract existing smokers, combined with hero-centred advertisements to attract new smokers. <span class="hlt">Philip</span> Morris's campaigns featured Hollywood movie personalities popular with young men, including James Coburn, Pierce Brosnan, Roger Moore, and Charlie Sheen. Event sponsorships allowed television access despite restrictions. When reinstatement of television restrictions was threatened in the late 1980s, <span class="hlt">Philip</span> Morris more than doubled its television advertising budget and increased sponsorship of televised events. By adopting voluntary advertising standards, transnational companies delayed a television advertising ban for over a decade. Conclusions: Television image advertising was important to establish a market, and it has been enhanced using Hollywood personalities. Television advertising bans are essential measures to prevent industry penetration of new markets, and are less effective without concurrent limits on sponsorship and promotion. Comprehensive advertising restrictions, as included in the Framework Convention for Tobacco Control, are vital for countries where transnational tobacco companies have yet to penetrate the market. PMID:15564622</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15564622','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15564622"><span>How <span class="hlt">Philip</span> Morris unlocked the Japanese cigarette market: lessons for global tobacco control.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lambert, A; Sargent, J D; Glantz, S A; Ling, P M</p> <p>2004-12-01</p> <p>The Framework Convention on Tobacco Control includes tobacco advertising restrictions that are strongly opposed by the tobacco industry. Marketing strategies used by transnational tobacco companies to open the Japanese market in the absence of such restrictions are described. Analysis of internal company documents. Between 1982 and 1987 transnational tobacco companies influenced the Japanese government through the US Trade Representative to open distribution networks and eliminate advertising restrictions. US cigarette exports to Japan increased 10-fold between 1985 and 1996. Television advertising was central to opening the market by projecting a popular image (despite a small actual market share) to attract existing smokers, combined with hero-centred advertisements to attract new smokers. <span class="hlt">Philip</span> Morris's campaigns featured Hollywood movie personalities popular with young men, including James Coburn, Pierce Brosnan, Roger Moore, and Charlie Sheen. Event sponsorships allowed television access despite restrictions. When reinstatement of television restrictions was threatened in the late 1980s, <span class="hlt">Philip</span> Morris more than doubled its television advertising budget and increased sponsorship of televised events. By adopting voluntary advertising standards, transnational companies delayed a television advertising ban for over a decade. Television image advertising was important to establish a market, and it has been enhanced using Hollywood personalities. Television advertising bans are essential measures to prevent industry penetration of new markets, and are less effective without concurrent limits on sponsorship and promotion. Comprehensive advertising restrictions, as included in the Framework Convention for Tobacco Control, are vital for countries where transnational tobacco companies have yet to penetrate the market.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22395906-dosimetric-evaluation-eclipse-aaa-algorithm-millennium-mlc-cranial-intensity-modulated-radiosurgery','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22395906-dosimetric-evaluation-eclipse-aaa-algorithm-millennium-mlc-cranial-intensity-modulated-radiosurgery"><span>A dosimetric evaluation of the Eclipse <span class="hlt">AAA</span> algorithm and Millennium 120 MLC for cranial intensity-modulated radiosurgery</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Moragues, Sandra; Pozo, Miquel</p> <p>2014-07-01</p> <p>The aim of this study is to assess the accuracy of a convolution-based algorithm (anisotropic analytical algorithm [<span class="hlt">AAA</span>]) implemented in the Eclipse planning system for intensity-modulated radiosurgery (IMRS) planning of small cranial targets by using a 5-mm leaf-width multileaf collimator (MLC). Overall, 24 patient-based IMRS plans for cranial lesions of variable size (0.3 to 15.1 cc) were planned (Eclipse, <span class="hlt">AAA</span>, version 10.0.28) using fixed field-based IMRS produced by a Varian linear accelerator equipped with a 120 MLC (5-mm width on central leaves). Plan accuracy was evaluated according to phantom-based measurements performed with radiochromic film (EBT2, ISP, Wayne, NJ). Film 2Dmore » dose distributions were performed with the FilmQA Pro software (version 2011, Ashland, OH) by using the triple-channel dosimetry method. Comparison between computed and measured 2D dose distributions was performed using the gamma method (3%/1 mm). Performance of the MLC was checked by inspection of the DynaLog files created by the linear accelerator during the delivery of each dynamic field. The absolute difference between the calculated and measured isocenter doses for all the IMRS plans was 2.5% ± 2.1%. The gamma evaluation method resulted in high average passing rates of 98.9% ± 1.4% (red channel) and 98.9% ± 1.5% (blue and green channels). DynaLog file analysis revealed a maximum root mean square error of 0.46 mm. According to our results, we conclude that the Eclipse/<span class="hlt">AAA</span> algorithm provides accurate cranial IMRS dose distributions that may be accurately delivered by a Varian linac equipped with a Millennium 120 MLC.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4131744','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4131744"><span>Substrate delivery by the <span class="hlt">AAA</span>+ ClpX and ClpC1 unfoldases activates the mycobacterial ClpP1P2 peptidase</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Schmitz, Karl R.; Sauer, Robert T.</p> <p>2014-01-01</p> <p>Summary Mycobacterial Clp-family proteases function via collaboration of the heteromeric ClpP1P2 peptidase with a <span class="hlt">AAA</span>+ partner, ClpX or ClpC1. These enzymes are essential for M. tuberculosis viability and are validated antibacterial drug targets, but the requirements for assembly and regulation of functional proteolytic complexes are poorly understood. Here, we report the reconstitution of protein degradation by mycobacterial Clp proteases in vitro and describe novel features of these enzymes that distinguish them from orthologs in other bacteria. Both ClpX and ClpC1 catalyze ATP-dependent unfolding and degradation of native protein substrates in conjunction with ClpP1P2, but neither mediates protein degradation with just ClpP1 or ClpP2. ClpP1P2 alone has negligible peptidase activity, but is strongly stimulated by translocation of protein substrates into ClpP1P2 by either <span class="hlt">AAA</span>+ partner. Interestingly, our results support a model in which both binding of a <span class="hlt">AAA</span>+ partner and protein-substrate delivery are required to stabilize active ClpP1P2. Our model has implications for therapeutically targeting ClpP1P2 in dormant M. tuberculosis, and our reconstituted systems should facilitate identification of novel Clp protease inhibitors and activators. PMID:24976069</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29772324','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29772324"><span>Morphology-related limitations of EVAR applicability in the treatment of <span class="hlt">AAA</span> in West-Central Poland.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dzieciuchowicz, Łukasz; Tomczak, Jolanta; Strauss, Ewa; Oszkinis, Grzegorz</p> <p>2018-05-14</p> <p>To analyze the current applicability of endovascular aneurysm repair (EVAR) in patients with an infrarenal abdominal aortic aneurysm (<span class="hlt">AAAs</span>) with indication for elective treatment in West-Central Poland. Computed tomography angiograms of 100 consecutive patients with infrarenal <span class="hlt">AAA</span> deemed to require treatment were analyzed with an OsiriX DICOM viewer in 3D-MPR mode. Proximal neck diameter, length, angulation, shape, the presence of thrombus and calcification, distal neck diameter, and morphology of the iliac arteries were determined. Three sets of morphological criteria were established. The optimal criteria consisted of a non-conical proximal neck without moderate or severe calcification or thrombus, with a diameter of 18-28 mm, length of ≥15 mm, and β angulation of <60%; a distal neck with a diameter of ≥20 mm; a landing zone in the common iliac arteries with a length of ≥ 10 mm and diameter of ≤ 20 mm; and external iliac arteries with diameters of ≥7 mm. The suboptimal criteria included proximal neck diameters of 18-32 mm, neck lengths ≥10 mm, infrarenal neck angulations of up to 75˚, and common iliac artery diameters of up to 25 mm. Finally, the extended suboptimal criteria included proximal neck diameters of 16-34 mm and infrarenal neck angulations ≤90˚, without limits in the maximal diameter of the common iliac arteries. The median maximum aneurysm diameter was 61 mm. The optimal, suboptimal, and extended suboptimal criteria were met by 23%, 32%, and 53% of patients, respectively. The most common deviations were wide, conical, and angulated proximal necks and aneurysmal iliac arteries. The majority of patients with <span class="hlt">AAA</span> deemed to be candidates for elective repair do not meet the most favorable criteria for EVAR. Availability of better endovascular solutions for conical, angulated, and wide necks and aneurysmal iliac arteries would likely expand EVAR applicability. Open repair remains a valid option. Copyright © 2018 Elsevier Inc. All rights</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2767394','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2767394"><span>“Working to shape what society's expectations of us should be”: <span class="hlt">Philip</span> Morris' societal alignment strategy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yang, J S; Malone, R E</p> <p>2009-01-01</p> <p>Background A key element of <span class="hlt">Philip</span> Morris's (PM's) corporate social responsibility initiatives is “societal alignment”, defined as “strategies and programs to meet society's expectations of a responsible tobacco company”. This study explored the genesis and implementation of <span class="hlt">Philip</span> Morris' (PM) societal alignment efforts. Methods The study retrieved and analysed approximately 375 previously undisclosed PM documents now available electronically. Using an iterative process, the study categorised themes and prepared a case analysis. Results Beginning in 1999, PM sought to become “societally aligned” by identifying expectations of a responsible tobacco company through public opinion research and developing and publicising programs to meet those expectations. Societal alignment was undertaken within the US and globally to ensure an environment favourable to PM's business objectives. Despite PM's claims to be “changing”, however, societal alignment in practice was highly selective. PM responded to public “expectations” largely by retooling existing positions and programs, while entirely ignoring other expectations that might have interfered with its business goals. It also appears that convincing employees of the value and authenticity of societal alignment was difficult. Conclusions As implementation of the Framework Convention on Tobacco Control proceeds, tobacco control advocates should closely monitor development of such “alignment” initiatives and expose the motivations and contradictions they reveal. PMID:18845623</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=dark+AND+matter&pg=4&id=EJ630685','ERIC'); return false;" href="https://eric.ed.gov/?q=dark+AND+matter&pg=4&id=EJ630685"><span>"Without Contraries Is No Progression": Dust as an All-Inclusive, Multifunctional Metaphor in <span class="hlt">Philip</span> Pullman's "His Dark Materials."</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Bird, Anne-Marie</p> <p>2001-01-01</p> <p>Draws on Milton's "Paradise Lost" and on motifs found within Gnostic mythology and the poetry of William Blake to explore how <span class="hlt">Philip</span> Pullman reworks the Judeo-Christian myth of the Fall in his trilogy, "His Dark Materials." Finds at its center "Dust": a conventional metaphor for human physicality in which good and evil, and spirit and matter…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26270280','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26270280"><span>"What Is Our Story?" <span class="hlt">Philip</span> Morris's Changing Corporate Narrative.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>McDaniel, Patricia A; Malone, Ruth E</p> <p>2015-10-01</p> <p>We sought to learn how employees reacted to changes in the corporate narrative of <span class="hlt">Philip</span> Morris Companies (PMC) in the late 1990s and early 2000s. We analyzed archival internal tobacco industry documents about PMC's creation of a new corporate story. In response to litigation and public opprobrium, PMC replaced its market success-oriented corporate narrative with a new one centered on responsibility. Although management sought to downplay inconsistencies between the old and new narratives, some employees reportedly had difficulty reconciling them, concerned that the responsibility focus might affect company profitability. However, others embraced the new narrative, suggesting radical ideas to prevent youth smoking. These ideas were not adopted. PMC's new narrative was unconvincing to many of its employees, who perceived it either as a threat to the company's continued profits or as incongruous with what they had previously been told. As it had done with the public, PMC misled its employees in explaining a narrative repositioning that would help the company continue business as usual. Moving toward a tobacco endgame will require ongoing discursive and symbolic efforts to disrupt this narrative.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21367566','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21367566"><span>Midterm outcomes of the Zenith Renu <span class="hlt">AAA</span> Ancillary Graft.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jim, Jeffrey; Rubin, Brian G; Geraghty, Patrick J; Money, Samuel R; Sanchez, Luis A</p> <p>2011-08-01</p> <p>The Zenith Renu abdominal aortic aneurysm (<span class="hlt">AAA</span>) Ancillary Graft (Cook Medical Inc, Bloomington, Ind) provides active proximal fixation for treatment of pre-existing endografts with failed or failing proximal fixation or seal. The purpose of this study was to evaluate the midterm outcomes of treatment with this device. From September 2005 to November 2006, a prospective, nonrandomized, multicenter, postmarket registry was utilized to collect physician experiences from 151 cases (89 converters and 62 main body extensions) at 95 institutions. Preoperative indications and procedural and postimplantation outcomes were collected and analyzed. Technical success and clinical success were determined as defined by the Society of Vascular Surgery reporting standards. Patients were predominantly male (87%) with a mean age of 77 years. The interval between the original endograft implantation to Renu treatment was 43.4 ± 18.7 months. The indications for treatment were endoleak (n = 111), migration (n = 136), or both (n = 94). Technical success was 98.0% with two cases of intraoperative conversion and one case of persistent type IA endoleak. The median follow-up for the cohort was 45.0 months (range, 0-56 months; interquartile range, 25.0 months). Overall, 32 cases had treatment failures that included at least one of the following: death (n = 5), type I/III endoleak (n = 18), graft infection (n = 1), thrombosis (n = 1), aneurysm enlargement >5 mm (n = 9), rupture (n = 4), conversion (n = 9, with 7 after 30 days), and migration (n = 1). Overall, the clinical success for the entire cohort during the follow-up period was 78.8% (119/151). The postmarket registry data confirm that the Zenith Renu <span class="hlt">AAA</span> Ancillary Graft can be used to treat endovascular repairs that failed due to proximal attachment failures. The salvage treatment with the Renu device had high technical success rate and resulted in clinical success in a majority of patients (78.8%). While failed endovascular repairs can</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4961139','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4961139"><span>Unfolding the mechanism of the <span class="hlt">AAA</span>+ unfoldase VAT by a combined cryo-EM, solution NMR study</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Huang, Rui; Ripstein, Zev A.; Augustyniak, Rafal; Lazniewski, Michal; Ginalski, Krzysztof; Kay, Lewis E.; Rubinstein, John L.</p> <p>2016-01-01</p> <p>The <span class="hlt">AAA</span>+ (ATPases associated with a variety of cellular activities) enzymes play critical roles in a variety of homeostatic processes in all kingdoms of life. Valosin-containing protein-like ATPase of Thermoplasma acidophilum (VAT), the archaeal homolog of the ubiquitous <span class="hlt">AAA</span>+ protein Cdc48/p97, functions in concert with the 20S proteasome by unfolding substrates and passing them on for degradation. Here, we present electron cryomicroscopy (cryo-EM) maps showing that VAT undergoes large conformational rearrangements during its ATP hydrolysis cycle that differ dramatically from the conformational states observed for Cdc48/p97. We validate key features of the model with biochemical and solution methyl-transverse relaxation optimized spectroscopY (TROSY) NMR experiments and suggest a mechanism for coupling the energy of nucleotide hydrolysis to substrate unfolding. These findings illustrate the unique complementarity between cryo-EM and solution NMR for studies of molecular machines, showing that the structural properties of VAT, as well as the population distributions of conformers, are similar in the frozen specimens used for cryo-EM and in the solution phase where NMR spectra are recorded. PMID:27402735</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017JPhCS.898f2042B','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017JPhCS.898f2042B"><span>HTTP as a Data Access Protocol: Trials with XrootD in CMS’s <span class="hlt">AAA</span> Project</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Balcas, J.; Bockelman, B. P.; Kcira, D.; Newman, H.; Vlimant, J.; Hendricks, T. W.; <author pre="for the"> CMS Collaboration</p> <p>2017-10-01</p> <p>The main goal of the project to demonstrate the ability of using HTTP data federations in a manner analogous to the existing <span class="hlt">AAA</span> infrastructure of the CMS experiment. An initial testbed at Caltech has been built and changes in the CMS software (CMSSW) are being implemented in order to improve HTTP support. The testbed consists of a set of machines at the Caltech Tier2 that improve the support infrastructure for data federations at CMS. As a first step, we are building systems that produce and ingest network data transfers up to 80 Gbps. In collaboration with <span class="hlt">AAA</span>, HTTP support is enabled at the US redirector and the Caltech testbed. A plugin for CMSSW is being developed for HTTP access based on the DaviX software. It will replace the present fork/exec or curl for HTTP access. In addition, extensions to the XRootD HTTP implementation are being developed to add functionality to it, such as client-based monitoring identifiers. In the future, patches will be developed to better integrate HTTP-over-XRootD with the Open Science Grid (OSG) distribution. First results of the transfer tests using HTTP are presented in this paper together with details about the initial setup.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/6513422-provenance-petrofacies-upper-devonian-sandstones-philip-smith-mountains-arctic-quandrangles-brooks-range-alaska-final-report-project','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/6513422-provenance-petrofacies-upper-devonian-sandstones-philip-smith-mountains-arctic-quandrangles-brooks-range-alaska-final-report-project"><span>Provenance and petrofacies, Upper Devonian sandstones, <span class="hlt">Philip</span> Smith Mountains and Arctic quandrangles, Brooks Range, Alaska: Final report, Project No. 3</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Anderson, A.V.; Coney, P.J.</p> <p>1987-11-01</p> <p>Late Devonian sandstone beds are exposed as allochthonous sequences that extend for over 1000 km along the east-west strike of the Brooks Range in northern Alaska. These horizons, at least in part, record Late Devonian tectonism and deposition along the southern margin of the Arctic Alaska block. This study identifies clastic petrofacies in the western <span class="hlt">Philip</span> Smith Mountains and southern Arctic quadrangles and infers the composition of the source terrane. The paleogeography is not known and the original distribution of lithofacies is uncertain, owing to the extensive post-depositional tectonism. In the study area the sandstones are exposed along rugged mountainmore » tops and high ridges. Although exposures are excellent, access is often difficult. Samples were collected from exposures near the western end of the Chandalar Shelf, Atigun Pass, and the Atigun River valley in the <span class="hlt">Philip</span> Smith Mountains quadrangle and from the Crow Nest Creek and Ottertail Creek areas in the Arctic quadrangle. 34 refs., 17 figs.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18653794','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18653794"><span>Philanthropy, politics and promotion: <span class="hlt">Philip</span> Morris' "charitable contributions" in Thailand.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>MacKenzie, Ross; Collin, Jeff</p> <p>2008-08-01</p> <p>The efforts of members of the tobacco industry to portray themselves as responsible corporations via ostensible commitment to improved labour practices and public philanthropy have attracted growing criticism. This is particularly true of corporate social responsibility (CSR) schemes undertaken in emerging nations that are designed to rehabilitate the tobacco industry's image among public, government and market opinions in North America and western Europe. In the case of Thailand, sponsorship of arts events and community groups has been one avenue of promoting the industry in a regulatory environment that severely curtails promotion and advertising. The Association of Southeast Asian Nations (ASEAN) Art Award, sponsored by <span class="hlt">Philip</span> Morris (PM) has provided one such outlet for 10 years. Analysis of PM funding announcements since the end of the ASEAN art programme in Thailand reveals that recent donations to tobacco-related community organisations reinforces the extent to which seemingly generous acts are driven by corporate self-interest rather than social responsibility.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28994128','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28994128"><span>Validity of automated measurement of left ventricular ejection fraction and volume using the <span class="hlt">Philips</span> EPIQ system.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hovnanians, Ninel; Win, Theresa; Makkiya, Mohammed; Zheng, Qi; Taub, Cynthia</p> <p>2017-11-01</p> <p>To assess the efficiency and reproducibility of automated measurements of left ventricular (LV) volumes and LV ejection fraction (LVEF) in comparison to manually traced biplane Simpson's method. This is a single-center prospective study. Apical four- and two-chamber views were acquired in patients in sinus rhythm. Two operators independently measured LV volumes and LVEF using biplane Simpson's method. In addition, the image analysis software a2DQ on the <span class="hlt">Philips</span> EPIQ system was applied to automatically assess the LV volumes and LVEF. Time spent on each analysis, using both methods, was documented. Concordance of echocardiographic measures was evaluated using intraclass correlation (ICC) and Bland-Altman analysis. Manual tracing and automated measurement of LV volumes and LVEF were performed in 184 patients with a mean age of 67.3 ± 17.3 years and BMI 28.0 ± 6.8 kg/m 2 . ICC and Bland-Altman analysis showed good agreements between manual and automated methods measuring LVEF, end-systolic, and end-diastolic volumes. The average analysis time was significantly less using the automated method than manual tracing (116 vs 217 seconds/patient, P < .0001). Automated measurement using the novel image analysis software a2DQ on the <span class="hlt">Philips</span> EPIQ system produced accurate, efficient, and reproducible assessment of LV volumes and LVEF compared with manual measurement. © 2017, Wiley Periodicals, Inc.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_11");'>11</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li class="active"><span>13</span></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_13 --> <div id="page_14" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="261"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29848500','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29848500"><span>In Vivo Molecular Characterization of Abdominal Aortic Aneurysms Using Fibrin-Specific Magnetic Resonance Imaging.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Botnar, René M; Brangsch, Julia; Reimann, Carolin; Janssen, Christian H P; Razavi, Reza; Hamm, Bernd; Makowski, Marcus R</p> <p>2018-05-30</p> <p>The incidence of abdominal aortic aneurysms (<span class="hlt">AAAs</span>) will significantly increase during the next decade. Novel biomarkers, besides diameter, are needed for a better characterization of aneurysms and the estimation of the risk of rupture. Fibrin is a key protein in the formation of focal hematoma associated with the dissection of the aortic wall and the development of larger thrombi during the progression of <span class="hlt">AAAs</span>. This study evaluated the potential of a fibrin-specific magnetic resonance (MR) probe for the in vivo characterization of the different stages of <span class="hlt">AAAs</span>. <span class="hlt">AAAs</span> spontaneously developed in ApoE -/- mice following the infusion of angiotensin-II (Ang-II, 1 μg/kg -1 ·per minute). An established fibrin-specific molecular MR probe (EP2104R, 10 μmol/kg -1 ) was administered after 1 to 4 weeks following Ang-II infusion (n=8 per group). All imaging experiments were performed on a clinical 3T Achieva MR system with a microscopy coil (<span class="hlt">Philips</span> Healthcare, Netherlands). The development of <span class="hlt">AAA</span>-associated fibrin-rich hematoma and thrombi was assessed. The high signal generated by the fibrin probe enabled high-resolution MR imaging for an accurate assessment and quantification of the relative fibrin composition of focal hematoma and thrombi. Contrast-to-noise-ratios (CNRs) and R1-relaxation rates following the administration of the fibrin probe were in good agreement with ex vivo immunohistomorphometry ( R 2 =0.83 and 0.85) and gadolinium concentrations determined by inductively coupled plasma mass spectroscopy ( R 2 =0.78 and 0.72). The fibrin-specific molecular MR probe allowed the delineation and quantification of changes in fibrin content in early and advanced <span class="hlt">AAAs</span>. Fibrin MRI could provide a novel in vivo biomarker to improve the risk stratification of patients with aortic aneurysms. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28835175','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28835175"><span>Beneficial effect of statins on total mortality in abdominal aortic aneurysm (<span class="hlt">AAA</span>) repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mathisen, Sven Ross; Abdelnoor, Michael</p> <p>2017-10-01</p> <p>In this single center, retrospective cohort study we wished to compare early and total mortality for all patients treated for abdominal aortic aneurysms (<span class="hlt">AAA</span>) with open surgery who were taking statins compared to those who were not. A cohort of 640 patients with <span class="hlt">AAA</span> was treated with open surgery between 1999 and 2012. Patients were consecutively recruited from a source population of 390,000; 21.3% were female, and the median age was 73 years. The median follow-up was 3.93 years, with an interquartile range of 1.79-6.58 years. The total follow-up was 2855 patient-years. An explanatory strategy was used. The propensity score (PS) was implemented to control for selection bias and confounders. The crude effect of statin use showed a 78% reduction of the 30-day mortality. A stratified analysis using the Mantel-Haenszel method on quintiles of the PS gave an adjusted effect of the odds ratio equal to 0.43 (95% CI: 0.18-0.96), indicating a 57% reduction of the 30-day mortality for statin users. The adjusted rate ratio was 0.62 (95% CI: 0.45-0.83), indicating a reduction of long-term mortality of 38% for statin users compared to non-users for a median follow-up of 3.93 years. This retrospective cohort study showed a significant beneficial effect of statin use on early and long-term survival for patients treated with open surgery. To be conclusive, our results need to be replicated by a randomized clinical trial.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016JPhCS.771a2045D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016JPhCS.771a2045D"><span>Effect of microgravity simulation using 3D clinostat on cavendish banana (Musa acuminata <span class="hlt">AAA</span> Group) ripening process</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Dwivany, Fenny Martha; Esyanti, Rizkita R.; Prapaisie, Adeline; Puspa Kirana, Listya; Latief, Chunaeni; Ginaldi, Ari</p> <p>2016-11-01</p> <p>The objective of the research was to determine the effect of microgravity simulation by 3D clinostat on Cavendish banana (Musa acuminata <span class="hlt">AAA</span> group) ripening process. In this study, physical, physiological changes as well as genes expression were analysed. The result showed that in microgravity simulation condition ripening process in banana was delayed and the MaACOl, MaACSl and MaACS5 gene expression were affected.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29028367','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29028367"><span><span class="hlt">Philip</span> Hillkowitz The "Granddaddy of Medical Technologists" and Cofounder of the American Society for Clinical Pathologists and the Jewish Consumptives' Relief Society.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wright, James R; Abrams, Jeanne</p> <p>2018-01-01</p> <p>- In the early 20th century, the future of hospital-based clinical pathology practice was uncertain and this situation led to the formation of the American Society for Clinical Pathologists in 1922. <span class="hlt">Philip</span> Hillkowitz, MD, and Ward Burdick, MD, were its cofounders. No biography of Hillkowitz exists. - To explore the life, beliefs, and accomplishments of <span class="hlt">Philip</span> Hillkowitz. - Available primary and secondary historical sources were reviewed. - Hillkowitz, the son of a Russian rabbi, immigrated to America as an 11-year-old child in 1885. He later attended medical school in Cincinnati, Ohio, and then moved to Colorado, where he began his clinical practice, which transitioned into a clinical pathology practice. In Denver, he met Charles Spivak, MD, another Jewish immigrant and together they established the Jewish Consumptives' Relief Society, an ethnically sensitive tuberculosis sanatorium that flourished in the first half of the 20th century because of its national fundraising network. In 1921, Hillkowitz and Burdick, also a Denver-based pathologist, successively organized the pathologists in Denver, followed by the state of Colorado. Early the next year, they formed the American Society for Clinical Pathologists (ASCP). Working with the American College of Surgeons, the ASCP put hospital-based practice of clinical pathology on solid footing in the 1920s. Hillkowitz then established and oversaw the ASCP Board of Registry of Medical Technologists. - <span class="hlt">Philip</span> Hillkowitz changed the directions of clinical pathology and tuberculosis treatment in 20th century America, while simultaneously serving as a successful ethnic power broker within both the American Jewish and Eastern European immigrant communities.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4428354','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4428354"><span>The <span class="hlt">AAA</span>+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Matias, Pedro M.; Baek, Sung Hee; Bandeiras, Tiago M.; Dutta, Anindya; Houry, Walid A.; Llorca, Oscar; Rosenbaum, Jean</p> <p>2015-01-01</p> <p>Pontin and Reptin are related partner proteins belonging to the <span class="hlt">AAA</span>+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10–12, 2014, and reported significant new advances on the mechanisms of action of these two <span class="hlt">AAA</span>+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models. PMID:25988184</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25988184','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25988184"><span>The <span class="hlt">AAA</span>+ proteins Pontin and Reptin enter adult age: from understanding their basic biology to the identification of selective inhibitors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Matias, Pedro M; Baek, Sung Hee; Bandeiras, Tiago M; Dutta, Anindya; Houry, Walid A; Llorca, Oscar; Rosenbaum, Jean</p> <p>2015-01-01</p> <p>Pontin and Reptin are related partner proteins belonging to the <span class="hlt">AAA</span>+ (ATPases Associated with various cellular Activities) family. They are implicated in multiple and seemingly unrelated processes encompassing the regulation of gene transcription, the remodeling of chromatin, DNA damage sensing and repair, and the assembly of protein and ribonucleoprotein complexes, among others. The 2nd International Workshop on Pontin and Reptin took place at the Instituto de Tecnologia Química e Biológica António Xavier in Oeiras, Portugal on October 10-12, 2014, and reported significant new advances on the mechanisms of action of these two <span class="hlt">AAA</span>+ ATPases. The major points under discussion were related to the mechanisms through which these proteins regulate gene transcription, their roles as co-chaperones, and their involvement in pathophysiology, especially in cancer and ciliary biology and disease. Finally, they may become anticancer drug targets since small chemical inhibitors were shown to produce anti-tumor effects in animal models.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1381242','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1381242"><span>The defeat of <span class="hlt">Philip</span> Morris' 'California Uniform Tobacco Control Act'.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Macdonald, H; Aguinaga, S; Glantz, S A</p> <p>1997-01-01</p> <p>OBJECTIVES: This paper describes the strategies used by <span class="hlt">Philip</span> Morris and other tobacco companies to promote a California initiative (Proposition 188) preempting local control of tobacco and those used by public health groups to defeat the initiative. METHODS: Interviews with key informants were conducted, and the written record was reviewed. RESULTS: Tobacco companies nearly succeeded in passing Proposition 188 by presenting it as a pro-health measure that would prevent children from obtaining cigarettes and provide protection against secondhand smoke. Public health groups defeated it by highlighting tobacco industry backing. A private charitable foundation also played an innovative role by financing a non-partisan public education campaign. CONCLUSIONS: Public health forces must be alert to sophisticated efforts by the tobacco industry to enact preemptive state legislation by making it look like tobacco control legislation. The coalition structure that emerged in the "No on 188" campaign represents an effective model for future tobacco control activities. The new role of charitable foundations defined in the Proposition 188 campaign can be used in other public health issues. Images FIGURE 1 PMID:9431289</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Adam+AND+Eve&id=EJ746996','ERIC'); return false;" href="https://eric.ed.gov/?q=Adam+AND+Eve&id=EJ746996"><span>"A Heaven of Hell, a Hell of Heaven": "His Dark Materials," Inverted Theology, and the End of <span class="hlt">Philip</span> Pullman's Authority</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Padley, Jonathan; Padley, Kenneth</p> <p>2006-01-01</p> <p>This article argues that <span class="hlt">Philip</span> Pullman's "His Dark Materials" may be read as a series which attempts to assault the Christian doctrine of God. We believe that this demonstrably accords with Pullman's personal views, and that, through his story, he seeks to foster such views in his readership. However, the accuracy of his attack falls short of its…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29272563','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29272563"><span>A comparison between <span class="hlt">Philips</span> and Tomtec for left ventricular deformation and volume measurements in neonatal intensive care patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>de Waal, Koert; Phad, Nilkant</p> <p>2018-03-01</p> <p>Two-dimensional speckle tracking echocardiography is an emerging technique for analyzing cardiac function in newborns. Strain is a highly reliable and reproducible parameter, and reference values have been established for term and preterm newborns. Its implementation into clinical practice has been slow, partly due to lack of inter-vendor consistency. Our aim was to compare recent versions of <span class="hlt">Philips</span> and Tomtec speckle tracking software for deformation and semiautomated volume and area measurements in neonatal intensive care patients. Longitudinal and circumferential deformation and cavity dimensions (volume, area) were determined off line from apical and short-axis images in 50 consecutive newborns with a median birthweight of 760 g (range 460-3200 g). Absolute mean endocardial global longitudinal strain measurements were similar between vendors, but with wide limits of agreement (<span class="hlt">Philips</span> -18.9 [2.1]%, Tomtec -18.6 [2.5]%, bias -0.3 [1.7]%, and limits of agreement -3.6%-3.1%). Longitudinal strain rate and circumferential measurements showed poor correlation. All volume and area measurements correlated well between the vendors, but with significant bias. Global longitudinal strain measurements compared well between vendors but wide limits of agreement, suggesting that longitudinal measurements are preferred using similar hardware and software. © 2017, Wiley Periodicals, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21666138','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21666138"><span>Design as dream and self-representation: <span class="hlt">Philip</span> Johnson and the Glass House of Atreus.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tutter, Adele</p> <p>2011-06-01</p> <p><span class="hlt">Philip</span> Johnson's masterpiece--the Glass House--is compared to a dream and conceptualized as containing encrypted and embedded representations of the self. Freud's masterpiece--The Interpretation of Dreams--is the theoretical and methodological model for this approach to design-as-dream. Drawing on Johnson's words and forms set in biographical, historical, and cultural context, interpretive paths are traced from manifest design elements of the Glass House to overdetermined latent meanings, yielding new and surprising insights into the Glass House, its elusive architect, and the process of its design. A mirror that reflects an image, a lens that focuses it, and a prism that reveals its components, the Glass House turns a lucid eye onto its maker.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29735657','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29735657"><span>Cotranslocational processing of the protein substrate calmodulin by an <span class="hlt">AAA</span>+ unfoldase occurs via unfolding and refolding intermediates.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Augustyniak, Rafal; Kay, Lewis E</p> <p>2018-05-22</p> <p>Protein remodeling by <span class="hlt">AAA</span>+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT <span class="hlt">AAA</span>+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29518510','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29518510"><span>Expression in Whole Blood Samples of miRNA-191 and miRNA-455-3p in Patients with <span class="hlt">AAA</span> and Their Relationship to Clinical Outcomes after Endovascular Repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tenorio, Emanuel Junio Ramos; Braga, Andre Felipe Farias; Tirapelli, Daniela Pretti Da Cunha; Ribeiro, Mauricio Serra; Piccinato, Carlos Eli; Joviliano, Edwaldo Edner</p> <p>2018-03-05</p> <p>The purpose of this study was to quantify and evaluate the expression response of miRNA-191 and miRNA-455-3p endovascular repair of abdominal aortic aneurysm (<span class="hlt">AAA</span>) based in whole blood samples. This report describes a prospective study of a single center of 30 patients with <span class="hlt">AAA</span> who underwent endovascular repair. Blood samples were collected preoperatively and 6 months postoperatively. The differential expression of the miRNAs was performed by the real-time polymerase chain reaction method, after extraction of the RNA from the blood samples at the 2 moments. In addition, bioinformatic tools were used to determine pathophysiological pathways related to <span class="hlt">AAA</span>. The miR-191 and miR-455-3p were overexpressed preoperatively. After 6 months postoperatively, miR-191 (median 0.98, IQR 0.5-2.1, P < 0.0001) and miR-455-3p (median 1.4, IQR 0.6-3.1, P = 0.0003) presented a significant reduction in their expressions. There was no correlation between the diameter of the aneurysm and the expression of the miRNAs studied. In addition, analysis of the influence of the various types of devices used for the endovascular treatment of <span class="hlt">AAA</span> showed no significant differences in the expression of miR-191 and miR-455-3p. Exclusion of the aneurysmal sac after endovascular treatment induces a decrease in the expression of the studied miRNAs in whole blood samples, which suggests a possible use of them as biomarkers of therapeutic success. Copyright © 2018 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22739451','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22739451"><span>Commentary on Adele Tutter's "Design as dream and self-representation: <span class="hlt">Philip</span> Johnson and the Glass House of Atreus".</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Danze, Elizabeth A; Sonnenberg, Stephen M</p> <p>2012-06-01</p> <p>In this discussion of Adele Tutter's "Design as Dream and Self-Representation: <span class="hlt">Philip</span> Johnson and the Glass House of Atreus" (JAPA 59/3), the architect Elizabeth Danze and the psychoanalyst Stephen Sonnenberg highlight what they see as the most important of Tutter's contributions as regards an understanding of Johnson's work. They then discuss those contributions as they illuminate the study of the relationship of architecture and design, on the one hand, and psychoanalysis on the other.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://rosap.ntl.bts.gov/view/dot/14973','DOTNTL'); return false;" href="https://rosap.ntl.bts.gov/view/dot/14973"><span>Materials Related Forensic Analysis and Special Testing : Drying Shrinkage Evaluation of Bridge Decks with Class <span class="hlt">AAA</span> and Class W/WD Type K Cement</span></a></p> <p><a target="_blank" href="http://ntlsearch.bts.gov/tris/index.do">DOT National Transportation Integrated Search</a></p> <p></p> <p>2001-07-01</p> <p>This work pertains to preparation of concrete drying shrinkage data for proposed concrete mixtures during normal concrete : trial batch verification. Selected concrete mixtures will include PennDOT Classes <span class="hlt">AAA</span> and AA and will also include the use of ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/5615866-stoking-fierce-green-fire-review-philip-shabecoff-history-environmental-movement','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/5615866-stoking-fierce-green-fire-review-philip-shabecoff-history-environmental-movement"><span>Stoking a fierce green fire: A review of <span class="hlt">Philip</span> Shabecoff's history of the environmental movement</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Williams, D.</p> <p></p> <p>Environmental journalist <span class="hlt">Philip</span> Shabecoff begins his book on the American environmental movement, A Fierce Green Fire by guiding the reader across the American landscape as it might have looked to a 15th-century European. He creates a verdant land populated with unharried wildlife and noble savages, all living in absolute harmony. Sadly, this paradise is spoiled by villainous Europeans who invade the Edenic garden and, within a few hundred years, transform it into Hell's backyard. This sets the stage for Shabecoff's discussion of those who fought to protect the environment by making the environmental decision-making process more democratic and, therefore, lessmore » destructive.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26292526','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26292526"><span>Avian Diseases: The Creation and Evolution of P. <span class="hlt">Philip</span> Levine's Enduring Gift.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Calnek, Bruce W</p> <p>2015-03-01</p> <p>This account has two aims. The first is to provide a tribute to Dr. Pincus <span class="hlt">Philip</span> Levine, the founder of Avian Diseases. It addresses several facets of the life and times of this remarkable and interesting personality, giving some insight into the why and how he came to establish the journal. It touches on his background; his character; his astute and searching mind; his ability to interact with others; his influence on veterinary, and especially avian, medicine; and his teaching genius and reveals the positive force he was in his interactions with others. Then, it turns to a celebration of the first half-century of the journal that he created, essentially single-handedly, and reviews some of the history regarding the stimulus, birthing pains, and gradual evolution of the journal through a succession of editors, business managers, and supporting casts to the publication that we see today, nearly 50 yr later.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24038307','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24038307"><span>ACB-PCR measurement of spontaneous and furan-induced H-ras codon 61 CAA to CTA and CAA to <span class="hlt">AAA</span> mutation in B6C3F1 mouse liver.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Banda, Malathi; Recio, Leslie; Parsons, Barbara L</p> <p>2013-10-01</p> <p>Furan is a rodent liver carcinogen, but the mode of action for furan hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors carrying H-ras codon 61 CAA to <span class="hlt">AAA</span> mutation increased in furan-treated mice. Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to quantify early, carcinogen-induced increases in tumor-associated mutations. The present pilot study investigated whether furan drives clonal expansion of pre-existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and CAA to <span class="hlt">AAA</span> mutations were measured in DNA isolated from liver tissue of female mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week for three weeks, using five mice per treatment group. Spontaneous levels of mutation were low, with two of five control mice having an H-ras codon 61 CTA or <span class="hlt">AAA</span> mutant fraction (MF) greater than 10(-5) . Several furan-treated mice had H-ras codon 61 <span class="hlt">AAA</span> or CTA MFs greater than those measured in control mice and lower bound estimates of induced MF were calculated. However, no statistically-significant differences were observed between treatment groups. Therefore, while sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis examined in this study (three weeks), there was not a significant expansion of H-ras mutant cells. Copyright © 2013 Wiley Periodicals, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5559722','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5559722"><span>The <span class="hlt">AAA</span>+ ATPase p97, a cellular multitool</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Stach, Lasse</p> <p>2017-01-01</p> <p>The <span class="hlt">AAA</span>+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. PMID:28819009</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28214350','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28214350"><span>Upregulation of MicroRNA-15a Contributes to Pathogenesis of Abdominal Aortic Aneurysm (<span class="hlt">AAA</span>) by Modulating the Expression of Cyclin-Dependent Kinase Inhibitor 2B (CDKN2B).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gao, Peng; Si, Jiyuan; Yang, Bin; Yu, Jixiang</p> <p>2017-02-18</p> <p>BACKGROUND The objective of the present study was to identify the association between miR-15a-5p and CDKN2B, and their roles in regulating the development of abdominal aortic aneurysm (<span class="hlt">AAA</span>). MATERIAL AND METHODS We searched the miRNA database online (www.mirdb.org) and used a luciferase reporter assay system to study the regulatory relationship between miR-15a-5p and CDKN2B. We also conducted real-time PCR and Western blot analysis to study the mRNA and protein expression level of CDKN2B among different patient groups (participants with abdominal aortic aneurysm (<span class="hlt">AAA</span>) and normal controls) or cells treated with scramble control, miR-15a-5p mimics, CDKN2B siRNA, and miR-15a-5p inhibitors. RESULTS We found that CDKN2B was a virtual target of miR-15a-5p with potential binding sites in the 3'UTR of CDKN2B (77-83 bp). We also showed that miR-15a-5p could bind to the CDKN2B 3'UTR, resulting in a significant decrease in luciferase activity compared with the scramble control. Furthermore, we found that the cells isolated from <span class="hlt">AAA</span> participants showed an over-expression of miR-15a-5p compared to the normal controls, while the CDKN2B mRNA and protein expression level of the <span class="hlt">AAA</span> group were much lower than the normal control group. Additionally, the expression of CDKN2B mRNA and the protein of the cells transfected with miR-15a-5p mimics and CDKN2B siRNA was downregulated, while the cells showed upregulated expression subsequent to transfection with miR-15a-5p inhibitors compared to the scramble control. CONCLUSIONS The data revealed a negative regulatory role of miR-15a-5p in the apoptosis of smooth muscle cells via targeting CDKN2B, and showed that miR-15a-5p could be a novel therapeutic target of <span class="hlt">AAA</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20013734','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20013734"><span>Georg <span class="hlt">Philip</span> Nenter and medicine "by notes" in the 18th century.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bonfante, Luciana; D'Angelo, Angela; Komninos, Georgios; Antonello, Augusto</p> <p>2009-01-01</p> <p>Even though it is true that the medical historiography of the 18th century is lacking in great scientific personalities, it is equally true that the entire century is characterized by continuous efforts to encapsulate the medical area of knowledge, acquired until then, in precise and systematic outlines, to serve the academic teaching of the subject of medicine. Georg <span class="hlt">Philip</span> Nenter, a pupil of Georg Ernst Stahl and a professor of medicine in the University of Strasburg, could not help being influenced by that atmosphere. He added though, in our opinion, a touch of remarkable modernity. In fact his volume Fundamenta medicinae teoretico-pratica (Venice, 1735) is a wonderful collection of the notes taken during his lectures. The description of various diseases - renal diseases in particular - maintains a very systematic development of the subject through various chapters (definition, clinical manifestations, differential diagnosis, prognosis, treatment and examples of specific prescriptions), as if students were being addressed.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_12");'>12</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li class="active"><span>14</span></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_14 --> <div id="page_15" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="281"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29956789','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29956789"><span>TIMP‑3 suppresses the proliferation and migration of SMCs from the aortic neck of atherosclerotic <span class="hlt">AAA</span> in rabbits, via decreased MMP‑2 and MMP‑9 activity, and reduced TNF‑α expression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhai, Huan; Qi, Xun; Li, Zixuan; Zhang, Wei; Li, Chenguang; Ji, Lu; Xu, Ke; Zhong, Hongshan</p> <p>2018-06-26</p> <p>The present study investigated the role of tissue inhibitor of matrix metalloproteinase‑3 (TIMP‑3) in regulating the proliferation, migration, apoptosis and activity of matrix metalloproteinase (MMP)‑2 and ‑9, during the development of an atherosclerotic abdominal artery aneurysm (<span class="hlt">AAA</span>). Experiments were conducted using rabbit <span class="hlt">AAA</span> neck (NA) smooth muscle cells (SMCs), to investigate the potential for TIMP‑3 to be used as a novel stent coating in preventing aortic dilation adjacent to the <span class="hlt">AAA</span>. The atherosclerotic <span class="hlt">AAA</span> model was induced in New Zealand white rabbits via a 6‑week high‑cholesterol diet, followed by incubation of the targeted aortic region with elastase. SMCs were isolated from the aorta adjacent to the aneurysm 30 days after <span class="hlt">AAA</span> model induction, and stimulated with 3, 10, 30 or 100 ng/ml TIMP‑3. Cell proliferation was investigated using Cell Counting Kit‑8 reagent, migration was examined using a Boyden chamber assay and apoptotic rate was analyzed using the Annexin V‑fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA were used to measure the activity of MMP‑2 and MMP‑9, and the expression of tumor necrosis factor‑α (TNF‑α), respectively. Analysis of cell proliferation indicated that 10, 30 and 100 ng/ml TIMP‑3 reduced cell viability. Cell migration was decreased by 10, 30 and 100 ng/ml TIMP‑3. MMP‑2 activity was inhibited by 10, 30 and 100 ng/ml TIMP‑3, and MMP‑9 activity was suppressed by 30 and 100 ng/ml TIMP‑3. The protein levels of secreted TNF‑α were reduced by 10, 30 and 100 ng/ml TIMP‑3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP‑3 to attenuate migration and proliferation, and to inhibit the activity of MMP‑2, MMP‑9 and TNF‑α secretion of NA SMCs. In conclusion, TIMP‑3 may be considered a potential therapeutic drug for use in a novel drug‑eluting stent, to attenuate the progressive dilation of the aortic NA.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27895781','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27895781"><span>9-<span class="hlt">AAA</span> inhibits growth and induces apoptosis in human melanoma A375 and rat prostate adenocarcinoma AT-2 and Mat-LyLu cell lines but does not affect the growth and viability of normal fibroblasts.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Korohoda, Włodzimierz; Hapek, Anna; Pietrzak, Monika; Ryszawy, Damian; Madeja, Zbigniew</p> <p>2016-11-01</p> <p>The present study found that, similarly to 5-fluorouracil, low concentrations (1-10 µM) of 9-aminoacridine (9-<span class="hlt">AAA</span>) inhibited the growth of the two rat prostate cancer AT-2 and Mat-LyLu cell lines and the human melanoma A375 cell line. However, at the same concentrations, 9-<span class="hlt">AAA</span> had no effect on the growth and apoptosis of normal human skin fibroblasts (HSFs). The differences between the cellular responses of the AT-2 and Mat-LyLu cell lines, which differ in malignancy, were found to be relatively small compared with the differences between normal HSFs and the cancer cell lines. Visible effects on the cell growth and survival of tumor cell lines were observed after 24-48 h of treatment with 9-<span class="hlt">AAA</span>, and increased over time. The inhibition of cancer cell growth was found to be due to the gradually increasing number of cells dying by apoptosis, which was observed using two methods, direct counting and FlowSight analysis. Simultaneously, cell motile activity decreased to the same degree in cancer and normal cells within the first 8 h of incubation in the presence of 9-<span class="hlt">AAA</span>. The results presented in the current study suggest that short-lasting tests for potential anticancer substances can be insufficient; which may result in cell type-dependent differences in the responses of cells to tested compounds that act with a delay being overlooked. The observed differences in responses between normal human fibroblasts and cancer cells to 9-<span class="hlt">AAA</span> show the requirement for additional studies to be performed simultaneously on differently reacting cancer and normal cells, to determine the molecular mechanisms responsible for these differences.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5423775','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5423775"><span>Structure of a <span class="hlt">AAA</span>+ unfoldase in the process of unfolding substrate</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ripstein, Zev A; Huang, Rui; Augustyniak, Rafal; Kay, Lewis E; Rubinstein, John L</p> <p>2017-01-01</p> <p><span class="hlt">AAA</span>+ unfoldases are thought to unfold substrate through the central pore of their hexameric structures, but how this process occurs is not known. VAT, the Thermoplasma acidophilum homologue of eukaryotic CDC48/p97, works in conjunction with the proteasome to degrade misfolded or damaged proteins. We show that in the presence of ATP, VAT with its regulatory N-terminal domains removed unfolds other VAT complexes as substrate. We captured images of this transient process by electron cryomicroscopy (cryo-EM) to reveal the structure of the substrate-bound intermediate. Substrate binding breaks the six-fold symmetry of the complex, allowing five of the six VAT subunits to constrict into a tight helix that grips an ~80 Å stretch of unfolded protein. The structure suggests a processive hand-over-hand unfolding mechanism, where each VAT subunit releases the substrate in turn before re-engaging further along the target protein, thereby unfolding it. DOI: http://dx.doi.org/10.7554/eLife.25754.001 PMID:28390173</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1256062-structural-characterization-newly-identified-component-carboxysomes-aaa+-domain-protein-csocbbq','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1256062-structural-characterization-newly-identified-component-carboxysomes-aaa+-domain-protein-csocbbq"><span>Structural Characterization of a Newly Identified Component of α-Carboxysomes: The <span class="hlt">AAA</span>+ Domain Protein CsoCbbQ</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Sutter, Markus; Roberts, Evan W.; Gonzalez, Raul C.; ...</p> <p>2015-11-05</p> <p>Carboxysomes are bacterial microcompartments that enhance carbon fixation by concentrating ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and its substrate CO 2 within a proteinaceous shell. They are found in all cyanobacteria, some purple photoautotrophs and many chemoautotrophic bacteria. Carboxysomes consist of a protein shell that encapsulates several hundred molecules of RuBisCO, and contain carbonic anhydrase and other accessory proteins. Genes coding for carboxysome shell components and the encapsulated proteins are typically found together in an operon. The α-carboxysome operon is embedded in a cluster of additional, conserved genes that are presumably related to its function. In many chemoautotrophs, products of the expanded carboxysomemore » locus include CbbO and CbbQ, a member of the <span class="hlt">AAA</span>+ domain superfamily. We bioinformatically identified subtypes of CbbQ proteins and show that their genes frequently co-occur with both Form IA and Form II RuBisCO. The α-carboxysome-associated ortholog, CsoCbbQ, from Halothiobacillus neapolitanus forms a hexamer in solution and hydrolyzes ATP. The crystal structure shows that CsoCbbQ is a hexamer of the typical <span class="hlt">AAA</span>+ domain; the additional C-terminal domain, diagnostic of the CbbQ subfamily, structurally fills the inter-monomer gaps, resulting in a distinctly hexagonal shape. Finally, we show that CsoCbbQ interacts with CsoCbbO and is a component of the carboxysome shell, the first example of ATPase activity associated with a bacterial microcompartment.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title42-vol1/pdf/CFR-2012-title42-vol1-sec137-375.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title42-vol1/pdf/CFR-2012-title42-vol1-sec137-375.pdf"><span>42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8...</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-10-01</p> <p>... section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title42-vol1/pdf/CFR-2013-title42-vol1-sec137-375.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title42-vol1/pdf/CFR-2013-title42-vol1-sec137-375.pdf"><span>42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8...</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-10-01</p> <p>... section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title42-vol1/pdf/CFR-2014-title42-vol1-sec137-375.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title42-vol1/pdf/CFR-2014-title42-vol1-sec137-375.pdf"><span>42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8...</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-10-01</p> <p>... section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title42-vol1/pdf/CFR-2010-title42-vol1-sec137-375.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title42-vol1/pdf/CFR-2010-title42-vol1-sec137-375.pdf"><span>42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8...</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-10-01</p> <p>... section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title42-vol1/pdf/CFR-2011-title42-vol1-sec137-375.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title42-vol1/pdf/CFR-2011-title42-vol1-sec137-375.pdf"><span>42 CFR 137.375 - Are Tribally-owned facilities constructed under section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8...</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-10-01</p> <p>... section 509 of the Act [25 U.S.C. 458<span class="hlt">aaa</span>-8] eligible for replacement, maintenance, and improvement funds..., DEPARTMENT OF HEALTH AND HUMAN SERVICES TRIBAL SELF-GOVERNANCE Construction Other § 137.375 Are Tribally..., maintenance, and improvement funds on the same basis as if title to such property were vested in the United...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16314341','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16314341"><span>Levels of H-ras codon 61 CAA to <span class="hlt">AAA</span> mutation: response to 4-ABP-treatment and Pms2-deficiency.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Parsons, Barbara L; Delongchamp, Robert R; Beland, Frederick A; Heflich, Robert H</p> <p>2006-01-01</p> <p>DNA mismatch repair (MMR) deficiencies result in increased frequencies of spontaneous mutation and tumor formation. In the present study, we tested the hypothesis that a chemically-induced mutational response would be greater in a mouse with an MMR-deficiency than in the MMR-proficient mouse models commonly used to assay for chemical carcinogenicity. To accomplish this, the induction of H-ras codon 61 CAA--><span class="hlt">AAA</span> mutation was examined in Pms2 knockout mice (Pms2-/-, C57BL/6 background) and sibling wild-type mice (Pms2+/+). Groups of five or six neonatal male mice were treated with 0.3 micromol 4-aminobiphenyl (4-ABP) or the vehicle control, dimethylsulfoxide. Eight months after treatment, liver DNAs were isolated and analysed for levels of H-ras codon 61 CAA--><span class="hlt">AAA</span> mutation using allele-specific competitive blocker-PCR. In Pms2-proficient and Pms2-deficient mice, 4-ABP treatment caused an increase in mutant fraction (MF) from 1.65x10(-5) to 2.91x10(-5) and from 3.40x10(-5) to 4.70x10(-5), respectively. Pooling data from 4-ABP-treated and control mice, the approximately 2-fold increase in MF observed in Pms2-deficient as compared with Pms2-proficient mice was statistically significant (P=0.0207) and consistent with what has been reported previously in terms of induction of G:C-->T:A mutation in a Pms2-deficient background. Pooling data from both genotypes, the increase in H-ras MF in 4-ABP-treated mice, as compared with control mice, did not reach the 95% confidence level of statistical significance (P=0.0606). The 4-ABP treatment caused a 1.76-fold and 1.38-fold increase in average H-ras MF in Pms2-proficient and Pms2-deficient mice, respectively. Furthermore, the levels of induced mutation in Pms2-proficient and Pms2-deficient mice were nearly identical (1.26x10(-5) and 1.30x10(-5), respectively). We conclude that Pms2-deficiency does not result in an amplification of the H-ras codon 61 CAA--><span class="hlt">AAA</span> mutational response induced by 4-ABP.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29222574','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29222574"><span>Improving Hearing Aid Self-Efficacy and Utility Through Revising a Hearing Aid User Guide: A Pilot Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>McMullan, Alexandra; Kelly-Campbell, Rebecca J; Wise, Kim</p> <p>2018-03-08</p> <p>This pilot study aimed to investigate whether revising a hearing aid user guide (<span class="hlt">HAUG</span>) is associated with improved hearing aid self-efficacy and utility performance. In Part 1, an <span class="hlt">HAUG</span> was evaluated using the Suitability Assessment of Material (SAM) and readability formulas (Flesch Reading Ease [Flesch, 1943], Flesch-Kincaid Readability Formula [Kincaid, Fishburne, Rogers, & Chissom, 1957], and Simple Measure of Gobbledygook [McLaughlin, 1969]). The <span class="hlt">HAUG</span> was revised using results from the SAM and best practice guidelines. The revision included generating a video. In Part 2, 30 adults with hearing impairment were randomly assigned to use either the original guide (N = 15) or the revised guide and video (N = 15) to perform a utility task. Participants' self-efficacy was measured using the Basic and Advanced Handling subscales of the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids questionnaire. SAM and readability were compared between the original and revised guides (Doak, Doak, & Root, 1996). SAM and readability were improved following the revision. Participants in the revised guide group performed significantly better on the utility task and on the Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids subscales than participants in the original guide group. These results are encouraging as they indicate that there is scope to influence self-efficacy and utility performance through the use of appropriate <span class="hlt">HAUGs</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21708944','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21708944"><span>DnaA protein DNA-binding domain binds to Hda protein to promote inter-<span class="hlt">AAA</span>+ domain interaction involved in regulatory inactivation of DnaA.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Keyamura, Kenji; Katayama, Tsutomu</p> <p>2011-08-19</p> <p>Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the <span class="hlt">AAA</span>+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda <span class="hlt">AAA</span>+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the <span class="hlt">AAA</span>+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3190739','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3190739"><span>DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-<span class="hlt">AAA</span>+ Domain Interaction Involved in Regulatory Inactivation of DnaA*</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Keyamura, Kenji; Katayama, Tsutomu</p> <p>2011-01-01</p> <p>Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the <span class="hlt">AAA</span>+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda <span class="hlt">AAA</span>+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the <span class="hlt">AAA</span>+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3971404','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3971404"><span>Inter-ring rotations of <span class="hlt">AAA</span> ATPase p97 revealed by electron cryomicroscopy</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yeung, Heidi O.; Förster, Andreas; Bebeacua, Cecilia; Niwa, Hajime; Ewens, Caroline; McKeown, Ciarán; Zhang, Xiaodong; Freemont, Paul S.</p> <p>2014-01-01</p> <p>The type II <span class="hlt">AAA</span>+ protein p97 is involved in numerous cellular activities, including endoplasmic reticulum-associated degradation, transcription activation, membrane fusion and cell-cycle control. These activities are at least in part regulated by the ubiquitin system, in which p97 is thought to target ubiquitylated protein substrates within macromolecular complexes and assist in their extraction or disassembly. Although ATPase activity is essential for p97 function, little is known about how ATP binding or hydrolysis is coupled with p97 conformational changes and substrate remodelling. Here, we have used single-particle electron cryomicroscopy (cryo-EM) to study the effect of nucleotides on p97 conformation. We have identified conformational heterogeneity within the cryo-EM datasets from which we have resolved two major p97 conformations. A comparison of conformations reveals inter-ring rotations upon nucleotide binding and hydrolysis that may be linked to the remodelling of target protein complexes. PMID:24598262</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20132442','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20132442"><span>Novel essential residues of Hda for interaction with DnaA in the regulatory inactivation of DnaA: unique roles for Hda <span class="hlt">AAA</span> Box VI and VII motifs.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Nakamura, Kenta; Katayama, Tsutomu</p> <p>2010-04-01</p> <p>Escherichia coli ATP-DnaA initiates chromosomal replication. For preventing extra-initiations, a complex of ADP-Hda and the DNA-loaded replicase clamp promotes DnaA-ATP hydrolysis, yielding inactive ADP-DnaA. However, the Hda-DnaA interaction mode remains unclear except that the Hda Box VII Arg finger (Arg-153) and DnaA sensor II Arg-334 within each <span class="hlt">AAA</span>(+) domain are crucial for the DnaA-ATP hydrolysis. Here, we demonstrate that direct and functional interaction of ADP-Hda with DnaA requires the Hda residues Ser-152, Phe-118 and Asn-122 as well as Hda Arg-153 and DnaA Arg-334. Structural analyses suggest intermolecular interactions between Hda Ser-152 and DnaA Arg-334 and between Hda Phe-118 and the DnaA Walker B motif region, in addition to an intramolecular interaction between Hda Asn-122 and Arg-153. These interactions likely sustain a specific association of ADP-Hda and DnaA, promoting DnaA-ATP hydrolysis. Consistently, ATP-DnaA and ADP-DnaA interact with the ADP-Hda-DNA-clamp complex with similar affinities. Hda Phe-118 and Asn-122 are contained in the Box VI region, and their hydrophobic and electrostatic features are basically conserved in the corresponding residues of other <span class="hlt">AAA</span>(+) proteins, suggesting a conserved role for Box VI. These findings indicate novel interaction mechanisms for Hda-DnaA as well as a potentially fundamental mechanism in <span class="hlt">AAA</span>(+) protein interactions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17187196','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17187196"><span>Postural stabilizing effect of alfacalcidol and active absorbable algal calcium (<span class="hlt">AAA</span> Ca) compared with calcium carbonate assessed by computerized posturography.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fujita, Takuo; Nakamura, Shoji; Ohue, Mutsumi; Fujii, Yoshio; Miyauchi, Akimitsu; Takagi, Yasuyuki; Tsugeno, Hirofumi</p> <p>2007-01-01</p> <p>Sway and postural instability have drawn attention as a risk factor for osteoporotic fracture, in addition to low bone mineral density (BMD) and poor bone quality. In view of the fracture-reducing effect of alfacalcidol and active absorbable algal calcium (<span class="hlt">AAA</span> Ca) not readily explained by rather mild increases of BMD, attempts were made to evaluate postural stabilizing effect of alfacalcidol, <span class="hlt">AAA</span> Ca, and calcium carbonate (CaCO(3)) by computerized posturography. Track of the gravity center was analyzed to calculate parameters related to tract length, track range, and track density to express the degree of sway before and after supplementation in 126 subjects ranging in age between 20 and 81 years randomly divided into four groups. Supplementation with <span class="hlt">AAA</span> Ca containing 900 mg elemental Ca (group A), no calcium (group B), CaCO(3) also containing 900 mg elemental Ca (group C), or alfacalcidol (group D) continued daily for 12 months. For each parameter, the ratio closed eye value/open eye value (Romberg ratio) was calculated to detect aggravation of sway by eye closure. Age, parameters of Ca and P, and proportions of subjects with fracture and those with low BMD showed no marked deviation among the groups. With eyes open, significant decreases of a track range parameter (REC) from group B was noted in groups A (P = 0.0397) and D (P = 0.0296), but not in group C according to multiple comparison by Scheffe, indicating superior postural stabilizing effect of A and D over C. In the first 2 months, a significant fall was already evident in REC from group B in group D (P = 0.0120) with eyes open. Paired comparison of sway parameters before and after supplementation revealed a significant increase of track density parameter (LNGA), indicating sway control efficiency and a significant decrease of REC in groups A and D compared to group B with eyes open. With eyes closed, only group A showed a significant improvement from group B (P = 0.0456; Fig. 1), with a significant</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4566529','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4566529"><span>“What Is Our Story?” <span class="hlt">Philip</span> Morris’s Changing Corporate Narrative</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Malone, Ruth E.</p> <p>2015-01-01</p> <p>Objectives. We sought to learn how employees reacted to changes in the corporate narrative of <span class="hlt">Philip</span> Morris Companies (PMC) in the late 1990s and early 2000s. Methods. We analyzed archival internal tobacco industry documents about PMC’s creation of a new corporate story. Results. In response to litigation and public opprobrium, PMC replaced its market success–oriented corporate narrative with a new one centered on responsibility. Although management sought to downplay inconsistencies between the old and new narratives, some employees reportedly had difficulty reconciling them, concerned that the responsibility focus might affect company profitability. However, others embraced the new narrative, suggesting radical ideas to prevent youth smoking. These ideas were not adopted. Conclusions. PMC’s new narrative was unconvincing to many of its employees, who perceived it either as a threat to the company’s continued profits or as incongruous with what they had previously been told. As it had done with the public, PMC misled its employees in explaining a narrative repositioning that would help the company continue business as usual. Moving toward a tobacco endgame will require ongoing discursive and symbolic efforts to disrupt this narrative. PMID:26270280</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4174999','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4174999"><span>2013 <span class="hlt">Philip</span> S. Portoghese Medicinal Chemistry Lectureship: Drug Discovery Targeting Allosteric Sites†</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2015-01-01</p> <p>The identification of sites on receptors topographically distinct from the orthosteric sites, so-called allosteric sites, has heralded novel approaches and modes of pharmacology for target modulation. Over the past 20 years, our understanding of allosteric modulation has grown significantly, and numerous advantages, as well as caveats (e.g., flat structure–activity relationships, species differences, “molecular switches”), have been identified. For multiple receptors and proteins, numerous examples have been described where unprecedented levels of selectivity are achieved along with improved physiochemical properties. While not a panacea, these novel approaches represent exciting opportunities for tool compound development to probe the pharmacology and therapeutic potential of discrete molecular targets, as well as new medicines. In this Perspective, in commemoration of the 2013 <span class="hlt">Philip</span> S. Portoghese Medicinal Chemistry Lectureship (LindsleyC. W.Adventures in allosteric drug discovery. Presented at the 246th National Meeting of the American Chemical Society, Indianapolis, IN, September 10, 2013; The 2013 Portoghese Lectureship), several vignettes of drug discovery campaigns targeting novel allosteric mechanisms will be recounted, along with lessons learned and guidelines that have emerged for successful lead optimization. PMID:25180768</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1456939','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1456939"><span>Conformational changes in the <span class="hlt">AAA</span> ATPase p97–p47 adaptor complex</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Beuron, Fabienne; Dreveny, Ingrid; Yuan, Xuemei; Pye, Valerie E; Mckeown, Ciaran; Briggs, Louise C; Cliff, Matthew J; Kaneko, Yayoi; Wallis, Russell; Isaacson, Rivka L; Ladbury, John E; Matthews, Steve J; Kondo, Hisao; Zhang, Xiaodong; Freemont, Paul S</p> <p>2006-01-01</p> <p>The <span class="hlt">AAA</span>+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at ∼20 Å resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes. PMID:16601695</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5019419','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5019419"><span>The Multivesicular Bodies (MVBs)-Localized <span class="hlt">AAA</span> ATPase LRD6-6 Inhibits Immunity and Cell Death Likely through Regulating MVBs-Mediated Vesicular Trafficking in Rice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Liang, Sihui; Liang, Ruihong; Zhou, Xiaogang; Chen, Zhixiong; Zhao, Wen; Wang, Jing; Li, Weitao; He, Min; Yuan, Can; Miyamoto, Koji; Ma, Bingtian; Wang, Jichun; Qin, Peng; Chen, Weilan; Wang, Yuping; Wang, Wenming; Wu, Xianjun; Yamane, Hisakazu; Zhu, Lihuang; Li, Shigui; Chen, Xuewei</p> <p>2016-01-01</p> <p>Previous studies have shown that multivesicular bodies (MVBs)/endosomes-mediated vesicular trafficking may play key roles in plant immunity and cell death. However, the molecular regulation is poorly understood in rice. Here we report the identification and characterization of a MVBs-localized <span class="hlt">AAA</span> ATPase LRD6-6 in rice. Disruption of LRD6-6 leads to enhanced immunity and cell death in rice. The ATPase activity and homo-dimerization of LRD6-6 is essential for its regulation on plant immunity and cell death. An ATPase inactive mutation (LRD6-6E315Q) leads to dominant-negative inhibition in plants. The LRD6-6 protein co-localizes with the MVBs marker protein RabF1/ARA6 and interacts with ESCRT-III components OsSNF7 and OsVPS2. Further analysis reveals that LRD6-6 is required for MVBs-mediated vesicular trafficking and inhibits the biosynthesis of antimicrobial compounds. Collectively, our study shows that the <span class="hlt">AAA</span> ATPase LRD6-6 inhibits plant immunity and cell death most likely through modulating MVBs-mediated vesicular trafficking in rice. PMID:27618555</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_13");'>13</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li class="active"><span>15</span></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_15 --> <div id="page_16" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="301"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/6042047','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/6042047"><span>Uranium hydrogeochemical and stream sediment reconnaissance of the <span class="hlt">Philip</span> Smith Mountains NTMS quadrangle, Alaska</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Not Available</p> <p>1981-09-01</p> <p>Results of a hydrogeochemical and stream sediment reconnaissance of the <span class="hlt">Philip</span> Smith Mountains NTMS quadrangle, Alaska are presented. In addition to this abbreviated data release, more complete data are available to the public in machine-readable form. In this data release are location data, field analyses, and laboratory analyses of several different sample media. For the sake of brevity, many field site observations have not been included in this volume. These data are, however, available on the magnetic tape. Appendices A and B describe the sample media and summarize the analytical results for each medium. The data were subsetted by onemore » of the Los Alamos National Laboratory (LANL) sorting programs into groups of stream sediment and lake sediment samples. For each group which contains a sufficient number of observations, statistical tables, tables of raw data, and 1:1000000 scale maps of pertinent elements have been included in this report.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25331730','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25331730"><span>A Chilling Example? Uruguay, <span class="hlt">Philip</span> Morris International, and WHO's Framework Convention on Tobacco Control.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Russell, Andrew; Wainwright, Megan; Mamudu, Hadii</p> <p>2015-06-01</p> <p>The World Health Organization's Framework Convention on Tobacco Control (FCTC) is the first international public health treaty to address the global spread of tobacco products. Ethnographic research at the fourth meeting of the FCTC's Conference of the Parties in Uruguay highlights the role of the FCTC in recalibrating the relationship between international trade and investment agreements and those of global public health. Specifically, we chart the origins and development of the Punta del Este Declaration, tabled by Uruguay at the conference, to counter a legal request by <span class="hlt">Philip</span> Morris International, the world's largest tobacco transnational, for arbitration by the International Centre for the Settlement of Investment Disputes over Uruguay's alleged violations of several international trade and investment treaties. We argue that medical anthropologists should give greater consideration to global health governance and diplomacy as a potential counterweight to the 'politics of resignation' associated with corporate capitalism. © 2014 by the American Anthropological Association.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016JPhCS.694a2022M','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016JPhCS.694a2022M"><span>Comparison of build-up region doses in oblique tangential 6 MV photon beams calculated by <span class="hlt">AAA</span> and CCC algorithms in breast Rando phantom</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Masunun, P.; Tangboonduangjit, P.; Dumrongkijudom, N.</p> <p>2016-03-01</p> <p>The purpose of this study is to compare the build-up region doses on breast Rando phantom surface with the bolus covered, the doses in breast Rando phantom and also the doses in a lung that is the heterogeneous region by two algorithms. The <span class="hlt">AAA</span> in Eclipse TPS and the collapsed cone convolution algorithm in Pinnacle treatment planning system were used to plan in tangential field technique with 6 MV photon beam at 200 cGy total doses in Breast Rando phantom with bolus covered (5 mm and 10 mm). TLDs were calibrated with Cobalt-60 and used to measure the doses in irradiation process. The results in treatment planning show that the doses in build-up region and the doses in breast phantom were closely matched in both algorithms which are less than 2% differences. However, overestimate of doses in a lung (L2) were found in <span class="hlt">AAA</span> with 13.78% and 6.06% differences at 5 mm and 10 mm bolus thickness, respectively when compared with CCC algorithm. The TLD measurements show the underestimate in buildup region and in breast phantom but the doses in a lung (L2) were overestimated when compared with the doses in the two plannings at both thicknesses of the bolus.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006PMB....51..943L','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006PMB....51..943L"><span>Validation of a Monte Carlo simulation of the <span class="hlt">Philips</span> Allegro/GEMINI PET systems using GATE</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Lamare, F.; Turzo, A.; Bizais, Y.; Cheze LeRest, C.; Visvikis, D.</p> <p>2006-02-01</p> <p>A newly developed simulation toolkit, GATE (Geant4 Application for Tomographic Emission), was used to develop a Monte Carlo simulation of a fully three-dimensional (3D) clinical PET scanner. The <span class="hlt">Philips</span> Allegro/GEMINI PET systems were simulated in order to (a) allow a detailed study of the parameters affecting the system's performance under various imaging conditions, (b) study the optimization and quantitative accuracy of emission acquisition protocols for dynamic and static imaging, and (c) further validate the potential of GATE for the simulation of clinical PET systems. A model of the detection system and its geometry was developed. The accuracy of the developed detection model was tested through the comparison of simulated and measured results obtained with the Allegro/GEMINI systems for a number of NEMA NU2-2001 performance protocols including spatial resolution, sensitivity and scatter fraction. In addition, an approximate model of the system's dead time at the level of detected single events and coincidences was developed in an attempt to simulate the count rate related performance characteristics of the scanner. The developed dead-time model was assessed under different imaging conditions using the count rate loss and noise equivalent count rates performance protocols of standard and modified NEMA NU2-2001 (whole body imaging conditions) and NEMA NU2-1994 (brain imaging conditions) comparing simulated with experimental measurements obtained with the Allegro/GEMINI PET systems. Finally, a reconstructed image quality protocol was used to assess the overall performance of the developed model. An agreement of <3% was obtained in scatter fraction, with a difference between 4% and 10% in the true and random coincidence count rates respectively, throughout a range of activity concentrations and under various imaging conditions, resulting in <8% differences between simulated and measured noise equivalent count rates performance. Finally, the image quality</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29081535','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29081535"><span>"Why shall wee have peace to bee made slaves": Indian Surrenderers During and After King <span class="hlt">Philip</span>'s War.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fisher, Linford D</p> <p>2017-01-01</p> <p>This paper is an investigation of the treatment of surrenderers in King <span class="hlt">Philip</span>'s War (1675-1676) in New England, particularly with regard to enslavement. Fear of slavery was a tangible, deep concern for most New England natives involved in the war. Threats of enslavement influenced the involvement of native individuals and groups, driving some into deeper "rebellion" and others to surrender. Each colony had differing policies for surrendering natives, but generally the thousands of surrenderers received far worse treatment than they expected, facing execution, overseas enslavement, local limited-term enslavement, and forced relocation. Perhaps the most fascinating element of this saga is the way that English-allied native leaders worked hard to influence the treatment of surrenderers, helping them to escape to New York, harboring runaways, and in other ways trying to keep natives out of English households.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22642342-su-plan2pdf-software-tool-automatic-plan-report-philips-pinnacle-tps','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22642342-su-plan2pdf-software-tool-automatic-plan-report-philips-pinnacle-tps"><span>SU-F-T-94: Plan2pdf - a Software Tool for Automatic Plan Report for <span class="hlt">Philips</span> Pinnacle TPS</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Wu, C</p> <p></p> <p>Purpose: To implement an automatic electronic PDF plan reporting tool for <span class="hlt">Philips</span> Pinnacle treatment planning system (TPS) Methods: An electronic treatment plan reporting software is developed by us to enable fully automatic PDF report from Pinnacle TPS to external EMR programs such as MOSAIQ. The tool is named “plan2pdf”. plan2pdf is implemented using Pinnacle scripts, Java and UNIX shell scripts, without any external program needed. plan2pdf supports full auto-mode and manual mode reporting. In full auto-mode, with a single mouse click, plan2pdf will generate a detailed Pinnacle plan report in PDF format, which includes customizable cover page, Pinnacle plan summary,more » orthogonal views through each plan POI and maximum dose point, DRR for each beam, serial transverse views captured throughout the dose grid at a user specified interval, DVH and scorecard windows. The final PDF report is also automatically bookmarked for each section above for convenient plan review. The final PDF report can either be saved on a user specified folder on Pinnacle, or it can be automatically exported to an EMR import folder via a user configured FTP service. In manual capture mode, plan2pdf allows users to capture any Pinnacle plan by full screen, individual window or rectangular ROI drawn on screen. Furthermore, to avoid possible patients’ plan mix-up during auto-mode reporting, a user conflict check feature is included in plan2pdf: it prompts user to wait if another patient is being exported by plan2pdf by another user. Results: plan2pdf is tested extensively and successfully at our institution consists of 5 centers, 15 dosimetrists and 10 physicists, running Pinnacle version 9.10 on Enterprise servers. Conclusion: plan2pdf provides a highly efficient, user friendly and clinical proven platform for all <span class="hlt">Philips</span> Pinnacle users, to generate a detailed plan report in PDF format for external EMR systems.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2006AGUFM.U44C..06P','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2006AGUFM.U44C..06P"><span><span class="hlt">AAAS</span> Mass Media Science and Engineering Fellowship Program: Building Communication Skills in Young Scientists</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Pasco, S.</p> <p>2006-12-01</p> <p>The <span class="hlt">AAAS</span> Mass Media Science &Engineering Fellowship program has succeeded in training scientists to become more effective communicators for more than 30 years. The program places advanced science, engineering and mathematics students at media sites to work as science reporters for ten weeks each summer. <span class="hlt">AAAS</span> places between 15 to 20 students a year at newspapers, magazines and radio stations. Our goal is to create better science communicators who understand their role in fostering the public's understanding of science. Fellows leave the program with a greater awareness of how to communicate complex issues by making the connection as to why people should be interested in certain developments, and more specifically, how they will impact their communities. 2004 AGU Fellow Rei Ueyama put her lessons learned to good use during her Fellowship at the Sacramento Bee. "In a regional paper like The Bee, a (story) also had to have a local touch. I needed to show why people in Sacramento (or California) should bother to read the story. One example is the story I wrote about seeding the ocean with iron particles to fight global warming. Since ocean fertilization is a global issue, I had to clearly specify the reason why The Bee and not The New York Times was running the story. The local angle I chose was to point out that the core group of scientists involved in this study was from Monterey Bay, Calif." Many alumni tell us the program has been an integral force in shaping the course of their career. Similarly, sites often report that having a scientist on staff is an invaluable resource that allows them to cover additional science stories as well as report some technical stories in more depth. The American Geophysical Union has sponsored a Mass Media Fellow since 1997. Sponsorship allows affiliate program partners to establish connections with young professionals in their field. They are then also able to take advantage of the communication skills resident in their alumni base</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2794243','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2794243"><span><span class="hlt">Philip</span> Morris’s Health Information Web Site Appears Responsible but Undermines Public Health</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Smith, Elizabeth A.; Malone, Ruth E.</p> <p>2009-01-01</p> <p>Many people may search for information about tobacco use, the largest cause of preventable mortality in the United States, on the Internet. In 1999, <span class="hlt">Philip</span> Morris U.S.A. (PM), the country’s biggest cigarette manufacturer, posted a Web site and launched a campaign to encourage people to obtain information about tobacco and health issues there. The company asserted that its goal was to deliver the messages of the public health community about tobacco. However, internal tobacco company documents reveal that the site was a public relations effort intended to help the company avoid punishment and regulation. Examination of the language on the Web site reveals many contradictions and omissions that may undermine public health messages. Among these are vague and confusing information about addiction, tar, and nicotine, a lack of motivators to quit smoking, and silence about tobacco-related mortality. By appearing to join with public health organizations in disseminating “responsible” messages about tobacco, PM may improve its image, thus facilitating its ability to continue to sell its lethal products. Public health nurses should be prepared to examine health information on the Internet for subtle biases, to counter PM’s specific language about smoking to patients, and to challenge PM’s larger corporate goals. PMID:18950420</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23838199','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23838199"><span>Highly sensitive and selective detection of dopamine based on hollow gold nanoparticles-graphene nanocomposite modified electrode.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhu, Wencai; Chen, Ting; Ma, Xuemei; Ma, Houyi; Chen, Shenhao</p> <p>2013-11-01</p> <p>Highly dispersed hollow gold-graphene (<span class="hlt">HAu-G</span>) nanocomposites were synthesized by a two-step method. The immobilization of hollow gold nanoparticles (HAu NPs) onto the surface of graphene sheets was achieved by mixing an aqueous solution of HAu NPs with a poly(N-vinylpyrrolidone)-functionalized graphene dispersion at room temperature. A glassy carbon electrode (GCE) was modified with the nanocomposites, and the as-prepared modified electrode displayed high electrocatalytic activity and extraordinary electronic transport properties. Amperometric detection of dopamine (DA) performed with the <span class="hlt">HAu-G</span> modified electrode exhibits a good linearity between 0.08 and 600 μM with a low detection limit of 0.05 μM (S/N=3) and also possesses good reproducibility and operational stability. The interference of ascorbic acid (AA) and uric acid (UA) can be excluded when using differential pulse voltammetric technique. In addition, this type of modified electrode can also be applied to the determination of DA content in dopamine hydrochloride injection. It is obvious that the <span class="hlt">HAu-G</span> modified electrode provides a new way to detect dopamine sensitively and selectively. Copyright © 2013 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26059123','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26059123"><span>Characterisation of pectins extracted from banana peels (Musa <span class="hlt">AAA</span>) under different conditions using an experimental design.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Happi Emaga, Thomas; Ronkart, Sébastien N; Robert, Christelle; Wathelet, Bernard; Paquot, Michel</p> <p>2008-05-15</p> <p>An experimental design was used to study the influence of pH (1.5 and 2.0), temperature (80 and 90°C) and time (1 and 4h) on extraction of pectin from banana peels (Musa <span class="hlt">AAA</span>). Yield of extracted pectins, their composition (neutral sugars, galacturonic acid, and degree of esterification) and some macromolecular characteristics (average molecular weight, intrinsic viscosity) were determined. It was found that extraction pH was the most important parameter influencing yield and pectin chemical composition. Lower pH values negatively affected the galacturonic acid content of pectin, but increased the pectin yield. The values of degree of methylation decreased significantly with increasing temperature and time of extraction. The average molecular weight ranged widely from 87 to 248kDa and was mainly influenced by pH and extraction time. Copyright © 2007 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3337166','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3337166"><span>Integrated regulation of PIKK-mediated stress responses by <span class="hlt">AAA</span>+ proteins RUVBL1 and RUVBL2</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Izumi, Natsuko; Yamashita, Akio; Ohno, Shigeo</p> <p>2012-01-01</p> <p>Proteins of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family are activated by various cellular stresses, including DNA damage, premature termination codon and nutritional status, and induce appropriate cellular responses. The importance of PIKK functions in the maintenance of genome integrity, accurate gene expression and the proper control of cell growth/proliferation is established. Recently, ATPase associated diverse cellular activities (<span class="hlt">AAA</span>+) proteins RUVBL1 and RUVBL2 (RUVBL1/2) have been shown to be common regulators of PIKKs. The RUVBL1/2 complex regulates PIKK-mediated stress responses through physical interactions with PIKKs and by controlling PIKK mRNA levels. In this review, the functions of PIKKs in stress responses are outlined and the physiological significance of the integrated regulation of PIKKs by the RUVBL1/2 complex is presented. We also discuss a putative “PIKK regulatory chaperone complex” including other PIKK regulators, Hsp90 and the Tel2 complex. PMID:22540023</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24222501','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24222501"><span>In vitro propagation and assessment of the genetic fidelity of Musa acuminata (<span class="hlt">AAA</span>) cv. Vaibalhla derived from immature male flowers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hrahsel, Lalremsiami; Basu, Adreeja; Sahoo, Lingaraj; Thangjam, Robert</p> <p>2014-02-01</p> <p>An efficient in vitro propagation method has been developed for the first time for Musa acuminata (<span class="hlt">AAA</span>) cv. Vaibalhla, an economically important banana cultivar of Mizoram, India. Immature male flowers were used as explants. Murashige and Skoog's (MS) medium supplemented with plant growth regulators (PGRs) were used for the regeneration process. Out of different PGR combinations, MS medium supplemented with 2 mg L(-1) 6-benzylaminopurine (BAP) + 0.5 mg L(-1) α-naphthalene acetic acid (NAA) was optimal for production of white bud-like structures (WBLS). On this medium, explants produced the highest number of buds per explant (4.30). The highest percentage (77.77) and number (3.51) of shoot formation from each explants was observed in MS medium supplemented with 2 mg L(-1) kinetin + 0.5 mg L(-1) NAA. While MS medium supplemented with a combination of 2 mg L(-1) BAP + 0.5 mg L(-1) NAA showed the maximum shoot length (14.44 cm). Rooting efficiency of the shoots was highest in the MS basal medium without any PGRs. The plantlets were hardened successfully in the greenhouse with 96% survival rate. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were employed to assess the genetic stability of in vitro regenerated plantlets of M. acuminata (<span class="hlt">AAA</span>) cv. Vaibalhla. Eight RAPD and 8 ISSR primers were successfully used for the analysis from the 40 RAPD and 30 ISSR primers screened initially. The amplified products were monomorphic across all the regenerated plants and were similar to the mother plant. The present standardised protocol will find application in mass production, conservation and genetic transformation studies of this commercially important banana.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2596576','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2596576"><span>Fiscal versus social responsibility: how <span class="hlt">Philip</span> Morris shaped the public funds divestment debate</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wander, N; Malone, R E</p> <p>2006-01-01</p> <p>Calls for institutional investors to divest (sell off) tobacco stocks threaten the industry's share values, publicise its bad behaviour, and label it as a politically unacceptable ally. US tobacco control advocates began urging government investment and pension funds to divest as a matter of responsible social policy in 1990. Following the initiation of Medicaid recovery lawsuits in 1994, advocates highlighted the contradictions between state justice departments suing the industry, and state health departments expanding tobacco control programmes, while state treasurers invested in tobacco companies. <span class="hlt">Philip</span> Morris (PM), the most exposed US company, led the divestment opposition, consistently framing the issue as one of responsible fiscal policy. It insisted that funds had to be managed for the exclusive interest of beneficiaries, not the public at large, and for high share returns above all. This paper uses tobacco industry documents to show how PM sought to frame both the rhetorical contents and the legal contexts of the divestment debate. While tobacco stock divestment was eventually limited to only seven (but highly visible) states, US advocates focused public attention on the issue in at least 18 others plus various local jurisdictions. This added to ongoing, effective campaigns to denormalise and delegitimise the tobacco industry, dividing it from key allies. Divestment as a delegitimisation tool could have both advantages and disadvantages as a tobacco control strategy in other countries. PMID:16728755</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16728755','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16728755"><span>Fiscal versus social responsibility: how <span class="hlt">Philip</span> Morris shaped the public funds divestment debate.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wander, N; Malone, R E</p> <p>2006-06-01</p> <p>Calls for institutional investors to divest (sell off) tobacco stocks threaten the industry's share values, publicise its bad behaviour, and label it as a politically unacceptable ally. US tobacco control advocates began urging government investment and pension funds to divest as a matter of responsible social policy in 1990. Following the initiation of Medicaid recovery lawsuits in 1994, advocates highlighted the contradictions between state justice departments suing the industry, and state health departments expanding tobacco control programmes, while state treasurers invested in tobacco companies. <span class="hlt">Philip</span> Morris (PM), the most exposed US company, led the divestment opposition, consistently framing the issue as one of responsible fiscal policy. It insisted that funds had to be managed for the exclusive interest of beneficiaries, not the public at large, and for high share returns above all. This paper uses tobacco industry documents to show how PM sought to frame both the rhetorical contents and the legal contexts of the divestment debate. While tobacco stock divestment was eventually limited to only seven (but highly visible) states, US advocates focused public attention on the issue in at least 18 others plus various local jurisdictions. This added to ongoing, effective campaigns to denormalise and delegitimise the tobacco industry, dividing it from key allies. Divestment as a delegitimisation tool could have both advantages and disadvantages as a tobacco control strategy in other countries.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25884950','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25884950"><span>Comparison of doses and NTCP to risk organs with enhanced inspiration gating and free breathing for left-sided breast cancer radiotherapy using the <span class="hlt">AAA</span> algorithm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Edvardsson, Anneli; Nilsson, Martin P; Amptoulach, Sousana; Ceberg, Sofie</p> <p>2015-04-10</p> <p>The purpose of this study was to investigate the potential dose reduction to the heart, left anterior descending (LAD) coronary artery and the ipsilateral lung for patients treated with tangential and locoregional radiotherapy for left-sided breast cancer with enhanced inspiration gating (EIG) compared to free breathing (FB) using the <span class="hlt">AAA</span> algorithm. The radiobiological implication of such dose sparing was also investigated. Thirty-two patients, who received tangential or locoregional adjuvant radiotherapy with EIG for left-sided breast cancer, were retrospectively enrolled in this study. Each patient was CT-scanned during FB and EIG. Similar treatment plans, with comparable target coverage, were created in the two CT-sets using the <span class="hlt">AAA</span> algorithm. Further, the probability of radiation induced cardiac mortality and pneumonitis were calculated using NTCP models. For tangential treatment, the median V25Gy for the heart and LAD was decreased for EIG from 2.2% to 0.2% and 40.2% to 0.1% (p < 0.001), respectively, whereas there was no significant difference in V20Gy for the ipsilateral lung (p = 0.109). For locoregional treatment, the median V25Gy for the heart and LAD was decreased for EIG from 3.3% to 0.2% and 51.4% to 5.1% (p < 0.001), respectively, and the median ipsilateral lung V20Gy decreased from 27.0% for FB to 21.5% (p = 0.020) for EIG. The median excess cardiac mortality probability decreased from 0.49% for FB to 0.02% for EIG (p < 0.001) for tangential treatment and from 0.75% to 0.02% (p < 0.001) for locoregional treatment. There was no significant difference in risk of radiation pneumonitis for tangential treatment (p = 0.179) whereas it decreased for locoregional treatment from 6.82% for FB to 3.17% for EIG (p = 0.004). In this study the <span class="hlt">AAA</span> algorithm was used for dose calculation to the heart, LAD and left lung when comparing the EIG and FB techniques for tangential and locoregional radiotherapy of breast cancer patients. The results support the dose and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22420639','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22420639"><span>Corporate image and public health: an analysis of the <span class="hlt">Philip</span> Morris, Kraft, and Nestlé websites.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smith, Elizabeth</p> <p>2012-01-01</p> <p>Companies need to maintain a good reputation to do business; however, companies in the infant formula, tobacco, and processed food industries have been identified as promoting disease. Such companies use their websites as a means of promulgating a positive public image, thereby potentially reducing the effectiveness of public health campaigns against the problems they perpetuate. The author examined documents from the websites of <span class="hlt">Philip</span> Morris, Kraft, and Nestlé for issue framing and analyzed them using Benoit's typology of corporate image repair strategies. All three companies defined the problems they were addressing strategically, minimizing their own responsibility and the consequences of their actions. They proposed solutions that were actions to be taken by others. They also associated themselves with public health organizations. Health advocates should recognize industry attempts to use relationships with health organizations as strategic image repair and reject industry efforts to position themselves as stakeholders in public health problems. Denormalizing industries that are disease vectors, not just their products, may be critical in realizing positive change.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3362195','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3362195"><span>Corporate Image and Public Health: An Analysis of the <span class="hlt">Philip</span> Morris, Kraft, and Nestlé Websites</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>SMITH, ELIZABETH</p> <p>2012-01-01</p> <p>Companies need to maintain a good reputation to do business; however, companies in the infant formula, tobacco, and processed food industries have been identified as promoting disease. Such companies use their websites as a means of promulgating a positive public image, thereby potentially reducing the effectiveness of public health campaigns against the problems they perpetuate. The author examined documents from the websites of <span class="hlt">Philip</span> Morris, Kraft, and Nestlé for issue framing and analyzed them using Benoit’s typology of corporate image repair strategies. All three companies defined the problems they were addressing strategically, minimizing their own responsibility and the consequences of their actions. They proposed solutions that were actions to be taken by others. They also associated themselves with public health organizations. Health advocates should recognize industry attempts to use relationships with health organizations as strategic image repair and reject industry efforts to position themselves as stakeholders in public health problems. Denormalizing industries that are disease vectors, not just their products, may be critical in realizing positive change. PMID:22420639</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23416349','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23416349"><span>Agreement between activity-monitoring devices during home rehabilitation: a substudy of the <span class="hlt">AAA</span> STOP trial.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Myers, Jonathan; Dupain, Mandi; Vu, Andrew; Jaffe, Alyssa; Smith, Kimberly; Fonda, Holly; Dalman, Ronald</p> <p>2014-01-01</p> <p>As part of a home-based rehabilitation program, 24 older adult patients (71 ± 3 years) with abdominal aortic aneurysm (<span class="hlt">AAA</span>) disease underwent 3 days (12 awake hr/day) of activity monitoring using an accelerometer (ACC), a pedometer, and a heart rate (HR) monitor, and recorded hourly activity logs. Subjects then underwent an interview to complete a 3-day activity recall questionnaire (3-DR). Mean energy expenditure (EE) in kcals/ day for HR, ACC, and 3-DR were 1,687 ± 458, 2,068 ± 529, and 1,974 ± 491, respectively. Differences in EE were not significant between 3-DR and ACC, but HR differed from both ACC (p < .001) and 3-DR (p < .01). ACC and 3-DR had the highest agreement, with a coefficient of variation of 7.9% and r = .86. Thus, ACC provided a reasonably accurate reflection of EE based the criterion measure, an activity recall questionnaire. ACC can be effectively used to monitor EE to achieve an appropriate training stimulus during home-based cardiac rehabilitation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1390878-aaa+-atpase-trip13-remodels-horma-domains-through-terminal-engagement-unfolding','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1390878-aaa+-atpase-trip13-remodels-horma-domains-through-terminal-engagement-unfolding"><span>The <span class="hlt">AAA</span>+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan</p> <p></p> <p>Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The <span class="hlt">AAA</span>+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “poremore » loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2012AcSpA..89..294V','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2012AcSpA..89..294V"><span>Interaction studies of resistomycin from Streptomyces aurantiacus <span class="hlt">AAA</span>5 with calf thymus DNA and bovine serum albumin</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Vijayabharathi, R.; Sathyadevi, P.; Krishnamoorthy, P.; Senthilraja, D.; Brunthadevi, P.; Sathyabama, S.; Priyadarisini, V. Brindha</p> <p>2012-04-01</p> <p>Resistomycin, a secondary metabolite produced by Streptomyces aurantiacus <span class="hlt">AAA</span>5. The binding interaction of resistomycin with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) was investigated by spectrophotometry, spectrofluorimetry, circular dichroism (CD) and synchronous fluorescence techniques under physiological conditions in vitro. Absorption spectral studies along with the fluorescence competition with ethidium bromide measurements and circular dichroism clearly suggest that the resistomycin bind with CT DNA relatively strong via groove binding. BSA interaction results revealed that the drug was found to quench the fluorescence intensity of the protein through a static quenching mechanism. The number of binding sites 'n' and apparent binding constant 'K' calculated according to the Scatchard equation exhibit a good binding property to bovine serum albumin protein. In addition, the results observed from synchronous fluorescence measurements clearly demonstrate the occurrence of conformational changes of BSA upon addition of the test compound.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_14");'>14</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li class="active"><span>16</span></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_16 --> <div id="page_17" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="321"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA236155','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA236155"><span>Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (<span class="hlt">AAA</span>-NAVY-AVG NAVY)</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1990-01-01</p> <p>Q-COC’) -4 M’i (a -4 c"a(aeo - ( D 0 AC 1 -ao f-.r qva 0(%Ioa.4 ()t a. c~cv(vc4 z *Za in -0f (4Jl w -44- m - .41 C,4 Ui 0 C4 IC4 P- -a l~~II I II cLE E...AO-A236 155iiiilulll l I l 1990 ANNUAL Prime Contract Awards Over $25,000 by Major System, Contractor and State Part 1 (<span class="hlt">AAA</span>-NAVY-AVG NAVY) WHS...Special . 1 -9 __28284 pages I1 ~ . - e21 M(%I% cm -40W -4 I4 m V .. 4 mt WC)a r a- 4-r w~l w zl- qt qt V .4- 01-4 41-4 . 40 o r Lu V) c I OL 9 C U c</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3192828','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3192828"><span>Whole-Exome Sequencing Identifies Homozygous AFG3L2 Mutations in a Spastic Ataxia-Neuropathy Syndrome Linked to Mitochondrial m-<span class="hlt">AAA</span> Proteases</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Martinelli, Paola; Cherukuri, Praveen F.; Teer, Jamie K.; Hansen, Nancy F.; Cruz, Pedro; Mullikin for the NISC Comparative Sequencing Program, James C.; Blakesley, Robert W.; Golas, Gretchen; Kwan, Justin; Sandler, Anthony; Fuentes Fajardo, Karin; Markello, Thomas; Tifft, Cynthia; Blackstone, Craig; Rugarli, Elena I.; Langer, Thomas; Gahl, William A.; Toro, Camilo</p> <p>2011-01-01</p> <p>We report an early onset spastic ataxia-neuropathy syndrome in two brothers of a consanguineous family characterized clinically by lower extremity spasticity, peripheral neuropathy, ptosis, oculomotor apraxia, dystonia, cerebellar atrophy, and progressive myoclonic epilepsy. Whole-exome sequencing identified a homozygous missense mutation (c.1847G>A; p.Y616C) in AFG3L2, encoding a subunit of an m-<span class="hlt">AAA</span> protease. m-<span class="hlt">AAA</span> proteases reside in the mitochondrial inner membrane and are responsible for removal of damaged or misfolded proteins and proteolytic activation of essential mitochondrial proteins. AFG3L2 forms either a homo-oligomeric isoenzyme or a hetero-oligomeric complex with paraplegin, a homologous protein mutated in hereditary spastic paraplegia type 7 (SPG7). Heterozygous loss-of-function mutations in AFG3L2 cause autosomal-dominant spinocerebellar ataxia type 28 (SCA28), a disorder whose phenotype is strikingly different from that of our patients. As defined in yeast complementation assays, the AFG3L2Y616C gene product is a hypomorphic variant that exhibited oligomerization defects in yeast as well as in patient fibroblasts. Specifically, the formation of AFG3L2Y616C complexes was impaired, both with itself and to a greater extent with paraplegin. This produced an early-onset clinical syndrome that combines the severe phenotypes of SPG7 and SCA28, in additional to other “mitochondrial” features such as oculomotor apraxia, extrapyramidal dysfunction, and myoclonic epilepsy. These findings expand the phenotype associated with AFG3L2 mutations and suggest that AFG3L2-related disease should be considered in the differential diagnosis of spastic ataxias. PMID:22022284</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5437159','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5437159"><span>The Diverse <span class="hlt">AAA</span>+ Machines that Repair Inhibited Rubisco Active Sites</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mueller-Cajar, Oliver</p> <p>2017-01-01</p> <p>Gaseous carbon dioxide enters the biosphere almost exclusively via the active site of the enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). This highly conserved catalyst has an almost universal propensity to non-productively interact with its substrate ribulose 1,5-bisphosphate, leading to the formation of dead-end inhibited complexes. In diverse autotrophic organisms this tendency has been counteracted by the recruitment of dedicated <span class="hlt">AAA</span>+ (ATPases associated with various cellular activities) proteins that all use the energy of ATP hydrolysis to remodel inhibited Rubisco active sites leading to release of the inhibitor. Three evolutionarily distinct classes of these Rubisco activases (Rcas) have been discovered so far. Green and red-type Rca are mostly found in photosynthetic eukaryotes of the green and red plastid lineage respectively, whereas CbbQO is associated with chemoautotrophic bacteria. Ongoing mechanistic studies are elucidating how the various motors are utilizing both similar and contrasting strategies to ultimately perform their common function of cracking the inhibited Rubisco active site. The best studied mechanism utilized by red-type Rca appears to involve transient threading of the Rubisco large subunit C-terminal peptide, reminiscent of the action performed by Clp proteases. As well as providing a fascinating example of convergent molecular evolution, Rca proteins can be considered promising crop-improvement targets. Approaches aiming to replace Rubisco in plants with improved enzymes will need to ensure the presence of a compatible Rca protein. The thermolability of the Rca protein found in crop plants provides an opportunity to fortify photosynthesis against high temperature stress. Photosynthesis also appears to be limited by Rca when light conditions are fluctuating. Synthetic biology strategies aiming to enhance the autotrophic CO2 fixation machinery will need to take into consideration the requirement for Rubisco activases</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5624289','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5624289"><span>The Rice <span class="hlt">AAA</span>-ATPase OsFIGNL1 Is Essential for Male Meiosis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhang, Peipei; Zhang, Yingxin; Sun, Lianping; Sinumporn, Sittipun; Yang, Zhengfu; Sun, Bin; Xuan, Dandan; Li, Zihe; Yu, Ping; Wu, Weixun; Wang, Kejian; Cao, Liyong; Cheng, Shihua</p> <p>2017-01-01</p> <p>Meiosis is crucial in reproduction of plants and ensuring genetic diversity. Although several genes involved in homologous recombination and DNA repair have been reported, their functions in rice (Oryza sativa) male meiosis remain poorly understood. Here, we isolated and characterized the rice OsFIGNL1 (OsFidgetin-like 1) gene, encoding a conserved <span class="hlt">AAA</span>-ATPase, and explored its function and importance in male meiosis and pollen formation. The rice Osfignl1 mutant exhibited normal vegetative growth, but failed to produce seeds and displayed pollen abortion phenotype. Phenotypic comparisons between the wild-type and Osfignl1 mutant demonstrated that OsFIGNL1 is required for anther development, and that the recessive mutation of this gene causes male sterility in rice. Complementation and CRISPR/Cas9 experiments demonstrated that wild-type OsFIGNL1 is responsible for the male sterility phenotype. Subcellular localization showed that OsFIGNL1-green fluorescent protein was exclusively localized in the nucleus of rice protoplasts. Male meiosis in the Osfignl1 mutant exhibited abnormal chromosome behavior, including chromosome bridges and multivalent chromosomes at diakinesis, lagging chromosomes, and chromosome fragments during meiosis. Yeast two-hybrid assays demonstrated OsFIGNL1 could interact with RAD51A1, RAD51A2, DMC1A, DMC1B, and these physical interactions were further confirmed by BiFC assay. Taken together, our results suggest that OsFIGNL1 plays an important role in regulation of male meiosis and anther development. PMID:29021797</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5633344','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5633344"><span>The <span class="hlt">AAA</span> protein Msp1 mediates clearance of excess tail-anchored proteins from the peroxisomal membrane</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Weir, Nicholas R; Kamber, Roarke A; Martenson, James S</p> <p>2017-01-01</p> <p>Msp1 is a conserved <span class="hlt">AAA</span> ATPase in budding yeast localized to mitochondria where it prevents accumulation of mistargeted tail-anchored (TA) proteins, including the peroxisomal TA protein Pex15. Msp1 also resides on peroxisomes but it remains unknown how native TA proteins on mitochondria and peroxisomes evade Msp1 surveillance. We used live-cell quantitative cell microscopy tools and drug-inducible gene expression to dissect Msp1 function. We found that a small fraction of peroxisomal Pex15, exaggerated by overexpression, is turned over by Msp1. Kinetic measurements guided by theoretical modeling revealed that Pex15 molecules at mitochondria display age-independent Msp1 sensitivity. By contrast, Pex15 molecules at peroxisomes are rapidly converted from an initial Msp1-sensitive to an Msp1-resistant state. Lastly, we show that Pex15 interacts with the peroxisomal membrane protein Pex3, which shields Pex15 from Msp1-dependent turnover. In sum, our work argues that Msp1 selects its substrates on the basis of their solitary membrane existence. PMID:28906250</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2005BAAS...37.1552T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2005BAAS...37.1552T"><span>Obituary: <span class="hlt">Philip</span> Morrison, 1915-2005</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Trimble, Virginia</p> <p>2005-12-01</p> <p><span class="hlt">Philip</span> Morrison, who died 22 April 2005 in Cambridge, Massachusetts, was born in Somerville, New Jersey on 7 November 1915 to Moses and Tilly (née Rosenbloom) Morrison. Early childhood polio confined him for extended periods, during which he apparently developed his remarkable skill at speed reading. Speed writing (leading to a bibliography of more than 600 items) came later, and his memory must always have been exceedingly retentive. Morrison went on from the public and private schools of Pittsburgh, Pennsylvania to receive a BS in physics from Carnegie Institute of Technology (now Carnegie Mellon) in 1936. At the University of California, Berkeley, he joined the Young Communist League and later the Communist Party, letting his membership lapse in the early 1940s when work and war came to seem more important. He was officially the student of J. Robert Oppenheimer and worked also with postdocs Robert Serber and Leonard Schiff and with a number of his fellow Oppenheimer students (a spectacular crew, which included Robert Christy, Sidney Dancoff, Bernard Peters [born Pietrkowski], Hartland Snyder, Joseph Weinberg, Dale Corson, Giovanni Rossi Lomanitz, David Bohm, and Eugene Cooper). Following his 1940 PhD, Phil (his preferred signature) taught for a year at San Francisco State and then at University of Illinois (where he replaced Dancoff, who had gone on to a year at Institute for Advanced Study, Princeton). From Illinois, Morrison was recruited to the Metallurgy Lab (uranium project) at the University of Chicago by Christy in 1942. There he worked on the design for the Hanford Reactor, the main source of plutonium for the Trinity and Nagasaki bombs. He seems to have been sensitive to human relationships even in that context and was the author of a "Dear Opje" letter to Oppenheimer pointing out that the lack of cooperation between management and the scientists was getting in the way of the project. Morrison's early research was largely in theoretical nuclear physics</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22409666-tu-bre-clinical-implications-aaa-commissioning-errors-ability-common-commissioning-credentialing-procedures-detect-them','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22409666-tu-bre-clinical-implications-aaa-commissioning-errors-ability-common-commissioning-credentialing-procedures-detect-them"><span>TU-C-BRE-05: Clinical Implications of <span class="hlt">AAA</span> Commissioning Errors and Ability of Common Commissioning ' Credentialing Procedures to Detect Them</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>McVicker, A; Oldham, M; Yin, F</p> <p>2014-06-15</p> <p>Purpose: To test the ability of the TG-119 commissioning process and RPC credentialing to detect errors in the commissioning process for a commercial Treatment Planning System (TPS). Methods: We introduced commissioning errors into the commissioning process for the Anisotropic Analytical Algorithm (<span class="hlt">AAA</span>) within the Eclipse TPS. We included errors in Dosimetric Leaf Gap (DLG), electron contamination, flattening filter material, and beam profile measurement with an inappropriately large farmer chamber (simulated using sliding window smoothing of profiles). We then evaluated the clinical impact of these errors on clinical intensity modulated radiation therapy (IMRT) plans (head and neck, low and intermediate riskmore » prostate, mesothelioma, and scalp) by looking at PTV D99, and mean and max OAR dose. Finally, for errors with substantial clinical impact we determined sensitivity of the RPC IMRT film analysis at the midpoint between PTV and OAR using a 4mm distance to agreement metric, and of a 7% TLD dose comparison. We also determined sensitivity of the 3 dose planes of the TG-119 C-shape IMRT phantom using gamma criteria of 3% 3mm. Results: The largest clinical impact came from large changes in the DLG with a change of 1mm resulting in up to a 5% change in the primary PTV D99. This resulted in a discrepancy in the RPC TLDs in the PTVs and OARs of 7.1% and 13.6% respectively, which would have resulted in detection. While use of incorrect flattening filter caused only subtle errors (<1%) in clinical plans, the effect was most pronounced for the RPC TLDs in the OARs (>6%). Conclusion: The <span class="hlt">AAA</span> commissioning process within the Eclipse TPS is surprisingly robust to user error. When errors do occur, the RPC and TG-119 commissioning credentialing criteria are effective at detecting them; however OAR TLDs are the most sensitive despite the RPC currently excluding them from analysis.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22626711-su-end-end-validation-mv-high-dose-rate-photon-beam-configured-eclipse-aaa-algorithm-using-golden-beam-data-sbrt-treatments-using-rapidarc','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22626711-su-end-end-validation-mv-high-dose-rate-photon-beam-configured-eclipse-aaa-algorithm-using-golden-beam-data-sbrt-treatments-using-rapidarc"><span>SU-F-P-39: End-To-End Validation of a 6 MV High Dose Rate Photon Beam, Configured for Eclipse <span class="hlt">AAA</span> Algorithm Using Golden Beam Data, for SBRT Treatments Using RapidArc</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Ferreyra, M; Salinas Aranda, F; Dodat, D</p> <p></p> <p>Purpose: To use end-to-end testing to validate a 6 MV high dose rate photon beam, configured for Eclipse <span class="hlt">AAA</span> algorithm using Golden Beam Data (GBD), for SBRT treatments using RapidArc. Methods: Beam data was configured for Varian Eclipse <span class="hlt">AAA</span> algorithm using the GBD provided by the vendor. Transverse and diagonals dose profiles, PDDs and output factors down to a field size of 2×2 cm2 were measured on a Varian Trilogy Linac and compared with GBD library using 2% 2mm 1D gamma analysis. The MLC transmission factor and dosimetric leaf gap were determined to characterize the MLC in Eclipse. Mechanical andmore » dosimetric tests were performed combining different gantry rotation speeds, dose rates and leaf speeds to evaluate the delivery system performance according to VMAT accuracy requirements. An end-to-end test was implemented planning several SBRT RapidArc treatments on a CIRS 002LFC IMRT Thorax Phantom. The CT scanner calibration curve was acquired and loaded in Eclipse. PTW 31013 ionization chamber was used with Keithley 35617EBS electrometer for absolute point dose measurements in water and lung equivalent inserts. TPS calculated planar dose distributions were compared to those measured using EPID and MapCheck, as an independent verification method. Results were evaluated with gamma criteria of 2% dose difference and 2mm DTA for 95% of points. Results: GBD set vs. measured data passed 2% 2mm 1D gamma analysis even for small fields. Machine performance tests show results are independent of machine delivery configuration, as expected. Absolute point dosimetry comparison resulted within 4% for the worst case scenario in lung. Over 97% of the points evaluated in dose distributions passed gamma index analysis. Conclusion: Eclipse <span class="hlt">AAA</span> algorithm configuration of the 6 MV high dose rate photon beam using GBD proved efficient. End-to-end test dose calculation results indicate it can be used clinically for SBRT using RapidArc.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25688103','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25688103"><span>Unique ATPase site architecture triggers cis-mediated synchronized ATP binding in heptameric <span class="hlt">AAA</span>+-ATPase domain of flagellar regulatory protein FlrC.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dey, Sanjay; Biswas, Maitree; Sen, Udayaditya; Dasgupta, Jhimli</p> <p>2015-04-03</p> <p>Bacterial enhancer-binding proteins (bEBPs) oligomerize through <span class="hlt">AAA</span>(+) domains and use ATP hydrolysis-driven energy to isomerize the RNA polymerase-σ(54) complex during transcriptional initiation. Here, we describe the first structure of the central <span class="hlt">AAA</span>(+) domain of the flagellar regulatory protein FlrC (FlrC(C)), a bEBP that controls flagellar synthesis in Vibrio cholerae. Our results showed that FlrC(C) forms heptamer both in nucleotide (Nt)-free and -bound states without ATP-dependent subunit remodeling. Unlike the bEBPs such as NtrC1 or PspF, a novel cis-mediated "all or none" ATP binding occurs in the heptameric FlrC(C), because constriction at the ATPase site, caused by loop L3 and helix α7, restricts the proximity of the trans-protomer required for Nt binding. A unique "closed to open" movement of Walker A, assisted by trans-acting "Glu switch" Glu-286, facilitates ATP binding and hydrolysis. Fluorescence quenching and ATPase assays on FlrC(C) and mutants revealed that although Arg-349 of sensor II, positioned by trans-acting Glu-286 and Tyr-290, acts as a key residue to bind and hydrolyze ATP, Arg-319 of α7 anchors ribose and controls the rate of ATP hydrolysis by retarding the expulsion of ADP. Heptameric state of FlrC(C) is restored in solution even with the transition state mimicking ADP·AlF3. Structural results and pulldown assays indicated that L3 renders an in-built geometry to L1 and L2 causing σ(54)-FlrC(C) interaction independent of Nt binding. Collectively, our results underscore a novel mechanism of ATP binding and σ(54) interaction that strives to understand the transcriptional mechanism of the bEBPs, which probably interact directly with the RNA polymerase-σ(54) complex without DNA looping. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24178669','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24178669"><span>Random amplified polymorphic DNA (RAPD) detection of dwarf off-types in micropropagated Cavendish (Musa spp. <span class="hlt">AAA</span>) bananas.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Damasco, O P; Graham, G C; Henry, R J; Adkins, S W; Smiths, M K; Godwin, I D</p> <p>1996-11-01</p> <p>A RAPD marker specific to the dwarf off-type (hereafter known as dwarf) from micropropagation of Cavendish banana (Musa spp. <span class="hlt">AAA</span>) cultivars New Guinea Cavendish and Williams was identified following an analysis of 57 normal (true-to-type) and 59 dwarf plants generated from several different micropropagation events. Sixty-six random decamer primers were used in the initial screen, of which 19 (28.8%) revealed polymorphisms between normal and dwarf plants. Primer OPJ-04 (5'-CCGAACACGG-3') was found to amplify an approx. 1.5 kb band which was consistently present in all normal but absent in all dwarf plants of both cultivars. Reliable detection of dwarf plants was achieved using this marker, providing the only available means ofin vitro detection of dwarfs. The use of this marker could facilitate early detection and elimination of dwarfs from batches of micropropagated bananas, and may be a useful tool in determining what factors in the tissue culture process lead to this off type production.Other micropropagation-induced RAPD polymorphisms were observed but were not associated with the dwarf trait.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1748121','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1748121"><span><span class="hlt">Philip</span> Morris toxicological experiments with fresh sidestream smoke: more toxic than mainstream smoke</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Schick, S; Glantz, S</p> <p>2005-01-01</p> <p>Background: Exposure to secondhand smoke causes lung cancer; however, there are little data in the open literature on the in vivo toxicology of fresh sidestream cigarette smoke to guide the debate about smoke-free workplaces and public places. Objective: To investigate the unpublished in vivo research on sidestream cigarette smoke done by <span class="hlt">Philip</span> Morris Tobacco Company during the 1980s at its Institut für Biologische Forschung (INBIFO). Methods: Analysis of internal tobacco industry documents now available at the University of California San Francisco Legacy Tobacco Documents Library and other websites. Results: Inhaled fresh sidestream cigarette smoke is approximately four times more toxic per gram total particulate matter (TPM) than mainstream cigarette smoke. Sidestream condensate is approximately three times more toxic per gram and two to six times more tumourigenic per gram than mainstream condensate by dermal application. The gas/vapour phase of sidestream smoke is responsible for most of the sensory irritation and respiratory tract epithelium damage. Fresh sidestream smoke inhibits normal weight gain in developing animals. In a 21day exposure, fresh sidestream smoke can cause damage to the respiratory epithelium at concentrations of 2 µg/l TPM. Damage to the respiratory epithelium increases with longer exposures. The toxicity of whole sidestream smoke is higher than the sum of the toxicities of its major constituents. Conclusion: Fresh sidestream smoke at concentrations commonly encountered indoors is well above a 2 µg/m3 reference concentration (the level at which acute effects are unlikely to occur), calculated from the results of the INBIFO studies, that defines acute toxicity to humans. Smoke-free public places and workplaces are the only practical way to protect the public health from the toxins in sidestream smoke. PMID:16319363</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29315927','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29315927"><span>The major-effect quantitative trait locus CsARN6.1 encodes an <span class="hlt">AAA</span> ATPase domain-containing protein that is associated with waterlogging stress tolerance by promoting adventitious root formation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Xu, Xuewen; Ji, Jing; Xu, Qiang; Qi, Xiaohua; Weng, Yiqun; Chen, Xuehao</p> <p>2018-03-01</p> <p>In plants, the formation of hypocotyl-derived adventitious roots (ARs) is an important morphological acclimation to waterlogging stress; however, its genetic basis remains fragmentary. Here, through combined use of bulked segregant analysis-based whole-genome sequencing, SNP haplotyping and fine genetic mapping, we identified a candidate gene for a major-effect QTL, ARN6.1, that was responsible for waterlogging tolerance due to increased AR formation in the cucumber line Zaoer-N. Through multiple lines of evidence, we show that CsARN6.1 is the most possible candidate for ARN6.1 which encodes an <span class="hlt">AAA</span> ATPase. The increased formation of ARs under waterlogging in Zaoer-N could be attributed to a non-synonymous SNP in the coiled-coil domain region of this gene. CsARN6.1 increases the number of ARs via its ATPase activity. Ectopic expression of CsARN6.1 in Arabidopsis resulted in better rooting ability and lateral root development in transgenic plants. Transgenic cucumber expressing the CsARN6.1 Asp allele from Zaoer-N exhibited a significant increase in number of ARs compared with the wild type expressing the allele from Pepino under waterlogging conditions. Taken together, these data support that the <span class="hlt">AAA</span> ATPase gene CsARN6.1 has an important role in increasing cucumber AR formation and waterlogging tolerance. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25575319','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25575319"><span>Silence, death, and D/discourse: critical literary practices with lesbian seniors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Robson, Claire; Sumara, Dennis</p> <p>2015-01-01</p> <p>This article reports on a federally funded research project in which old lesbians were invited to separate out and examine the complicated strands of lives lived through times of great social change-times in which notions of "woman," "sexuality," and "subjectivity" have been both over- and under-determined by dominant discourse (Stein, 1997). We argue, with <span class="hlt">Haug</span> (1992), that close attention to the personal is central to critical feminist perspectives and that writers can become more aware of normalizing cultural influences when they pay close attention to language. In this article, we support our position with a case study of one participant in our "language school" (<span class="hlt">Haug</span>, 1992). As we analyzed her written life narratives and oral testimony, we conclude that she was able to reconsider comfortable "coming out" narratives in order to construct new meaning and to challenge her understandings of the past.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017AGUFM.V33D0548S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017AGUFM.V33D0548S"><span>Structurally bound sulfide and sulfate in apatite from the <span class="hlt">Philips</span> Mine iron oxide - apatite deposit, New York, USA: A tracer of redox changes</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Sadove, G.; Konecke, B.; Fiege, A.; Simon, A. C.</p> <p>2017-12-01</p> <p>Multiple competing hypotheses attempt to explain the genesis of iron oxide-apatite (IOA) ore deposits. Many studies have investigated the chemistry of apatite because the abundances of F and Cl can distinguish magmatic vs. hydrothermal processes. Recent experiments demonstrate that apatite incorporates S6+, S4+, and S2-, and that total sulfur (∑S) as well as the S6+/∑S ratio in apatite vary systematically as a function of oxygen fugacity [1], providing information about sulfur budget and redox. Here, we present results from X-ray absorption near-edge structure (XANES) spectroscopy at the S K-edge, electron microprobe analyses, cathodoluminescence (CL) imaging, and element mapping of apatite from the <span class="hlt">Philip</span>'s Mine IOA deposit, southern Adirondack Mountains, USA. The <span class="hlt">Philip</span>'s Mine apatite contains inclusions of pyrite and pyrrhotite, where the latter includes iron oxide and Ni-rich domains. The apatite also contains inclusions of monazite, and exhibits complex CL zonation coincident with variations in the abundances of REE and S. The presence of monazite fingerprints fluid-mediated dissolution-reprecipitation of originally REE-enriched apatite [2]. The S XANES spectra reveal varying proportions of structurally bound S6+ and S2-, as the S6+/∑S ratio ranges from sulfide-only to sulfate-only. Notably, sulfide-dominated domains contain higher S contents than sulfate-dominated regions. These observations are consistent with co-crystallization of apatite and monosulfide solid solution (MSS) at reducing conditions, followed by decomposition of MSS to pyrrhotite, pyrite and intermediate solid solution (ISS, which is not preserved; [3]). Metasomatism of that assemblage by an oxidized fluid resulted in formation of monazite in apatite and iron oxide domains in pyrrhotite. We conclude that the deposit formed by a H2S-Fe-rich volatile phase, possibly evolved from a rather primitive magmatic source, which is consistent with the low Ti content of magnetite. The deposit was</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28583292','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28583292"><span>Design of experiments in medical physics: Application to the <span class="hlt">AAA</span> beam model validation.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dufreneix, S; Legrand, C; Di Bartolo, C; Bremaud, M; Mesgouez, J; Tiplica, T; Autret, D</p> <p>2017-09-01</p> <p>The purpose of this study is to evaluate the usefulness of the design of experiments in the analysis of multiparametric problems related to the quality assurance in radiotherapy. The main motivation is to use this statistical method to optimize the quality assurance processes in the validation of beam models. Considering the Varian Eclipse system, eight parameters with several levels were selected: energy, MLC, depth, X, Y 1 and Y 2 jaw dimensions, wedge and wedge jaw. A Taguchi table was used to define 72 validation tests. Measurements were conducted in water using a CC04 on a TrueBeam STx, a TrueBeam Tx, a Trilogy and a 2300IX accelerator matched by the vendor. Dose was computed using the <span class="hlt">AAA</span> algorithm. The same raw data was used for all accelerators during the beam modelling. The mean difference between computed and measured doses was 0.1±0.5% for all beams and all accelerators with a maximum difference of 2.4% (under the 3% tolerance level). For all beams, the measured doses were within 0.6% for all accelerators. The energy was found to be an influencing parameter but the deviations observed were smaller than 1% and not considered clinically significant. Designs of experiment can help define the optimal measurement set to validate a beam model. The proposed method can be used to identify the prognostic factors of dose accuracy. The beam models were validated for the 4 accelerators which were found dosimetrically equivalent even though the accelerator characteristics differ. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=storytelling+AND+research+AND+paper&pg=3&id=EJ1099429','ERIC'); return false;" href="https://eric.ed.gov/?q=storytelling+AND+research+AND+paper&pg=3&id=EJ1099429"><span>Collective Biography and Memory Work: Girls Reading Fiction</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Gannon, Susanne</p> <p>2015-01-01</p> <p>Collective biography draws on memory work methods developed initially by feminist sociologists (<span class="hlt">Haug</span> et al., 1987) where people collaboratively examined the social and discursive resources through which they take themselves up as particular gendered subjects in the world. Their own memories become resources to investigate processes of…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2926356','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2926356"><span>The Hospital for Special Surgery 1972–1989; <span class="hlt">Philip</span> D. Wilson, Jr., Eighth Surgeon-in-Chief</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2010-01-01</p> <p>After nearly a decade as the seventh Surgeon-in-Chief (1963–1972) of The Hospital for Special Surgery (HSS), Robert Lee Patterson, Jr., MD (1907–1994) retired, having repaired adverse relations between HSS and the New York Hospital-Cornell Medical Center. Patterson, who had first joined the staff of The Hospital for the Ruptured and Crippled in 1936 as a Visiting Surgeon, was able to accomplish this very challenging task mainly through his close relationship with Preston Wade, MD (1901–1982), a general surgeon who had served with Patterson as Co-Chief of the combined New York Hospital-HSS Fracture service. The Board of Trustees of the New York Society for the Relief of the Ruptured and Crippled appointed <span class="hlt">Philip</span> D. Wilson, Jr. MD, as the eighth Surgeon-in-Chief of The Hospital for Special Surgery. He assumed that office on July 1, 1972. Wilson, who had joined the staff as an Orthopaedic Surgeon to the Out-Patient Department in 1951, had trained as an orthopaedic resident at HSS from 1948 to 1950 and in 1951, finished his residency at the University of California Hospital Medical Center, San Francisco. During his 17 years as Surgeon-in-Chief, he led the hospital into the advanced field of implant research and development and building a world-class center for patient care. Additionally, many other orthopaedic services such as Sports Medicine, Scoliosis and Metabolic Bone Diseases became the leaders in their fields. Supporting Departments of Rheumatology, Anesthesia and others were likewise recognized foremost in the country. PMID:21886524</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=immortal&pg=2&id=ED298019','ERIC'); return false;" href="https://eric.ed.gov/?q=immortal&pg=2&id=ED298019"><span>Zoroastrianism: The Rediscovery of Missing Chapters in Man's Religious History. Teaching Aids for the Study of Inner Asia, No. 6.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Boyce, Mary</p> <p></p> <p>Some modern scholars of Zoroastrianism, a faith still practiced in Iran and India today, are convinced that the doctrines of post-exilic Judaism and Christianity concerning monotheism, righteousness, and the final judgment and resurrection have roots in this ancient religion. Beginning with Martin <span class="hlt">Haug</span>, a 19th centurey German philologist, the…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19108600','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19108600"><span>"A good personal scientific relationship": <span class="hlt">Philip</span> Morris scientists and the Chulabhorn Research Institute, Bangkok.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mackenzie, Ross; Collin, Jeff</p> <p>2008-12-23</p> <p>This paper examines the efforts of consultants affiliated with <span class="hlt">Philip</span> Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005. This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships. The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is raised by the CRI's recently awarded status</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015SPIE.9537E..15H','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015SPIE.9537E..15H"><span>In-situ monitoring of blood glucose level for dialysis machine by <span class="hlt">AAA</span>-battery-size ATR Fourier spectroscopy</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Hosono, Satsuki; Sato, Shun; Ishida, Akane; Suzuki, Yo; Inohara, Daichi; Nogo, Kosuke; Abeygunawardhana, Pradeep K.; Suzuki, Satoru; Nishiyama, Akira; Wada, Kenji; Ishimaru, Ichiro</p> <p>2015-07-01</p> <p>For blood glucose level measurement of dialysis machines, we proposed <span class="hlt">AAA</span>-battery-size ATR (Attenuated total reflection) Fourier spectroscopy in middle infrared light region. The proposed one-shot Fourier spectroscopic imaging is a near-common path and spatial phase-shift interferometer with high time resolution. Because numerous number of spectral data that is 60 (= camera frame rare e.g. 60[Hz]) multiplied by pixel number could be obtained in 1[sec.], statistical-averaging improvement realize high-accurate spectral measurement. We evaluated the quantitative accuracy of our proposed method for measuring glucose concentration in near-infrared light region with liquid cells. We confirmed that absorbance at 1600[nm] had high correlations with glucose concentrations (correlation coefficient: 0.92). But to measure whole-blood, complex light phenomenon caused from red blood cells, that is scattering and multiple reflection or so, deteriorate spectral data. Thus, we also proposed the ultrasound-assisted spectroscopic imaging that traps particles at standing-wave node. Thus, if ATR prism is oscillated mechanically, anti-node area is generated around evanescent light field on prism surface. By elimination complex light phenomenon of red blood cells, glucose concentration in whole-blood will be quantify with high accuracy. In this report, we successfully trapped red blood cells in normal saline solution with ultrasonic standing wave (frequency: 2[MHz]).</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA009482','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA009482"><span>A NASTRAN Vibration Model of the AH-1G Helicopter Airframe. Volume 1</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1974-06-01</p> <p>Bulkhead .012 ZZ 1863343 Bulkhead .012 <span class="hlt">AAA</span> 1863345 Bulkhead .012 j EBB 1863546 Bulkhead .012 j ccc 1863746 Bulkhead .012 \\ ODD 1863748...123 12) 123 RULE <span class="hlt">AAA</span> <span class="hlt">AAA</span> <span class="hlt">AAA</span> <span class="hlt">AAA</span> BBB EBB <span class="hlt">AAA</span> <span class="hlt">AAA</span> <span class="hlt">AAA</span> <span class="hlt">AAA</span> BBB BBB OMIT D.O.F. 456 456 123 123 123 123 123 123 123 123 RULE...load in the member Increases. The program determines the section properties, unsytnmetrical bending stresses, element loads and shear flows for a</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/1002883-engagement-arginine-finger-atp-triggers-large-conformational-changes-ntrc1-aaa+-atpase-remodeling-bacterial-rna-polymerase','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/1002883-engagement-arginine-finger-atp-triggers-large-conformational-changes-ntrc1-aaa+-atpase-remodeling-bacterial-rna-polymerase"><span>Engagement of Arginine Finger to ATP Triggers Large Conformational Changes in NtrC1 <span class="hlt">AAA</span>+ ATPase for Remodeling Bacterial RNA Polymerase</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Chen, Baoyu; Sysoeva, Tatyana A.; Chowdhury, Saikat</p> <p></p> <p>The NtrC-like <span class="hlt">AAA</span>+ ATPases control virulence and other important bacterial activities through delivering mechanical work to {sigma}54-RNA polymerase to activate transcription from {sigma}54-dependent genes. We report the first crystal structure for such an ATPase, NtrC1 of Aquifex aeolicus, in which the catalytic arginine engages the {gamma}-phosphate of ATP. Comparing the new structure with those previously known for apo and ADP-bound states supports a rigid-body displacement model that is consistent with large-scale conformational changes observed by low-resolution methods. First, the arginine finger induces rigid-body roll, extending surface loops above the plane of the ATPase ring to bind {sigma}54. Second, ATP hydrolysismore » permits Pi release and retraction of the arginine with a reversed roll, remodeling {sigma}54-RNAP. This model provides a fresh perspective on how ATPase subunits interact within the ring-ensemble to promote transcription, directing attention to structural changes on the arginine-finger side of an ATP-bound interface.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5072712','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5072712"><span>Chronic Kidney Disease Is Positively and Diabetes Mellitus Is Negatively Associated with Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Uchida, Haruhito A.; Kakio, Yuki; Umebayashi, Ryoko; Okuyama, Yuka; Fujii, Yasuhiro; Ozawa, Susumu; Yoshida, Masashi; Oshima, Yu; Sano, Shunji; Wada, Jun</p> <p>2016-01-01</p> <p>Background and Aims Chronic kidney disease (CKD) and diabetes mellitus (DM) are considered as risk factors for cardiovascular diseases. The purpose of this study was to clarify the relationship of CKD and DM with the presence of abdominal aortic aneurysm (<span class="hlt">AAA</span>). Methods We enrolled 261 patients with <span class="hlt">AAA</span> (<span class="hlt">AAA</span>+) and age-and-sex matched 261 patients without <span class="hlt">AAA</span> (<span class="hlt">AAA</span>-) at two hospitals between 2008 and 2014, and examined the association between the risk factors and the presence of <span class="hlt">AAA</span>. Furthermore, in order to investigate the prevalence of <span class="hlt">AAA</span> in each group, we enrolled 1126 patients with CKD and 400 patients with DM. Results The presence of CKD in patients with <span class="hlt">AAA</span>+ was significantly higher than that in patients with <span class="hlt">AAA</span>- (<span class="hlt">AAA</span>+; 65%, <span class="hlt">AAA</span>-; 52%, P = 0.004). The presence of DM in patients with <span class="hlt">AAA</span>+ was significantly lower than that in patients with <span class="hlt">AAA</span>- (<span class="hlt">AAA</span>+; 17%, <span class="hlt">AAA</span>-; 35%, P < 0.001). A multivariate logistic regression analysis demonstrated that hypertension, ischemic heart disease and CKD were independent determinants, whereas, DM was a negatively independent determinant, for the presence of <span class="hlt">AAA</span>. The prevalence of <span class="hlt">AAA</span> in patients with CKD 65 years old and above was 5.1%, whereas, that in patients with DM 65 years old and above was only 0.6%. Conclusion CKD is a positively associated with the presence of <span class="hlt">AAA</span>. In contrast, DM is a negatively associated with the presence of <span class="hlt">AAA</span> in Japanese population. PMID:27764090</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5705786','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5705786"><span>Phenotype–genotype spectrum of <span class="hlt">AAA</span> syndrome from Western India and systematic review of literature</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Patt, Hiren; Koehler, Katrin; Lodha, Sailesh; Yerawar, Chaitanya; Huebner, Angela; Thakkar, Kunal; Arya, Sneha; Nair, Sandhya; Goroshi, Manjunath; Ganesh, Hosahithlu; Sarathi, Vijaya; Lila, Anurag; Bandgar, Tushar; Shah, Nalini</p> <p>2017-01-01</p> <p>Objective To study genotype–phenotype spectrum of triple A syndrome (TAS). Methods Retrospective chart analysis of Indian TAS patients (cohort 1, n = 8) and review of genotyped TAS cases reported in world literature (cohort 2, n = 133, 68 publications). Results Median age at presentation was 4.75 years (range: 4–10) and 5 years (range: 1–42) for cohorts 1 and 2, respectively. Alacrima, adrenal insufficiency (AI), achalasia and neurological dysfunction (ND) were seen in 8/8, 8/8, 7/8 and 4/8 patients in cohort 1, and in 99, 91, 93 and 79% patients in cohort 2, respectively. In both cohorts, alacrima was present since birth while AI and achalasia manifested before ND. Mineralocorticoid deficiency (MC) was uncommon (absent in cohort 1, 12.5% in cohort 2). In cohort 1, splice-site mutation in exon 1 (p.G14Vfs*45) was commonest, followed by a deletion in exon 8 (p.S255Vfs*36). Out of 65 mutations in cohort 2, 14 were recurrent and five exhibited regional clustering. AI was more prevalent, more often a presenting feature, and was diagnosed at younger age in T group (those with truncating mutations) as compared to NT (non-truncating mutations) group. ND was more prevalent, more common a presenting feature, with later age at onset in NT as compared to T group. Conclusion Clinical profile of our patients is similar to that of patients worldwide. Alacrima is the earliest and most consistent finding. MC deficiency is uncommon. Some recurrent mutations show regional clustering. p.G14Vfs*45 and p.S255Vfs*36 account for majority of <span class="hlt">AAAS</span> mutations in our cohort. Phenotype of T group differs from that of NT group and merits future research. PMID:29180348</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27807644','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27807644"><span>Differential proteome analysis during early somatic embryogenesis in Musa spp. <span class="hlt">AAA</span> cv. Grand Naine.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kumaravel, Marimuthu; Uma, Subbaraya; Backiyarani, Suthanthiram; Saraswathi, Marimuthu Somasundaram; Vaganan, Muthu Mayil; Muthusamy, Muthusamy; Sajith, Kallu Purayil</p> <p>2017-01-01</p> <p>Endogenous hormone secretion proteins along with stress and defense proteins play predominant role in banana embryogenesis. This study reveals the underlying molecular mechanism during transition from vegetative to embryogenic state. Banana (Musa spp.) is well known globally as a food fruit crop for millions. The requirement of quality planting material of banana is enormous. Although mass multiplication through tissue culture is in vogue, high-throughput techniques like somatic embryogenesis (SE) as a mass multiplication tool needs to be improved. Apart from clonal propagation, SE has extensive applications in genetic improvement and mutation. SE in banana is completely genome-dependent and most of the commercial cultivars exhibit recalcitrance. Thus, understanding the molecular basis of embryogenesis in Musa will help to develop strategies for mass production of quality planting material. In this study, differentially expressed proteins between embryogenic calli (EC) and non-embryogenic calli (NEC) with respect to the explant, immature male flower buds (IMFB), of cv. Grand Naine (<span class="hlt">AAA</span>) were determined using two-dimensional gel electrophoresis (2DE). The 2DE results were validated through qRT-PCR. In total, 65 proteins were identified: 42 were highly expressed and 23 were less expressed in EC compared to NEC and IMFB. qRT-PCR analysis of five candidate proteins, upregulated in EC, were well correlated with expression at transcript level. Further analysis of proteins showed that embryogenesis in banana is associated with the control of oxidative stress. The regulation of ROS scavenging system and protection of protein structure occurred in the presence of heat shock proteins. Alongside, high accumulation of stress-related cationic peroxidase and plant growth hormone-related proteins like indole-3-pyruvate monooxygenase and adenylate isopentenyltransferase in EC revealed the association with the induction of SE.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4081943','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4081943"><span>Sequential Actions of the <span class="hlt">AAA</span>-ATPase Valosin-containing Protein (VCP)/p97 and the Proteasome 19 S Regulatory Particle in Sterol-accelerated, Endoplasmic Reticulum (ER)-associated Degradation of 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase*</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Morris, Lindsey L.; Hartman, Isamu Z.; Jun, Dong-Jae; Seemann, Joachim; DeBose-Boyd, Russell A.</p> <p>2014-01-01</p> <p>Accelerated endoplasmic reticulum (ER)-associated degradation (ERAD) of the cholesterol biosynthetic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase results from its sterol-induced binding to ER membrane proteins called Insig-1 and Insig-2. This binding allows for subsequent ubiquitination of reductase by Insig-associated ubiquitin ligases. Once ubiquitinated, reductase becomes dislocated from ER membranes into the cytosol for degradation by 26 S proteasomes through poorly defined reactions mediated by the <span class="hlt">AAA</span>-ATPase valosin-containing protein (VCP)/p97 and augmented by the nonsterol isoprenoid geranylgeraniol. Here, we report that the oxysterol 25-hydroxycholesterol and geranylgeraniol combine to trigger extraction of reductase across ER membranes prior to its cytosolic release. This conclusion was drawn from studies utilizing a novel assay that measures membrane extraction of reductase by determining susceptibility of a lumenal epitope in the enzyme to in vitro protease digestion. Susceptibility of the lumenal epitope to protease digestion and thus membrane extraction of reductase were tightly regulated by 25-hydroxycholesterol and geranylgeraniol. The reaction was inhibited by RNA interference-mediated knockdown of either Insigs or VCP/p97. In contrast, reductase continued to become membrane-extracted, but not cytosolically dislocated, in cells deficient for <span class="hlt">AAA</span>-ATPases of the proteasome 19 S regulatory particle. These findings establish sequential roles for VCP/p97 and the 19 S regulatory particle in the sterol-accelerated ERAD of reductase that may be applicable to the ERAD of other substrates. PMID:24860107</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29705087','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29705087"><span>Long-term outcomes after repair of symptomatic abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chandra, Venita; Trang, Karen; Virgin-Downey, Whitt; Dalman, Ronald L; Mell, Matthew W</p> <p>2018-04-25</p> <p>Previous studies have reported increased perioperative mortality of nonruptured symptomatic abdominal aortic aneurysms (Sx-<span class="hlt">AAA</span>) compared with asymptomatic elective <span class="hlt">AAA</span> (E-<span class="hlt">AAA</span>) repairs, but no long-term-outcomes have been reported. We sought to compare long-term outcomes of Sx-<span class="hlt">AAA</span> and E-<span class="hlt">AAA</span> after repair at a single academic institution. Patients receiving <span class="hlt">AAA</span> repair for Sx-<span class="hlt">AAA</span> and E-<span class="hlt">AAA</span> from 1995 through 2015 were included. Ruptured <span class="hlt">AAA</span> and suprarenal or thoracoabdominal <span class="hlt">AAA</span> were excluded. Demographics, comorbidities, and operative approach were collected. Long-term mortality was the primary outcome, determined by chart review or link to Social Security Death Index. Additionally, long-term mortality and reinterventions were compared after groups were matched with nearest neighbor propensity to reduce bias. <span class="hlt">AAA</span> repair was performed for 1054 E-<span class="hlt">AAA</span> (383 open repair [36%], 671 endovascular aneurysm repair [EVAR] [64%]), and 139 symptomatic aneurysms (60 open repair [43%], 79 EVAR [57%]). Age (73 years vs 74 years; P = .13) and aneurysm diameter were similar between Sx-<span class="hlt">AAA</span> and E-<span class="hlt">AAA</span> (6.0 cm vs 5.8 cm; P = .5). The proportion of women was higher for Sx-<span class="hlt">AAA</span> (26% vs 16%; P = .003), as was the proportion of non-Caucasians (40% vs 29%; P = .009). After propensity matching, there were no differences between groups for patient characteristics, <span class="hlt">AAA</span> diameter, treatment modality, or comorbidities, including hypertension, coronary artery disease, congestive heart failure, diabetes, hyperlipidemia, lung disease, diabetes, renal disease, and smoking history. Women were treated for Sx-<span class="hlt">AAA</span> at significantly smaller aortic diameters; however, compared with men (5.1 cm vs 6.3 cm; P < .001). Perioperative mortality was 5.0% for Sx-<span class="hlt">AAA</span> and 2.3% for E-<span class="hlt">AAA</span> (P = .055). By life-table analysis, Sx-<span class="hlt">AAA</span> had lower 5-year (62% vs 71%) and 10-year (39% vs 51%) survivals (P = .01) compared with E-<span class="hlt">AAA</span> for the entire cohort. Similar trends were observed for 5-year and 10-year mortality</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA163586','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA163586"><span>Introduction to Free Atoms and Particles.</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1986-01-01</p> <p>34 Vol. I (R. Abramovitch. ed.). pp. 42. 46. 47. 44. 65, Plenum, New York. 1979. 9. P. L. Timms. in " Cryochemistry " (M. Moskovits and G. Ozin. eds.). p. 61...in ’ Cryochemistry " (M. Moskovits and G. Ozin. eds.). p. 261. * Wiley (interscicnce). New York, 1976. 15. R. H. <span class="hlt">Hauge</span>, S. E. Grandsen. and J. L</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA110109','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA110109"><span>Transactions of the Twenty-Seventh Conference of Army Mathematicians.</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1982-01-01</p> <p>Mixtures," Phil . Trans. R. Soc., London, 292, 45-99 (1979). 26. G. Tsatsaronis, "Prediction of Propagating Laminar Flames in Methane, Oxygen, Nitrogen...work of E. J. <span class="hlt">Haug</span> and his coworkers; the work of M. A. Chace, N. Orlandea, J. J. Uicker, etc; Beckett , R. E., Pan, K. C., and Chu, S. C., J. Engg. Ind</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29896039','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29896039"><span>Abdominal Aortic Aneurysm: Evolving Controversies and Uncertainties.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Carino, Davide; Sarac, Timur P; Ziganshin, Bulat A; Elefteriades, John A</p> <p>2018-06-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is defined as a permanent dilatation of the abdominal aorta that exceeds 3 cm. Most <span class="hlt">AAAs</span> arise in the portion of abdominal aorta distal to the renal arteries and are defined as infrarenal. Most <span class="hlt">AAAs</span> are totally asymptomatic until catastrophic rupture. The strongest predictor of <span class="hlt">AAA</span> rupture is the diameter. Surgery is indicated to prevent rupture when the risk of rupture exceeds the risk of surgery. In this review, we aim to analyze this disease comprehensively, starting from an epidemiological perspective, exploring etiology and pathophysiology, and concluding with surgical controversies. We will pursue these goals by addressing eight specific questions regarding <span class="hlt">AAA</span>: (1) Is the incidence of <span class="hlt">AAA</span> increasing? (2) Are ultrasound screening programs for <span class="hlt">AAA</span> effective? (3) What causes <span class="hlt">AAA</span>: Genes versus environment? (4) Animal models: Are they really relevant? (5) What pathophysiology leads to <span class="hlt">AAA</span>? (6) Indications for <span class="hlt">AAA</span> surgery: Are surgeons over-eager to operate? (7) Elective <span class="hlt">AAA</span> repair: Open or endovascular? (8) Emergency <span class="hlt">AAA</span> repair: Open or endovascular?</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28336521','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28336521"><span>Defending strong tobacco packaging and labelling regulations in Uruguay: transnational tobacco control network versus <span class="hlt">Philip</span> Morris International.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Crosbie, Eric; Sosa, Particia; Glantz, Stanton A</p> <p>2018-03-01</p> <p>Describe the process of enacting and defending strong tobacco packaging and labelling regulations in Uruguay amid <span class="hlt">Philip</span> Morris International's (PMI) legal threats and challenges. Triangulated government legislation, news sources and interviews with policy-makers and health advocates in Uruguay. In 2008 and 2009, the Uruguayan government enacted at the time the world's largest pictorial health warning labels (80% of front and back of package) and prohibited different packaging or presentations for cigarettes sold under a given brand. PMI threatened to sue Uruguay in international courts if these policies were implemented. The Vazquez administration maintained the regulations, but a week prior to President Vazquez's successor, President Mujica, took office on 1 March 2010 PMI announced its intention to file an investment arbitration dispute against Uruguay in the International Centre for the Settlement of Investment Disputes. Initially, the Mujica administration announced it would weaken the regulations to avoid litigation. In response, local public health groups in Uruguay enlisted former President Vazquez and international health groups and served as brokers to develop a collaboration with the Mujica administration to defend the regulations. This united front between the Uruguayan government and the transnational tobacco control network paid off when Uruguay defeated PMI's investment dispute in July 2016. To replicate Uruguay's success, other countries need to recognise that strong political support, an actively engaged local civil society and financial and technical support are important factors in overcoming tobacco industry's legal threats to defend strong public health regulations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2605886','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2605886"><span>“A Good Personal Scientific Relationship”: <span class="hlt">Philip</span> Morris Scientists and the Chulabhorn Research Institute, Bangkok</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>MacKenzie, Ross; Collin, Jeff</p> <p>2008-01-01</p> <p>Background This paper examines the efforts of consultants affiliated with <span class="hlt">Philip</span> Morris (PM), the world's leading transnational tobacco corporation, to influence scientific research and training in Thailand via the Chulabhorn Research Institute (CRI). A leading Southeast Asian institute for environmental health science, the CRI is headed by Professor Dr. Her Royal Highness Princess Chulabhorn, the daughter of the King of Thailand, and it has assumed international significance via its designation as a World Health Organization (WHO) Collaborating Centre in December 2005. Methods and Findings This paper analyses previously confidential tobacco industry documents that were made publicly available following litigation in the United States. PM documents reveal that ostensibly independent overseas scientists, now identified as industry consultants, were able to gain access to the Thai scientific community. Most significantly, PM scientist Roger Walk has established close connections with the CRI. Documents indicate that Walk was able to use such links to influence the study and teaching of environmental toxicology in the institute and to develop relations with key officials and local scientists so as to advance the interests of PM within Thailand and across Asia. While sensitivities surrounding royal patronage of the CRI make public criticism extremely difficult, indications of ongoing involvement by tobacco industry consultants suggest the need for detailed scrutiny of such relationships. Conclusions The establishment of close links with the CRI advances industry strategies to influence scientific research and debate around tobacco and health, particularly regarding secondhand smoke, to link with academic institutions, and to build relationships with national elites. Such strategies assume particular significance in the national and regional contexts presented here amid the globalisation of the tobacco pandemic. From an international perspective, particular concern is</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25882069','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25882069"><span>Aortic iron overload with oxidative stress and inflammation in human and murine abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sawada, Hisashi; Hao, Hiroyuki; Naito, Yoshiro; Oboshi, Makiko; Hirotani, Shinichi; Mitsuno, Masataka; Miyamoto, Yuji; Hirota, Seiichi; Masuyama, Tohru</p> <p>2015-06-01</p> <p>Although iron is an essential element for maintaining physiological function, excess iron leads to tissue damage caused by oxidative stress and inflammation. Oxidative stress and inflammation play critical roles for the development of abdominal aortic aneurysm (<span class="hlt">AAA</span>). However, it has not been investigated whether iron plays a role in <span class="hlt">AAA</span> formation through oxidative stress and inflammation. We, therefore, examined whether iron is involved in the pathophysiology of <span class="hlt">AAA</span> formation using human <span class="hlt">AAA</span> walls and murine <span class="hlt">AAA</span> models. Human aortic walls were collected from 53 patients who underwent cardiovascular surgery (non-<span class="hlt">AAA</span>=34; <span class="hlt">AAA</span>=19). Murine <span class="hlt">AAA</span> was induced by infusion of angiotensin II to apolipoprotein E knockout mice. Iron was accumulated in human and murine <span class="hlt">AAA</span> walls compared with non-<span class="hlt">AAA</span> walls. Immunohistochemistry showed that both 8-hydroxy-2'-deoxyguanosine and CD68-positive areas were increased in <span class="hlt">AAA</span> walls compared with non-<span class="hlt">AAA</span> walls. The extent of iron accumulated area positively correlated with that of 8-hydroxy-2'-deoxyguanosine expression area and macrophage infiltration area in human and murine <span class="hlt">AAA</span> walls. We next investigated the effects of dietary iron restriction on <span class="hlt">AAA</span> formation in mice. Iron restriction reduced the incidence of <span class="hlt">AAA</span> formation with attenuation of oxidative stress and inflammation. Aortic expression of transferrin receptor 1, intracellular iron transport protein, was increased in human and murine <span class="hlt">AAA</span> walls, and transferrin receptor 1-positive area was similar to areas where iron accumulated and F4/80 were positive. Iron is involved in the pathophysiology of <span class="hlt">AAA</span> formation with oxidative stress and inflammation. Dietary iron restriction could be a new therapeutic strategy for <span class="hlt">AAA</span> progression. © 2015 American Heart Association, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27374068','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27374068"><span>Aortic outflow occlusion predicts rupture of abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Crawford, Jeffrey D; Chivukula, Venkat Keshav; Haller, Stephen; Vatankhah, Nasibeh; Bohannan, Colin J; Moneta, Gregory L; Rugonyi, Sandra; Azarbal, Amir F</p> <p>2016-12-01</p> <p>Current threshold recommendations for elective abdominal aortic aneurysm (<span class="hlt">AAA</span>) repair are based solely on maximal <span class="hlt">AAA</span> diameter. Peak wall stress (PWS) has been demonstrated to be a better predictor than <span class="hlt">AAA</span> diameter of <span class="hlt">AAA</span> rupture risk. However, PWS calculations are time-intensive, not widely available, and therefore not yet clinically practical. In addition, PWS analysis does not account for variations in wall strength between patients. We therefore sought to identify surrogate clinical markers of increased PWS and decreased aortic wall strength to better predict <span class="hlt">AAA</span> rupture risk. Patients treated at our institution from 2001 to 2014 for ruptured <span class="hlt">AAA</span> (r<span class="hlt">AAA</span>) were retrospectively identified and grouped into patients with small r<span class="hlt">AAA</span> (maximum diameter <6 cm) or large r<span class="hlt">AAA</span> (>6 cm). Patients with large (>6 cm) non-r<span class="hlt">AAA</span> were also identified sequentially from 2009 for comparison. Demographics, vascular risk factors, maximal aortic diameter, and aortic outflow occlusion (AOO) were recorded. AOO was defined as complete occlusion of the common, internal, or external iliac artery. Computational fluid dynamics and finite element analysis simulations were performed to calculate wall stress distributions and to extract PWS. We identified 61 patients with r<span class="hlt">AAA</span>, of which 15 ruptured with <span class="hlt">AAA</span> diameter <60 mm (small r<span class="hlt">AAA</span> group). Patients with small r<span class="hlt">AAAs</span> were more likely to have peripheral arterial disease (PAD) and chronic obstructive pulmonary disease (COPD) than were patients in the large non-r<span class="hlt">AAA</span> group. Patients with small r<span class="hlt">AAAs</span> were also more likely to have AOO compared with non-r<span class="hlt">AAAs</span> >60 mm (27% vs 8%; P = .047). Among all patients with r<span class="hlt">AAAs</span>, those with AOO ruptured at smaller mean <span class="hlt">AAA</span> diameters than in patients without AOO (62.1 ± 11.8 mm vs 72.5 ± 16.4 mm; P = .024). PWS calculations of a representative small r<span class="hlt">AAA</span> and a large non-r<span class="hlt">AAA</span> showed a substantial increase in PWS with AOO. We demonstrate that AOO, PAD, and COPD in <span class="hlt">AAA</span> are associated with r<span class="hlt">AAAs</span> at</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26083878','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26083878"><span>A practical method to standardise and optimise the <span class="hlt">Philips</span> DoseRight 2.0 CT automatic exposure control system.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wood, T J; Moore, C S; Stephens, A; Saunderson, J R; Beavis, A W</p> <p>2015-09-01</p> <p>Given the increasing use of computed tomography (CT) in the UK over the last 30 years, it is essential to ensure that all imaging protocols are optimised to keep radiation doses as low as reasonably practicable, consistent with the intended clinical task. However, the complexity of modern CT equipment can make this task difficult to achieve in practice. Recent results of local patient dose audits have shown discrepancies between two <span class="hlt">Philips</span> CT scanners that use the DoseRight 2.0 automatic exposure control (AEC) system in the 'automatic' mode of operation. The use of this system can result in drifting dose and image quality performance over time as it is designed to evolve based on operator technique. The purpose of this study was to develop a practical technique for configuring examination protocols on four CT scanners that use the DoseRight 2.0 AEC system in the 'manual' mode of operation. This method used a uniform phantom to generate reference images which form the basis for how the AEC system calculates exposure factors for any given patient. The results of this study have demonstrated excellent agreement in the configuration of the CT scanners in terms of average patient dose and image quality when using this technique. This work highlights the importance of CT protocol harmonisation in a modern Radiology department to ensure both consistent image quality and radiation dose. Following this study, the average radiation dose for a range of CT examinations has been reduced without any negative impact on clinical image quality.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23803276','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23803276"><span>Staff members' perceptions of an animal-assisted activity.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bibbo, Jessica</p> <p>2013-07-01</p> <p>To examine the perceptions of staff members toward the implementation of an animal-assisted activity (<span class="hlt">AAA</span>) in an outpatient regional cancer center. Quasi-experimental, post-test design. An adult outpatient regional cancer center in northern California. 34 facility staff members. Self-report questionnaire following four weeks of <span class="hlt">AAA</span> visitation. Visits took place three times a week for a total of 12 visits. Perceptions of the <span class="hlt">AAA</span>. Previous perceptions toward <span class="hlt">AAA</span> influenced the perceptions of the visitation's efficacy. Direct and indirect interaction with the visiting <span class="hlt">AAA</span> teams was positively associated with perceptions of the <span class="hlt">AAA</span>. A disagreement occurred that the <span class="hlt">AAA</span> had caused extra stress or work for staff. Enjoyment of interacting with the dog handler was not significantly different from interacting with the dog; however, it was more positively correlated to acceptance of the <span class="hlt">AAA</span>. The study provided evidence that the <span class="hlt">AAA</span> was generally accepted by staff members. Individual staff members' perceptions of dogs and <span class="hlt">AAAs</span> can influence their receptivity to <span class="hlt">AAA</span> interventions. Interaction with <span class="hlt">AAA</span> teams should be voluntary and available for patients and staff members. <span class="hlt">AAA</span> may be introduced into facilities without creating the perception of extra stress or work for staff members. Providing staff the opportunity to interact with visiting <span class="hlt">AAA</span> teams may be beneficial for the success of such programs. The human handler in <span class="hlt">AAA</span> teams may play a vital role in the staff acceptance of such programs.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4832331','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4832331"><span>Structural insights into the Escherichia coli lysine decarboxylases and molecular determinants of interaction with the <span class="hlt">AAA</span>+ ATPase RavA</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kandiah, Eaazhisai; Carriel, Diego; Perard, Julien; Malet, Hélène; Bacia, Maria; Liu, Kaiyin; Chan, Sze W. S.; Houry, Walid A.; Ollagnier de Choudens, Sandrine; Elsen, Sylvie; Gutsche, Irina</p> <p>2016-01-01</p> <p>The inducible lysine decarboxylase LdcI is an important enterobacterial acid stress response enzyme whereas LdcC is its close paralogue thought to play mainly a metabolic role. A unique macromolecular cage formed by two decamers of the Escherichia coli LdcI and five hexamers of the <span class="hlt">AAA</span>+ ATPase RavA was shown to counteract acid stress under starvation. Previously, we proposed a pseudoatomic model of the LdcI-RavA cage based on its cryo-electron microscopy map and crystal structures of an inactive LdcI decamer and a RavA monomer. We now present cryo-electron microscopy 3D reconstructions of the E. coli LdcI and LdcC, and an improved map of the LdcI bound to the LARA domain of RavA, at pH optimal for their enzymatic activity. Comparison with each other and with available structures uncovers differences between LdcI and LdcC explaining why only the acid stress response enzyme is capable of binding RavA. We identify interdomain movements associated with the pH-dependent enzyme activation and with the RavA binding. Multiple sequence alignment coupled to a phylogenetic analysis reveals that certain enterobacteria exert evolutionary pressure on the lysine decarboxylase towards the cage-like assembly with RavA, implying that this complex may have an important function under particular stress conditions. PMID:27080013</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009BAAS...41..579S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009BAAS...41..579S"><span>Obituary: <span class="hlt">Philip</span> M. Solomon, 1939-2008</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Scoville, Nick</p> <p>2009-01-01</p> <p><span class="hlt">Philip</span> Solomon, one of the pioneers and leading researchers in molecular astrophysics, died on 30 April 2008 at his apartment on the upper west side of Manhattan after a battle with cancer. His pioneering research included both theoretical and very extensive observational studies of stellar atmospheres, interstellar molecules, high redshift galaxies, and the Earth's stratosphere. Phil was Distinguished Professor at The State University of New York [SUNY], Stony Brook, where he had been since 1974. Phil was born on 29 March 1939 in Manhattan, New York City, to Nat and Betty Solomon. Nat Solomon was a labor organizer and a printer. Phil attended the University of Wisconsin, where he received his BS in 1959 and where he met his future wife Sheila who was studying art. His Ph.D., "On the Role of Light Molecules in Astrophysics," was also from the University of Wisconsin under the guidance of Art Code and Bob Bless. After postdoctoral positions at Princeton and lectureships at Columbia and the University of California, San Diego, Phil spent two years as a Professor at the University of Minnesota. After two years at the Institute for Advanced Study in Princeton, he came to SUNY, Stony Brook, as Professor of Astronomy in the Department of Earth and Space Sciences. In 1988 Phil was selected as a Humboldt Senior Distinguished Scientist, and, in 1999, he was honored with the rank of Distinguished Professor at SUNY. Phil took sabbatical and other leaves at Churchill College and the Institute of Astronomy, Cambridge; the Institute for Advanced Study; l'Ecole Normale Superieure, Paris; Institut d'Astrophysique, Paris; and the Institut de Radioastronomie Millimetrique [IRAM], France. Phil published more than 160 papers and supervised seven Ph.D. students. He served on numerous review, visiting, and advisory panels. Phil's first theoretical research focused on opacity and abundance of light molecules such as H2, CO, and CN in stellar atmospheres, but then shifted quickly to the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29587155','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29587155"><span>CXCL8 hyper-signaling in the aortic abdominal aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kokje, Vivianne B C; Gäbel, Gabor; Dalman, Ron L; Koole, Dave; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N</p> <p>2018-08-01</p> <p>There are indications for elevated CXCL8 levels in abdominal aortic aneurysm disease (<span class="hlt">AAA</span>). CXCL8 is concurrently involved in neutrophil-mediated inflammation and angiogenesis, two prominent and distinctive characteristics of <span class="hlt">AAA</span>. As such we considered an evaluation of a role for CXCL8 in <span class="hlt">AAA</span> progression relevant. ELISA's, real time PCR and array analysis were used to explore CXCL8 signaling in <span class="hlt">AAA</span> wall samples. A role for CXCL8 in <span class="hlt">AAA</span> disease was tested through the oral CXCR1/2 antagonist DF2156A in the elastase model of <span class="hlt">AAA</span> disease. There is an extreme disparity in aortic wall CXCL8 content between <span class="hlt">AAA</span> and aortic atherosclerotic disease (median [IQR] aortic wall CXCL8 content: 425 [141-1261] (<span class="hlt">AAA</span>) vs. 23 [2.8-89] (atherosclerotic aorta) µg/g protein (P < 1 · 10 -14 )), and abundant expression of the CXCR1 and 2 receptors in <span class="hlt">AAA</span>. Array analysis followed by pathway analysis showed that CXCL8 hyper-expression in <span class="hlt">AAA</span> is followed increased by IL-8 signaling (Z-score for <span class="hlt">AAA</span> vs. atherosclerotic control: 2.97, p < 0.0001). Interference with CXCL8 signaling through DF2156A fully abrogated <span class="hlt">AAA</span> formation and prevented matrix degradation in the murine elastase model of <span class="hlt">AAA</span> disease (p < 0.001). CXCL8-signaling is a prominent and distinctive feature of <span class="hlt">AAA</span>, interference with the pathway constitutes a promising target for medical stabilization of <span class="hlt">AAA</span>. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29628493','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29628493"><span>Effect of a High-sucrose Diet on Abdominal Aortic Aneurysm Development in a Hypoperfusion-induced Animal Model.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Miyamoto, Chie; Kugo, Hirona; Hashimoto, Keisuke; Sawaragi, Ayaka; Zaima, Nobuhiro; Moriyama, Tatsuya</p> <p>2018-05-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a vascular disease that results in rupture of the abdominal aorta. The risk factors for the development of <span class="hlt">AAA</span> include smoking, male sex, hypertension, and age. <span class="hlt">AAA</span> has a high mortality rate, but therapy for <span class="hlt">AAA</span> is restricted to surgery in cases of large aneurysms. Clarifying the effect of dietary food on the development of <span class="hlt">AAA</span> would be helpful for patients with <span class="hlt">AAAs</span>. However, the relationship between dietary habits and the development of <span class="hlt">AAA</span> is largely unknown. In our previous study, we demonstrated that adipocytes in vascular wall can induce the rupture of <span class="hlt">AAA</span>. Therefore, we focused on the diet-induced abnormal triglyceride metabolism, which has the potential to drive <span class="hlt">AAA</span> development. In this study, we have evaluated the effects of a high-sucrose diet on the development of <span class="hlt">AAA</span> in a vascular hypoperfusion-induced animal model. A high sucrose diet induced high serum TG level and fatty liver. However, the <span class="hlt">AAA</span> rupture risk and the <span class="hlt">AAA</span> diameter were not significantly different between the control and high-sucrose groups. The intergroup differences in the elastin degradation score and collagen-positive area were insignificant. Moreover, matrix metalloproteinases, macrophages, and monocyte chemoattractant protein-1-positive areas did not differ significantly between groups. These results suggest that a high-sucrose diet does not affect the appearance of vascular adipocyte and <span class="hlt">AAA</span> development under the vascular hypoperfusion condition.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29685677','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29685677"><span>Spatial Analysis of Hospital Incidence and in Hospital Mortality of Abdominal Aortic Aneurysms in Germany: Secondary Data Analysis of Nationwide Hospital Episode (DRG) Data.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kuehnl, Andreas; Salvermoser, Michael; Erk, Alexander; Trenner, Matthias; Schmid, Volker; Eckstein, Hans-Henning</p> <p>2018-06-01</p> <p>This study aimed to analyze the spatial distribution and regional variation of the hospital incidence and in hospital mortality of abdominal aortic aneurysms (<span class="hlt">AAA</span>) in Germany. German DRG statistics (2011-2014) were analysed. Patients with ruptured <span class="hlt">AAA</span> (r<span class="hlt">AAA</span>, I71.3, treated or not) and patients with non-ruptured <span class="hlt">AAA</span> (nr<span class="hlt">AAA</span>, I71.4, treated by open or endovascular aneurysm repair) were included. Age, sex, and risk standardisation was done using standard statistical procedures. Regional variation was quantified using systematic component of variation. To analyse spatial auto-correlation and spatial pattern, global Moran's I and Getis-Ord Gi* were calculated. A total of 50,702 cases were included. Raw hospital incidence of <span class="hlt">AAA</span> was 15.7 per 100,000 inhabitants (nr<span class="hlt">AAA</span> 13.1; all r<span class="hlt">AAA</span> 2.7; treated r<span class="hlt">AAA</span> 1.6). The standardised hospital incidence of <span class="hlt">AAA</span> ranged from 6.3 to 30.3 per 100,000. Systematic component of variation proportion was 96% in nr<span class="hlt">AAA</span> and 55% in treated r<span class="hlt">AAA</span>. Incidence rates of all <span class="hlt">AAA</span> were significantly clustered with above average values in the northwestern parts of Germany and below average values in the south and eastern regions. Standardised mortality of nr<span class="hlt">AAA</span> ranged from 1.7% to 4.3%, with that of treated r<span class="hlt">AAA</span> ranging from 28% to 52%. Regional variation and spatial distribution of standardised mortality was not different from random. There was significant regional variation and clustering of the hospital incidence of <span class="hlt">AAA</span> in Germany, with higher rates in the northwest and lower rates in the southeast. There was no significant variation in standardised (age/sex/risk) mortality between counties. Copyright © 2018. Published by Elsevier B.V.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3188334','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3188334"><span>Through tobacco industry eyes: civil society and the FCTC process from <span class="hlt">Philip</span> Morris and British American Tobacco’s perspectives</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Gonzalez, Mariaelena; Green, Lawrence W; Glantz, Stanton A</p> <p>2011-01-01</p> <p>Objective To analyse the models <span class="hlt">Philip</span> Morris (PM) and British American Tobacco (BAT) used internally to understand tobacco control non-governmental organizations (NGOs) and their relationship to the global tobacco control policy-making process that resulted in the Framework Convention for Tobacco Control (FCTC). Methods Analysis of internal tobacco industry documents in the Legacy Tobacco Document Library. Results PM contracted with Mongoven, Biscoe, and Duchin, Inc. (MBD, a consulting firm specialising in NGO surveillance) as advisors. MBD argued that because NGOs are increasingly linked to epistemic communities, NGOs could insert themselves into the global policy-making process and influence the discourse surrounding the treaty-making process. MBD advised PM to insert itself into the policy-making process, mimicking NGO behaviour. BAT’s Consumer and Regulatory Affairs (CORA) department argued that global regulation emerged from the perception (by NGOs and governments) that the industry could not regulate itself, leading to BAT advocating social alignment and self-regulation to minimise the impact of the FCTC. Most efforts to block or redirect the FCTC failed. Conclusions PM and BAT articulated a global policy-making environment in which NGOs are key, non-state stakeholders, and as a result, internationalised some of their previous national-level strategies. After both companies failed to prevent the FCTC, their strategies began to align. Multinational corporations have continued to successfully employ some of the strategies outlined in this paper at the local and national level while being formally excluded from ongoing FCTC negotiations at the global level. PMID:21636611</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29754727','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29754727"><span>[Identifying barriers to screening for abdominal aortic aneurysm in general practice: Qualitative study of 14 general practitioners in Paris].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Niclot, J; Stansal, A; Saint-Lary, O; Lazareth, I; Priollet, P</p> <p>2018-05-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a silent pathology with often fatal consequences in case of rupture. <span class="hlt">AAA</span> screening, recommended in France and many other countries, has shown its effectiveness in reducing specific mortality. However, <span class="hlt">AAA</span> screening rate remains insufficient. To identify barriers to <span class="hlt">AAA</span> screening in general practice. Qualitative study carried out during 2016 among general practitioners based in Paris. Fourteen physicians were included. Most of the barriers were related to the physician: unawareness about <span class="hlt">AAA</span> and screening recommendations, considering <span class="hlt">AAA</span> as a secondary question not discussed with the patient, abdominal aorta not included in cardiovascular assessment, no search for a familial history of <span class="hlt">AAA</span>, <span class="hlt">AAA</span> considered a question for the specialist, lack of time, lack of training, numerous screenings to propose, oversight. Some barriers are related to the patient: unawareness of the pathology and family history of <span class="hlt">AAA</span>, refusal, questioning the pertinence of the doctor's comments, failure to respect the care pathway. Others are related to <span class="hlt">AAA</span>: source of anxiety, low prevalence, rarity of complications. The remaining barriers are related to screening: cost-benefit and risk-benefit ratios, sonographer unavailability, constraint for the patient, overmedicalization. Information and training of general practitioners about <span class="hlt">AAA</span> must be strengthened in order to optimize <span class="hlt">AAA</span> screening and reduce specific mortality. Copyright © 2018. Published by Elsevier Masson SAS.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4009235','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4009235"><span>Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kuivaniemi, Helena; Ryer, Evan J.; Elmore, James R.; Hinterseher, Irene; Smelser, Diane T.; Tromp, Gerard</p> <p>2014-01-01</p> <p>An abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. <span class="hlt">AAAs</span> are often asymptomatic and are discovered as incidental findings in imaging studies or when the <span class="hlt">AAA</span> ruptures leading to a medical emergency. <span class="hlt">AAAs</span> are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of <span class="hlt">AAA</span> increases the person's risk for <span class="hlt">AAA</span>. Interestingly, diabetes has been shown to be a protective factor for <span class="hlt">AAA</span> in many large studies. Hallmarks of <span class="hlt">AAA</span> pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in <span class="hlt">AAA</span> development and progression. In this Outlook paper, we summarize our recent studies on <span class="hlt">AAA</span> including clinical studies related to surgical repair of <span class="hlt">AAA</span> and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks. PMID:24834361</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4550325','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4550325"><span>Hypoperfusion of the Adventitial Vasa Vasorum Develops an Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sasaki, Takeshi; Sano, Masaki; Yamamoto, Naoto; Saito, Takaaki; Inuzuka, Kazunori; Hayasaka, Takahiro; Goto-Inoue, Naoko; Sugiura, Yuki; Sato, Kohji; Kugo, Hirona; Moriyama, Tatsuya; Konno, Hiroyuki; Setou, Mitsutoshi; Unno, Naoki</p> <p>2015-01-01</p> <p>The aortic wall is perfused by the adventitial vasa vasorum (VV). Tissue hypoxia has previously been observed as a manifestation of enlarged abdominal aortic aneurysms (<span class="hlt">AAAs</span>). We sought to determine whether hypoperfusion of the adventitial VV could develop <span class="hlt">AAAs</span>. We created a novel animal model of adventitial VV hypoperfusion with a combination of a polyurethane catheter insertion and a suture ligation of the infrarenal abdominal aorta in rats. VV hypoperfusion caused tissue hypoxia and developed infrarenal <span class="hlt">AAA</span>, which had similar morphological and pathological characteristics to human <span class="hlt">AAA</span>. In human <span class="hlt">AAA</span> tissue, the adventitial VV were stenotic in both small <span class="hlt">AAAs</span> (30–49 mm in diameter) and in large <span class="hlt">AAAs</span> (> 50 mm in diameter), with the sac tissue in these <span class="hlt">AAAs</span> being ischemic and hypoxic. These results indicate that hypoperfusion of adventitial VV has critical effects on the development of infrarenal <span class="hlt">AAA</span>. PMID:26308526</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4279216','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4279216"><span>Designation as “Unfit for Open Repair” Is Associated With Poor Outcomes After Endovascular Aortic Aneurysm Repair</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>De Martino, Randall R.; Brooke, Benjamin S.; Robinson, William; Schanzer, Andres; Indes, Jeffrey E.; Wallaert, Jessica B.; Nolan, Brian W.; Cronenwett, Jack L.; Goodney, Philip P.</p> <p>2014-01-01</p> <p>Background Endovascular aortic aneurysm repair (EVAR) is often offered to patients with abdominal aortic aneurysms (<span class="hlt">AAAs</span>) considered preoperatively to be unfit for open <span class="hlt">AAA</span> repair (o<span class="hlt">AAA</span>). This study describes the short- and long-term outcomes of patients undergoing EVAR with <span class="hlt">AAAs</span> <6.5 cm who are considered unfit for o<span class="hlt">AAA</span>. Methods and Results We analyzed elective EVARs for <span class="hlt">AAAs</span> <6.5 cm diameter in the Vascular Study Group of New England (2003–2011). Patients were designated as fit or unfit for o<span class="hlt">AAA</span> by the treating surgeon. End points included in-hospital major adverse events and long-term mortality. We identified patient characteristics associated with being unfit for open repair and predictors of survival using multivariable analyses. Of 1653 EVARs, 309 (18.7%) patients were deemed unfit for o<span class="hlt">AAA</span>. These patients were more likely to have advanced age, cardiac disease, chronic obstructive pulmonary disease, and larger aneurysms at the time of repair (54 versus 56 mm, P=0.001). Patients unfit for o<span class="hlt">AAA</span> had higher rates of cardiac (7.8% versus 3.1%, P<0.01) and pulmonary (3.6 versus 1.6, P<0.01) complications and worse survival rates at 5 years (61% versus 80%; log rank P<0.01) compared with those deemed fit for o<span class="hlt">AAA</span>. Finally, patients designated as unfit for o<span class="hlt">AAA</span> had worse survival, even adjusting for patient characteristics and aneurysm size (hazard ratio, 1.6; 95% confidence interval, 1.2–2.2; P<0.01). Conclusions In patients with <span class="hlt">AAAs</span> <6.5 cm, designation by the operating surgeon as unfit for o<span class="hlt">AAA</span> provides insight into both short- and long-term efficacy of EVAR. Patients unable to tolerate o<span class="hlt">AAA</span> may not benefit from EVAR unless their risk of <span class="hlt">AAA</span> rupture is very high. PMID:24046399</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5072406','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5072406"><span>Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne</p> <p>2016-01-01</p> <p>Male sex is a risk factor for abdominal aortic aneurysm (<span class="hlt">AAA</span>). Within the <span class="hlt">AAA</span> adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of <span class="hlt">AAA</span>, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of <span class="hlt">AAA</span> patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of <span class="hlt">AAA</span> patients and age/sex-matched non-<span class="hlt">AAA</span> patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of <span class="hlt">AAA</span> patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-<span class="hlt">AAA</span> PBMC, whereas there was no difference between female <span class="hlt">AAA</span> and non-<span class="hlt">AAA</span> patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all <span class="hlt">AAA</span> patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in <span class="hlt">AAA</span> patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to <span class="hlt">AAA</span>-pathogenesis. The <span class="hlt">AAA</span>-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of <span class="hlt">AAA</span> patients. PMID:27474483</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15072079','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15072079"><span>The Israeli Patient's Rights Law: evidence for deprofessionalization?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Anson, O</p> <p>1999-01-01</p> <p>In this paper, the Israeli Patient's Rights Law of 1996 is discussed within the framework of <span class="hlt">Haug</span>'s predicted process of deprofessionalization. It is argued that the law reflects global processes such as the diffusion of knowledge, consumerism, and values that emphasize human rights and democracy. By guaranteeing patients' access to medical information, by submitting medical decisions to extra-professional regulation, the law erodes professional power.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dggs.alaska.gov/pubs/id/1780','SCIGOVWS'); return false;" href="http://www.dggs.alaska.gov/pubs/id/1780"><span>Publications - PDF 97-29I | Alaska Division of Geological & Geophysical</span></a></p> <p><a target="_blank" href="http://www.science.gov/aboutsearch.html">Science.gov Websites</a></p> <p></p> <p></p> <p>igneous rocks <em>of</em> <em>the</em> Tanana B-1 Quadrangle and vicinity Authors: Newberry, R.J., and <span class="hlt">Haug</span>, S.A , and Sr isotopic data for igneous rocks <em>of</em> <em>the</em> Tanana B-1 Quadrangle and vicinity: Alaska Division <em>of</em> ; Isotopes; Plutonic; STATEMAP Project; Trace <em>Elements</em>; Volcanic Top <em>of</em> Page Department <em>of</em> Natural Resources</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4811126','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4811126"><span>Matricellular protein CCN3 mitigates abdominal aortic aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zhang, Chao; van der Voort, Dustin; Shi, Hong; Qing, Yulan; Hiraoka, Shuichi; Takemoto, Minoru; Yokote, Koutaro; Moxon, Joseph V.; Norman, Paul; Rittié, Laure; Atkins, G. Brandon; Gerson, Stanton L.; Shi, Guo-Ping; Golledge, Jonathan; Dong, Nianguo; Perbal, Bernard; Prosdocimo, Domenick A.</p> <p>2016-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a major cause of morbidity and mortality; however, the mechanisms that are involved in disease initiation and progression are incompletely understood. Extracellular matrix proteins play an integral role in modulating vascular homeostasis in health and disease. Here, we determined that the expression of the matricellular protein CCN3 is strongly reduced in rodent <span class="hlt">AAA</span> models, including angiotensin II–induced <span class="hlt">AAA</span> and elastase perfusion–stimulated <span class="hlt">AAA</span>. CCN3 levels were also reduced in human <span class="hlt">AAA</span> biopsies compared with those in controls. In murine models of induced <span class="hlt">AAA</span>, germline deletion of Ccn3 resulted in severe phenotypes characterized by elastin fragmentation, vessel dilation, vascular inflammation, dissection, heightened ROS generation, and smooth muscle cell loss. Conversely, overexpression of CCN3 mitigated both elastase- and angiotensin II–induced <span class="hlt">AAA</span> formation in mice. BM transplantation experiments suggested that the <span class="hlt">AAA</span> phenotype of CCN3-deficient mice is intrinsic to the vasculature, as <span class="hlt">AAA</span> was not exacerbated in WT animals that received CCN3-deficient BM and WT BM did not reduce <span class="hlt">AAA</span> severity in CCN3-deficient mice. Genetic and pharmacological approaches implicated the ERK1/2 pathway as a critical regulator of CCN3-dependent <span class="hlt">AAA</span> development. Together, these results demonstrate that CCN3 is a nodal regulator in <span class="hlt">AAA</span> biology and identify CCN3 as a potential therapeutic target for vascular disease. PMID:26974158</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29682508','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29682508"><span>A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Parthasarathy, Anutthaman; Cross, Penelope J; Dobson, Renwick C J; Adams, Lily E; Savka, Michael A; Hudson, André O</p> <p>2018-01-01</p> <p>Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (<span class="hlt">AAA</span>) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the <span class="hlt">AAA</span> pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The <span class="hlt">AAA</span> and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the <span class="hlt">AAA</span> by microbes and plants, and the branching out of <span class="hlt">AAA</span> metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of <span class="hlt">AAA</span> must obtain these primary metabolites from their diet. Therefore, the metabolism of <span class="hlt">AAA</span> by the host animal and the resident microflora are important for the health of all animals. In addition, the <span class="hlt">AAA</span> metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful <span class="hlt">AAA</span>-derived compounds produced by gut bacteria are discussed. Apart from the <span class="hlt">AAA</span> biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with <span class="hlt">AAA</span> catabolism in plants, <span class="hlt">AAA</span> degradation via the monoamine and kynurenine pathways in animals, and <span class="hlt">AAA</span> catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key <span class="hlt">AAA</span>-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5897657','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5897657"><span>A Three-Ring Circus: Metabolism of the Three Proteogenic Aromatic Amino Acids and Their Role in the Health of Plants and Animals</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Parthasarathy, Anutthaman; Cross, Penelope J.; Dobson, Renwick C. J.; Adams, Lily E.; Savka, Michael A.; Hudson, André O.</p> <p>2018-01-01</p> <p>Tyrosine, phenylalanine and tryptophan are the three aromatic amino acids (<span class="hlt">AAA</span>) involved in protein synthesis. These amino acids and their metabolism are linked to the synthesis of a variety of secondary metabolites, a subset of which are involved in numerous anabolic pathways responsible for the synthesis of pigment compounds, plant hormones and biological polymers, to name a few. In addition, these metabolites derived from the <span class="hlt">AAA</span> pathways mediate the transmission of nervous signals, quench reactive oxygen species in the brain, and are involved in the vast palette of animal coloration among others pathways. The <span class="hlt">AAA</span> and metabolites derived from them also have integral roles in the health of both plants and animals. This review delineates the de novo biosynthesis of the <span class="hlt">AAA</span> by microbes and plants, and the branching out of <span class="hlt">AAA</span> metabolism into major secondary metabolic pathways in plants such as the phenylpropanoid pathway. Organisms that do not possess the enzymatic machinery for the de novo synthesis of <span class="hlt">AAA</span> must obtain these primary metabolites from their diet. Therefore, the metabolism of <span class="hlt">AAA</span> by the host animal and the resident microflora are important for the health of all animals. In addition, the <span class="hlt">AAA</span> metabolite-mediated host-pathogen interactions in general, as well as potential beneficial and harmful <span class="hlt">AAA</span>-derived compounds produced by gut bacteria are discussed. Apart from the <span class="hlt">AAA</span> biosynthetic pathways in plants and microbes such as the shikimate pathway and the tryptophan pathway, this review also deals with <span class="hlt">AAA</span> catabolism in plants, <span class="hlt">AAA</span> degradation via the monoamine and kynurenine pathways in animals, and <span class="hlt">AAA</span> catabolism via the 3-aryllactate and kynurenine pathways in animal-associated microbes. Emphasis will be placed on structural and functional aspects of several key <span class="hlt">AAA</span>-related enzymes, such as shikimate synthase, chorismate mutase, anthranilate synthase, tryptophan synthase, tyrosine aminotransferase, dopachrome tautomerase, radical dehydratase, and type</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5027488','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5027488"><span>The Pch2 <span class="hlt">AAA</span>+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A.</p> <p>2016-01-01</p> <p>Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved <span class="hlt">AAA</span>+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. PMID:27257060</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27257060','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27257060"><span>The Pch2 <span class="hlt">AAA</span>+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Herruzo, Esther; Ontoso, David; González-Arranz, Sara; Cavero, Santiago; Lechuga, Ana; San-Segundo, Pedro A</p> <p>2016-09-19</p> <p>Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved <span class="hlt">AAA</span>+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21496030','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21496030"><span>Ultrastructural changes and the distribution of arabinogalactan proteins during somatic embryogenesis of banana (Musa spp. <span class="hlt">AAA</span> cv. 'Yueyoukang 1').</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pan, Xiao; Yang, Xiao; Lin, Guimei; Zou, Ru; Chen, Houbin; Samaj, Jozef; Xu, Chunxiang</p> <p>2011-08-01</p> <p>A better understanding of somatic embryogenesis in banana (Musa spp.) may provide a practical way to improve regeneration of banana plants. In this study, we applied scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to visualize the ultrastructural changes during somatic embryogenesis of banana (Musa <span class="hlt">AAA</span> cv. 'Yueyoukang 1'). We also used histological and immunohistochemical techniques with 16 monoclonal antibodies to study the spatial distribution and cellular/subcellular localization of different arabinogalactan protein (AGP) components of the cell wall during somatic embryogenesis. Histological study with periodic acid-Schiff staining documented diverse embryogenic stages from embryogenic cells (ECs) to the late embryos. SEM revealed a mesh-like structure on the surface of proembryos which represented an early structural marker of somatic embryogenesis. TEM showed that ECs were rich in juvenile mitochondria, endoplasmic reticulum and Golgi stacks. Cells in proembryos and early globular embryos resembled ECs, but they were more vacuolated, showed more regular nuclei and slightly more developed organelles. Immunocytochemical study revealed that the signal of most AGP epitopes was stronger in starch-rich cells when compared with typical ECs. The main AGP component in the extracellular matrix surface network of banana proembryos was the MAC204 epitope. Later, AGP immunolabelling patterns varied with the developmental stages of the embryos. These results about developmental regulation of AGP epitopes along with developmental changes in the ultrastructure of cells are providing new insights into the somatic embryogenesis of banana. Copyright © Physiologia Plantarum 2011.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19648133','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19648133"><span>An examination of the effect on cigarette prices and promotions of <span class="hlt">Philip</span> Morris USA penalties to stores that sell cigarettes to minors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Feighery, E C; Schleicher, N C; Ribisl, K M; Rogers, T</p> <p>2009-12-01</p> <p>The purpose of this study was to assess the potential impact of public policies to regulate price discounting strategies on retail cigarette prices and advertising. <span class="hlt">Philip</span> Morris USA (PM USA) has a policy designed to sanction stores violating state laws banning illegal tobacco sales to minors by temporarily suspending price discounting incentives. This study examined the impact of those sanctions on retail cigarette prices and sales promotion advertising. In November 2006, the California Attorney General's Office informed PM USA that 196 stores were found guilty of illegal underage sales. Of these, 109 stores that participated in the PM USA Retail Leaders Program were notified that their merchandising and/or promotional resources would be suspended for the month of April 2007. The remaining 87 stores were not sanctioned and served as a comparison group. Trained raters assessed advertising and prices of selected PM USA brands in these stores pre-penalty and during the penalty phase. There were no significant differences between sanctioned and non-sanctioned stores on median changes in price and sales promotion advertising from the pre-penalty to the penalty phase. The lack of impact on cigarette prices and advertising indicate that the PM USA policy may be flawed in its design or execution. If public policies are developed to restrain cigarette price discounting strategies, they should be crafted to ensure compliance and preclude possible compensatory actions by retailers.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3149637','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3149637"><span>Developmental Localization and Methylesterification of Pectin Epitopes during Somatic Embryogenesis of Banana (Musa spp. <span class="hlt">AAA</span>)</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Xu, Chunxiang; Zhao, Lu; Pan, Xiao; Šamaj, Jozef</p> <p>2011-01-01</p> <p>Background The plant cell walls play an important role in somatic embryogenesis and plant development. Pectins are major chemical components of primary cell walls while homogalacturonan (HG) is the most abundant pectin polysaccharide. Developmental regulation of HG methyl-esterification degree is important for cell adhesion, division and expansion, and in general for proper organ and plant development. Methodology/Principal Findings Developmental localization of pectic homogalacturonan (HG) epitopes and the (1→4)-β-D-galactan epitope of rhamnogalacturonan I (RG-I) and degree of pectin methyl-esterification (DM) were studied during somatic embryogenesis of banana (Musa spp. <span class="hlt">AAA</span>). Histological analysis documented all major developmental stages including embryogenic cells (ECs), pre-globular, globular, pear-shaped and cotyledonary somatic embryos. Histochemical staining of extracellularly secreted pectins with ruthenium red showed the most intense staining at the surface of pre-globular, globular and pear-shaped somatic embryos. Biochemical analysis revealed developmental regulation of galacturonic acid content and DM in diverse embryogenic stages. Immunodots and immunolabeling on tissue sections revealed developmental regulation of highly methyl-esterified HG epitopes recognized by JIM7 and LM20 antibodies during somatic embryogenesis. Cell walls of pre-globular/globular and late-stage embryos contained both low methyl-esterified HG epitopes as well as partially and highly methyl-esterified ones. Extracellular matrix which covered surface of early developing embryos contained pectin epitopes recognized by 2F4, LM18, JIM5, JIM7 and LM5 antibodies. De-esterification of cell wall pectins by NaOH caused a decrease or an elimination of immunolabeling in the case of highly methyl-esterified HG epitopes. However, immunolabeling of some low methyl-esterified epitopes appeared stronger after this base treatment. Conclusions/Significance These data suggest that both low</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24599423','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24599423"><span>From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Martinez-Pinna, R; Lindholt, J S; Madrigal-Matute, J; Blanco-Colio, L M; Esteban-Salan, M; Torres-Fonseca, M M; Lefebvre, T; Delbosc, S; Laustsen, J; Driss, F; Vega de Ceniga, M; Gouya, L; Weiss, G; Egido, J; Meilhac, O; Michel, J-B; Martin-Ventura, J</p> <p>2014-07-03</p> <p>Iron deposits are observed in tissue of abdominal aortic aneurysm (<span class="hlt">AAA</span>) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in <span class="hlt">AAA</span> patients, and tested if they could serve as biomarkers of <span class="hlt">AAA</span>. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in <span class="hlt">AAA</span> tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in <span class="hlt">AAA</span> patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in <span class="hlt">AAA</span> subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in <span class="hlt">AAA</span> patients. The association of low haemoglobin with <span class="hlt">AAA</span> presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of <span class="hlt">AAA</span> patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in <span class="hlt">AAA</span> patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among <span class="hlt">AAA</span> patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to <span class="hlt">AAA</span> subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in <span class="hlt">AAA</span> patients. Low haemoglobin levels are independently associated to <span class="hlt">AAA</span> presence and clinical outcome.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26158885','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26158885"><span>Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik</p> <p>2015-09-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAAs</span>) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between <span class="hlt">AAAs</span> and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on <span class="hlt">AAAs</span> specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the <span class="hlt">AAA</span>. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The <span class="hlt">AAA</span>-spine interaction is accounted for using a penalty method when the <span class="hlt">AAA</span> surface meets the spine surface. The simulation results show that, while the radial growth of the <span class="hlt">AAA</span> wall is prevented on the posterior side due to the spine acting as a constraint, the <span class="hlt">AAA</span> expands faster on the anterior side, leading to higher curvature and asymmetry in the <span class="hlt">AAA</span> configuration compared to the simulation excluding the spine. Accordingly, the <span class="hlt">AAA</span> wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the <span class="hlt">AAA</span>-spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of <span class="hlt">AAAs</span> but also provides a framework to account for the interactions between an enlarging <span class="hlt">AAA</span> and the spine for a better rupture potential assessment and management of <span class="hlt">AAA</span> patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27834688','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27834688"><span>Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tang, Weihong; Yao, Lu; Roetker, Nicholas S; Alonso, Alvaro; Lutsey, Pamela L; Steenson, Carol C; Lederle, Frank A; Hunter, David W; Bengtson, Lindsay G S; Guan, Weihua; Missov, Emil; Folsom, Aaron R</p> <p>2016-12-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is an important vascular disease in older adults, but data on lifetime risk of <span class="hlt">AAA</span> are sparse. We examined lifetime risk of <span class="hlt">AAA</span> in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and <span class="hlt">AAAs</span>. In ARIC study (Atherosclerosis Risk in Communities), 15 792 participants were recruited at visit 1 in 1987 to 1989 and followed up through 2013. Longitudinal smoking status was defined using smoking behavior ascertained from visit 1 (1987-1989) to visit 4 (1996-1998). We followed up participants for incident, clinical <span class="hlt">AAAs</span> using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through 2011 and identified 590 incident <span class="hlt">AAAs</span>. An abdominal ultrasound was conducted in 2011 to 2013 in 5911 surviving participants, and 75 asymptomatic <span class="hlt">AAAs</span> were identified. We estimated the lifetime risk of <span class="hlt">AAA</span> from the index age 45 years through 85 years of age. At age 45, the lifetime risk for <span class="hlt">AAA</span> was 5.6% (95% confidence interval, 4.8-6.1) and was higher in men (8.2%) and current smokers (10.5%). Smokers who quit smoking between visit 1 and visit 4 had a 29% lower <span class="hlt">AAA</span> lifetime risk compared with continuous smokers but had a higher risk than pre-visit 1 quitters. The lifetime risk of rupture or medical intervention was 1.6% (95% confidence interval, 1.2-1.8). Smoking, white race, male sex, greater height, and greater low-density lipoprotein or total cholesterol were associated with an increased risk of clinical <span class="hlt">AAA</span> and asymptomatic <span class="hlt">AAA</span>. At least 1 in 9 middle-aged current smokers developed <span class="hlt">AAA</span> in their lifetime. Smoking cessation reduced the lifetime risk of <span class="hlt">AAA</span>. © 2016 American Heart Association, Inc.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10214980','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10214980"><span>Aryl acylamidase activity exhibited by butyrylcholinesterase is higher in chick than in horse, but much lower than in fetal calf serum.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Weitnauer, E; Robitzki, A; Layer, P G</p> <p>1998-10-02</p> <p>Several side activities have been attributed to butyrylcholinesterase (BChE), including aryl acylamidase (<span class="hlt">AAA</span>) activity, which is an amidase-like activity with unknown physiological function splitting the artificial substrate o-nitroacetanilide. For avians, extensive developmental data have pointed to neurogenetic functions of BChE, however, a possible <span class="hlt">AAA</span> activity of BChE has not been studied. In this study, we first compare the relative levels of <span class="hlt">AAA</span> exhibited by BChE in whole sera from chick, fetal calves (FCS) and horse. Remarkably, FCS exhibits a 400-fold higher ratio of <span class="hlt">AAA</span>/BChE than horse and 80-fold higher than chick serum. We then show that an immunoisolated preparation of BChE from chicken serum presents significant activity for <span class="hlt">AAA</span>. Both in sera and with the purified enzyme, the <span class="hlt">AAA</span> activity is fully inhibited by anticholinesterase drugs, showing that <span class="hlt">AAA</span> activity is exclusively conveyed by the BChE molecule. Noticeably, <span class="hlt">AAA</span> inhibition even occurs at lower drug concentrations than that of BChE activity itself. Moreover, <span class="hlt">AAA</span> is sensitive to serotonin. These data indicate that (1) <span class="hlt">AAA</span> is a general feature of serum BChE of vertebrates including avians, (2) <span class="hlt">AAA</span> is effectively inhibited by cholinergic and serotonergic agents, and (3) <span class="hlt">AAA</span> may have a developmental role, since it is much pronounced in a serum from fetal animals. Functionally, deamination of neuropeptides, a link between cholinergic and serotonergic neurotransmitter systems, and roles in lipoprotein metabolism could be relevant.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://pubs.usgs.gov/circ/1983/0759/report.pdf','USGSPUBS'); return false;" href="https://pubs.usgs.gov/circ/1983/0759/report.pdf"><span>The Alaska Mineral Resource Assessment Program : guide to information contained in folio of geologic and mineral resource maps of the <span class="hlt">Philip</span> Smith Mountains quadrangle, Alaska</span></a></p> <p><a target="_blank" href="http://pubs.er.usgs.gov/pubs/index.jsp?view=adv">USGS Publications Warehouse</a></p> <p>Reiser, H.N.; Brosge, W.P.; Hamilton, T.D.; Singer, D.A.; Menzie, W. D.; Bird, K.J.; Cady, J.W.; Le Compte, J. R.; Cathrall, J.B.</p> <p>1983-01-01</p> <p>The geology and mineral resources of the <span class="hlt">Philip</span> Smith Mountains quadrangle were virtually unexplored until the investigations for oil began in northern Alaska. Construction of the Trans-Alaskan Pipeline System has now made the quadrangle accessible by road. In 1975 and 1976 a team of geologists, geochemists, and geophysicists investigated the quadrangle in order to assess its mineral resource potential. This report is a guide to the resulting folio of twelve maps that describe the geology, stream sediment geochemistry, aeromagnetic features, Landsat imagery, and mineral resources of the area. The bedrock geology and aeromagnetic surveys show that mineral deposits associated with intrusive rocks are probably absent. However, the geology and geochemical anomalies do indicate the possibility of vein and strata-bound deposits of copper, lead, and zinc in the Paleozoic shale and carbonate rocks in the southern part of the quadrangle and of stratabound deposits of zinc and copper in the Permian and Mesozoic shales along the mountain front. The northwestern part of the quadrangle has a low to moderate potential for oil or gas; Mississippian carbonate rocks are the most likely reservoir. The only minerals produced to date have been construction materials.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25131598','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25131598"><span>Meta-analysis of peak wall stress in ruptured, symptomatic and intact abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Khosla, S; Morris, D R; Moxon, J V; Walker, P J; Gasser, T C; Golledge, J</p> <p>2014-10-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is an important cause of sudden death; however, there are currently incomplete means to predict the risk of <span class="hlt">AAA</span> rupture. <span class="hlt">AAA</span> peak wall stress (PWS) can be estimated using finite element analysis (FEA) methods from computed tomography (CT) scans. The question is whether <span class="hlt">AAA</span> PWS can predict <span class="hlt">AAA</span> rupture. The aim of this systematic review was to compare PWS in patients with ruptured and intact <span class="hlt">AAA</span>. The MEDLINE database was searched on 25 May 2013. Case-control studies assessing PWS in asymptomatic intact, and acutely symptomatic or ruptured <span class="hlt">AAA</span> from CT scans using FEA were included. Data were extracted independently. A random-effects model was used to calculate standard mean differences (SMDs) for PWS measurements. Nine studies assessing 348 individuals were identified and used in the meta-analysis. Results from 204 asymptomatic intact and 144 symptomatic or ruptured <span class="hlt">AAAs</span> showed that PWS was significantly greater in the symptomatic/ ruptured <span class="hlt">AAAs</span> compared with the asymptomatic intact <span class="hlt">AAAs</span> (SMD 0·95, 95 per cent confidence interval 0·71 to 1·18; P < 0·001). The findings remained significant after adjustment for mean systolic blood pressure, standardized at 120 mmHg (SMD 0·68, 0·39 to 0·96; P < 0·001). Minimal heterogeneity between studies was noted (I(2)  = 0 per cent). This study suggests that PWS is greater in symptomatic or ruptured <span class="hlt">AAA</span> than in asymptomatic intact <span class="hlt">AAA</span>. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5147037','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5147037"><span>Variations in Abdominal Aortic Aneurysm Care: A Report From the International Consortium of Vascular Registries</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sedrakyan, Art; Mao, Jialin; Venermo, Maarit; Faizer, Rumi; Debus, Sebastian; Behrendt, Christian-Alexander; Scali, Salvatore; Altreuther, Martin; Schermerhorn, Marc; Beiles, Barry; Szeberin, Zoltan; Eldrup, Nikolaj; Danielsson, Gudmundur; Thomson, Ian; Wigger, Pius; Björck, Martin; Cronenwett, Jack L.; Mani, Kevin</p> <p>2016-01-01</p> <p>Background: This project by the ICVR (International Consortium of Vascular Registries), a collaboration of 11 vascular surgical quality registries, was designed to evaluate international variation in the contemporary management of abdominal aortic aneurysm (<span class="hlt">AAA</span>) with relation to recommended treatment guidelines from the Society for Vascular Surgery and the European Society for Vascular Surgery. Methods: Registry data for open and endovascular <span class="hlt">AAA</span> repair (EVAR) during 2010 to 2013 were collected from 11 countries. Variations in patient selection and treatment were compared across countries and across centers within countries. Results: Among 51 153 patients, 86% were treated for intact <span class="hlt">AAA</span> (i<span class="hlt">AAA</span>) and 14% for ruptured <span class="hlt">AAA</span>. Women constituted 18% of the entire cohort (range, 12% in Switzerland–21% in the United States; P<0.01). Intact <span class="hlt">AAAs</span> were repaired at diameters smaller than recommended by guidelines in 31% of men (<5.5 cm; range, 6% in Iceland–41% in Germany; P<0.01) and 12% of women with i<span class="hlt">AAA</span> (<5 cm; range, 0% in Iceland–16% in the United States; P<0.01). Overall, use of EVAR for i<span class="hlt">AAA</span> varied from 28% in Hungary to 79% in the United States (P<0.01) and for ruptured <span class="hlt">AAA</span> from 5% in Denmark to 52% in the United States (P<0.01). In addition to the between-country variations, significant variations were present between centers in each country in terms of EVAR use and rate of small <span class="hlt">AAA</span> repair. Countries that more frequently treated small <span class="hlt">AAAs</span> tended to use EVAR more frequently (trend: correlation coefficient, 0.51; P=0.14). Octogenarians made up 23% of all patients, ranging from 12% in Hungary to 29% in Australia (P<0.01). In countries with a fee-for-service reimbursement system (Australia, Germany, Switzerland, and the United States), the proportions of small <span class="hlt">AAA</span> (33%) and octogenarians undergoing i<span class="hlt">AAA</span> repair (25%) were higher compared with countries with a population-based reimbursement model (small <span class="hlt">AAA</span> repair, 16%; octogenarians, 18%; P<0.01). In general</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12616444','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12616444"><span>Epidemiology and outcome of aortic aneurysms in Hong Kong.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cheng, Stephen W K; Ting, Albert C W; Tsang, Simon H Y</p> <p>2003-02-01</p> <p>The objective of this study was to determine epidemiology and mortality statistics for abdominal aortic aneurysms (<span class="hlt">AAAs</span>) in Hong Kong. Data from three sources were obtained and analyzed: (1) Hong Kong Hospital Authority discharge statistics for 1999 and 2000; (2) a survey on aortic aneurysms in public hospitals conducted by the Working Group of Vascular Surgery; and (3) the Department of Surgery, University of Hong Kong Medical Center aortic aneurysm database. The disease pattern, distribution, and operative mortality were determined. The annual incidence of <span class="hlt">AAA</span> in Hong Kong is 13.7 per 100,000 population and 105 per 100,000 for those aged 65 and above. About 10% of the <span class="hlt">AAAs</span> that presented were ruptured. The mean age of the <span class="hlt">AAA</span> patients was 74 years, with 84% of them over age 65. The operative repair rate for <span class="hlt">AAAs</span> was low, being only 8% for intact aneurysms and 54% for ruptured ones. Overall, 45% of all aneurysm repairs were performed for a ruptured <span class="hlt">AAA</span>. There is diverse practice between major vascular centers and smaller regional hospitals. The territory-wide operative mortality rates for intact and ruptured aneurysms were 10% (range 4-24%) and 70% (range 38--100%), respectively. There was no gender bias in the rupture and operative rates. The overall mortality was 17% for intact <span class="hlt">AAAs</span> and 78% for ruptured <span class="hlt">AAAs</span>. The average length of hospital stay was 19 days for elective <span class="hlt">AAA</span> surgery and 13 days for ruptured <span class="hlt">AAAs</span>. The number of operations in high-volume centers is increasing with a concomitant decrease in operative mortality. There are no definitive data to indicate that the incidence of <span class="hlt">AAAs</span> is rising, but a trend toward an increasing number of operations in referral centers is noted. The low repair rates for intact <span class="hlt">AAAs</span> and the high proportion of repairs for ruptured aneurysms suggest that <span class="hlt">AAAs</span> are undertreated in Hong Kong.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4536993','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4536993"><span>Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Moran, Corey S.; Schreurs, Charlotte; Lindeman, Jan H. N.; Walker, Philip J.; Nataatmadja, Maria; West, Malcolm; Holdt, Lesca M.; Hinterseher, Irene; Pilarsky, Christian; Golledge, Jonathan</p> <p>2015-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human <span class="hlt">AAA</span> and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small <span class="hlt">AAAs</span> (≤ 55mm), 29 patients with large <span class="hlt">AAAs</span> (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large <span class="hlt">AAAs</span>, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large <span class="hlt">AAAs</span>. Examples of validated genes included CTLA4 (2.01-fold upregulated in small <span class="hlt">AAA</span>, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large <span class="hlt">AAA</span> with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large <span class="hlt">AAA</span>, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the <span class="hlt">AAA</span> and AOD transcriptomes were very different suggesting that <span class="hlt">AAA</span> and AOD have distinct pathogenic mechanisms. PMID:25944698</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28912007','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28912007"><span>Adventitial adipogenic degeneration is an unidentified contributor to aortic wall weakening in the abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Doderer, Stefan A; Gäbel, Gabor; Kokje, Vivianne B C; Northoff, Bernd H; Holdt, Lesca M; Hamming, Jaap F; Lindeman, Jan H N</p> <p>2018-06-01</p> <p>The processes driving human abdominal aortic aneurysm (<span class="hlt">AAA</span>) progression are not fully understood. Although antiinflammatory and proteolytic strategies effectively quench aneurysm progression in preclinical models, so far all clinical interventions failed. These observations hint at an incomplete understanding of the processes involved in <span class="hlt">AAA</span> progression and rupture. Interestingly, strong clinical and molecular associations exist between popliteal artery aneurysms (PAAs) and <span class="hlt">AAAs</span>; however, PAAs have an extremely low propensity to rupture. We thus reasoned that differences between these aneurysms may provide clues toward (auxiliary) processes involved in <span class="hlt">AAA</span>-related wall debilitation. A better understanding of the pathophysiologic processes driving <span class="hlt">AAA</span> growth can contribute to pharmaceutical treatments in the future. Aneurysmal wall samples were collected during open elective and emergency repair. Control perirenal aorta was obtained during kidney transplantation, and reference popliteal tissue obtained from the anatomy department. This study incorporates various techniques including (immuno)histochemistry, Western Blot, quantitative polymerase chain reaction, microarray, and cell culture. Histologic evaluation of <span class="hlt">AAAs</span>, PAAs, and control aorta shows extensive medial (PAA) and transmural fibrosis (<span class="hlt">AAA</span>), and reveals abundant adventitial adipocytes aggregates as an exclusive phenomenon of <span class="hlt">AAAs</span> (P < .001). Quantitative polymerase chain reaction, immunohistochemistry, Western blotting, and microarray analysis showed enrichment of adipogenic mediators (C/EBP family P = .027; KLF5 P < .000; and peroxisome proliferator activated receptor-γ, P = .032) in <span class="hlt">AAA</span> tissue. In vitro differentiation tests indicated a sharply increased adipogenic potential of <span class="hlt">AAA</span> adventitial mesenchymal cells (P < .0001). Observed enrichment of adipocyte-related genes and pathways in ruptured <span class="hlt">AAA</span> (P < .0003) supports an association between the extent of fatty degeneration and rupture. This</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2009AGUFMED14A..02W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2009AGUFMED14A..02W"><span>Science, Society, and Social Networking</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>White, K. S.; Lohwater, T.</p> <p>2009-12-01</p> <p>The increased use of social networking is changing the way that scientific societies interact with their members and others. The American Association for the Advancement of Science (<span class="hlt">AAAS</span>) uses a variety of online networks to engage its members and the broader scientific community. <span class="hlt">AAAS</span> members and non-members can interact with <span class="hlt">AAAS</span> staff and each other on <span class="hlt">AAAS</span> sites on Facebook, YouTube, and Twitter, as well as blogs and forums on the <span class="hlt">AAAS</span> website (www.<span class="hlt">aaas</span>.org). These tools allow scientists to more readily become engaged in policy by providing information on current science policy topics as well as methods of involvement. For example, members and the public can comment on policy-relevant stories from Science magazine’s ScienceInsider blog, download a weekly policy podcast, receive a weekly email update of policy issues affecting the scientific community, or watch a congressional hearing from their computer. <span class="hlt">AAAS</span> resource websites and outreach programs, including Communicating Science (www.<span class="hlt">aaas</span>.org/communicatingscience), Working with Congress (www.<span class="hlt">aaas</span>.org/spp/cstc/) and Science Careers (http://sciencecareers.sciencemag.org) also provide tools for scientists to become more personally engaged in communicating their findings and involved in the policy process.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27161550','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27161550"><span>Intervisceral artery origins in patients with abdominal aortic aneurysmal disease; evidence for systemic vascular remodelling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bailey, Damian M; Evans, Tom G; Thomas, Kate Gower; White, Richard D; Twine, Chistopher P; Lewis, Michael H; Williams, Ian M</p> <p>2016-08-01</p> <p>What is the central question of this study? To what extent focal abdominal aortic aneurysmal (<span class="hlt">AAA</span>) disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between distances of the intervisceral artery origins and <span class="hlt">AAA</span> location/size in patients with disease compared with healthy patients. What is the main finding and its importance? Intervisceral artery distances were shown to be consistently greater in <span class="hlt">AAA</span> patients, highlighting the systemic nature of <span class="hlt">AAA</span> disease that extends proximally to the abdominal aorta and its branches. The anatomical description of the natural variation in visceral artery origins has implications for the design of stent grafts and planning complex open aortic surgery. The initial histopathology of abdominal aortic aneurysmal (<span class="hlt">AAA</span>) disease is atherosclerotic, later diverting towards a distinctive dilating rather than occlusive aortic phenotype. To what extent focal <span class="hlt">AAA</span> disease is associated with systemic remodelling of the vascular tree remains unknown. The present study examined whether anatomical differences exist between the intervisceral artery origins and <span class="hlt">AAA</span> location/size in patients with <span class="hlt">AAA</span> disease (<span class="hlt">AAA</span>+) relative to those without (<span class="hlt">AAA</span>-). Preoperative contrast-enhanced computerized tomograms were reviewed in 90 consecutive <span class="hlt">AAA</span>+ patients scheduled for open repair who underwent an infrarenal (n = 45), suprarenal (n = 26) or supracoeliac clamp (n = 19). These were compared with 39 age-matched <span class="hlt">AAA</span>- control patients. Craniocaudal measurements were recorded from the distal origin of the coeliac artery to the superior mesenteric artery and from the origin of the superior mesenteric artery to both renal artery origins. Serial blood samples were obtained for estimation of the glomerular filtration rate before and after surgery. Intervisceral artery origins were shown to be consistently greater in <span class="hlt">AAA</span>+ patients (P < 0.05 versus <span class="hlt">AAA</span>-), although</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26409846','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26409846"><span>Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Skibba, Afshin A; Evans, James R; Hopkins, Steven P; Yoon, H Richard; Katras, Tony; Kalbfleisch, John H; Rush, Daniel S</p> <p>2015-12-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAAs</span>) may rupture at smaller diameters in women than in men, and women may be at higher risk and have poorer outcomes in elective and emergent interventions because of age and comorbidities. Practice guidelines recommending elective <span class="hlt">AAA</span> repair at >5.5 cm are gender neutral and may not adequately reflect increased risks in women or the potential advantages of elective lower risk endovascular procedures. Patients with a diagnosis of <span class="hlt">AAA</span> discharged from a single referral hospital during a 14-year period were identified for retrospective analysis. A total of 2121 patients with <span class="hlt">AAAs</span> were studied, 499 women (23.5%) and 1622 men (76.5%). Women were older and had a greater incidence of hypertension, smoking, chronic obstructive pulmonary disease, dyslipidemia, and renal insufficiency. Intact <span class="hlt">AAAs</span> in 467 women had a mean diameter of 4.4 ± 1.3 cm compared with 1538 men at 5.0 ± 1.4 cm (P < .01). The ruptured <span class="hlt">AAAs</span> in 32 women (6.4%) had a mean diameter of 6.1 ± 1.5 cm compared with 84 men (5.2%) at 7.7 ± 1.9 cm (P < .01). Women had a twofold increased frequency of <span class="hlt">AAA</span> rupture than men at all size intervals (P < .01). The frequency of ruptured <span class="hlt">AAAs</span> <5.5 cm among 10 of 32 women with ruptured <span class="hlt">AAAs</span> was 31.3%; among 7 of 84 men with ruptured <span class="hlt">AAAs</span>, it was 8.3% (P < .01). The frequency of ruptured <span class="hlt">AAAs</span> <5.5 cm in all 383 women with <span class="hlt">AAAs</span> <5.5 cm was 2.6%; in 1042 men, it was 0.6% (P < .01). Of the 1211 <span class="hlt">AAA</span> repairs, 574 (47.4%) were open aneurysm repair (OAR) and 637 (52.6%) were endovascular aneurysm repair (EVAR). Mortality after elective OAR in 475 patients of both sexes was 5.1%; for EVAR in 676 patients, mortality was 1.6% (P < .01). No differences in mortality with respect to OAR or EVAR were found between the female and male cohorts in either intact or ruptured <span class="hlt">AAAs</span>. Women with <span class="hlt">AAAs</span> are older and have a higher frequency of cardiovascular risk factors than men. Women rupture <span class="hlt">AAAs</span> with a greater frequency than men at all size intervals and have a</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3499938','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3499938"><span>Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E</p> <p>2012-01-01</p> <p>Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (<span class="hlt">AAA</span>). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in <span class="hlt">AAA</span> patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with <span class="hlt">AAA</span> and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured <span class="hlt">AAA</span> compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured <span class="hlt">AAA</span> (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured <span class="hlt">AAA</span> (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small <span class="hlt">AAA</span> compared to large <span class="hlt">AAA</span>. In conclusion, Hcy does not seem to be a useful biomarker in <span class="hlt">AAA</span> disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small <span class="hlt">AAA</span>. PMID:23173106</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23173106','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23173106"><span>Abdominal aortic aneurysm and the association with serum levels of Homocysteine, vitamins B6, B12 and Folate.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lindqvist, Markus; Hellström, Anders; Henriksson, Anders E</p> <p>2012-01-01</p> <p>Previous investigations have shown hyperhomocysteinemi in patients with abdominal aortic aneurysm (<span class="hlt">AAA</span>). In the present study we evaluated the circulating level of homocysteine (Hcy) in relation to renal function, vitamins B6, B12 and folate status in <span class="hlt">AAA</span> patients with special regard to aneurysm size, and rupture. Hcy, Creatinine, B6, B12 and folate were measured in 119 patients with <span class="hlt">AAA</span> and 36 controls without aneurysm matched by age, gender and smoking habit. As expected there was a weak correlation between Hcy and vitamins B6, B12 or folate. We found similar levels of Hcy, B6 and folic acid in patients with nonruptured <span class="hlt">AAA</span> compared to the control group matched by age, gender and smoking habit. There was no correlation between maximum diameter of the nonruptured <span class="hlt">AAA</span> (n=78) and Hcy, B6 or folate. However, the present study shows a significant inverse correlation between maximum diameter of the nonruptured <span class="hlt">AAA</span> (n=78) and B12 (r = -0.304, p=0.007) with significant higher levels in small <span class="hlt">AAA</span> compared to large <span class="hlt">AAA</span>. In conclusion, Hcy does not seem to be a useful biomarker in <span class="hlt">AAA</span> disease. The unexpected finding of B12 levels correlating to aneurysm diameter warrants urgent further investigation of B12 supplement to prevent progression of small <span class="hlt">AAA</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29460048','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29460048"><span>Abdominal aortic aneurysms: pre- and post-procedural imaging.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hallett, Richard L; Ullery, Brant W; Fleischmann, Dominik</p> <p>2018-05-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a relatively common, potentially life-threatening disorder. Rupture of <span class="hlt">AAA</span> is potentially catastrophic with high mortality. Intervention for <span class="hlt">AAA</span> is indicated when the aneurysm reaches 5.0-5.5 cm or more, when symptomatic, or when increasing in size > 10 mm/year. <span class="hlt">AAA</span> can be accurately assessed by cross-sectional imaging including computed tomography angiography and magnetic resonance angiography. Current options for intervention in <span class="hlt">AAA</span> patients include open surgery and endovascular aneurysm repair (EVAR), with EVAR becoming more prevalent over time. Cross-sectional imaging plays a crucial role in <span class="hlt">AAA</span> surveillance, pre-procedural assessment, and post-EVAR management. This paper will discuss the current role of imaging in the assessment of <span class="hlt">AAA</span> patients prior to intervention, in evaluation of procedural complications, and in long-term follow-up of EVAR patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28912363','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28912363"><span>TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lareyre, Fabien; Clément, Marc; Raffort, Juliette; Pohlod, Stefanie; Patel, Meghana; Esposito, Bruno; Master, Leanne; Finigan, Alison; Vandestienne, Marie; Stergiopulos, Nikolaos; Taleb, Soraya; Trachet, Bram; Mallat, Ziad</p> <p>2017-11-01</p> <p>Current experimental models of abdominal aortic aneurysm (<span class="hlt">AAA</span>) do not accurately reproduce the major features of human <span class="hlt">AAA</span>. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity-a guardian of vascular integrity and immune homeostasis-would impair vascular healing in models of nondissecting <span class="hlt">AAA</span> and would lead to sustained aneurysmal growth until rupture. Here, we test this hypothesis in the elastase-induced <span class="hlt">AAA</span> model in mice. We analyze <span class="hlt">AAA</span> development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. <span class="hlt">AAA</span> growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits <span class="hlt">AAA</span> severity. However, blockade of IL-1β after disease initiation has no effect on <span class="hlt">AAA</span> progression to rupture. Endogenous TGFβ activity is required for the healing of <span class="hlt">AAA</span>. TGFβ blockade may be harnessed to generate new models of <span class="hlt">AAA</span> with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of <span class="hlt">AAA</span> and will be useful in the identification of new therapeutic targets. © 2017 American Heart Association, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28256324','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28256324"><span>Time trends in hospital admissions and mortality due to abdominal aortic aneurysms in France, 2002-2013.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Robert, M; Juillière, Y; Gabet, A; Kownator, S; Olié, V</p> <p>2017-05-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAA</span>) are serious disease with a high fatality rate but recent epidemiologic data showed a decrease of <span class="hlt">AAA</span> mortality. Our objective was to estimate, in France, the hospitalization, inhospital mortality and mortality rates due to <span class="hlt">AAA</span> and to analyze their trends over time. Hospitalization data were extracted from the hospital discharge summaries in the national database between 2002 and 2013. The analysis covered all patients hospitalized for <span class="hlt">AAA</span> as a principal diagnosis. During the same period, all death certificates mentioning <span class="hlt">AAA</span> as an initial cause of death were included in the study. Crude and standardized rates were calculated according to age and sex. Poisson regression was used to analyze the average annual percent change. In 2013, there were 8853 patients hospitalized for <span class="hlt">AAA</span> in France (7986 unruptured and 867 ruptured). Between 2002 and 2013, the rate of patients hospitalized for unruptured <span class="hlt">AAA</span> decreased slightly in men (-5.0%) but increased in women (+5.2%). By contrast, the rate of patients hospitalized for ruptured <span class="hlt">AAA</span> has decreased by >20% in men and women. The proportion of endovascular treatment of unruptured <span class="hlt">AAA</span> rose from <10% in 2005 to 35% in women and 40% in men in 2013. In 2013, 939 deaths from <span class="hlt">AAA</span> were recorded. Mortality for this disease declined significantly from 2002 to 2013 in men and women. The unfavorable epidemiological trends in women and important evolution of the management of <span class="hlt">AAA</span> call for an epidemiological surveillance of this disease. Copyright © 2017 Elsevier B.V. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27126477','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27126477"><span>Two C-C Family Chemokines, Eotaxin and RANTES, Are Novel Independent Plasma Biomarkers for Abdominal Aortic Aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jones, Gregory T; Phillips, L Victoria; Williams, Michael J A; van Rij, Andre M; Kabir, Tasnuva D</p> <p>2016-04-28</p> <p>Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm (<span class="hlt">AAA</span>). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of <span class="hlt">AAA</span>. Tissue profiles of 27 inflammatory cytokine were examined in <span class="hlt">AAA</span> (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T-cell expressed and secreted (RANTES), eotaxin, and macrophage inflammatory protein 1 beta (MIP-1b), had increased expression in <span class="hlt">AAA</span>, particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor (bFGF) had reduced expression in all layers of the <span class="hlt">AAA</span> wall. Examination of the circulating plasma profiles of <span class="hlt">AAA</span> (n=442) and <span class="hlt">AAA</span>-free controls (n=970) suggested a (risk factor adjusted) <span class="hlt">AAA</span>-association with eotaxin, RANTES, and high sensitivity C-reactive protein (hsCRP). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with <span class="hlt">AAA</span> (odds ratio, 4.8; 95% CI, 3.5-6.7; P<0.0001), independent of age, sex, history of ischemic heart disease, and smoking. Contrary to reports suggesting a distinct T helper 2-associated inflammatory profile in <span class="hlt">AAA</span>, this current study suggests a more-generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES. In combination with hsCRP, these markers may have potential utility as <span class="hlt">AAA</span> biomarkers. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4574855','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4574855"><span>Computational Growth and Remodeling of Abdominal Aortic Aneurysms Constrained by the Spine</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Farsad, Mehdi; Zeinali-Davarani, Shahrokh; Choi, Jongeun; Baek, Seungik</p> <p>2015-01-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAAs</span>) evolve over time, and the vertebral column, which acts as an external barrier, affects their biomechanical properties. Mechanical interaction between <span class="hlt">AAAs</span> and the spine is believed to alter the geometry, wall stress distribution, and blood flow, although the degree of this interaction may depend on <span class="hlt">AAAs</span> specific configurations. In this study, we use a growth and remodeling (G&R) model, which is able to trace alterations of the geometry, thus allowing us to computationally investigate the effect of the spine for progression of the <span class="hlt">AAA</span>. Medical image-based geometry of an aorta is constructed along with the spine surface, which is incorporated into the computational model as a cloud of points. The G&R simulation is initiated by local elastin degradation with different spatial distributions. The AAA–spine interaction is accounted for using a penalty method when the <span class="hlt">AAA</span> surface meets the spine surface. The simulation results show that, while the radial growth of the <span class="hlt">AAA</span> wall is prevented on the posterior side due to the spine acting as a constraint, the <span class="hlt">AAA</span> expands faster on the anterior side, leading to higher curvature and asymmetry in the <span class="hlt">AAA</span> configuration compared to the simulation excluding the spine. Accordingly, the <span class="hlt">AAA</span> wall stress increases on the lateral, posterolateral, and the shoulder regions of the anterior side due to the AAA–spine contact. In addition, more collagen is deposited on the regions with a maximum diameter. We show that an image-based computational G&R model not only enhances the prediction of the geometry, wall stress, and strength distributions of <span class="hlt">AAAs</span> but also provides a framework to account for the interactions between an enlarging <span class="hlt">AAA</span> and the spine for a better rupture potential assessment and management of <span class="hlt">AAA</span> patients. PMID:26158885</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2001SPIE.4362...89D','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2001SPIE.4362...89D"><span>Successful marriage: American Panel Corporation and LG <span class="hlt">Philips</span> LCD custom-designed avionic, shipboard, and rugged ground vehicle display modules from a consumer-oriented fabrication facility</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Dunn, William; Garrett, Kimberly S.</p> <p>2001-09-01</p> <p>American panel corporation (APC) believes the use of custom designed (instead of ruggedized commercial) AMLCD cells is the only way to meet the specific environmental and performance requirements of the military/commercial avionic, shipboard and rugged ground vehicle markets. The APC/LG.<span class="hlt">Philips</span> LCD (LG) custom approach mitigates risk to the end-user in many ways. As a part of the APC/LG long- term agreement LG has committed to provide module level equivalent (form, fit and function equivalent) panels for a period of ten years. No other commercial glass manufacturer has provided such an agreement. With the use of LG's commercial production manufacturing capabilities, APC/LG can provide the opportunity to procure a lifetime buy for any program with delivery of the entire lot within six months of order placement. This ensures that the entire production program will receive identical glass for every unit. The APC/LG relationship works where others have failed due to the number of years spent cultivating the mutual trust and respect necessary for establishing such a partnership, LG's interest in capturing the market share of this niche application, and the magnitude of the initial up-front investment by APC in engineering, tooling, facilities, production equipment, and LCD cell inventory.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/AD1018858','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/AD1018858"><span>Using Genetic Buffering Relationships Identified in Fission Yeast To Elucidate the Molecular Pathology of Tuberous Sclerosis</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2016-07-01</p> <p>5’-aat tat ttt ata tgg aat gag caa gta tgt ttt atc ata att gac cag ttc att tca agg acc ttc <span class="hlt">aaa</span> aat ata cct acg aat tcg agc tcg ttt <span class="hlt">aaa</span> c-3’), or...oTsc13 (5’-tta aga gtt cag att tgc ttt atg tgg tta ttc tgc tga agg tcc taa ttt att gac gtt gaa <span class="hlt">aaa</span> taa agg cca cat agc gga tcc ccg ggt taa tta a-3...and oTsc14 (5’-ata <span class="hlt">aaa</span> <span class="hlt">aaa</span> att aat taa tga tgg caa ggc aca atc gta atc aat ctt tta att tag gac ttt tta tat gcc ctt atg gcg aat tcg agc tcg ttt <span class="hlt">aaa</span> c</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19515587','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19515587"><span>Matrix metalloproteinase-2 gene variants and abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smallwood, L; Warrington, N; Allcock, R; van Bockxmeer, F; Palmer, L J; Iacopetta, B; Golledge, J; Norman, P E</p> <p>2009-08-01</p> <p>To investigate associations between two polymorphisms of the matrix metalloproteinase-2 gene (MMP2) and the incidence and progression of abdominal aortic aneurysm (<span class="hlt">AAA</span>). Cases and controls were recruited from a trial of screening for <span class="hlt">AAAs</span>. The association between two variants of MMP2 (-1360C>T, and +649C>T) in men with <span class="hlt">AAA</span> (n=678) and in controls (n=659) was examined using multivariate analyses. The association with <span class="hlt">AAA</span> expansion (n=638) was also assessed. In multivariate analyses with adjustments for multiple testing, no association between either SNP and <span class="hlt">AAA</span> presence or expansion was detected. MMP2 -1360C>T and +649C>T variants are not risk factors for <span class="hlt">AAA</span>.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17903648','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17903648"><span>The interleukin-10-1082 'A' allele and abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Bown, Matthew J; Lloyd, Geraint M; Sandford, Rebecca M; Thompson, John R; London, Nicholas J M; Samani, Nilesh J; Sayers, Robert D</p> <p>2007-10-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAA</span>) are caused by inflammatory processes in the wall of the aorta resulting in degradation of structural proteins. This inflammatory process is mediated, in part, by cytokines, and interleukin-10 (IL-10) is a predominantly anti-inflammatory cytokine. A single nucleotide polymorphism in the promoter region of the IL-10 gene that affects transcription has been associated with <span class="hlt">AAA</span> in a small study. The aim of this study was to determine whether this polymorphism is associated with <span class="hlt">AAA</span> and also examine its effect on the growth of small <span class="hlt">AAA</span>. A case control study was performed. A total of 389 patients with <span class="hlt">AAA</span> and 404 healthy controls were recruited. IL-10-1082 polymorphisms were determined by polymerase chain reaction-based methods. In the case of patients with small <span class="hlt">AAA</span> (<5.5 cm), serial size measurements were recorded to determine mean growth rate. There was a statistically significant difference both in allele and genotype frequencies between the case and control groups with the IL-10-1082 'A' allele being more common in the <span class="hlt">AAA</span> group (P = .006). In the <span class="hlt">AAA</span> group, genotype frequencies were as follows: GG 84, GA 201, and AA 104. In the control group, the genotype frequencies were GG 118, GA 205, and AA 81. The odds ratio for the 'A' allele as a risk factor for <span class="hlt">AAA</span> was 1.50 (95% confidence interval 1.09 to 2.07). Regression modeling revealed that the IL-10-1082 genotype was, however, not independently associated with <span class="hlt">AAA</span> if age, tobacco use, hypertension, and history of coronary or peripheral artery disease was taken into account. There was a trend towards lower plasma IL-10 level in IL-10 AA carriers, but the IL-10 'A' allele did not have any discernible effect on the growth of small <span class="hlt">AAA</span>. This study demonstrates that the IL-10-1082 'A' allele is associated with <span class="hlt">AAA</span>, although this association is likely to be secondary to an association between IL-10-1082 genotype and other markers of cardiovascular disease rather than <span class="hlt">AAA</span> per se.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28433630','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28433630"><span>Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki</p> <p>2017-06-03</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and <span class="hlt">AAA</span> development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed <span class="hlt">AAAs</span>. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- <span class="hlt">AAAs</span> compared with WT <span class="hlt">AAAs</span>, which were accompanied by advanced fibrosis in the tunica media of MURC -/- <span class="hlt">AAAs</span>. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- <span class="hlt">AAAs</span> compared with WT <span class="hlt">AAAs</span> at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- <span class="hlt">AAAs</span> exhibited attenuated JNK activity compared with WT <span class="hlt">AAAs</span>. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, <span class="hlt">AAAs</span> were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates <span class="hlt">AAA</span> progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against <span class="hlt">AAA</span> progression. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA499787','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA499787"><span>The Antiaircraft Journal. Volume 94, Number 6, November-December 1951</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1951-12-01</p> <p>authorized by the Visiting Forces Act. Getting their heads together, the Yanks and Tommies have discovered each other to be pretty regular fellows...Francis A., to 3Sth <span class="hlt">AAA</span> Brig, Ft Meade, Md. McDaniel, Otto L., to Hq Fourth Army, Ft Sam Houston, Tex. Pape, Robin B., to SOth <span class="hlt">AAA</span> Gp, Ft Totten , NY...to 71 Sth <span class="hlt">AAA</span> Gun Bn, Ft Totten , NJ. Kee, Pat M., to 209th <span class="hlt">AAA</span> Gp, Indiantown Gap, Pa. Kennaman, Jack R., to SOlst <span class="hlt">AAA</span> Gun Bn, North Richland, Wash</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA509804','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA509804"><span>The Antiaircraft Journal. Volume 95, Number 2, March-April 1952</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1952-04-01</p> <p>Command, Yoko- hama. Breuning, E. G., Far East Command, Yoko- hama Cacchiotti, Ralph R., 31st <span class="hlt">AAA</span> Brig., Ft Lewis, Wash. Colbert , Edward F., 197th <span class="hlt">AAA</span> Gp...Wilbur B., 47th <span class="hlt">AAA</span> Brig., Cp Stew- art, Ga. Frick, Edwin J., 336th <span class="hlt">AAA</span> Gun Bn, Cp Ed- wards. Mass. Gildon, Milo E., USA Alaska, Fort Richard- son</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19050809','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19050809"><span>The accuracy of combined physical examination and ultrasonography for the detection of abdominal aorta aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cârstea, Doina; Streba, Letiţia Adela Maria; Glodeanu, Adina; Cârstea, A P; Vancu, Mihaela; Ninulescu, Ana-Maria</p> <p>2008-01-01</p> <p>Atherosclerosis is the most frequent cause in the appearance of an abdominal aorta aneurysm (<span class="hlt">AAA</span>) and plays an important role in his development. Most <span class="hlt">AAA</span> does not cause any symptoms, especially when talking about elderly patients, however, many of those aneurysms can be detected during physical examination. Their detection is very important because the natural evolution and the major reason in treating <span class="hlt">AAA</span> is their tendency to rupture. We present the case of an adult man with a complex clinical pathology, but not related to the <span class="hlt">AAA</span>. The diagnosis of the <span class="hlt">AAA</span> has been suspicion through palpation, and the abdominal ultrasound exam confirmed it. This case is particular interesting, as the <span class="hlt">AAA</span> requires surgical intervention, while patient's health status was poor. An essential issue is establishing the importance of the <span class="hlt">AAA</span> screening, when there are no symptoms present. For now, there are not satisfactory studies to be used as a guide.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19695303','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19695303"><span>High aryl acylamidase activity associated with cobra venom acetylcholinesterase: biological significance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rajesh, Ramanna V; Layer, Paul G; Boopathy, Rathanam</p> <p>2009-01-01</p> <p>Investigation of the non-classical functions of cholinesterases (ChEs) has been the subject of interest in the past three decades. One of which is aryl acylamidase (<span class="hlt">AAA</span>) activity associated with ChEs, but characterized in in vitro, as an enzyme, splitting the artificial substrate o-nitroacetanilide with unknown physiological function. In the present study, we have compared levels of <span class="hlt">AAA</span> activity of AChE from different sources like goat brain, electric eel organ and from venoms of different snakes. Remarkably cobra venom showed the highest <span class="hlt">AAA</span> activity and also high <span class="hlt">AAA</span>/AChE ratio. Both serotonergenic and cholinergic inhibitors inhibited the cobra venom <span class="hlt">AAA</span> activity in a concentration dependent manner, which also underlines the association of <span class="hlt">AAA</span> with AChE of cobra venom. The study becomes interesting because of i) the cobra venom AChE exists in monomeric globular forms; ii) in Alzheimer's disease too the most abundant forms of cholinesterases are monomeric globular forms, thought to be involved in the pathogenesis of Alzheimer's disease; iii) the effect of Alzheimer's disease drugs on the <span class="hlt">AAA</span> activity of cobra venom, indicated that <span class="hlt">AAA</span> activity of cobra venom was more sensitive than AChE and iv) Huperzine and Tacrine showed more pronounced effect on <span class="hlt">AAA</span>. Thus, this study elucidates the high <span class="hlt">AAA</span> associated with cobra venom AChE may serve as one of the prominent activity to test the pharmacological effect of AD drugs, as other sources were found to have lower activity.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3897527','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3897527"><span>Homocysteine Level and Risk of Abdominal Aortic Aneurysm: A Meta-Analysis</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Cao, Hui; Hu, Xinhua; Zhang, Qiang; Li, Jun; Wang, Junpeng; Shao, Yang; Liu, Bing; Xin, Shijie</p> <p>2014-01-01</p> <p>Objectives Previous studies have reported inconsistent findings regarding the association between elevated plasma homocysteine (Hcy) levels and abdominal aortic aneurysm (<span class="hlt">AAA</span>). We investigated this association between Hcy levels in patients with <span class="hlt">AAA</span> and unaffected controls by conducting a meta-analysis and systematic review. Methods We conducted a systematic literature search (up to August 2013) of the PubMed database and Embase. We selected observational studies that evaluated Hcy levels in subjects with <span class="hlt">AAA</span> compared to unaffected controls. Criteria for inclusion were the assessment of baseline Hcy and risk of <span class="hlt">AAA</span> as an outcome. The results were presented as odd ratio (OR) and corresponding 95% confidence intervals (CI) comparing <span class="hlt">AAA</span> patients to the control subjects. Results 7 studies with 6,445 participants were identified and analyzed. Overall, elevated plasma Hcy was associated with an increased risk of <span class="hlt">AAA</span> (3.29; 95% CI 1.66–6.51). The pooled adjusted OR from a random effect model of only men participants in the <span class="hlt">AAA</span> compared with the control group was 2.36 (95% CI 0.63–8.82). Conclusion This meta-analysis and systematic review suggested that Hcy significantly increased the risk of <span class="hlt">AAA</span>. PMID:24465733</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29732374','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29732374"><span>Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan</p> <p>2018-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of <span class="hlt">AAA</span>, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for <span class="hlt">AAAs</span>. However, these treatments are not appropriate for the majority of <span class="hlt">AAAs</span>, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of <span class="hlt">AAA</span>. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as <span class="hlt">AAA</span>. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of <span class="hlt">AAA</span>. Mechanisms of action underlying the effects of CHMs on <span class="hlt">AAA</span> are also discussed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19228900','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19228900"><span>Enhancing human-animal relationships through veterinary medical instruction in animal-assisted therapy and animal-assisted activities.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schaffer, Caroline Brunsman</p> <p>2008-01-01</p> <p>Instruction in animal-assisted therapy (AAT) and animal-assisted activities (<span class="hlt">AAAs</span>) teaches veterinary medical students to confidently and assertively maximize the benefits and minimize the risks of this union of animals and people. Instruction in AAT/<span class="hlt">AAA</span> also addresses requirements by the American Veterinary Medical Association Council on Education that accredited schools/colleges of veterinary medicine include in their standard curriculum the topics of the human-animal bond, behavior, and the contributions of the veterinarian to the overall public and professional health care teams. Entry-level veterinarians should be prepared to: (1) assure that animals who provide AAT/<span class="hlt">AAA</span> are healthy enough to visit nursing homes, hospitals, or other institutions; (2) promote behavior testing that selects animals who will feel safe, comfortable, and connected; (3) advise facilities regarding infection control and ways to provide a safe environment where the animals, their handlers, and the people being visited will not be injured or become ill; and (4) advocate for their patients and show compassion for their clients when animals are determined to be inappropriate participants in AAT/<span class="hlt">AAA</span> programs. This article presents AAT/<span class="hlt">AAA</span> terminology, ways in which veterinarians can advocate for AAT/<span class="hlt">AAA</span>, the advantages of being involved in AAT/<span class="hlt">AAA</span>, a model AAT/<span class="hlt">AAA</span> practicum from Tuskegee University's School of Veterinary Medicine (TUSVM), and examples of co-curricular activities in AAT/<span class="hlt">AAA</span> by TUSVM's student volunteers.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26980774','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26980774"><span>Lipoprotein(a) Levels in Patients With Abdominal Aortic Aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kotani, Kazuhiko; Sahebkar, Amirhossein; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Mariscalco, Giovanni; Jones, Steven R; Martin, Seth; Blaha, Michael J; Toth, Peter P; Rizzo, Manfredi; Kostner, Karam; Rysz, Jacek; Banach, Maciej</p> <p>2017-02-01</p> <p>Circulating markers relevant to the development of abdominal aortic aneurysm (<span class="hlt">AAA</span>) are currently required. Lipoprotein(a), Lp(a), is considered a candidate marker associated with the presence of <span class="hlt">AAA</span>. The present meta-analysis aimed to evaluate the association between circulating Lp(a) levels and the presence of <span class="hlt">AAA</span>. The PubMed-based search was conducted up to April 30, 2015, to identify the studies focusing on Lp(a) levels in patients with <span class="hlt">AAA</span> and controls. Quantitative data synthesis was performed using a random effects model, with standardized mean difference (SMD) and 95% confidence interval (CI) as summary statistics. Overall, 9 studies were identified. After a combined analysis, patients with <span class="hlt">AAA</span> were found to have a significantly higher level of Lp(a) compared to the controls (SMD: 0.87, 95% CI: 0.41-1.33, P < .001). This result remained robust in the sensitivity analysis, and its significance was not influenced after omitting each of the included studies from the meta-analysis. The present meta-analysis confirmed a higher level of circulating Lp(a) in patients with <span class="hlt">AAA</span> compared to controls. High Lp(a) levels can be associated with the presence of <span class="hlt">AAA</span>, and Lp(a) may be a marker in screening for <span class="hlt">AAA</span>. Further studies are needed to establish the clinical utility of measuring Lp(a) in the prevention and management of <span class="hlt">AAA</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5146935','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5146935"><span>Quantitative HDL Proteomics Identifies Peroxiredoxin-6 as a Biomarker of Human Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Burillo, Elena; Jorge, Inmaculada; Martínez-López, Diego; Camafeita, Emilio; Blanco-Colio, Luis Miguel; Trevisan-Herraz, Marco; Ezkurdia, Iakes; Egido, Jesús; Michel, Jean-Baptiste; Meilhac, Olivier; Vázquez, Jesús; Martin-Ventura, Jose Luis</p> <p>2016-01-01</p> <p>High-density lipoproteins (HDLs) are complex protein and lipid assemblies whose composition is known to change in diverse pathological situations. Analysis of the HDL proteome can thus provide insight into the main mechanisms underlying abdominal aortic aneurysm (<span class="hlt">AAA</span>) and potentially detect novel systemic biomarkers. We performed a multiplexed quantitative proteomics analysis of HDLs isolated from plasma of <span class="hlt">AAA</span> patients (N = 14) and control study participants (N = 7). Validation was performed by western-blot (HDL), immunohistochemistry (tissue), and ELISA (plasma). HDL from <span class="hlt">AAA</span> patients showed elevated expression of peroxiredoxin-6 (PRDX6), HLA class I histocompatibility antigen (HLA-I), retinol-binding protein 4, and paraoxonase/arylesterase 1 (PON1), whereas α-2 macroglobulin and C4b-binding protein were decreased. The main pathways associated with HDL alterations in <span class="hlt">AAA</span> were oxidative stress and immune-inflammatory responses. In <span class="hlt">AAA</span> tissue, PRDX6 colocalized with neutrophils, vascular smooth muscle cells, and lipid oxidation. Moreover, plasma PRDX6 was higher in <span class="hlt">AAA</span> (N = 47) than in controls (N = 27), reflecting increased systemic oxidative stress. Finally, a positive correlation was recorded between PRDX6 and <span class="hlt">AAA</span> diameter. The analysis of the HDL proteome demonstrates that redox imbalance is a major mechanism in <span class="hlt">AAA</span>, identifying the antioxidant PRDX6 as a novel systemic biomarker of <span class="hlt">AAA</span>. PMID:27934969</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26072115','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26072115"><span>Understanding the molecular mechanism of aryl acylamidase activity of acetylcholinesterase - An in silico study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chinnadurai, Raj Kumar; Saravanaraman, Ponne; Boopathy, Rathanam</p> <p>2015-08-15</p> <p>Acetylcholinesterase (AChE) exhibits two different activities, namely esterase and aryl acylamidase (<span class="hlt">AAA</span>). Unlike esterase, <span class="hlt">AAA</span> activity of AChE is inhibited by the active site inhibitors while remaining unaffected by the peripheral anionic site inhibitors. This differential inhibitory pattern of active and peripheral anionic site inhibitors on the <span class="hlt">AAA</span> activity remains unanswered. To answer this, we investigated the mechanism of binding and trafficking of <span class="hlt">AAA</span> substrates using in silico tools. Molecular docking of serotonin and <span class="hlt">AAA</span> substrates (o-nitroacetanilide, and o-nitrotrifluoroacetanilide,) onto AChE shows that these compounds bind at the side door of AChE. Thus, we conceived that the <span class="hlt">AAA</span> substrates prefer the side door to reach the active site for their catalysis. Further, steered molecular dynamics simulations show that the force required for binding and trafficking of the <span class="hlt">AAA</span> substrate through the side door is comparatively lesser than their dissociation (900kJ/mol/nm). Among the two substrates, o-nitrotrifluoroacetanilide required lesser force (380kJ/mol/nm) than o-nitroacetanilide the (550kJ/mol/nm) for its binding, thus validating o-nitrotrifluoroacetanilide as a better substrate. With these observations, we resolve that the <span class="hlt">AAA</span> activity of AChE is mediated through its side door. Therefore, binding of PAS inhibitors at the main door of AChE remain ineffective against <span class="hlt">AAA</span> activity. Copyright © 2015 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3865307','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3865307"><span>Notch γ-Secretase Inhibitor Dibenzazepine Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in ApoE Knockout Mice by Multiple Mechanisms</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Zheng, Yue-Hong; Li, Fang-Da; Tian, Cui; Ren, Hua-Liang; Du, Jie; Li, Hui-Hua</p> <p>2013-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a life-threatening aortic disease in the elderly. Activation of Notch1 pathway plays a critical role in the development of <span class="hlt">AAA</span>, but the underlying mechanisms remain poorly understood. In the present study, we explored the mechanisms by which Notch1 activation regulates angiotensin II (Ang II)-induced <span class="hlt">AAA</span> formation and evaluated the therapeutic potential of a new Notch γ-secretase inhibitor, dibenzazepine (DBZ), for the treatment of <span class="hlt">AAA</span>. Apolipoprotein E knockout (Apo E−/−) mice infused for 4 weeks with Ang II (1000 ng/kg/min, IP) using osmotic mini-pumps were received an intraperitoneal injection of either vehicle or 1 mg/kg/d DBZ. Notch1 signaling was activated in <span class="hlt">AAA</span> tissue from both Ang II-infused Apo E−/− mice and human undergoing <span class="hlt">AAA</span> repair in vivo, with increased expression of Notch intracellular domain (NICD) and its target gene Hes1, and this effect was effectively blocked by DBZ. Moreover, infusion of Ang II markedly increased the incidence and severity of <span class="hlt">AAA</span> in Apo E−/− mice. In contrast, inhibition of Notch activation by DBZ prevented <span class="hlt">AAA</span> formation in vivo. Furthermore, DBZ markedly prevented Ang II-stimulated accumulation of macrophages and CD4+ T cells, and ERK-mediated angiogenesis, simultaneously reversed Th2 response, in vivo. In conclusion, these findings provide new insight into the multiple mechanisms of Notch signaling involved in <span class="hlt">AAA</span> formation and suggest that γ-secretase inhibitor DBZ might be a novel therapeutic drug for treating <span class="hlt">AAAS</span>. PMID:24358274</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23953891','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23953891"><span>Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Walford, Geoffrey A; Davis, Jaclyn; Warner, A Sofia; Ackerman, Rachel J; Billings, Liana K; Chamarthi, Bindu; Fanelli, Rebecca R; Hernandez, Alicia M; Huang, Chunmei; Khan, Sabina Q; Littleton, Katherine R; Lo, Janet; McCarthy, Rita M; Rhee, Eugene P; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S; Wang, Thomas J; Altshuler, David; Grant, Richard W; Clish, Clary B; Gerszten, Robert E; Florez, Jose C</p> <p>2013-12-01</p> <p>Elevated circulating levels of branched chain and aromatic amino acids (BCAA/<span class="hlt">AAAs</span>) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/<span class="hlt">AAAs</span> decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/<span class="hlt">AAAs</span> also signal an early response to commonly used medical therapies for T2D. A liquid chromatography-mass spectrometry approach was used to measure BCAA/<span class="hlt">AAAs</span> in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: (1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; (2) two days of twice daily metformin 500 mg orally; and (3) a 75-g OGTT. Percent change in BCAA/<span class="hlt">AAAs</span> was determined after each intervention. Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/<span class="hlt">AAAs</span> decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/<span class="hlt">AAAs</span> increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/<span class="hlt">AAAs</span> decreased in all subjects (P<0.05). BCAA/<span class="hlt">AAAs</span> changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/<span class="hlt">AAAs</span> may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. © 2013.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3833885','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3833885"><span>Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Walford, Geoffrey A.; Davis, Jaclyn; Warner, A. Sofia; Ackerman, Rachel J.; Billings, Liana K.; Chamarthi, Bindu; Fanelli, Rebecca R.; Hernandez, Alicia M.; Huang, Chunmei; Khan, Sabina Q.; Littleton, Katherine R.; Lo, Janet; McCarthy, Rita M.; Rhee, Eugene P.; Deik, Amy; Stolerman, Elliot; Taylor, Andrew; Hudson, Margo S.; Wang, Thomas J.; Altshuler, David; Grant, Richard W.; Clish, Clary B.; Gerszten, Robert E.; Florez, Jose C.</p> <p>2013-01-01</p> <p>Objective Elevated circulating levels of branched chain and aromatic amino acids (BCAA/<span class="hlt">AAAs</span>) are associated with insulin resistance and incident type 2 diabetes (T2D). BCAA/<span class="hlt">AAAs</span> decrease acutely during an oral glucose tolerance test (OGTT), a diagnostic test for T2D. It is unknown whether changes in BCAA/<span class="hlt">AAAs</span> also signal an early response to commonly used medical therapies for T2D. Materials and Methods A liquid chromatography-mass spectrometry approach was used to measure BCAA/<span class="hlt">AAAs</span> in 30 insulin sensitive (IS) and 30 insulin resistant (IR) subjects before and after: 1) one dose of a sulfonylurea medication, glipizide, 5 mg orally; 2) two days of twice daily metformin 500 mg orally; and 3) a 75-gram OGTT. Percent change in BCAA/<span class="hlt">AAAs</span> was determined after each intervention. Results Following glipizide, which increased insulin and decreased glucose in both subject groups, BCAA/<span class="hlt">AAAs</span> decreased in the IS subjects only (all P<0.05). Following metformin, which decreased glucose and insulin in only the IR subjects, 4 BCAA/<span class="hlt">AAAs</span> increased in the IR subjects at or below P=0.05, and none changed in the IS subjects. Following OGTT, which increased glucose and insulin in all subjects, BCAA/<span class="hlt">AAAs</span> decreased in all subjects (P<0.05). Conclusions BCAA/<span class="hlt">AAAs</span> changed acutely during glipizide and metformin administration, and the magnitude and direction of change differed by the insulin resistance status of the individual and the intervention. These results indicate that BCAA/<span class="hlt">AAAs</span> may be useful biomarkers for monitoring the early response to therapeutic interventions for T2D. PMID:23953891</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/12917841','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/12917841"><span>Genetic analysis on HLA loci in Japanese patients with abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sugimoto, T; Sada, M; Miyamoto, T; Yao, H</p> <p>2003-08-01</p> <p>autoimmunity has been proposed as one of the pathogenesis of abdominal aortic aneurysm (<span class="hlt">AAA</span>). There is also a likelihood that when aorto-iliac occlusive disease (AIOD) coexists with <span class="hlt">AAA</span>, some other occlusive atherosclerotic diseases, such as ischemic heart disease and cerebrovascular disease, may develop, leading to a very poor long-term prognosis. Previous studies using serological HLA typing showed that HLA-DR15 was a risk factor for <span class="hlt">AAA</span>. In this study, we performed HLA-DNA typing by PCR to clarify the relationship between <span class="hlt">AAA</span> and HLA genotypes in Japanese patients with <span class="hlt">AAA</span>. In addition, we analyzed whether HLA genotypes are involved in the pathogenesis of AIOD. we examined 78 HLA genotypes of class I (HLA-A and -B) and class II (HLA-DR) and found that 60.4 and 30.4% of 49 <span class="hlt">AAA</span> patients had HLA-A2 and HLA-B61, respectively. These frequencies were significantly higher than those in control individuals (HLA-A2, p < 0.05; HLA-B61, p < 0.005). We also found that 55.6% of nine <span class="hlt">AAA</span> patients with AIOD had both HLA-B52 and HLA-DR B1*1502. In contrast, only 10.0% each of 40 <span class="hlt">AAA</span> patients without AIOD showed HLA-B53 or HLA-DR B1*1502. this study showed that HLA A-2 and HLA B-61, but not HLA DR-15, were important genetic risk factors for the development of <span class="hlt">AAA</span> among the Japanese population. We also found high frequencies of HLA-B52 and HLA-DR B1*1502 in the <span class="hlt">AAA</span> patients with AIOD than in those without, although this must be confirmed using a larger number of <span class="hlt">AAA</span> patients with AIOD.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5417566','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5417566"><span>Inhibition of plasmin-mediated TAFI activation may affect development but not progression of abdominal aortic aneurysms</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Bridge, Katherine; Revill, Charlotte; Macrae, Fraser; Bailey, Marc; Yuldasheva, Nadira; Wheatcroft, Stephen; Butlin, Roger; Foster, Richard; Scott, D. Julian; Gils, Ann; Ariёns, Robert</p> <p>2017-01-01</p> <p>Objective Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (<span class="hlt">AAA</span>) disease. The role of TAFI inhibition on <span class="hlt">AAA</span> formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on <span class="hlt">AAA</span> development and progression. Methods Using the Angiotensin II model of <span class="hlt">AAA</span>, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with <span class="hlt">AAA</span> rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of <span class="hlt">AAA</span> from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once <span class="hlt">AAA</span> were already established had no effect on the progression of <span class="hlt">AAA</span> in this model. Conclusions The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of <span class="hlt">AAA</span>, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent <span class="hlt">AAA</span> progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of <span class="hlt">AAA</span> development, but not in its progression. PMID:28472123</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5903296','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5903296"><span>Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sun, Jingyuan; Deng, Hongping; Zhou, Zhen</p> <p>2018-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) was previously ascribed to weaken defective medial arterial/adventitial layers, for example, smooth muscle/fibroblast cells. Therefore, besides surgical repair, medications targeting the medial layer to strengthen the aortic wall are the most feasible treatment strategy for <span class="hlt">AAA</span>. However, so far, it is unclear whether such drugs have any beneficial effect on <span class="hlt">AAA</span> prognosis, rate of aneurysm growth, rupture, or survival. Notably, clinical studies have shown that <span class="hlt">AAA</span> is highly associated with endothelial dysfunction in the aged population. Additionally, animal models of endothelial dysfunction and endothelial nitric oxide synthase (eNOS) uncoupling had a very high rate of <span class="hlt">AAA</span> formation, indicating there is crucial involvement of the endothelium and a possible pharmacological solution targeting the endothelium in <span class="hlt">AAA</span> treatment. Endothelial cells have been found to trigger vascular wall remodeling by releasing proteases, or recruiting macrophages along with other neutrophils, into the medial layer. Moreover, inflammation and oxidative stress of the arterial wall were induced by endothelial dysfunction. Interestingly, there is a paradoxical differential correlation between diabetes and aneurysm formation in retinal capillaries and the aorta. Deciphering the significance of such a difference may explain current unsuccessful <span class="hlt">AAA</span> medications and offer a solution to this treatment challenge. It is now believed that <span class="hlt">AAA</span> and atherosclerosis are two separate but related diseases, based on their different clinical patterns which have further complicated the puzzle. Therefore, a thorough investigation of the interaction between endothelium and medial/adventitial layer may provide us a better understanding and new perspective on <span class="hlt">AAA</span> formation, especially after taking into account the importance of endothelium in the development of <span class="hlt">AAA</span>. Moreover, a novel medication strategy replacing the currently used, but suboptimal treatments for <span class="hlt">AAA</span>, could be</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA422382','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA422382"><span>Global Warming Could Have a Chilling Effect on the Military (Defense Horizons, Number 33, October 2003)</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2003-12-01</p> <p>Archaeology at the University of California at Santa Barbara, “is a chronicle of human vulnerability in the face of sudden climate change.”15 A bad...droughts. A growing body of evidence from joint archaeological and paleoclimatological studies is demonstrating that abrupt climate shifts may be linked to...<span class="hlt">Haug</span> et al., “Climate and the Collapse of Maya Civilization,” Science 299 (March 14, 2003). 17 P.B. deMenocal, “Cultural Responses to Climate Change</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26120253','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26120253"><span>Abdominal aortic aneurysm screening program in Poland.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jawien, A; Formankiewicz, B; Derezinski, T; Migdalski, A; Brazis, P; Woda, L</p> <p></p> <p>Screening for abdominal aortic aneurysms (<span class="hlt">AAA</span>) is currently recommended by several vascular societies. In countries where it has been introduced the prevalence of <span class="hlt">AAAs</span> differed greatly and was mainly related to cigarette smoking. The screening program also had an enormous impact on the decrease of <span class="hlt">AAA</span> ruptures and reduced mortality rate. These facts have led to the introduction of the first screening program for <span class="hlt">AAAs</span> in Poland. The aim of the study was to determine the prevalence of <span class="hlt">AAAs</span> among men aged 60 years and older undergoing ultrasound examination of the abdominal aorta. A single ultrasonography of the abdomen was performed to assess the aorta from the renal arteries to the bifurcation and the diameter of the aorta was measured at its widest point. The cut-off value for determining an aortic aneurysm was set at a diameter of ≥ 30 mm. All ultrasonography measurements were performed by physicians in outpatient departments throughout the Kuyavian-Pomeranian Province. Additionally, each subject had to fill out a questionnaire with demographic data, smoking habits, existing comorbidities and familial occurrence of <span class="hlt">AAAs</span>. The study was conducted from October 2009 to November 2011. The abdominal aorta ultrasound examinations were carried out in 1556 men aged 60 years and older. The prevalence of <span class="hlt">AAA</span> in the study population was 6.0 % (94 out of 1556). The average age of the men was 69 years (SD 6 years, range 60-92 years). In the study population 55 % of the men smoked or had smoked and 3 % were aware of the presence of <span class="hlt">AAAs</span> in family members. There were three risk factors significantly associated with the presence of <span class="hlt">AAAs</span>: age (p < 0.05), smoking (72.3 % vs 53.9 %, p = 0.004) and family history of <span class="hlt">AAAs</span> (9.6 % vs 2.7 %, p = 0.017). The prevalence of <span class="hlt">AAAs</span> among men in Poland is higher than in other European countries and the USA. The screening program for <span class="hlt">AAAs</span> is an easy and reliable method for detecting early stages of the disease and</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26603433','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26603433"><span>Vitamins and abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Takagi, Hisato; Umemoto, Takuya</p> <p>2017-02-01</p> <p>To summarize the association of vitamins (B6, B12, C, D, and E) and abdominal aortic aneurysm (<span class="hlt">AAA</span>), we reviewed clinical studies with a comprehensive literature research and meta-analytic estimates. To identify all clinical studies evaluating the association of vitamins B6/B12/C/D/E and <span class="hlt">AAA</span>, databases including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2015, using Web-based search engines (PubMed and OVID). For each case-control study, data regarding vitamin levels in both the <span class="hlt">AAA</span> and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Pooled analyses of the 4 case-control studies demonstrated significantly lower circulating vitamin B6 levels (SMD, -0.33; 95% CI, -0.55 to -0.11; P=0.003) but non-significantly lower vitamin B12 levels (SMD, -0.42; 95% CI, -1.09 to 0.25; P=0.22) in patients with <span class="hlt">AAA</span> than subjects without <span class="hlt">AAA</span>. Pooled analyses of the 2 case-control studies demonstrated significantly lower levels of circulating vitamins C (SMD, -0.71; 95% CI, -1.23 to -0.19; P=0.007) and E (SMD, -1.76; 95% CI, -2.93 to 0.60; P=0.003) in patients with <span class="hlt">AAA</span> than subjects without <span class="hlt">AAA</span>. Another pooled analysis of the 3 case-control studies demonstrated significantly lower circulating vitamin D (25-hydroxyvitamin D) levels (SMD, -0.25; 95% CI, -0.50 to -0.01; P=0.04) in patients with <span class="hlt">AAA</span> than subjects without <span class="hlt">AAA</span>. In a double-blind controlled trial, 4.0-year treatment with a high-dose folic acid and vitamin B6/B12 multivitamin in kidney transplant recipients did not reduce a rate of <span class="hlt">AAA</span> repair despite significant reduction in homocysteine level. In another randomized, double-blind, placebo-controlled trial, 5.8-year supplementation with α-tocopherol (vitamin E) had no preventive effect on large <span class="hlt">AAA</span> among male smokers. In clinical setting, although low circulating vitamins B6/C/D/E (not B12) levels are associated with <span class="hlt">AAA</span> presence, vitamins B6/B12/E</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29350999','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29350999"><span>Sex differences in abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boese, Austin C; Chang, Lin; Yin, Ke-Jie; Chen, Y Eugene; Lee, Jean-Pyo; Hamblin, Milton H</p> <p>2018-06-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a vascular disorder with a high case fatality rate in the instance of rupture. <span class="hlt">AAA</span> is a multifactorial disease, and the etiology is still not fully understood. <span class="hlt">AAA</span> is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against <span class="hlt">AAA</span> possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on <span class="hlt">AAA</span> pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17405412','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17405412"><span>In response to an open invitation for comments on <span class="hlt">AAAS</span> project 2061's Benchmark books on science. Part 1: documentation of serious errors in cell biology.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ling, Gilbert</p> <p>2006-01-01</p> <p>Project 2061 was founded by the American Association for the Advancement of Science (<span class="hlt">AAAS</span>) to improve secondary school science education. An in-depth study of ten 9 to 12th grade biology textbooks led to the verdict that none conveyed "Big Ideas" that would give coherence and meaning to the profusion of lavishly illustrated isolated details. However, neither the Project report itself nor the Benchmark books put out earlier by the Project carries what deserves the designation of "Big Ideas." Worse, in the two earliest-published Benchmark books, the basic unit of all life forms--the living cell--is described as a soup enclosed by a cell membrane, that determines what can enter or leave the cell. This is astonishing since extensive experimental evidence has unequivocally disproved this idea 60 years ago. A "new" version of the membrane theory brought in to replace the discredited (sieve) version is the pump model--currently taught as established truth in all high-school and college biology textbooks--was also unequivocally disproved 40 years ago. This comment is written partly in response to Bechmark's gracious open invitation for ideas to improve the books and through them, to improve US secondary school science education.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29884772','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29884772"><span>Peroxisomal monoubiquitinated PEX5 interacts with the <span class="hlt">AAA</span> ATPases PEX1 and PEX6 and is unfolded during its dislocation into the cytosol.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pedrosa, Ana G; Francisco, Tânia; Bicho, Diana; Dias, Ana F; Barros-Barbosa, Aurora; Hagmann, Vera; Dodt, Gabriele; Rodrigues, Tony A; Azevedo, Jorge E</p> <p>2018-06-08</p> <p>PEX1 and PEX6 are two members of the ATPases Associated with diverse cellular Activities (<span class="hlt">AAA</span>) family and the core components of the receptor export module (REM) of the peroxisomal matrix protein import machinery. Their role is to extract monoubiquitinated PEX5, the peroxisomal protein shuttling receptor, from the peroxisomal membrane docking/translocation module (DTM), so that a new cycle of protein transportation can start. Recent data have shown that PEX1 and PEX6 form a heterohexameric complex which unfolds substrates by processive threading. However, whether the natural substrate of the PEX1.PEX6 complex is monoubiquitinated PEX5 (Ub-PEX5) itself or some Ub-PEX5-interacting component(s) of the DTM remains unknown. In this work, we used an established cell-free in vitro system coupled with photoaffinity crosslinking and protein PEGylation assays to address this problem. We provide evidence suggesting that DTM-embedded Ub-PEX5 interacts directly with both PEX1 and PEX6 through its ubiquitin moiety and that the PEX5 polypeptide chain is globally unfolded during the ATP-dependent extraction event. These findings strongly suggest that DTM-embedded Ub-PEX5 is a bona fide substrate of the PEX1.PEX6 complex. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27492991','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27492991"><span>Abdominal aortic aneurysm repair in New Zealand: a validation of the Australasian Vascular Audit.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Khashram, Manar; Thomson, Ian A; Jones, Gregory T; Roake, Justin A</p> <p>2017-05-01</p> <p>In New Zealand (NZ), there are two major sources of operative data for abdominal aortic aneurysm (<span class="hlt">AAA</span>) repair: the Australasian Vascular Audit (AVA) and the National Minimum Data Set (NMDS). Since the introduction of the AVA in NZ, there has not been any attempt at the validation of outcome data. The aims of this study were to report the outcomes of <span class="hlt">AAA</span> repair and validate the <span class="hlt">AAA</span> data captured by AVA using the NMDS. <span class="hlt">AAA</span> procedures performed in NZ from January 2010 to December 2014 were extracted from the AVA and NMDS. Patients identified from the AVA had their survival status matched to the NMDS. Only primary <span class="hlt">AAA</span> procedures were included for the analysis, with re-interventions and graft infections excluded. Demographical, risk factors and outcome data were used for validation. The number of patients undergoing primary <span class="hlt">AAA</span> procedure from AVA and NMDS was 1713 and 2078, respectively. The AVA inpatient mortality for elective and rupture <span class="hlt">AAA</span> was 1.6 and 32.2%, respectively. The NMDS 30-day mortality from <span class="hlt">AAA</span> was 2.5 and 31.5%. Overall, 1604 patients were available for matching, and the NMDS correctly reported 98.1% of endovascular aneurysm repair and 94.2% of elective <span class="hlt">AAA</span> repairs; however, there were major differences in comorbidity reporting between the data sets. Both data sets were incomplete, but combining administrative (NMDS) and clinical (AVA) data sets provided a more accurate assessment of mortality figures. More than 80% of <span class="hlt">AAA</span> repairs are captured by AVA, but further work to improve compliance and comorbidity documentation is required. © 2016 Royal Australasian College of Surgeons.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29643699','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29643699"><span>Clinical Efficacy of Transthoracic Echocardiography for Screening Abdominal Aortic Aneurysm in Turkish Patients.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kilic, Salih; Saracoglu, Erhan; Cekici, Yusuf</p> <p>2018-03-01</p> <p>The objective of this study was to investigate the prevalence of abdominal aortic aneurysm (<span class="hlt">AAA</span>) in Turkish patients aged ≥ 65 years, and to demonstrate the applicability of echocardiography to <span class="hlt">AAA</span> screening. Transthoracic echocardiography (TTE) was performed in all consecutive patients aged ≥ 65 years who were referred to cardiology clinics or were referred from other outpatient clinics. The abdominal aorta (AA) of each patient was scanned using the same probe, and the time spent was recorded. Demographic and clinic characteristics of the patients were recorded at the end of the echocardiography. Among 1948 patients (mean age 70.9 ± 6 years; 49.8% male), the AA was visualized in 96.3%. <span class="hlt">AAA</span> was identified in 3.7% (69/1878) of the patients, of whom <span class="hlt">AAA</span> was previously known in 20.3% (n = 14). The prevalence of unknown <span class="hlt">AAA</span> was 2.93%. The average time needed to scan and measure the AA was 1 minute and 3 seconds (±23 seconds). Aortic root diameters were significantly higher in the patients with <span class="hlt">AAA</span> than in those without <span class="hlt">AAA</span> (34.7 ± 4.2 vs. 29.8 ± 4.7; p < 0.001). Age (per 1 year increase) [odds ratio (OR), 1.245; p < 0.001], male gender (OR, 5.382; p < 0.001), smoking (OR, 2.118; p = 0.037), and aortic root diameter (per 1 mm increase) (OR, 1.299; p < 0.001) were independent predictors of <span class="hlt">AAA</span>. This study is important in that it showed a high prevalence of <span class="hlt">AAA</span> in Turkish patients aged ≥ 65 years, and demonstrated that <span class="hlt">AAA</span> can be visualized in the majority of patients in as little as 1 minute during TTE.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/19497516','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/19497516"><span>Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Elmore, James R; Obmann, Melissa A; Kuivaniemi, Helena; Tromp, Gerard; Gerhard, Glenn S; Franklin, David P; Boddy, Amy M; Carey, David J</p> <p>2009-06-01</p> <p>The goal of this project was to identify genetic variants associated with abdominal aortic aneurysms (<span class="hlt">AAAs</span>). A genome wide association study was carried out using pooled DNA samples from 123 <span class="hlt">AAA</span> cases and 112 controls matched for age, gender, and smoking history using Affymetrix 500K single nucleotide polymorphism (SNP) arrays (Affymetrix, Inc, Santa Clara, Calif). The difference in mean allele frequency between cases and controls was calculated for each SNP and used to identify candidate genomic regions. Association of candidate SNPs with <span class="hlt">AAA</span> was confirmed by individual TaqMan genotype assays in a total of 2096 cases and controls that included an independent replication sample set. A genome wide association study of <span class="hlt">AAA</span> cases and controls identified a candidate <span class="hlt">AAA</span>-associated haplotype on chromosome 3p12.3. By individual genotype analysis, four SNPs in this region were significantly associated with <span class="hlt">AAA</span> in cases and controls from the original study population. One SNP in this region (rs7635818) was genotyped in a total of 502 cases and 736 controls from the original study population (P = .017) and 448 cases and 410 controls from an independent replication sample (P = .013; combined P value = .0028; combined odds ratio [OR] = 1.33). An even stronger association with <span class="hlt">AAA</span> was observed in a subset of smokers (391 cases, 241 controls, P = .00041, OR = 1.80), which represent the highest risk group for <span class="hlt">AAA</span>. The <span class="hlt">AAA</span>-associated haplotype is located approximately 200 kbp upstream of the CNTN3 gene transcription start site. This study identifies a region on chromosome 3 that is significantly associated with <span class="hlt">AAA</span> in 2 distinct study populations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29943223','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29943223"><span>Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ni, Xian-Qiang; Lu, Wei-Wei; Zhang, Jin-Sheng; Zhu, Qing; Ren, Jin-Ling; Yu, Yan-Rong; Liu, Xiu-Ying; Wang, Xiu-Jie; Han, Mei; Jing, Qing; Du, Jie; Tang, Chao-Shu; Qi, Yong-Fen</p> <p>2018-06-26</p> <p>Endoplasmic reticulum stress (ERS) is involved in the development of abdominal aortic aneurysm (<span class="hlt">AAA</span>). Since bioactive peptide intermedin (IMD)1-53 protects against <span class="hlt">AAA</span> formation, here we investigated whether IMD1-53 attenuates <span class="hlt">AAA</span> by inhibiting ERS. <span class="hlt">AAA</span> model was induced by angiotensin II (AngII) in ApoE KO mouse background. AngII-treated mouse aortas showed increased ERS gene transcription of caspase12, eukaryotic translation initiation factor 2a (eIf2a) and activating transcription factor 4(ATF4).The protein level of ERS marker glucose regulated protein 94(GRP94), ATF4 and C/EBP homologous protein 10(CHOP) was also up-regulated by AngII. Increased ERS levels were accompanied by severe VSMC apoptosis in human <span class="hlt">AAA</span> aorta. In vivo administration of IMD1-53 greatly reduced AngII-induced <span class="hlt">AAA</span> and abrogated the activation of ERS. To determine whether IMD inhibited <span class="hlt">AAA</span> by ameliorating ERS, we used 2 non-selective ERS inhibitors phenyl butyrate (4-PBA) and taurine (TAU). Similar to IMD, PBA, and TAU significantly reduced the incidence of <span class="hlt">AAA</span> and <span class="hlt">AAA</span>-related pathological disorders. In vitro, AngII infusion up-regulated CHOP, caspase12 expression and led to VSMC apoptosis. IMD siRNA aggravated the CHOP, caspase12-mediated VSMC apoptosis, which was abolished by ATF4 silencing. IMD infusion promoted the phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) in aortas in ApoE KO mice, and the AMPK inhibitor compound C abolished the protective effect of IMD on VSMC ERS and apoptosis induced by AngII. In conclusion, IMD may protect against <span class="hlt">AAA</span> formation by inhibiting ERS via activating AMPK phosphorylation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29914827','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29914827"><span>Geometric analysis of ruptured and nonruptured abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kimura, Masaru; Hoshina, Katsuyuki; Miyahara, Kazuhiro; Nitta, Jun; Kobayashi, Masaharu; Yamamoto, Sota; Ohshima, Marie</p> <p>2018-06-15</p> <p>The objective of this study was to use parameters to determine the geometric differences between ruptured abdominal aortic aneurysms (<span class="hlt">AAAs</span>) and nonruptured <span class="hlt">AAAs</span>. Computed tomography data of 38 ruptured <span class="hlt">AAAs</span> and 215 electively repaired (nonruptured) <span class="hlt">AAAs</span> were collected from multiple institutes. We compared the ruptured <span class="hlt">AAA</span> group and nonruptured <span class="hlt">AAA</span> group with 1:1 matching by using the Mahalanobis distance, which was calculated using the patient's age, sex, and <span class="hlt">AAA</span> diameter. We selected the longitudinal <span class="hlt">AAA</span> image in multiplanar reconstruction view, placed a hypothetical ellipse on the aneurysm's protruded curve, and placed a circle on the portion connecting the aneurysm and the aorta. We then measured the aspect ratio (the vertical diameter divided by the horizontal diameter) and fillet radius (the radius of arc). The aspect ratio was significantly lower in the ruptured group than in the nonruptured group (2.02 ± 0.53 vs 2.60 ± 1.02; P = .002), as was the fillet radius (0.28 ± 0.18 vs 0.81 ± 0.44; P < .001). Receiver operating characteristic analysis revealed that the area under the curve of the aspect ratio was 0.688, and the optimal cutoff point was 2.23, with sensitivity and specificity of 0.55 and 0.76, respectively. The area under the curve of the fillet radius was 0.933, and the optimal cutoff was 0.347, with sensitivity and specificity of 0.97 and 0.87, respectively. The geometric analysis performed in this study revealed that ruptured <span class="hlt">AAAs</span> had a smaller fillet radius and smaller aspect ratio than nonruptured <span class="hlt">AAAs</span> did. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1422474','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1422474"><span>Variation in Death Rate After Abdominal Aortic Aneurysmectomy in the United States</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Dimick, Justin B.; Stanley, James C.; Axelrod, David A.; Kazmers, Andris; Henke, Peter K.; Jacobs, Lloyd A.; Wakefield, Thomas W.; Greenfield, Lazar J.; Upchurch, Gilbert R.</p> <p>2002-01-01</p> <p>Objective To determine whether high-volume hospitals (HVHs) have lower in-hospital death rates after abdominal aortic aneurysm (<span class="hlt">AAA</span>) repair compared with low-volume hospitals (LVHs). Summary Background Data Select statewide studies have shown that HVHs have superior outcomes compared with LVHs for <span class="hlt">AAA</span> repair, but they may not be representative of the true volume–outcome relationship for the entire United States. Methods Patients undergoing repair of intact or ruptured <span class="hlt">AAAs</span> in the Nationwide Inpatient Sample (NIS) for 1996 and 1997 were included (n = 13,887) for study. The NIS represents a 20% stratified random sample representative of all U.S. hospitals. Unadjusted and case mix-adjusted analyses were performed. Results The overall death rate was 3.8% for intact <span class="hlt">AAA</span> repair and 47% for ruptured <span class="hlt">AAA</span> repair. For repair of intact <span class="hlt">AAAs</span>, HVHs had a lower death rate than LVHs. The death rate after repair of ruptured <span class="hlt">AAA</span> was also slightly lower at HVHs. In a multivariate analysis adjusting for case mix, having surgery at an LVH was associated with a 56% increased risk of in-hospital death. Other independent risk factors for in-hospital death included female gender, age older than 65 years, aneurysm rupture, urgent or emergent admission, and comorbid disease. Conclusions This study from a representative national database documents that HVHs have a significantly lower death rate than LVHs for repair of both intact and ruptured <span class="hlt">AAA</span>. These data support the regionalization of patients to HVHs for <span class="hlt">AAA</span> repair. PMID:11923615</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2874128','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2874128"><span>Association of statin prescription with small abdominal aortic aneurysm progression</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ferguson, Craig D.; Clancy, Paula; Bourke, Bernard; Walker, Philip J.; Dear, Anthony; Buckenham, Tim; Norman, Paul; Golledge, Jonathan</p> <p>2009-01-01</p> <p>Background Statins have been suggested to reduce expansion of abdominal aortic aneurysms (<span class="hlt">AAA</span>) independent of lipid lowering effects. Methods We assessed the association of statin treatment and serum low density lipoprotein (LDL) concentrations with small <span class="hlt">AAA</span> expansion. 652 patients undergoing surveillance of small <span class="hlt">AAAs</span> were entered into the study from five vascular centers. In a subset fasting lipids (n=451) and other biomarkers (n=216) were measured. <span class="hlt">AAA</span> diameter was followed by ultrasound surveillance for a median of 5 years. Results 349 (54%) of the patients were prescribed statins. Adjusting for other risk factors statin prescription was not associated with <span class="hlt">AAA</span> growth (odds ratio, OR, 1.23, 95% confidence interval, CI, 0.86–1.76). Above median <span class="hlt">AAA</span> growth was positively associated with initial diameter (OR 1.78 per 4.35mm larger initial aortic diameter, 95% CI 1.49–2.14) and negatively associated with diabetes (OR 0.37, 95% CI 0.22–0.62). Above median serum LDL concentration was not associated with <span class="hlt">AAA</span> growth. Patients receiving statins had lower serum C-reactive protein concentrations but similar matrix metalloproteinase-9 and interleukin-6 concentrations to those not prescribed these medications. Conclusions We found no association between statin prescription or LDL concentration with <span class="hlt">AAA</span> expansion. The results do not support the findings of smaller studies and suggest that statins may have no benefit in reducing <span class="hlt">AAA</span> progression. PMID:20152231</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17170369','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17170369"><span>Association between osteopontin and human abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Golledge, Jonathan; Muller, Juanita; Shephard, Neil; Clancy, Paula; Smallwood, Linda; Moran, Corey; Dear, Anthony E; Palmer, Lyle J; Norman, Paul E</p> <p>2007-03-01</p> <p>In vitro and animal studies have implicated osteopontin (OPN) in the pathogenesis of aortic aneurysm. The relationship between serum concentration of OPN and variants of the OPN gene with human abdominal aortic aneurysm (<span class="hlt">AAA</span>) was investigated. OPN genotypes were examined in 4227 subjects in which aortic diameter and clinical risk factors were measured. Serum OPN was measured by ELISA in two cohorts of 665 subjects. The concentration of serum OPN was independently associated with the presence of <span class="hlt">AAA</span>. Odds ratios (and 95% confidence intervals) for upper compared with lower OPN tertiles in predicting presence of <span class="hlt">AAA</span> were 2.23 (1.29 to 3.85, P=0.004) for the population cohort and 4.08 (1.67 to 10.00, P=0.002) for the referral cohort after adjusting for other risk factors. In 198 patients with complete follow-up of aortic diameter at 3 years, initial serum OPN predicted <span class="hlt">AAA</span> growth after adjustment for other risk factors (standardized coefficient 0.24, P=0.001). The concentration of OPN in the aortic wall was greater in patients with small <span class="hlt">AAAs</span> (30 to 50 mm) than those with aortic occlusive disease alone. There was no association between five single nucleotide polymorphisms or haplotypes of the OPN gene and aortic diameter or <span class="hlt">AAA</span> expansion. Serum and tissue concentrations of OPN are associated with human <span class="hlt">AAA</span>. We found no relationship between variation of the OPN gene and <span class="hlt">AAA</span>. OPN may be a useful biomarker for <span class="hlt">AAA</span> presence and growth.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29313113','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29313113"><span>Epidemiology and contemporary management of abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ullery, Brant W; Hallett, Richard L; Fleischmann, Dominik</p> <p>2018-05-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is most commonly defined as a maximal diameter of the abdominal aorta in excess of 3 cm in either anterior-posterior or transverse planes or, alternatively, as a focal dilation ≥ 1.5 times the diameter of the normal adjacent arterial segment. Risk factors for the development of <span class="hlt">AAA</span> include age > 60, tobacco use, male gender, Caucasian race, and family history of <span class="hlt">AAA</span>. Aneurysm growth and rupture risk appear to be associated with persistent tobacco use, female gender, and chronic pulmonary disease. The majority of <span class="hlt">AAAs</span> are asymptomatic and detected incidentally on various imaging studies, including abdominal ultrasound, and computed tomographic angiography. Symptoms associated with <span class="hlt">AAA</span> may include abdominal or back pain, thromboembolization, atheroembolization, aortic rupture, or development of an arteriovenous or aortoenteric fistula. The Screening Abdominal Aortic Aneurysms Efficiently (SAAAVE) Act provides coverage for a one-time screening abdominal ultrasound at age 65 for men who have smoked at least 100 cigarettes and women who have family history of <span class="hlt">AAA</span> disease. Medical management is recommended for asymptomatic patients with <span class="hlt">AAAs</span> < 5 cm in diameter and focuses on modifiable risk factors, including smoking cessation and blood pressure control. Primary indications for intervention in patients with <span class="hlt">AAA</span> include development of symptoms, rupture, rapid aneurysm growth (> 5 mm/6 months), or presence of a fusiform aneurysm with maximum diameter of 5.5 cm or greater. Intervention for <span class="hlt">AAA</span> includes conventional open surgical repair and endovascular aortic stent graft repair.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5919947','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5919947"><span>Chinese Herbal Medicine as a Potential Treatment of Abdominal Aortic Aneurysm</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Seto, Sai Wang; Chang, Dennis; Kiat, Hosen; Wang, Ning; Bensoussan, Alan</p> <p>2018-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is an irreversible condition where the abdominal aorta is dilated leading to potentially fatal consequence of aortic rupture. Multiple mechanisms are involved in the development and progression of <span class="hlt">AAA</span>, including chronic inflammation, oxidative stress, vascular smooth muscle (VSMC) apoptosis, immune cell infiltration and extracellular matrix (ECM) degradation. Currently surgical therapies, including minimally invasive endovascular aneurysm repair (EVAR), are the only viable interventions for <span class="hlt">AAAs</span>. However, these treatments are not appropriate for the majority of <span class="hlt">AAAs</span>, which measure <50 mm. Substantial effort has been invested to identify and develop pharmaceutical treatments such as statins and doxycycline for this potentially lethal condition but these interventions failed to offer a cure or to retard the progression of <span class="hlt">AAA</span>. Chinese herbal medicine (CHM) has been used for the management of cardiovascular diseases for thousands of years in China and other Asian countries. The unique multi-component and multi-target property of CHMs makes it a potentially ideal therapy for multifactorial diseases such as <span class="hlt">AAA</span>. In this review, we review the current scientific evidence to support the use of CHMs for the treatment of <span class="hlt">AAA</span>. Mechanisms of action underlying the effects of CHMs on <span class="hlt">AAA</span> are also discussed. PMID:29732374</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.sciencemag.org','SCIGOVWS'); return false;" href="http://www.sciencemag.org"><span>Science | <span class="hlt">AAAS</span></span></a></p> <p><a target="_blank" href="http://www.science.gov/aboutsearch.html">Science.gov Websites</a></p> <p></p> <p></p> <p>be caused by haywire immune system eating brain connections <em>CRISPR</em> Stopping CRISPR's genome-editing scissors from snipping out of control <em>CRISPR</em> patent hearing produces no clear winner, only 'soft signals ' Did a Swedish researcher eat the first <em>CRISPR</em> meal ever served? Top articles in Careers dollars in a</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://images.nasa.gov/#/details-367-AAA.html','SCIGOVIMAGE-NASA'); return false;" href="https://images.nasa.gov/#/details-367-AAA.html"><span>367-<span class="hlt">AAA</span></span></a></p> <p><a target="_blank" href="https://images.nasa.gov/">NASA Image and Video Library</a></p> <p></p> <p>1969-11-18</p> <p>Apollo 12 Public Affairs Officer (PAO) Mission Commentary, November 17-18, 1969. This is 3.25 hours of audio covering communications occurring between 82 hours, 41 minutes into the mission, through 86 hours, 38 minutes which was on November 17, 1969, 21:03 CST until November 18, 1969, 1:00 CST. Communication is quite sparse on the recording, with large sections of silence or miscellaneous noise. Transcript of audio is available at http://www.jsc.nasa.gov/history/mission_trans/AS12_PAO.PDF, on pages 239-259 of the 979-page document.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25344531','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25344531"><span>The <span class="hlt">AAA</span>-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mérai, Zsuzsanna; Chumak, Nina; García-Aguilar, Marcelina; Hsieh, Tzung-Fu; Nishimura, Toshiro; Schoft, Vera K; Bindics, János; Slusarz, Lucyna; Arnoux, Stéphanie; Opravil, Susanne; Mechtler, Karl; Zilberman, Daniel; Fischer, Robert L; Tamaru, Hisashi</p> <p>2014-11-11</p> <p>Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved <span class="hlt">AAA</span>-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48A(NPL4) complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4234600','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4234600"><span>The <span class="hlt">AAA</span>-ATPase molecular chaperone Cdc48/p97 disassembles sumoylated centromeres, decondenses heterochromatin, and activates ribosomal RNA genes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mérai, Zsuzsanna; Chumak, Nina; García-Aguilar, Marcelina; Hsieh, Tzung-Fu; Nishimura, Toshiro; Schoft, Vera K.; Bindics, János; Ślusarz, Lucyna; Arnoux, Stéphanie; Opravil, Susanne; Mechtler, Karl; Zilberman, Daniel; Fischer, Robert L.; Tamaru, Hisashi</p> <p>2014-01-01</p> <p>Centromeres mediate chromosome segregation and are defined by the centromere-specific histone H3 variant (CenH3)/centromere protein A (CENP-A). Removal of CenH3 from centromeres is a general property of terminally differentiated cells, and the persistence of CenH3 increases the risk of diseases such as cancer. However, active mechanisms of centromere disassembly are unknown. Nondividing Arabidopsis pollen vegetative cells, which transport engulfed sperm by extended tip growth, undergo loss of CenH3; centromeric heterochromatin decondensation; and bulk activation of silent rRNA genes, accompanied by their translocation into the nucleolus. Here, we show that these processes are blocked by mutations in the evolutionarily conserved <span class="hlt">AAA</span>-ATPase molecular chaperone, CDC48A, homologous to yeast Cdc48 and human p97 proteins, both of which are implicated in ubiquitin/small ubiquitin-like modifier (SUMO)-targeted protein degradation. We demonstrate that CDC48A physically associates with its heterodimeric cofactor UFD1-NPL4, known to bind ubiquitin and SUMO, as well as with SUMO1-modified CenH3 and mutations in NPL4 phenocopy cdc48a mutations. In WT vegetative cell nuclei, genetically unlinked ribosomal DNA (rDNA) loci are uniquely clustered together within the nucleolus and all major rRNA gene variants, including those rDNA variants silenced in leaves, are transcribed. In cdc48a mutant vegetative cell nuclei, however, these rDNA loci frequently colocalized with condensed centromeric heterochromatin at the external periphery of the nucleolus. Our results indicate that the CDC48ANPL4 complex actively removes sumoylated CenH3 from centromeres and disrupts centromeric heterochromatin to release bulk rRNA genes into the nucleolus for ribosome production, which fuels single nucleus-driven pollen tube growth and is essential for plant reproduction. PMID:25344531</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23652818','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23652818"><span>Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. <span class="hlt">AAA</span> group, cv. Cavendish).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Zhuo; Huang, Suzhen; Jia, Caihong; Liu, Juhua; Zhang, Jianbin; Xu, Biyu; Jin, Zhiqiang</p> <p>2013-09-01</p> <p>Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. <span class="hlt">AAA</span> group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29916384','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29916384"><span>Benefits and harms of screening men for abdominal aortic aneurysm in Sweden: a registry-based cohort study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Johansson, Minna; Zahl, Per Henrik; Siersma, Volkert; Jørgensen, Karsten Juhl; Marklund, Bertil; Brodersen, John</p> <p>2018-06-16</p> <p>Large reductions in the incidence of abdominal aortic aneurysm (<span class="hlt">AAA</span>) and <span class="hlt">AAA</span>-related mortality mean that results from randomised trials of screening for the disorder might be out-dated. The aim of this study was to estimate the effect of <span class="hlt">AAA</span> screening in Sweden on disease-specific mortality, incidence, and surgery. Individual data on the incidence of <span class="hlt">AAA</span>, <span class="hlt">AAA</span> mortality, and surgery for <span class="hlt">AAA</span> in a cohort of men aged 65 years who were invited to screening between 2006 and 2009, were compared with data from an age-matched contemporaneous cohort of men who were not invited for <span class="hlt">AAA</span> screening. We also analysed national data for all men aged 40-99 years between Jan 1, 1987, and Dec 31, 2015, to explore background trends. Adjustment for confounding was done by weighting the analyses with a propensity score obtained from a logistic regression model on cohort year, marital status, educational level, income, and whether the patient already had an <span class="hlt">AAA</span> diagnosis at baseline. Adjustment for differential attrition was also done by weighting the analyses with the inverse probability of still being in the cohort 6 years after screening. Generalised estimating equations were used to adjust the variance for repeated measurement and in response to the weighting. <span class="hlt">AAA</span> mortality in Swedish men has decreased from 36 to ten deaths per 100 000 men aged 65-74 years between the early 2000s and 2015. Mortality decreased at similar rates in all Swedish counties, irrespective of whether <span class="hlt">AAA</span> screening was offered. After 6 years with screening, we found a non-significant reduction in <span class="hlt">AAA</span> mortality associated with screening (adjusted odds ratio [aOR] 0·76, 95% CI 0·38-1·51), which means that two men (95% CI -3 to 7) avoid death from <span class="hlt">AAA</span> for every 10 000 men offered screening. Screening was associated with increased odds of <span class="hlt">AAA</span> diagnosis (aOR 1·52, 95% CI 1·16-1·99; p=0·002) and an increased risk of elective surgery (aOR 1·59, 95% CI 1·20-2·10; p=0·001), such that for every 10 000 men</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15172783','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15172783"><span>Learning from <span class="hlt">Philip</span> Morris: Japan Tobacco's strategies regarding evidence of tobacco health harms as revealed in internal documents from the American tobacco industry.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Iida, Kaori; Proctor, Robert N</p> <p>2004-05-29</p> <p>Japan is in the midst of a rapid increase in tobacco-related disease mortality, following the rapid growth of smoking after WWII. Stomach cancer was the country's leading cause of cancer death for most of the 20th century, until lung cancer took over this position in 1993. Cigarettes are the major cause of lung cancer in Japan, but the country's leading manufacturer, Japan Tobacco, two thirds of which is owned by the Japanese government, continues to question whether tobacco is a major cause of disease and death. Japanese courts do not have the power to subpoena a company's internal records, which has made it difficult to document Japan Tobacco's strategies concerning tobacco and health. Our interpretation of online archives of internal documents from American tobacco companies, however, is that Japan Tobacco has long known about the potential health risks involved in smoking and has sought to obstruct effective tobacco control. Beginning in the mid-1980s, these efforts were often co-ordinated with American tobacco manufacturers. The documentary evidence shows that cigarette manufacturer <span class="hlt">Philip</span> Morris in particular assisted with and sometimes also supervised Japan Tobacco's actions and statements on smoking and health. In one instance, data gathered for an article published by the Japan Public Monopoly Corporation (Japan Tobacco's predecessor) were deliberately altered to lower the reported value of a hazard indicator (nicotine concentration in the air). International collaboration has made it easier for companies such as Japan Tobacco to develop effective anti-antismoking strategies. Evidence of such global industry collaborations might grow as lawsuits begin to be filed in other nations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29169074','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29169074"><span>Flow stagnation volume and abdominal aortic aneurysm growth: Insights from patient-specific computational flow dynamics of Lagrangian-coherent structures.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Joly, Florian; Soulez, Gilles; Garcia, Damien; Lessard, Simon; Kauffmann, Claude</p> <p>2018-01-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAA</span>) are localized, commonly-occurring dilations of the aorta. When equilibrium between blood pressure (loading) and wall mechanical resistance is lost, rupture ensues, and patient death follows, if not treated immediately. Experimental and numerical analyses of flow patterns in arteries show direct correlations between wall shear stress and wall mechano-adaptation with the development of zones prone to thrombus formation. For further insights into <span class="hlt">AAA</span> flow topology/growth interaction, a workout of patient-specific computational flow dynamics (CFD) is proposed to compute finite-time Lyapunov exponents and extract Lagrangian-coherent structures (LCS). This computational model was first compared with 4-D phase-contrast magnetic resonance imaging (MRI) in 5 patients. To better understand the impact of flow topology and transport on <span class="hlt">AAA</span> growth, hyperbolic, repelling LCS were computed in 1 patient during 8-year follow-up, including 9 volumetric morphologic <span class="hlt">AAA</span> measures by computed tomography-angiography (CTA). LCS defined barriers to Lagrangian jet cores entering <span class="hlt">AAA</span>. Domains enclosed between LCS and the aortic wall were considered to be stagnation zones. Their evolution was studied during <span class="hlt">AAA</span> growth. Good correlation - 2-D cross-correlation coefficients of 0.65, 0.86 and 0.082 (min, max, SD) - was obtained between numerical simulations and 4-D MRI acquisitions in 6 specific cross-sections from 4 patients. In follow-up study, LCS divided <span class="hlt">AAA</span> lumens into 3 dynamically-isolated zones: 2 stagnation volumes lying in dilated portions of the <span class="hlt">AAA</span>, and circulating volume connecting the inlet to the outlet. The volume of each zone was tracked over time. Although circulating volume remained unchanged during 8-year follow-up, the <span class="hlt">AAA</span> lumen and main stagnation zones grew significantly (8 cm 3 /year and 6 cm 3 /year, respectively). This study reveals that transient transport topology can be quantified in patient-specific <span class="hlt">AAA</span> during disease progression</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23084731','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23084731"><span>Disparities in outcomes for Hispanic patients undergoing endovascular and open abdominal aortic aneurysm repair.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Williams, Timothy K; Schneider, Eric B; Black, James H; Lum, Ying Wei; Freischlag, Julie A; Perler, Bruce A; Abularrage, Christopher J</p> <p>2013-01-01</p> <p>Previous studies have demonstrated racial and ethnic disparities associated with the outcomes of abdominal aortic aneurysm (<span class="hlt">AAA</span>) repair, although little is known about the influence of race and ethnicity on the costs associated with these disparities. The current study was undertaken to examine the influence of race and ethnicity on the outcomes of endovascular (EVAR) and open repair (open <span class="hlt">AAA</span>) of unruptured <span class="hlt">AAA</span> and its effect on costs in contemporary practice. The Nationwide Inpatient Sample (2005 to 2008) was queried using ICD-9-CM codes for unruptured <span class="hlt">AAA</span> (441.4). The primary outcomes were mortality and total hospital charges. Multivariate analyses were performed adjusting for age, gender, race, comorbidities (Charlson index), year, insurance type, and hospital characteristics. A total of 62,728 patients underwent EVAR and 24,253 patients underwent open <span class="hlt">AAA</span>. White patients (72%) were more likely to undergo EVAR than Hispanic (69%) or black patients (69%; P = 0.02). On univariate analysis, in-hospital mortality after EVAR was increased in Hispanic patients compared with white patients (1% vs 2%; P = 0.02). There were no differences in mortality after EVAR between white and black patients, and there were no racial or ethnic differences in mortality after open <span class="hlt">AAA</span>. Hispanic ethnicity remained an independent risk factor for increased mortality after <span class="hlt">AAA</span> repair on multivariate analysis (RR 1.64; 95% CI [1.05 to 2.57]; P = 0.03). Hispanic ethnicity was associated with increased hospital charges compared with white ethnicity after both EVAR ($108,886 vs $77,748; P < 0.001) and open <span class="hlt">AAA</span> ($134,356 vs $85,536; P < 0.001) and for black patients after open <span class="hlt">AAA</span> ($101,168 vs $85,536; P = 0.04). Hispanic ethnicity is an independent risk factor for mortality after <span class="hlt">AAA</span> repair independent of insurance type or hospital characteristics. There were dramatic disparities in hospital costs for Hispanic patients undergoing either EVAR or open <span class="hlt">AAA</span> and for black patients after open <span class="hlt">AAA</span></p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22649185-su-comparative-analysis-pencil-beam-anisotropic-analytical-algorithm-aaa-stereotactic-body-radiation-therapy-sbrt-thoracic-spine','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22649185-su-comparative-analysis-pencil-beam-anisotropic-analytical-algorithm-aaa-stereotactic-body-radiation-therapy-sbrt-thoracic-spine"><span></span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Badkul, R; Nicolai, W; Pokhrel, D</p> <p></p> <p>Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(<span class="hlt">AAA</span>) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with <span class="hlt">AAA</span> algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and <span class="hlt">AAA</span> algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the <span class="hlt">AAA</span> DVH values with respect to PB plan values as standard, although <span class="hlt">AAA</span> predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with <span class="hlt">AAA</span> calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with <span class="hlt">AAA</span> algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. <span class="hlt">AAA</span> overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for <span class="hlt">AAA</span> algorithm as compared to PB. Conclusion: <span class="hlt">AAA</span> overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by <span class="hlt">AAA</span> versus PB. Spinal cord dose was overestimated by <span class="hlt">AAA</span> versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26114401','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26114401"><span>Safety assessment of a novel active ingredient, acetyl aspartic acid, according to the EU Cosmetics Regulation and the Scientific Committee on Consumer Safety guidelines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Daly, P; Moran, G</p> <p>2015-10-01</p> <p>Acetyl aspartic acid (<span class="hlt">A-A-A</span>) was proposed as a new novel active ingredient for use in cosmetics. The safety of <span class="hlt">A-A-A</span> was assessed by following an in-house-developed 'New Ingredient Testing Strategy', which was designed in accordance with the Scientific Committee on Consumer Safety (SCCS) notes of guidance and the requirements of Annex I of the EU Cosmetics Regulation. The aim of the project was to determine whether <span class="hlt">A-A-A</span> was safe for use in cosmetics and to determine a maximum permitted safe level in the formulations. A literature review was conducted, consulting over 40 different information sources. This highlighted a number of gaps which required testing data. <span class="hlt">A-A-A</span> was tested for phototoxicity according to OECD test guideline 432, skin irritation according to OECD test guideline 439 and eye irritation according to OECD test guideline 437. Dermal absorption of <span class="hlt">A-A-A</span> was measured according to OECD test guideline 428 and was used to calculate the margin of safety (MoS). Finally, <span class="hlt">A-A-A</span> was tested in a human repeat insult patch test (HRIPT) and a 14-day in-use tolerance study. <span class="hlt">A-A-A</span> was non-phototoxic and was non-irritating to skin and eyes in in vitro testing. Dermal absorption was calculated to be 5%. The MoS for <span class="hlt">A-A-A</span> was 351, at a level of 5%, for all cosmetic product types, indicating no systemic safety toxicity concern. <span class="hlt">A-A-A</span> at 5% under occlusive patch on a panel of 50 adult volunteers induced no skin irritation or allergic reaction in the HRIPT study. Finally, repeated application of <span class="hlt">A-A-A</span> to the periocular area, twice per day for 14 days, in 21 female volunteers, demonstrated that 1% <span class="hlt">A-A-A</span> was well tolerated following dermatological and ophthalmological assessment in a cosmetic formulation. <span class="hlt">A-A-A</span> was assessed as safe by the cosmetic safety assessor for use in cosmetics at a level of 5% in all cosmetic product types, in line with the requirements of the EU Cosmetics Regulation and in accordance with the SCCS notes of guidance. © 2015 Society of Cosmetic</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/ADA093562','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/ADA093562"><span>Transactions of the Conference of Army Mathematicians (26th) Held at Hanover, New Hampshire on 10 - 12 June 1980.</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>1981-01-01</p> <p>the constants v and v, as functions of i. The constant v+" as in Linan’s problem, vanishcs for , 0 and is non -zero for " < 0, being controlled bv the...Affairs Officer, will serve as CRREL’s point of contact for administrative arrangements for the Conference. 3. We look forward to having the group ...Edward J. <span class="hlt">Haug</span> and Roger A. Wehage ............................ 89 ’APPLICATIONS OF DELAY FEEDBACK IN CONTROL SYSTEMS DESIGN> N. P. Coleman, E. Carroll</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3243707','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3243707"><span>The Toxic Effects of Cigarette Additives. <span class="hlt">Philip</span> Morris' Project Mix Reconsidered: An Analysis of Documents Released through Litigation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wertz, Marcia S.; Kyriss, Thomas; Paranjape, Suman; Glantz, Stanton A.</p> <p>2011-01-01</p> <p>Background In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze <span class="hlt">Philip</span> Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations. Methods and Findings We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as “Project MIX.” Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect. Conclusion The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29867175','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29867175"><span>Prospective Observational Evaluation of Time-Dependency of Adalimumab Immunogenicity and Drug Concentrations: The Poetic Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ungar, Bella; Engel, Tal; Yablecovitch, Doron; Lahat, Adi; Lang, Alon; Avidan, Benjamin; Har-Noy, Ofir; Carter, Dan; Levhar, Nina; Selinger, Limor; Neuman, Sandra; Natour, Ola Haj; Yavzori, Miri; Fudim, Ella; Picard, Orit; Kopylov, Uri; Chowers, Yehuda; Naftali, Timna; Broide, Efrat; Shachar, Eyal; Eliakim, Rami; Ben-Horin, Shomron</p> <p>2018-06-01</p> <p>Adalimumab is usually self-injected at home, making prospective serial-sampling studies challenging and scarce. This has led to a gap in knowledge about evolution of anti-adalimumab antibodies (<span class="hlt">AAAs</span>) over time and its correlation with clinical and inflammatory outcomes. A program for home visits by physicians at induction, every 3 months and at event of relapse, was established prospectively for Crohn's disease (CD) patients. At each visit, patients' clinical scores were determined and sera were obtained for C-reactive protein, drug, and <span class="hlt">AAA</span> levels. This cohort was compared to a parallel prospective cohort of infliximab-treated CD patients. In a subgroup of 29 patients, trough and in-between-trough levels were compared, to elucidate the importance of timing of sampling during the injection cycle. Ninety-eight CD patients starting adalimumab were prospectively followed (median follow-up 44 weeks) and 621 serum samples were analyzed. Thirty-three patients (32%) developed <span class="hlt">AAA</span>; 18/33 (55%) of them as early as week 2, and 26/33 (79%) by week 14. Induction period <span class="hlt">AAAs</span> were strongly associated with primary non-response (odds ratio (OR) = 5.4, 95% confidence interval (CI): 1.6-17.8, p = 0.005). As compared to antibodies-to-infliximab (ATI), <span class="hlt">AAA</span> formation rate over time was significantly lower (p = 0.01) and <span class="hlt">AAA</span> were much more specific-85% of <span class="hlt">AAA</span> events were associated with loss-of-response compared with 58% rate for ATI (p = 0.01). In 29 patients sampled serially during an injection cycle, levels of drug and <span class="hlt">AAA</span> seemed comparable between four time-points during a single cycle both in patients with or without <span class="hlt">AAA</span> (n = 8, n = 21, respectively). When followed prospectively and serially, <span class="hlt">AAAs</span> are found to arise earlier than previously appreciated and their impact may be more pronounced for primary rather than secondary, non-response. Drug and <span class="hlt">AAA</span> levels were similar both at trough and in-between injections, enabling to simplify therapeutic drug</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5319980','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5319980"><span>Mutant Analysis Reveals Allosteric Regulation of ClpB Disaggregase</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Franke, Kamila B.; Bukau, Bernd; Mogk, Axel</p> <p>2017-01-01</p> <p>The members of the hexameric <span class="hlt">AAA</span>+ disaggregase of E. coli and S. cerevisiae, ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (<span class="hlt">AAA</span>-1, <span class="hlt">AAA</span>-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the <span class="hlt">AAA</span>-1 ring to downregulate ATP hydrolysis. Keeping M-domains displaced from the <span class="hlt">AAA</span>-1 ring by association with Hsp70 increases ATPase activity due to enhanced communication between protomers. This communication involves conserved arginine fingers. The control of ClpB/Hsp104 activity is crucial, as hyperactive mutants with permanently dissociated M-domains exhibit cellular toxicity. Here, we analyzed <span class="hlt">AAA</span>-1 inter-ring communication in relation to the M-domain mediated ATPase regulation, by subjecting a conserved residue of the <span class="hlt">AAA</span>-1 domain subunit interface of ClpB (A328) to mutational analysis. While all A328X mutants have reduced disaggregation activities, their ATPase activities strongly differed. ClpB-A328I/L mutants have reduced ATPase activity and when combined with the hyperactive ClpB-K476C M-domain mutation, suppress cellular toxicity. This underlines that ClpB ATPase activation by M-domain dissociation relies on increased subunit communication. The ClpB-A328V mutant in contrast has very high ATPase activity and exhibits cellular toxicity on its own, qualifying it as novel hyperactive ClpB mutant. ClpB-A328V hyperactivity is however, different from that of M-domain mutants as M-domains stay associated with the <span class="hlt">AAA</span>-1 ring. The high ATPase activity of ClpB-A328V primarily relies on the <span class="hlt">AAA</span>-2 ring and correlates with distinct conformational changes in the <span class="hlt">AAA</span>-2 catalytic site. These findings characterize the subunit interface residue A328 as crucial regulatory element to control ATP hydrolysis in both <span class="hlt">AAA</span> rings. PMID:28275610</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17996468','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17996468"><span>Polymorphisms of the interleukin-6 gene promoter and abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smallwood, L; Allcock, R; van Bockxmeer, F; Warrington, N; Palmer, L J; Iacopetta, B; Norman, P E</p> <p>2008-01-01</p> <p>Elevated levels of circulating interleukin-6 (IL-6) have been reported in patients with abdominal aortic aneurysms (<span class="hlt">AAAs</span>). Although this implicates inflammation as a cause of <span class="hlt">AAAs</span>, there is also evidence that the aneurysmal aorta may secrete IL-6 into the circulation as a result of aortic proteolysis. Genetic association studies are one means of trying to clarify the role of specific mediators in the causal pathway. The aim of the present study was to examine the association between variants of the IL-6 gene and <span class="hlt">AAAs</span>. An association study involving 677 men with screen-detected <span class="hlt">AAAs</span> and 656 age-matched controls was performed. Three variants in the IL-6 promoter region were analysed: IL-6-174G>C (rs1800795), IL-6-572G>C (rs1800796) and IL-6-597G>A (rs1800797). Univariate regression of SNP genotype on <span class="hlt">AAA</span> as a binary outcome was initially performed under a range of genetic models (additive, dominant and recessive). This was followed by multivariate analyses, testing the same models but including risk factors known to be associated with <span class="hlt">AAAs</span>. All analyses and haplotype estimation were performed under a generalized linear model framework. IL-6-572G>C polymorphism (frequency 1.5% in cases) was identified as an independent risk factor for <span class="hlt">AAA</span> with an odds ratio (OR) of 6.00 (95%CI: 1.22, 29.41) when applied to the recessive model. No association was seen in the additive or dominant models. In a multivariate analysis using the most common haplotype (h.111, frequency 48.7%) as a reference, h.211 (frequency 4.4%) was an independent risk factor for <span class="hlt">AAA</span> (OR 1.56, 95%CI: 1.02, 2.39). The IL-6 572G>C polymorphism (and h.211 haplotype) is associated with <span class="hlt">AAA</span>, however it is too rare to be an important cause of most <span class="hlt">AAAs</span>. This does not support the concept that the elevated level of IL-6 reported in patients with <span class="hlt">AAAs</span> is a primary cause of the aneurysmal process.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23612948','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23612948"><span>Low prevalence of abdominal aortic aneurysm in the Seychelles population aged 50 to 65 years.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yerly, Patrick; Madeleine, George; Riesen, Walter; Bovet, Pascal</p> <p>2013-03-01</p> <p>The prevalence of abdominal aortic aneurysm (<span class="hlt">AAA</span>) and its risk factors are well known in Western countries but few data are available from low- and middle- income countries. We are not aware of systematically collected population- based data on <span class="hlt">AAA</span> in the African region. We evaluated the prevalence of <span class="hlt">AAA</span> in a population- based cardiovascular survey conducted in the Republic of Seychelles in 2004 (Indian Ocean, African region). Among the 353 participants aged 50 to 64 years and screened with ultrasound, the prevalence of <span class="hlt">AAA</span> was 0.3% (95% CI: 0- 0.9) and the prevalence of ectatic dilatations of the abdominal aorta was 1.5% (95% CI: 0.2- 2.8). The prevalence of <span class="hlt">AAA</span> in the general population seemed lower in Seychelles than in Western countries, despite a high prevalence in Seychelles of risk factors of <span class="hlt">AAA</span>, such as smoking (in men), high blood pressure and hypercholesterolaemia.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2927355','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2927355"><span>Recent Advances in Molecular Mechanisms of Abdominal Aortic Aneurysm Formation</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Annambhotla, Suman; Bourgeois, Sebastian; Wang, Xinwen; Lin, Peter H.; Yao, Qizhi; Chen, Changyi</p> <p>2010-01-01</p> <p>Abdominal Aortic Aneurysm (<span class="hlt">AAA</span>) is an increasingly common clinical condition with fatal implications. It is associated with advanced age, male gender, cigarette smoking, atherosclerosis, hypertension, and genetic predisposition. Although significant evidence has emerged in the last decade, the molecular mechanisms of <span class="hlt">AAA</span> formation remains poorly understood. Currently, the treatment for <span class="hlt">AAA</span> remains primarily surgical with the lone innovation of endovascular therapy. With advance in the human genome, understanding precisely which molecules and genes mediate <span class="hlt">AAA</span> development and blocking their activity at the molecular level could lead to important new discoveries and therapies. This review summarizes recent updates in molecular mechanisms of <span class="hlt">AAA</span> formation including animal models, autoimmune components, infection, key molecules and cytokines, mechanical forces, genetics and pharmacotherapy. This review will be helpful to those who want to recognize the newest endeavors within the field and identify possible lines of investigation in <span class="hlt">AAA</span>. PMID:18259804</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25958166','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25958166"><span>Attenuation of aortic aneurysms with stem cells from different genders.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Davis, John P; Salmon, Morgan; Pope, Nicolas H; Lu, Guanyi; Su, Gang; Sharma, Ashish K; Ailawadi, Gorav; Upchurch, Gilbert R</p> <p>2015-11-01</p> <p>No medical therapies are yet available to slow abdominal aortic aneurysm (<span class="hlt">AAA</span>) growth. This study sought to investigate the effect of different genders of bone marrow-derived mesenchymal stem cells (MSC) on <span class="hlt">AAA</span> growth in a murine <span class="hlt">AAA</span> model. Given the decreased rate of <span class="hlt">AAA</span> in women, it is hypothesized that female MSC would attenuate <span class="hlt">AAA</span> growth more so than male MSC. Aortas of 8-10-wk-old male C57Bl/6 mice were perfused with purified porcine pancreatic elastase to induce <span class="hlt">AAA</span> formation. Bone marrow-derived MSC from male and female mice were dosed via tail vein injection (3 million cells per dose, 500 μL of volume per injection) on postaortic perfusion days 1, 3, and 5. Aortas were harvested after 14 d. Mean aortic dilation in the elastase group was 121 ± 5.2% (mean ± standard error of the mean), while male MSC inhibited <span class="hlt">AAA</span> growth (87.8 ± 6.9%, P = 0.008) compared with that of elastase. Female MSC showed the most marked attenuation of <span class="hlt">AAA</span> growth (75.2 ± 8.3% P = 0.0004). Proinflammatory cytokines tumor necrosis factor α, interleukin 1β, and monocyte chemotactic protein-1 (MCP-1) were only decreased in tissues treated with female MSC (P = 0.017, P = 0.001, and P < 0.0001, respectively, when compared with elastase). These data exhibit that female MSC more strongly attenuate <span class="hlt">AAA</span> growth in the murine model. Furthermore, female MSC and male MSC inhibit proinflammatory cytokines at varying levels. The effects of MSC on aortic tissue offer a promising insight into biologic therapies for future medical treatment of <span class="hlt">AAAs</span> in humans. Copyright © 2015 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28394003','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28394003"><span>The prevalence of abdominal aortic aneurysms in the rural/urban population in central Poland - Gniewkowo Aortic Study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dereziński, Tadeusz L; Fórmankiewicz, Bartosz; Migdalski, Arkadiusz; Brazis, Paweł; Jakubowski, Grzegorz; Woda, Łukasz; Jawień, Arkadiusz</p> <p>2017-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a widening of the aorta below the renal arteries with a diameter equal to or greater than 3 cm. The prevalence of <span class="hlt">AAA</span> is estimated at 4-8% in men aged 65 years or older and 1-2% among women over 65 years old. Participation in screening programmes has decreased the number of aortic ruptures. All men aged 60 years and older, and women aged 65 years and older living in the rural/urban commune in central Poland were invited to participate in the study. In total 922 persons (61% of the invited population) entered the study. The men were divided into two groups: 60-64 years old, and 65 years and older. Screening abdomen ultrasound was performed and demographic data was collected. Among the 922 examined persons two (1.01%) <span class="hlt">AAAs</span> were diagnosed in the group of men 60-64 years of age, three (0.82%) <span class="hlt">AAAs</span> amongst women ≥ 65 years old, and 33 (9.29%) <span class="hlt">AAAs</span> were found in the group of men aged 65 years and older. A positive relationship between the presence of <span class="hlt">AAA</span> and smoking (p = 0.0048), age of men (p = 0.0009), and history of myocardial infarction/acute coronary syndrome (MI/ACS) (p = 0.0079) was found. There was no correlation between the frequency of <span class="hlt">AAA</span> and diabetes mellitus (p = 0.46), hypertension (p = 0.38), and family history of <span class="hlt">AAA</span> (p = 0.44). The prevalence of <span class="hlt">AAA</span> in men aged 65 years and older is seemingly larger than in previously conducted studies, while among men 60-64 years of age and women aged ≥ 65 it is similar. Older age, smoking, and a history of MI/ACS were the most important risk factors of <span class="hlt">AAA</span> occurrence.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2017SPIE10333E..03W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2017SPIE10333E..03W"><span>Characterization of the mechanical behavior and pathophysiological state of abdominal aortic aneurysms based on 4D ultrasound strain imaging</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wittek, Andreas; Blase, Christopher; Derwich, Wojciech; Schmitz-Rixen, Thomas; Fritzen, Claus-Peter</p> <p>2017-06-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAA</span>) are a degenerative disease of the human aortic wall that may lead to weakening and eventually rupture of the wall with high mortality rates. Since the currently established criterion for surgical or endovascular treatment of the disease is imprecise in the individual case and treatment is not free of complications, the need for additional patient-individual biomarkers for short-term <span class="hlt">AAA</span> rupture risk as basis for improved clinical decision making. Time resolved 3D ultrasound combined with speckle tracking algorithms is a novel non-invasive medical imaging technique that provides full-field displacement and strain measurements of aortic and aneurysmal wall motion. This is patient-individual information that has not been used so far to assess wall strength and rupture risk. The current study uses simple statistical indices of the heterogeneous spatial distribution of in-plane strain components as biomarkers for the pathological state of the aortic and aneurysmal wall. The pathophysiological rationale behind this approach are the known changes in microstructural composition of the aortic wall with progression of <span class="hlt">AAA</span> development that results in increased stiffening and heterogeneity of the walls mechanical properties and in decreased wall strength. In a comparative analysis of the aortic wall motion of young volunteers without known cardiovascular diseases, aged arteriosclerotic patients without <span class="hlt">AAA</span>, and <span class="hlt">AAA</span> patients, mean values of all in-plane strain components were significantly reduced, and the heterogeneity of circumferential strain was significantly increased in the <span class="hlt">AAA</span> group compared to both other groups. The capacity of the proposed method to differentiate between wall motion of aged, arteriosclerotic patients and <span class="hlt">AAA</span> patients is a promising step towards a new method for in vivo assessment of <span class="hlt">AAA</span> wall strength or stratification of <span class="hlt">AAA</span> rupture risk as basis for improved clinical decision making on surgical or endovascular</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27567003','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27567003"><span>Plasma D-dimer as a predictor of the progression of abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Vele, E; Kurtcehajic, A; Zerem, E; Maskovic, J; Alibegovic, E; Hujdurovic, A</p> <p>2016-11-01</p> <p>Essentials D-dimer could provide important information about abdominal aortic aneurysm (<span class="hlt">AAA</span>) progression. The greatest diameter of the infrarenal aorta and the value of plasma D-dimer were determined. <span class="hlt">AAA</span> progression is correlated with increasing plasma D-dimer levels. The increasing value of plasma D-dimer could be a predictor of aneurysm progression. Background The natural course of abdominal aortic aneurysm (<span class="hlt">AAA</span>) is mostly asymptomatic and unpredictable. D-dimer could provide potentially important information about subsequent <span class="hlt">AAA</span> progression. Objectives The aims of this study were to establish the relationship between the progression of an abdominal aortic aneurysm (<span class="hlt">AAA</span>) and plasma D-dimer concentration over a 12-month period and determine the value of plasma D-dimer in patients with sub-aneurysmal aortic dilatation. Patients/Methods This was a prospective observational study that involved 33 patients with an <span class="hlt">AAA</span>, 30 patients with sub-aneurysmal aortic dilatation and 30 control subjects. The greatest diameter of the infrarenal aorta, which was assessed by ultrasound, and the value of plasma D-dimer were determined for all subjects at baseline assessment, as well as after 12 months for those with an <span class="hlt">AAA</span>. Results A positive correlation was found between the diameter of an <span class="hlt">AAA</span> and plasma D-dimer concentration at the baseline and the control measurement stages. There was a strong positive correlation between <span class="hlt">AAA</span> progression and increasing plasma D-dimer concentration over a 12-month period. Among patients with sub-aneurysmal aortic dilatation (n = 30), the value of plasma D-dimer was higher compared with matched controls (n = 30). Conclusions There is a strongly positive correlation between <span class="hlt">AAA</span> progression and increasing plasma D-dimer concentration. The value of plasma D-dimer is higher in patients with sub-aneurysmal aortic dilatation than in control subjects. © 2016 International Society on Thrombosis and Haemostasis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27771234','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27771234"><span>Comparison of Conscious Sedation and Asleep-Awake-Asleep Techniques for Awake Craniotomy.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dilmen, Ozlem Korkmaz; Akcil, Eren Fatma; Oguz, Abdulvahap; Vehid, Hayriye; Tunali, Yusuf</p> <p>2017-01-01</p> <p>Since awake craniotomy (AC) has become a standard of care for supratentorial tumour resection, especially in the motor and language cortex, determining the most appropriate anaesthetic protocol is very important. The aim of this retrospective study is to compare the effectiveness of conscious sedation (CS) to "awake-asleep-awake" (<span class="hlt">AAA</span>) techniques for supratentorial tumour resection. Forty-two patients undergoing CS and 22 patients undergoing <span class="hlt">AAA</span> were included in the study. The primary endpoint was to compare the CS and <span class="hlt">AAA</span> techniques with respect to intraoperative pain and agitation in patients undergoing supratentorial tumour resection. The secondary endpoint was comparison of the other intraoperative complications. This study results show that the incidence of intraoperative agitation and seizure were lower in the <span class="hlt">AAA</span> group than in the CS group. Intraoperative blood pressures were significantly higher in the CS group than in the <span class="hlt">AAA</span> group during the pinning and incision, but the level of blood pressures did not need antihypertensive treatment. Otherwise, blood pressures were significantly higher in the <span class="hlt">AAA</span> group than in the CS group during the neurological examination and the severity of hypertension needed statistically significant more antihypertensive treatment in the <span class="hlt">AAA</span> group. As a result of hypertension, the amount of intraoperative bleeding was higher in the <span class="hlt">AAA</span> group than in the CS group. In conclusion, the <span class="hlt">AAA</span> technique may provide better results with respect to agitation and seizure, but intraoperative hypertension needed a vigilant follow-up especially in the wake-up period. Copyright © 2016 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29456054','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29456054"><span>The Relationship Between Serum Interleukin-1α and Asymptomatic Infrarenal Abdominal Aortic Aneurysm Size, Morphology, and Growth Rates.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ahmad, Mehtab; Kuravi, Sahithi; Hodson, James; Rainger, G Ed; Nash, Gerard B; Vohra, Rajiv K; Bradbury, Andrew W</p> <p>2018-02-16</p> <p>In a pilot study, a relationship between abdominal aortic aneurysm (<span class="hlt">AAA</span>) diameter and serum interleukin (IL)-1α levels was reported, and that endothelial cell (EC) activation in vitro in response to serum from patients with <span class="hlt">AAA</span> was blocked by anti-IL-1α antibodies. The aim of the present study was to further investigate the relationship between serum IL-1α and asymptomatic infrarenal <span class="hlt">AAA</span> size, morphology, and growth rates. Serum IL-1α was measured using enzyme linked immunosorbent assay in 101 patients with asymptomatic, infrarenal <span class="hlt">AAA</span> and related to aneurysm size, morphology, and growth rates. IL-1α was measured in 101 patients. There was no statistically significant difference in mean age between men and women. IL-1α was detectable in 62.4% of patients; median IL-1α titre was 3.26 pg/mL. There was no statistically significant relationship between IL-1α and maximum <span class="hlt">AAA</span> antero-posterior diameter as measured by ultrasound (p = .649), <span class="hlt">AAA</span> morphology (aortic length [p = .394], sac [p = .369], and thrombus volume [p = .629]) as measured on computed tomography, absolute increase in <span class="hlt">AAA</span> diameter (p = .214), or <span class="hlt">AAA</span> growth rate (p = .230). IL-1α is detectable in the majority of patients with infrarenal <span class="hlt">AAA</span>, but the cause and clinical significance of this novel observation remains unknown. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22514726','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22514726"><span>Endothelial and smooth muscle cells from abdominal aortic aneurysm have increased oxidative stress and telomere attrition.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cafueri, Giuseppe; Parodi, Federica; Pistorio, Angela; Bertolotto, Maria; Ventura, Francesco; Gambini, Claudio; Bianco, Paolo; Dallegri, Franco; Pistoia, Vito; Pezzolo, Annalisa; Palombo, Domenico</p> <p>2012-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a complex multi-factorial disease with life-threatening complications. <span class="hlt">AAA</span> is typically asymptomatic and its rupture is associated with high mortality rate. Both environmental and genetic risk factors are involved in <span class="hlt">AAA</span> pathogenesis. Aim of this study was to investigate telomere length (TL) and oxidative DNA damage in paired blood lymphocytes, aortic endothelial cells (EC), vascular smooth muscle cells (VSMC), and epidermal cells from patients with <span class="hlt">AAA</span> in comparison with matched controls. TL was assessed using a modification of quantitative (Q)-FISH in combination with immunofluorescence for CD31 or α-smooth muscle actin to detect EC and VSMC, respectively. Oxidative DNA damage was investigated by immunofluorescence staining for 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG). Telomeres were found to be significantly shortened in EC, VSMC, keratinocytes and blood lymphocytes from <span class="hlt">AAA</span> patients compared to matched controls. 8-oxo-dG immunoreactivity, indicative of oxidative DNA damage, was detected at higher levels in all of the above cell types from <span class="hlt">AAA</span> patients compared to matched controls. Increased DNA double strand breaks were detected in <span class="hlt">AAA</span> patients vs controls by nuclear staining for γ-H2AX histone. There was statistically significant inverse correlation between TL and accumulation of oxidative DNA damage in blood lymphocytes from <span class="hlt">AAA</span> patients. This study shows for the first time that EC and VSMC from <span class="hlt">AAA</span> have shortened telomeres and oxidative DNA damage. Similar findings were obtained with circulating lymphocytes and keratinocytes, indicating the systemic nature of the disease. Potential translational implications of these findings are discussed.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5409053','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5409053"><span>Abdominal aortic aneurysm screening program using hand-held ultrasound in primary healthcare</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kostov, Belchin; Navarro González, Marta; Cararach Salami, Daniel; Pérez Jiménez, Alfonso; Gilabert Solé, Rosa; Bru Saumell, Concepció; Donoso Bach, Lluís; Villalta Martí, Mireia; González-de Paz, Luis; Ruiz Riera, Rafael; Riambau Alonso, Vicenç; Acar-Denizli, Nihan; Farré Almacellas, Marta; Ramos-Casals, Manuel; Benavent Àreu, Jaume</p> <p>2017-01-01</p> <p>We determined the feasibility of abdominal aortic aneurysm (<span class="hlt">AAA</span>) screening program led by family physicians in public primary healthcare setting using hand-held ultrasound device. The potential study population was 11,214 men aged ≥ 60 years attended by three urban, public primary healthcare centers. Participants were recruited by randomly-selected telephone calls. Ultrasound examinations were performed by four trained family physicians with a hand-held ultrasound device (Vscan®). <span class="hlt">AAA</span> observed were verified by confirmatory imaging using standard ultrasound or computed tomography. Cardiovascular risk factors were determined. The prevalence of <span class="hlt">AAA</span> was computed as the sum of previously-known aneurysms, aneurysms detected by the screening program and model-based estimated undiagnosed aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995 (98.5%) men had normal aortas and 15 (1.5%) had <span class="hlt">AAA</span> on Vscan®. Eleven out of 14 <span class="hlt">AAA</span>-cases (78.6%) had <span class="hlt">AAA</span> on confirmatory imaging (one patient died). The total prevalence of <span class="hlt">AAA</span> was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in whom <span class="hlt">AAA</span> was diagnosed incidentally. Multivariate logistic regression analysis identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the independent factor with the highest odds ratio. A screening program led by trained family physicians using hand-held ultrasound was a feasible, safe and reliable tool for the early detection of <span class="hlt">AAA</span>. PMID:28453577</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29848273','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29848273"><span>Inflammatory Cells and Proteases in Abdominal Aortic Aneurysm and its Complications.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Haiying, Jiang; Sasaki, Takeshi; Jin, Enze; Kuzuya, Masafumi; Cheng, Xianwu</p> <p>2018-05-30</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>), a common disease among elderly individuals, involves the progressive dilatation of the abdominal aorta as a consequence of degeneration. The mechanisms of <span class="hlt">AAA</span> formation, development and rupture are largely unknown. Surgical repair is the only available method of treatment since the lack of knowledge regarding the pathogenesis of <span class="hlt">AAA</span> has hindered the development of suitable medical treatments, particularly the development of drugs. In this review, we describe the inflammatory cells and proteases that may be involved in the formation and development of <span class="hlt">AAA</span>. This knowledge can contribute to the development of new drugs for <span class="hlt">AAA</span>. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015ITNS...62..669S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015ITNS...62..669S"><span>Data Processing for a High Resolution Preclinical PET Detector Based on <span class="hlt">Philips</span> DPC Digital SiPMs</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Schug, David; Wehner, Jakob; Goldschmidt, Benjamin; Lerche, Christoph; Dueppenbecker, Peter Michael; Hallen, Patrick; Weissler, Bjoern; Gebhardt, Pierre; Kiessling, Fabian; Schulz, Volkmar</p> <p>2015-06-01</p> <p>In positron emission tomography (PET) systems, light sharing techniques are commonly used to readout scintillator arrays consisting of scintillation elements, which are smaller than the optical sensors. The scintillating element is then identified evaluating the signal heights in the readout channels using statistical algorithms, the center of gravity (COG) algorithm being the simplest and mostly used one. We propose a COG algorithm with a fixed number of input channels in order to guarantee a stable calculation of the position. The algorithm is implemented and tested with the raw detector data obtained with the Hyperion-II D preclinical PET insert which uses <span class="hlt">Philips</span> Digital Photon Counting's (PDPC) digitial SiPMs. The gamma detectors use LYSO scintillator arrays with 30 ×30 crystals of 1 ×1 ×12 mm3 in size coupled to 4 ×4 PDPC DPC 3200-22 sensors (DPC) via a 2-mm-thick light guide. These self-triggering sensors are made up of 2 ×2 pixels resulting in a total of 64 readout channels. We restrict the COG calculation to a main pixel, which captures most of the scintillation light from a crystal, and its (direct and diagonal) neighboring pixels and reject single events in which this data is not fully available. This results in stable COG positions for a crystal element and enables high spatial image resolution. Due to the sensor layout, for some crystals it is very likely that a single diagonal neighbor pixel is missing as a result of the low light level on the corresponding DPC. This leads to a loss of sensitivity, if these events are rejected. An enhancement of the COG algorithm is proposed which handles the potentially missing pixel separately both for the crystal identification and the energy calculation. Using this advancement, we show that the sensitivity of the Hyperion-II D insert using the described scintillator configuration can be improved by 20-100% for practical useful readout thresholds of a single DPC pixel ranging from 17-52 photons. Furthermore</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29402733','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29402733"><span>Impact of isotropic constitutive descriptions on the predicted peak wall stress in abdominal aortic aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Man, V; Polzer, S; Gasser, T C; Novotny, T; Bursa, J</p> <p>2018-03-01</p> <p>Biomechanics-based assessment of Abdominal Aortic Aneurysm (<span class="hlt">AAA</span>) rupture risk has gained considerable scientific and clinical momentum. However, computation of peak wall stress (PWS) using state-of-the-art finite element models is time demanding. This study investigates which features of the constitutive description of <span class="hlt">AAA</span> wall are decisive for achieving acceptable stress predictions in it. Influence of five different isotropic constitutive descriptions of <span class="hlt">AAA</span> wall is tested; models reflect realistic non-linear, artificially stiff non-linear, or artificially stiff pseudo-linear constitutive descriptions of <span class="hlt">AAA</span> wall. Influence of the <span class="hlt">AAA</span> wall model is tested on idealized (n=4) and patient-specific (n=16) <span class="hlt">AAA</span> geometries. Wall stress computations consider a (hypothetical) load-free configuration and include residual stresses homogenizing the stresses across the wall. Wall stress differences amongst the different descriptions were statistically analyzed. When the qualitatively similar non-linear response of the <span class="hlt">AAA</span> wall with low initial stiffness and subsequent strain stiffening was taken into consideration, wall stress (and PWS) predictions did not change significantly. Keeping this non-linear feature when using an artificially stiff wall can save up to 30% of the computational time, without significant change in PWS. In contrast, a stiff pseudo-linear elastic model may underestimate the PWS and is not reliable for <span class="hlt">AAA</span> wall stress computations. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5696225','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5696225"><span>Effect of AMPK signal pathway on pathogenesis of abdominal aortic aneurysms</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yang, Le; Shen, Lin; Gao, Peixian; Li, Gang; He, Yuxiang; Wang, Maohua; Zhou, Hua; Yuan, Hai; Jin, Xing; Wu, Xuejun</p> <p>2017-01-01</p> <p>Background and aims Determine the effect of AMPK activation and inhibition on the development of <span class="hlt">AAA</span> (abdominal aortic aneurysm). Methods <span class="hlt">AAA</span> was induced in ApoE−/− mice by Ang II (Angiotensin II)-infusion. AICAR (5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside) was used as AMPK activator and Compound C was used as AMPK inhibitor. We further investigate the effect of metformin, a widely used anti-diabetic drug which could activate AMPK signal pathway, on the pathogenesis of aneurysm. Results Phospho-AMPK level was significantly decreased in <span class="hlt">AAA</span> tissue compared with control aortas. AICAR significantly reduced the incidence, severity and mortality of aneurysm in the Ang II-infusion model. AICAR also alleviated macrophage infiltration and neovascularity in Ang II infusion model at day 28. The expression of pro-inflammatory factors, angiogenic factors and the activity of MMPs were also alleviated by AICAR during <span class="hlt">AAA</span> induction. On the other hand, Compound C treatment did not exert obvious protective effect. AMPK activation may inhibit the activation of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT-3) during <span class="hlt">AAA</span> induction. Administration of metformin also activated AMPK signal pathway and retarded <span class="hlt">AAA</span> progression in Ang II infusion model. Conclusions Activation of AMPK signaling pathway may inhibit the Ang II-induced <span class="hlt">AAA</span> in mice. Metformin may be a promising approach to the treatment of <span class="hlt">AAA</span>. PMID:29190959</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4624089','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4624089"><span>Abdominal Aortic Aneurysm: Novel Mechanisms and Therapies</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Davis, Frank M.; Rateri, Debra L.; Daugherty, Alan</p> <p>2015-01-01</p> <p>Purpose of review Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for <span class="hlt">AAAs</span>. Recent Findings An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, MMP3, TGFβR2 and SORT1 loci, are associated with <span class="hlt">AAA</span> development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β and angiotensin II, are involved in the pathogenesis of <span class="hlt">AAAs</span>. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Recent preclinical investigations into pharmacological therapies for <span class="hlt">AAAs</span> have provided intriguing insight for roles of microRNAs to regulate many pathological pathways in <span class="hlt">AAA</span> development. Several large clinical trials are ongoing seeking to translate preclinical findings into therapeutic options. Summary Recent studies have identified many potential mechanisms involved in <span class="hlt">AAA</span> pathogenesis that provide insight for the development of a medical treatment for this disease. PMID:26352243</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26352243','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26352243"><span>Abdominal aortic aneurysm: novel mechanisms and therapies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Davis, Frank M; Rateri, Debra L; Daugherty, Alan</p> <p>2015-11-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a pathological condition of permanent dilation that portends the potentially fatal consequence of aortic rupture. This review emphasizes recent advances in mechanistic insight into aneurysm pathogenesis and potential pharmacologic therapies that are on the horizon for <span class="hlt">AAAs</span>. An increasing body of evidence demonstrates that genetic factors, including 3p12.3, DAB2IP, LDLr, LRP1, matrix metalloproteinase (MMP)-3, TGFBR2, and SORT1 loci, are associated with <span class="hlt">AAA</span> development. Current human studies and animal models have shown that many leukocytes and inflammatory mediators, such as IL-1, IL-17, TGF-β, and angiotensin II, are involved in the pathogenesis of <span class="hlt">AAAs</span>. Leukocytic infiltration into aortic media leads to smooth muscle cell depletion, generation of reactive oxygen species, and extracellular matrix fragmentation. Preclinical investigations into pharmacological therapies for <span class="hlt">AAAs</span> have provided intriguing insight into the roles of microRNAs in regulating many pathological pathways in <span class="hlt">AAA</span> development. Several large clinical trials are ongoing, seeking to translate preclinical findings into therapeutic options. Recent studies have identified many potential mechanisms involved in <span class="hlt">AAA</span> pathogenesis that provide insight into the development of a medical treatment for this disease.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28884122','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28884122"><span>Advanced Oxidation Protein Products and Carbonylated Proteins as Biomarkers of Oxidative Stress in Selected Atherosclerosis-Mediated Diseases.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gryszczyńska, Bogna; Formanowicz, Dorota; Budzyń, Magdalena; Wanic-Kossowska, Maria; Pawliczak, Elżbieta; Formanowicz, Piotr; Majewski, Wacław; Strzyżewski, Krzysztof Wojciech; Kasprzak, Magdalena P; Iskra, Maria</p> <p>2017-01-01</p> <p>The main question of this study was to evaluate the intensity of oxidative protein modification shown as advanced oxidation protein products (AOPP) and carbonylated proteins, expressed as protein carbonyl content (C=O) in abdominal aortic aneurysms (<span class="hlt">AAA</span>), aortoiliac occlusive disease (AIOD), and chronic kidney disease (CKD). The study was carried out in a group of 35 <span class="hlt">AAA</span> patients and 13 AIOD patients. However, CKD patients were divided into two groups: predialysis (PRE) included 50 patients or hemodialysis (HD) consisted of 34 patients. AOPP and C=O were measured using colorimetric assay kit, while C-reactive protein concentration was measured by high-sensitivity assay (hsCRP). The concentration of AOPP in both <span class="hlt">AAA</span> and AIOD groups was higher than in PRE and HD groups according to descending order: <span class="hlt">AAA</span>~AIOD > HD > PRE. The content of C=O was higher in the PRE group in comparison to AIOD and <span class="hlt">AAA</span> according to the descending order: PRE~HD > <span class="hlt">AAA</span>~AIOD. <span class="hlt">AAA</span>, AIOD, and CKD-related atherosclerosis (PRE and HD) contribute to the changes in the formation of AOPP and C=O. They may promote modification of proteins in a different way, probably due to the various factors that influence oxidative stress here.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3076426','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3076426"><span>Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Delbosc, Sandrine; Alsac, Jean-Marc; Journe, Clement; Louedec, Liliane; Castier, Yves; Bonnaure-Mallet, Martine; Ruimy, Raymond; Rossignol, Patrick; Bouchard, Philippe; Michel, Jean-Baptiste; Meilhac, Olivier</p> <p>2011-01-01</p> <p>Background Abdominal Aortic Aneurysms (<span class="hlt">AAAs</span>) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in <span class="hlt">AAA</span> growth may originate in part from repeated episodes of periodontal bacteremia. Methods and Findings Our results show that neutrophil activation in human <span class="hlt">AAA</span> was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human <span class="hlt">AAA</span> samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with <span class="hlt">AAA</span>. Using a rat model of <span class="hlt">AAA</span>, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. Conclusions Thus, the control of periodontal disease may represent a therapeutic target to limit human <span class="hlt">AAA</span> progression. PMID:21533243</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29873033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29873033"><span><span class="hlt">AAA</span>+ ATPases Reptin and Pontin as potential diagnostic and prognostic biomarkers in salivary gland cancer - a short report.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mikesch, Jan-Henrik; Hartmann, Wolfgang; Angenendt, Linus; Huber, Otmar; Schliemann, Christoph; Arteaga, Maria Francisca; Wardelmann, Eva; Rudack, Claudia; Berdel, Wolfgang E; Stenner, Markus; Grünewald, Inga</p> <p>2018-06-05</p> <p>Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metastasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse tumors. In recent years, the <span class="hlt">AAA</span>+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are frequently deregulated in cancer. The aim of this study was to assess the clinical and functional significance of Reptin and Pontin expression in SGC. Immunohistochemical staining of Pontin, Reptin, β-catenin, Cyclin D1, TP53 and MIB-1 was performed on a collection of 94 SGC tumor samples comprising 13 different histological subtypes using tissue microarrays. We found that Reptin and Pontin were expressed in the majority of SGC samples across all histological subtypes. Patients with a high Reptin expression showed a significantly inferior 5-year overall survival rate compared to patients with a low Reptin expression (47.7% versus 78.3%; p = 0.033), whereas no such difference was observed for Pontin. A high Reptin expression strongly correlated with a high expression of the proliferation marker MIB-1 (p = 0.003), the cell cycle regulator Cyclin D1 (p = 0.006), accumulation of TP53 as a surrogate p53 mutation marker (p = 0.042) and cytoplasmic β-catenin expression (p = 0.002). Increased Pontin expression was found to significantly correlate with both cytoplasmic and nuclear β-catenin expression (p = 0.037 and p = 0.018, respectively), which is indicative for its oncogenic function. Our results suggest a role of Reptin and Pontin in SGC tumor progression and/or patient survival. Therefore, SGC patients exhibiting a high Reptin expression may benefit from more aggressive therapeutic regimens. Future studies should clarify whether such patients may be considered</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28834214','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28834214"><span>Clinical implementation and evaluation of the Acuros dose calculation algorithm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M</p> <p>2017-09-01</p> <p>The main aim of this study is to validate the Acuros XB dose calculation algorithm for a Varian Clinac iX linac in our clinics, and subsequently compare it with the wildely used <span class="hlt">AAA</span> algorithm. The source models for both Acuros XB and <span class="hlt">AAA</span> were configured by importing the same measured beam data into Eclipse treatment planning system. Both algorithms were validated by comparing calculated dose with measured dose on a homogeneous water phantom for field sizes ranging from 6 cm × 6 cm to 40 cm × 40 cm. Central axis and off-axis points with different depths were chosen for the comparison. In addition, the accuracy of Acuros was evaluated for wedge fields with wedge angles from 15 to 60°. Similarly, variable field sizes for an inhomogeneous phantom were chosen to validate the Acuros algorithm. In addition, doses calculated by Acuros and <span class="hlt">AAA</span> at the center of lung equivalent tissue from three different VMAT plans were compared to the ion chamber measured doses in QUASAR phantom, and the calculated dose distributions by the two algorithms and their differences on patients were compared. Computation time on VMAT plans was also evaluated for Acuros and <span class="hlt">AAA</span>. Differences between dose-to-water (calculated by <span class="hlt">AAA</span> and Acuros XB) and dose-to-medium (calculated by Acuros XB) on patient plans were compared and evaluated. For open 6 MV photon beams on the homogeneous water phantom, both Acuros XB and <span class="hlt">AAA</span> calculations were within 1% of measurements. For 23 MV photon beams, the calculated doses were within 1.5% of measured doses for Acuros XB and 2% for <span class="hlt">AAA</span>. Testing on the inhomogeneous phantom demonstrated that <span class="hlt">AAA</span> overestimated doses by up to 8.96% at a point close to lung/solid water interface, while Acuros XB reduced that to 1.64%. The test on QUASAR phantom showed that Acuros achieved better agreement in lung equivalent tissue while <span class="hlt">AAA</span> underestimated dose for all VMAT plans by up to 2.7%. Acuros XB computation time was about three times faster than <span class="hlt">AAA</span> for VMAT plans, and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25690569','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25690569"><span>A Fragment-Based Ligand Screen Against Part of a Large Protein Machine: The ND1 Domains of the <span class="hlt">AAA</span>+ ATPase p97/VCP.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chimenti, Michael S; Bulfer, Stacie L; Neitz, R Jeffrey; Renslo, Adam R; Jacobson, Matthew P; James, Thomas L; Arkin, Michelle R; Kelly, Mark J S</p> <p>2015-07-01</p> <p>The ubiquitous <span class="hlt">AAA</span>+ ATPase p97 functions as a dynamic molecular machine driving several cellular processes. It is essential in regulating protein homeostasis, and it represents a potential drug target for cancer, particularly when there is a greater reliance on the endoplasmic reticulum-associated protein degradation pathway and ubiquitin-proteasome pathway to degrade an overabundance of secreted proteins. Here, we report a case study for using fragment-based ligand design approaches against this large and dynamic hexamer, which has multiple potential binding sites for small molecules. A screen of a fragment library was conducted by surface plasmon resonance (SPR) and followed up by nuclear magnetic resonance (NMR), two complementary biophysical techniques. Virtual screening was also carried out to examine possible binding sites for the experimental hits and evaluate the potential utility of fragment docking for this target. Out of this effort, 13 fragments were discovered that showed reversible binding with affinities between 140 µM and 1 mM, binding stoichiometries of 1:1 or 2:1, and good ligand efficiencies. Structural data for fragment-protein interactions were obtained with residue-specific [U-(2)H] (13)CH3-methyl-labeling NMR strategies, and these data were compared to poses from docking. The combination of virtual screening, SPR, and NMR enabled us to find and validate a number of interesting fragment hits and allowed us to gain an understanding of the structural nature of fragment binding. © 2015 Society for Laboratory Automation and Screening.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28359718','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28359718"><span>Impact of surgeon and hospital experience on outcomes of abdominal aortic aneurysm repair in New York State.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Meltzer, Andrew J; Connolly, Peter H; Schneider, Darren B; Sedrakyan, Art</p> <p>2017-09-01</p> <p>This study aimed to assess the impact of the surgeon's and hospital's experience on the outcomes of open surgical repair (OSR) and endovascular aneurysm repair (EVAR) of intact and ruptured abdominal aortic aneurysms (<span class="hlt">AAAs</span>) in New York State. New York Statewide Planning and Research Cooperative System data were used to identify patients undergoing <span class="hlt">AAA</span> repair from 2000 to 2011. Characteristics of the provider and hospital were determined by linkage to the New York Office of Professions and National Provider Identification databases. Distinct hierarchical logistic regression models for EVAR and OSR for intact and ruptured <span class="hlt">AAAs</span> were created to adjust for the patient's comorbidities and to evaluate the impact of the surgeon's and hospital's experience on outcomes. The provider's years since medical school graduation as well as annual volume of the facility and provider are examined in tertiles. Adjusted odds ratios and 95% confidence intervals are presented. A total of 18,842 patients underwent <span class="hlt">AAA</span> repair by a vascular surgeon. For intact <span class="hlt">AAAs</span> (n = 17,118), 26.2% of patients underwent OSR and 73.8% underwent EVAR. For ruptured <span class="hlt">AAAs</span> (n = 1724), 63.9% underwent OSR and 36.1% underwent EVAR. After intact <span class="hlt">AAA</span> repair, OSR adjusted outcomes were significantly influenced by the surgeon's annual volume but not by the facility's volume or the surgeon's age. The lowest volume providers (1-4 OSRs) had higher in-hospital mortality rates than high-volume (>11 OSRs) surgeons (adjusted odds ratio, 1.87 [95% confidence interval, 1.1-3.17]). Low-volume providers also had higher odds of major complications (1.23 [1-1.51]). For patients with intact <span class="hlt">AAA</span> undergoing EVAR, mortality was higher at low-volume facilities (2.6 [1.3-5.3] and 2.7 [1.5-4.8] for <33 EVARs and 34-81 EVARs, respectively). After OSR for ruptured <span class="hlt">AAA</span>, treatment at a low-volume facility (<9 OSRs for ruptured <span class="hlt">AAA</span>) was associated with greater mortality than at high-volume (>27 OSRs for ruptured <span class="hlt">AAA</span>) centers (1.56 [1</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/FR-2012-03-07/pdf/2012-5494.pdf','FEDREG'); return false;" href="https://www.gpo.gov/fdsys/pkg/FR-2012-03-07/pdf/2012-5494.pdf"><span>77 FR 13608 - Proposed Data Collections Submitted for Public Comment and Recommendations</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collection.action?collectionCode=FR">Federal Register 2010, 2011, 2012, 2013, 2014</a></p> <p></p> <p>2012-03-07</p> <p>... Against AIDS (<span class="hlt">AAA</span>) in 2009, a 5-year, multifaceted communication campaign consisting of several campaigns targeting various high-risk populations. The overall goals of <span class="hlt">AAA</span> are to increase HIV/AIDS awareness and reduce HIV incidence in the United States. Each <span class="hlt">AAA</span> campaign uses mass media and direct-to-consumer...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18980864','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18980864"><span>Abdominal aortic aneurysms: an autoimmune disease?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jagadesham, Vamshi P; Scott, D Julian A; Carding, Simon R</p> <p>2008-12-01</p> <p>Abdominal aortic aneurysms (<span class="hlt">AAAs</span>) are a multifactorial degenerative vascular disorder. One of the defining features of the pathophysiology of aneurysmal disease is inflammation. Recent developments in vascular and molecular cell biology have increased our knowledge on the role of the adaptive and innate immune systems in the initiation and propagation of the inflammatory response in aortic tissue. <span class="hlt">AAAs</span> share many features of autoimmune disease, including genetic predisposition, organ specificity and chronic inflammation. Here, this evidence is used to propose that the chronic inflammation observed in <span class="hlt">AAAs</span> is a consequence of a dysregulated autoimmune response against autologous components of the aortic wall that persists inappropriately. Identification of the molecular and cellular targets involved in <span class="hlt">AAA</span> formation will allow the development of therapeutic agents for the treatment of <span class="hlt">AAA</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28860231','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28860231"><span>Ultraviolet B Exposure Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Expanding CD4+Foxp3+ Regulatory T Cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hayashi, Tomohiro; Sasaki, Naoto; Yamashita, Tomoya; Mizoguchi, Taiji; Emoto, Takuo; Amin, Hilman Zulkifli; Yodoi, Keiko; Matsumoto, Takuya; Kasahara, Kazuyuki; Yoshida, Naofumi; Tabata, Tokiko; Kitano, Naoki; Fukunaga, Atsushi; Nishigori, Chikako; Rikitake, Yoshiyuki; Hirata, Ken-Ichi</p> <p>2017-08-31</p> <p>Pathogenic immune responses are known to play an important role in abdominal aortic aneurysm (<span class="hlt">AAA</span>) development. Ultraviolet B (UVB) irradiation has been demonstrated to have therapeutic potential not only for cutaneous diseases but also for systemic inflammatory diseases in mice by suppressing immunoinflammatory responses. We investigated the effect of UVB irradiation on experimental <span class="hlt">AAA</span>. We used an angiotensin II-induced <span class="hlt">AAA</span> model in apolipoprotein E-deficient mice fed a high-cholesterol diet. Mice aged 10 weeks were irradiated with 5 kJ/m 2 UVB once weekly for 6 weeks (UVB-irradiated, n=38; nonirradiated, n=42) and were euthanized for evaluation of <span class="hlt">AAA</span> formation at 16 weeks. Overall, 93% of angiotensin II-infused mice developed <span class="hlt">AAA</span>, with 60% mortality possibly because of aneurysm rupture. UVB irradiation significantly decreased the incidence (66%) and mortality (29%) of <span class="hlt">AAA</span> ( P =0.004 and P =0.006, respectively). UVB-irradiated mice had significantly smaller diameter <span class="hlt">AAA</span> ( P =0.008) and fewer inflammatory cells in the aortic aneurysm tissue than nonirradiated mice, along with systemic expansion of CD4 + Foxp3 + regulatory T cells and decreased effector CD4 + CD44 high CD62L low T cells in para-aortic lymph nodes. Genetic depletion of regulatory T cells abrogated these beneficial effects of UVB treatment, demonstrating a critical role of regulatory T cells. Our data suggest that UVB-dependent expansion of regulatory T cells has beneficial effects on experimental <span class="hlt">AAA</span> and may provide a novel strategy for the treatment of <span class="hlt">AAA</span>. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29649275','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29649275"><span>Evaluation of the relationship between plasma lipids and abdominal aortic aneurysm: A Mendelian randomization study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Weng, Lu-Chen; Roetker, Nicholas S; Lutsey, Pamela L; Alonso, Alvaro; Guan, Weihua; Pankow, James S; Folsom, Aaron R; Steffen, Lyn M; Pankratz, Nathan; Tang, Weihong</p> <p>2018-01-01</p> <p>Studies have reported that higher circulating levels of total cholesterol (TC), low-density lipoprotein (LDL) cholesterol and lower of high-density lipoprotein (HDL) cholesterol may be associated with increased risk of abdominal aortic aneurysm (<span class="hlt">AAA</span>). Whether dyslipidemia causes <span class="hlt">AAA</span> is still unclear and is potentially testable using a Mendelian randomization (MR) approach. We investigated the associations between blood lipids and <span class="hlt">AAA</span> using two-sample MR analysis with SNP-lipids association estimates from a published genome-wide association study of blood lipids (n = 188,577) and SNP-<span class="hlt">AAA</span> association estimates from European Americans (EAs) of the Atherosclerosis Risk in Communities (ARIC) study (n = 8,793). We used inverse variance weighted (IVW) MR as the primary method and MR-Egger regression and weighted median MR estimation as sensitivity analyses. Over a median of 22.7 years of follow-up, 338 of 8,793 ARIC participants experienced incident clinical <span class="hlt">AAA</span>. Using the IVW method, we observed positive associations of plasma LDL cholesterol and TC with the risk of <span class="hlt">AAA</span> (odds ratio (OR) = 1.55, P = 0.02 for LDL cholesterol and OR = 1.61, P = 0.01 for TC per 1 standard deviation of lipid increment). Using the MR-Egger regression and weighted median methods, we were able to validate the association of <span class="hlt">AAA</span> risk with TC, although the associations were less consistent for LDL cholesterol due to wider confidence intervals. Triglycerides and HDL cholesterol were not associated with <span class="hlt">AAA</span> in any of the MR methods. Assuming instrumental variable assumptions are satisfied, our finding suggests that higher plasma TC and LDL cholesterol are causally associated with the increased risk of <span class="hlt">AAA</span> in EAs.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26132508','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26132508"><span>In vivo topical application of acetyl aspartic acid increases fibrillin-1 and collagen IV deposition leading to a significant improvement of skin firmness.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Gillbro, J M; Merinville, E; Cattley, K; Al-Bader, T; Hagforsen, E; Nilsson, M; Mavon, A</p> <p>2015-10-01</p> <p>Acetyl aspartic acid (<span class="hlt">A-A-A</span>) was discovered through gene array analysis with corresponding Cmap analysis. We found that <span class="hlt">A-A-A</span> increased keratinocyte regeneration, inhibited dermal matrix metalloprotease (MMP) expression and relieved fibroblast stiffness through reduction of the fibroblast stiffness marker F-actin. Dermal absorption studies showed successful delivery to both the epidermal and dermal regions, and in-use trial demonstrated that 1% <span class="hlt">A-A-A</span> was well tolerated. In this study, the aim was to investigate whether <span class="hlt">A-A-A</span> could stimulate the synthesis of extracellular matrix supporting proteins in vivo and thereby improving the viscoelastic properties of human skin by conducting a dual histological and biophysical clinical study. Two separate double-blind vehicle-controlled in vivo studies were conducted using a 1% <span class="hlt">A-A-A</span> containing oil-in-water (o/w) emulsion. In the histological study, 16 female volunteers (>55 years of age) exhibiting photodamaged skin on their forearm were included, investigating the effect of a 12-day treatment of <span class="hlt">A-A-A</span> on collagen IV (COLIV) and fibrillin-1. In a subsequent pilot study, 0.1% retinol was used for comparison to <span class="hlt">A-A-A</span> (1%). The biomechanical properties of the skin were assessed in a panel of 16 women (>45 years of age) using the standard Cutometer MPA580 after topical application of the test products for 28 days. The use of multiple suction enabled the assessment of F4, an area parameter specifically representing skin firmness. Twelve-day topical application of 1% <span class="hlt">A-A-A</span> significantly increased COLIV and fibrillin with 13% and 6%, respectively, compared to vehicle. 1% <span class="hlt">A-A-A</span> and 0.1% retinol were found to significantly reduce F4 after 28 days of treatment by 15.8% and 14.7%, respectively, in the pilot Cutometer study. No significant difference was found between retinol and <span class="hlt">A-A-A</span>. However, only <span class="hlt">A-A-A</span> exhibited a significant effect vs. vehicle on skin firmness which indicated the incremental benefit of <span class="hlt">A-A-A</span> as a skin</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28326193','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28326193"><span>Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Lu; Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O; Matsumoto, Chisa; Manson, JoAnn E; Gaziano, J Michael; Sesso, Howard D</p> <p>2017-01-01</p> <p>Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (<span class="hlt">AAA</span>) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no <span class="hlt">AAA</span> at baseline, 471 reported a newly diagnosed <span class="hlt">AAA</span> during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m 2 , the multivariable hazard ratio (HR [95% CI]) of newly diagnosed <span class="hlt">AAA</span> was 1.30 [1.06-1.59] for BMI 25-<30 kg/m 2 and 1.69 [1.24-2.30] for BMI ≥ 30 kg/m 2 . The risk of diagnosed <span class="hlt">AAA</span> was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known <span class="hlt">AAA</span> risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed <span class="hlt">AAA</span> (HR = 0.79 [0.57-1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed <span class="hlt">AAA</span>, particularly over longer follow-up.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23288157','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23288157"><span>Peptide inhibitor of CXCL4-CCL5 heterodimer formation, MKEY, inhibits experimental aortic aneurysm initiation and progression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Iida, Yasunori; Xu, Baohui; Xuan, Haojun; Glover, Keith J; Tanaka, Hiroki; Hu, Xiaolei; Fujimura, Naoki; Wang, Wei; Schultz, Joshua R; Turner, Court R; Dalman, Ronald L</p> <p>2013-04-01</p> <p>Macrophages are critical contributors to abdominal aortic aneurysm (<span class="hlt">AAA</span>) disease. We examined the ability of MKEY, a peptide inhibitor of CXCL4-CCL5 interaction, to influence <span class="hlt">AAA</span> progression in murine models. <span class="hlt">AAAs</span> were created in 10-week-old male C57BL/6J mice by transient infrarenal aortic porcine pancreatic elastase infusion. Mice were treated with MKEY via intravenous injection either (1) before porcine pancreatic elastase infusion or (2) after aneurysm initiation. Immunostaining demonstrated CCL5 and CCR5 expression on aneurysmal aortae and mural monocytes/macrophages, respectively. MKEY treatment partially inhibited migration of adaptively transferred leukocytes into aneurysmal aortae in recipient mice. Although all vehicle-pretreated mice developed <span class="hlt">AAAs</span>, aneurysms formed in only 60% (3/5) and 14% (1/7) of mice pretreated with MKEY at 10 and 20 mg/kg, respectively. MKEY pretreatment reduced aortic diameter enlargement, preserved medial elastin fibers and smooth muscle cells, and attenuated mural macrophage infiltration, angiogenesis, and aortic metalloproteinase 2 and 9 expression after porcine pancreatic elastase infusion. MKEY initiated after porcine pancreatic elastase infusion also stabilized or reduced enlargement of existing <span class="hlt">AAAs</span>. Finally, MKEY treatment was effective in limiting <span class="hlt">AAA</span> formation after angiotensin II infusion in apolipoprotein E-deficient mice. MKEY suppresses <span class="hlt">AAA</span> formation and progression in 2 complementary experimental models. Peptide inhibition of CXCL4-CCL5 interactions may represent a viable translational strategy to limit progression of human <span class="hlt">AAA</span> disease.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15565595','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15565595"><span>Simultaneous repair of abdominal aortic aneurysm and resection of unexpected, associated abdominal malignancies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Illuminati, Giulio; Calio', Francesco G; D'Urso, Antonio; Lorusso, Riccardo; Ceccanei, Gianluca; Vietri, Francesco</p> <p>2004-12-15</p> <p>The management of unexpected intra-abdominal malignancy, discovered at laparotomy for elective treatment of an abdominal aortic aneurysm (<span class="hlt">AAA</span>), is controversial. It is still unclear whether both conditions should be treated simultaneously or a staged approach is to be preferred. To contribute in improving treatment guidelines, we retrospectively reviewed the records of patients undergoing laparotomy for elective <span class="hlt">AAA</span> repair. From January 1994 to March 2003, 253 patients underwent elective, trans-peritoneal repair of an <span class="hlt">AAA</span>. In four patients (1.6%), an associated, unexpected neoplasm was detected at abdominal exploration, consisting of one renal, one gastric, one ileal carcinoid, and one ascending colon tumor. All of them were treated at the same operation, after aortic repair and careful isolation of the prosthetic graft. The whole series' operative mortality was 3.6%. None of the patients simultaneously treated for <span class="hlt">AAA</span> and tumor resection died in the postoperative period. No graft-related infections were observed. Simultaneous treatment of <span class="hlt">AAA</span> and tumor did not prolong significantly the mean length of stay in the hospital, compared to standard treatment of <span class="hlt">AAA</span> alone. Except for malignancies of organs requiring major surgical resections, simultaneous <span class="hlt">AAA</span> repair and resection of an associated, unexpected abdominal neoplasm can be safely performed, in most of the patients, sparing the need for a second procedure. Endovascular grafting of the <span class="hlt">AAA</span> can be a valuable tool in simplifying simultaneous treatment, or in staging the procedures with a very short delay.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11034785','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11034785"><span>Distinct Effect of Benzalkonium Chloride on the Esterase and Aryl Acylamidase Activities of Butyrylcholinesterase.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jaganathan; Boopathy</p> <p>2000-08-01</p> <p>Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from vertebrates, other than their predominant acylcholine hydrolase (esterase) activity, display a genuine aryl acylamidase activity (<span class="hlt">AAA</span>) capable of hydrolyzing the synthetic substrate o-nitroacetanilide to o-nitroaniline. This <span class="hlt">AAA</span> activity is strongly inhibited by classical cholinesterase (ChE) inhibitors. In the present study, benzalkonium chloride (BAC), a cationic detergent widely used as a preservative in pharmaceutical preparations, has been shown to distinctly modulate the esterase and <span class="hlt">AAA</span> activities of BChEs. The detergent BAC was able to inhibit the esterase activity of human serum and horse serum BChEs and AChEs from electric eel and human erythrocyte. The remarkable property of BAC was its ability to profoundly activate the <span class="hlt">AAA</span> activity of human serum and horse serum BChEs but not the <span class="hlt">AAA</span> activity of AChEs. Thus BAC seem to preferentially activate the <span class="hlt">AAA</span> activity of BChEs alone. Results of the study using the ChE active site-specific inhibitor diisopropyl phosphorofluoridate indicated that BAC binds to the active site of ChEs. Furthermore, studies using a structural homolog of BAC indicated that the alkyl group of BAC is essential not only for its interaction with ChEs but also for its distinct effect on the esterase and <span class="hlt">AAA</span> activities of BChEs. This is the first report of a compound that inhibits the esterase activity, while simultaneously activating the <span class="hlt">AAA</span> activity, of BChEs. Copyright 2000 Academic Press.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22804761','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22804761"><span>Histopathological analysis of cellular localization of cathepsins in abdominal aortic aneurysm wall.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lohoefer, Fabian; Reeps, Christian; Lipp, Christina; Rudelius, Martina; Zimmermann, Alexander; Ockert, Stefan; Eckstein, Hans-Henning; Pelisek, Jaroslav</p> <p>2012-08-01</p> <p>An important feature of abdominal aortic aneurysm (<span class="hlt">AAA</span>) is the destruction of vessel wall, especially elastin and collagen. Besides matrix metalloproteinases, cathepsins are the most potent elastolytic enzymes. The expression of cathepsins with known elastolytic and collagenolytic activities in the individual cells within <span class="hlt">AAA</span> has not yet been determined. The vessel wall of 32 <span class="hlt">AAA</span> patients and 10 organ donors was analysed by immunohistochemistry for expression of cathepsins B, D, K, L and S, and cystatin C in all cells localized within <span class="hlt">AAA</span>. Luminal endothelial cells (ECs) of <span class="hlt">AAA</span> were positive for cathepsin D and partially for cathepsins B, K and S. Endothelial cells of the neovessels and smooth muscle cells in the media were positive for all cathepsins tested, especially for cathepsin B. In the inflammatory infiltrate all cathepsins were expressed in the following pattern: B > D = S > K = L. Macrophages showed the highest staining intensity for all cathepsins. Furthermore, weak overall expression of cystatin C was observed in all the cells localized in the <span class="hlt">AAA</span> with the exception of the ECs. There is markedly increased expression of the various cathepsins within the <span class="hlt">AAA</span> wall compared to healthy aorta. Our data are broadly consistent with a role for cathepsins in <span class="hlt">AAA</span>; and demonstrate expression of cathepsins D, B and S in phagocytic cells in the inflammatory infiltrate; and also may reveal a role for cathepsin B in lymphocytes. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22732574','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22732574"><span>On the potential increase of the oxidative stress status in patients with abdominal aortic aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pincemail, J; Defraigne, J O; Cheramy-Bien, J P; Dardenne, N; Donneau, A F; Albert, A; Labropoulos, N; Sakalihasan, N</p> <p>2012-01-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a major cause of preventable deaths in older patients. Oxidative stress has been suggested to play a key role in the pathogenesis of <span class="hlt">AAA</span>. However, only few studies have been conducted to evaluate the blood oxidative stress status of <span class="hlt">AAA</span> patients. Twenty seven <span class="hlt">AAA</span> patients (mean age of 70 years) divided into two groups according to <span class="hlt">AAA</span> size (≤ 50 or > 50 mm) were compared with an age-matched group of 18 healthy subjects. Antioxidants (vitamins C and E, β-carotene, glutathione, thiols, and ubiquinone), trace elements (selenium, copper, zinc, and copper/zinc ratio) and markers of oxidative damage to lipids (lipid peroxides, antibodies against oxidized patients, and isoprostanes) were measured in each subject. The comparison of the three groups by ordinal logistic regression showed a significant decrease of the plasma levels of vitamin C (P = 0.011), α-tocopherol (P = 0.016) but not when corrected for cholesterol values, β-carotene (P = 0.0096), ubiquinone (P = 0.014), zinc (P = 0.0035), and of selenium (P = 0.0038), as <span class="hlt">AAA</span> size increased. By contrast, specific markers of lipid peroxidation such as the Cu/Zn ratio (P = 0.046) and to a lesser extent isoprostanes (P = 0.052) increased. The present study emphasizes the potential role of the oxidative stress in <span class="hlt">AAA</span> disease and suggests that an antioxidant therapy could be of interest to delay <span class="hlt">AAA</span> progression.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5343258','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5343258"><span>Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Djousse, Luc; Song, Yiqing; Akinkuolie, Akintunde O.; Matsumoto, Chisa; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.</p> <p>2017-01-01</p> <p>Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (<span class="hlt">AAA</span>) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged ≥ 50 years who reported no <span class="hlt">AAA</span> at baseline, 471 reported a newly diagnosed <span class="hlt">AAA</span> during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) < 25 kg/m2, the multivariable hazard ratio (HR [95% CI]) of newly diagnosed <span class="hlt">AAA</span> was 1.30 [1.06–1.59] for BMI 25–<30 kg/m2 and 1.69 [1.24–2.30] for BMI ≥ 30 kg/m2. The risk of diagnosed <span class="hlt">AAA</span> was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known <span class="hlt">AAA</span> risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed <span class="hlt">AAA</span> (HR = 0.79 [0.57–1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during ≤ and >2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed <span class="hlt">AAA</span>, particularly over longer follow-up. PMID:28326193</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1514512','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1514512"><span>Abdominal Aortic Aneurysms in “High-Risk” Surgical Patients</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jordan, William D.; Alcocer, Francisco; Wirthlin, Douglas J.; Westfall, Andrew O.; Whitley, David</p> <p>2003-01-01</p> <p>Objective To evaluate the early results of endovascular grafting for high-risk surgical candidates in the treatment of abdominal aortic aneurysms (<span class="hlt">AAA</span>). Summary Background Data Since the approval of endoluminal grafts for treatment of <span class="hlt">AAA</span>, endovascular repair of <span class="hlt">AAA</span> (EVAR) has expanded to include patients originally considered too ill for open <span class="hlt">AAA</span> repair. However, some concern has been expressed regarding technical failure and the durability of endovascular grafts. Methods The University of Alabama at Birmingham (UAB) Computerized Vascular Registry identified all patients who underwent abdominal aneurysm repair between January 1, 2000, and June 12, 2002. Patients were stratified by type of repair (open <span class="hlt">AAA</span> vs. EVAR) and were classified as low risk or high risk. Patients with at least one of the following classifications were classified as high risk: age more than 80 years, chronic renal failure (creatinine > 2.0), compromised cardiac function (diminished ventricular function or severe coronary artery disease), poor pulmonary function, reoperative aortic procedure, a “hostile” abdomen, or an emergency operation. Death, systemic complications, and length of stay were tabulated for each group. Results During this 28-month period, 404 patients underwent <span class="hlt">AAA</span> repair at UAB. Eighteen patients (4.5%) died within 30 days of their repair or during the same hospitalization. Two hundred seventeen patients (53%) were classified as high risk. Two hundred fifty-nine patients (64%) underwent EVAR repair, and 130 (50%) of these were considered high-risk patients (including four emergency procedures). One hundred forty-five patients (36%) underwent open <span class="hlt">AAA</span> repair, including 15 emergency operations. All deaths occurred in the high-risk group: 12 (8.3%) died after open <span class="hlt">AAA</span> repair and 6 (2.3%) died after EVAR repair. Postoperative length of stay was shorter for EVAR repair compared to open <span class="hlt">AAA</span>. Conclusions High-risk and low-risk patients can undergo EVAR repair with a lower rate</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2007PhDT........30A','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2007PhDT........30A"><span>A knowledge-based design framework for airplane conceptual and preliminary design</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Anemaat, Wilhelmus A. J.</p> <p></p> <p>The goal of work described herein is to develop the second generation of Advanced Aircraft Analysis (<span class="hlt">AAA</span>) into an object-oriented structure which can be used in different environments. One such environment is the third generation of <span class="hlt">AAA</span> with its own user interface, the other environment with the same <span class="hlt">AAA</span> methods (i.e. the knowledge) is the <span class="hlt">AAA</span>-AML program. <span class="hlt">AAA</span>-AML automates the initial airplane design process using current <span class="hlt">AAA</span> methods in combination with AMRaven methodologies for dependency tracking and knowledge management, using the TechnoSoft Adaptive Modeling Language (AML). This will lead to the following benefits: (1) Reduced design time: computer aided design methods can reduce design and development time and replace tedious hand calculations. (2) Better product through improved design: more alternative designs can be evaluated in the same time span, which can lead to improved quality. (3) Reduced design cost: due to less training and less calculation errors substantial savings in design time and related cost can be obtained. (4) Improved Efficiency: the design engineer can avoid technically correct but irrelevant calculations on incomplete or out of sync information, particularly if the process enables robust geometry earlier. Although numerous advancements in knowledge based design have been developed for detailed design, currently no such integrated knowledge based conceptual and preliminary airplane design system exists. The third generation <span class="hlt">AAA</span> methods are tested over a ten year period on many different airplane designs. Using <span class="hlt">AAA</span> methods will demonstrate significant time savings. The <span class="hlt">AAA</span>-AML system will be exercised and tested using 27 existing airplanes ranging from single engine propeller, business jets, airliners, UAV's to fighters. Data for the varied sizing methods will be compared with <span class="hlt">AAA</span> results, to validate these methods. One new design, a Light Sport Aircraft (LSA), will be developed as an exercise to use the tool for designing a new airplane</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27692527','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27692527"><span>Adalimumab for Treatment of Noninfectious Uveitis: Immunogenicity and Clinical Relevance of Measuring Serum Drug Levels and Antidrug Antibodies.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cordero-Coma, Miguel; Calleja-Antolín, Sara; Garzo-García, Irene; Nuñez-Garnés, Ana M; Álvarez-Castro, Carolina; Franco-Benito, Manuel; Ruiz de Morales, Jose G</p> <p>2016-12-01</p> <p>To evaluate the rate of immunogenicity induced by adalimumab and its relationship with drug serum levels and clinical responses in patients with noninfectious uveitis. Prospective observational study. Consecutive patients from 1 referral center who initiated treatment with adalimumab for active noninfectious uveitis resistant to conventional therapy. All patients received 40 mg adalimumab every other week. Patients were evaluated clinically and immunologically before and after 4, 8, and 24 weeks of treatment. Clinical evaluation included assessment of changes in visual acuity, degree of inflammation in the anterior chamber and vitreous cavity, central macular thickness, and retinal angiographic leakage. Immunologic evaluation included assessment of serum trough adalimumab and antibodies against adalimumab (<span class="hlt">AAA</span>) levels and class II HLA typing. Twenty-five patients were enrolled. Overall, 18 of 25 patients (72%) showed a favorable clinical response to adalimumab therapy. Eleven patients (44%) achieved a complete response and 7 (28%) achieved a partial response. However, 7 of 25 patients (28%) were considered nonresponders. Median trough adalimumab serum levels were higher in responders than in nonresponders (P < 0.001). We observed <span class="hlt">AAA</span> positivity (<span class="hlt">AAA</span>+) at least 1 time point in 8 of 25 patients (32%), including 4 with transitory <span class="hlt">AAA</span> and 4 with permanent <span class="hlt">AAA</span>. In all patients with permanent <span class="hlt">AAA</span>+, trough adalimumab levels became undetectable (P < 0.001). However, in patients who demonstrated transitory <span class="hlt">AAA</span>+, no correlation was observed between <span class="hlt">AAA</span> titers and adalimumab trough levels (P = 0.2).Concomitant immunosuppression did not show any protective effect on adalimumab immunogenicity in our cohort. An association between the presence of <span class="hlt">AAA</span>+ and a worse uveitis outcome was observed only in patients with permanent <span class="hlt">AAA</span>+, which correlated with undetectable adalimumab trough levels (P = 0.014). Treatment of noninfectious uveitis with adalimumab is associated with high</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23864906','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23864906"><span>CFD modelling of abdominal aortic aneurysm on hemodynamic loads using a realistic geometry with CT.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Soudah, Eduardo; Ng, E Y K; Loong, T H; Bordone, Maurizio; Pua, Uei; Narayanan, Sriram</p> <p>2013-01-01</p> <p>The objective of this study is to find a correlation between the abdominal aortic aneurysm (<span class="hlt">AAA</span>) geometric parameters, wall stress shear (WSS), abdominal flow patterns, intraluminal thrombus (ILT), and <span class="hlt">AAA</span> arterial wall rupture using computational fluid dynamics (CFD). Real <span class="hlt">AAA</span> 3D models were created by three-dimensional (3D) reconstruction of in vivo acquired computed tomography (CT) images from 5 patients. Based on 3D <span class="hlt">AAA</span> models, high quality volume meshes were created using an optimal tetrahedral aspect ratio for the whole domain. In order to quantify the WSS and the recirculation inside the <span class="hlt">AAA</span>, a 3D CFD using finite elements analysis was used. The CFD computation was performed assuming that the arterial wall is rigid and the blood is considered a homogeneous Newtonian fluid with a density of 1050 kg/m(3) and a kinematic viscosity of 4 × 10(-3) Pa·s. Parallelization procedures were used in order to increase the performance of the CFD calculations. A relation between <span class="hlt">AAA</span> geometric parameters (asymmetry index ( β ), saccular index ( γ ), deformation diameter ratio ( χ ), and tortuosity index ( ε )) and hemodynamic loads was observed, and it could be used as a potential predictor of <span class="hlt">AAA</span> arterial wall rupture and potential ILT formation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5253231','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5253231"><span>Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.</p> <p>2017-01-01</p> <p>Rationale: Abdominal aortic aneurysm (<span class="hlt">AAA</span>) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of <span class="hlt">AAA</span>. Objective: To identify additional <span class="hlt">AAA</span> risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new <span class="hlt">AAA</span> risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead <span class="hlt">AAA</span> single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for <span class="hlt">AAA</span> seem to be specific for <span class="hlt">AAA</span> compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25457300','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25457300"><span>Beneficial Effects of Pre-operative Exercise Therapy in Patients with an Abdominal Aortic Aneurysm: A Systematic Review.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pouwels, S; Willigendael, E M; van Sambeek, M R H M; Nienhuijs, S W; Cuypers, P W M; Teijink, J A W</p> <p>2015-01-01</p> <p>The impact of post-operative complications in abdominal aortic aneurysm (<span class="hlt">AAA</span>) surgery is substantial, and increases with age and concomitant co-morbidities. This systematic review focuses on the possible effects of pre-operative exercise therapy (PET) in patients with <span class="hlt">AAA</span> on post-operative complications,aerobic capacity, physical fitness, and recovery. A systematic search on PET prior to <span class="hlt">AAA</span> surgery was conducted. The methodological quality of the included studies was rated using the Physiotherapy Evidence Database scale. The agreement between the reviewers was assessed with Cohen's kappa. Five studies were included, with a methodological quality ranging from moderate to good. Cohen's kappa was 0.79. Three studies focused on patients with an <span class="hlt">AAA</span> (without indication for surgical repair) with physical fitness as the outcome measure. One study focused on PET in patients awaiting <span class="hlt">AAA</span> surgery and one study focused on the effects of PET on post-operative complications, length of stay, and recovery. PET has beneficial effects on various physical fitness variables of patients with an <span class="hlt">AAA</span>. Whether this leads to less complications or faster recovery remains unclear. In view of the large impact of post-operative complications, it is valuable to explore the possible benefits of a PET program in <span class="hlt">AAA</span> surgery.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4750057','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4750057"><span>Hyperhomocysteinaemia is an independent risk factor of abdominal aortic aneurysm in a Chinese Han population</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Liu, Jie; Wei Zuo, Shang; Li, Yue; Jia, Xin; Jia, Sen Hao; Zhang, Tao; Xiang Song, Yu; Qi Wei, Ying; Xiong, Jiang; Hua Hu, Yong; Guo, Wei</p> <p>2016-01-01</p> <p>The associations between hyperhomocysteinaemia (HHcy), methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and abdominal aortic aneurysm (<span class="hlt">AAA</span>) remain controversial, with only few studies focused on these associations within the Chinese population. We performed subgroup and interaction analyses in a Chinese Han population to investigate these associations. In all, 155 <span class="hlt">AAA</span> patients and 310 control subjects were evaluated for serum total homocysteine levels and MTHFR C677T polymorphisms. Multiple logistic regression models were used to evaluate the aforementioned associations. Interaction and stratified analyses were conducted according to age, sex, smoking status, drinking status, and chronic disease histories. The multiple logistic analyses showed a significant association between HHcy and <span class="hlt">AAA</span> but no significant association between MTHFR C677T polymorphism and <span class="hlt">AAA</span>. The interaction analysis showed that age and peripheral arterial disease played an interactive role in the association between HHcy and <span class="hlt">AAA</span>, while drinking status played an interactive role in the association between MTHFR C677T polymorphism and <span class="hlt">AAA</span>. In conclusion, HHcy is an independent risk factor of <span class="hlt">AAA</span> in a Chinese Han population, especially in the elderly and peripheral arterial disease subgroups. Longitudinal studies and clinical trials aimed to reduce homocysteine levels are warranted to assess the causal nature of these relationships PMID:26865327</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27418160','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27418160"><span>Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; de Andrade, Mariza; Baas, Annette F; Blankensteijn, Jan D; Böttinger, Erwin P; Bown, Matthew J; Broderick, Joseph; Bijlenga, Philippe; Carrell, David S; Crawford, Dana C; Crosslin, David R; Ebeling, Christian; Eriksson, Johan G; Fornage, Myriam; Foroud, Tatiana; von Und Zu Fraunberg, Mikael; Friedrich, Christoph M; Gaál, Emília I; Gottesman, Omri; Guo, Dong-Chuan; Harrison, Seamus C; Hernesniemi, Juha; Hofman, Albert; Inoue, Ituro; Jääskeläinen, Juha E; Jones, Gregory T; Kiemeney, Lambertus A L M; Kivisaari, Riku; Ko, Nerissa; Koskinen, Seppo; Kubo, Michiaki; Kullo, Iftikhar J; Kuivaniemi, Helena; Kurki, Mitja I; Laakso, Aki; Lai, Dongbing; Leal, Suzanne M; Lehto, Hanna; LeMaire, Scott A; Low, Siew-Kee; Malinowski, Jennifer; McCarty, Catherine A; Milewicz, Dianna M; Mosley, Thomas H; Nakamura, Yusuke; Nakaoka, Hirofumi; Niemelä, Mika; Pacheco, Jennifer; Peissig, Peggy L; Pera, Joanna; Rasmussen-Torvik, Laura; Ritchie, Marylyn D; Rivadeneira, Fernando; van Rij, Andre M; Santos-Cortez, Regie Lyn P; Saratzis, Athanasios; Slowik, Agnieszka; Takahashi, Atsushi; Tromp, Gerard; Uitterlinden, André G; Verma, Shefali S; Vermeulen, Sita H; Wang, Gao T; Han, Buhm; Rinkel, Gabriël J E; de Bakker, Paul I W</p> <p>2016-07-14</p> <p>Intracranial aneurysms (IAs), abdominal aortic aneurysms (<span class="hlt">AAAs</span>), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, <span class="hlt">AAAs</span>, and TAAs. We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 <span class="hlt">AAA</span> cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, <span class="hlt">AAA</span>, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, <span class="hlt">AAA</span>-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (<span class="hlt">AAA</span>), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to <span class="hlt">AAA</span> (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to <span class="hlt">AAA</span> (OR=1.07; P=1.1×10(-3)). Although there was no evidence for polygenic overlap between IAs, <span class="hlt">AAAs</span>, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in <span class="hlt">AAAs</span>. These two loci will require further replication. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29779291','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29779291"><span>Abdominal aortic aneurysm: An update</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chuen, Jason; Theivendran, Mayo</p> <p>2018-05-01</p> <p>Abdominal aortic aneurysm (<span class="hlt">AAA</span>) remains one of the hallmark pathologies in vascular surgery and an area of intense research interest. Treatment options have expanded in recent years to increase the range of morphology suitable for endovascular aneurysm repair (EVAR), and with potential implications on treatment thresholds. This article is the first of two that will outline current treatment options for <span class="hlt">AAA</span>, including areas of controversy and research in <span class="hlt">AAA</span> disease, to inform the development of Australasian clinical guidelines and health policy. Medical therapy options remain limited and no aneurysm-specific pharmacotherapy is currently available. Recent years have witnessed a significant shift in <span class="hlt">AAA</span> surgery from open repair to EVAR and expansion of EVAR techniques. General management of cardiovascular risk factors remains key to reducing all-cause mortality for patients with <span class="hlt">AAA</span>.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28478022','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28478022"><span>The preventive and curative effects of melatonin against abdominal aortic aneurysm in rats.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Tekin, Gözde; İsbir, Selim; Şener, Göksel; Çevik, Özge; Çetinel, Şule; Dericioğlu, Okan; Arsan, Sinan; Çobanoğlu, Adnan</p> <p>2018-05-01</p> <p>Oxygen free radicals are important components involved in the histopathologic tissue alterations observed during abdominal aortic aneurysms (<span class="hlt">AAAs</span>). This study examined whether melatonin has protective or therapeutic effects against <span class="hlt">AAAs</span>. Sprague-Dawley rats were divided into four groups. A CaCl 2 model was used to induce <span class="hlt">AAA</span>. Starting on the operation day (Mel+<span class="hlt">AAA</span>+Mel group) or 4 weeks after the operation (<span class="hlt">AAA</span>+Mel group), the rats received intraperitoneal melatonin (10 mg/kg/day) for 6 and 2 weeks, respectively. The control and <span class="hlt">AAA</span> groups received vehicle for 2 weeks after the sham operation and <span class="hlt">AAA</span> induction, respectively. Angiographic measurements were recorded at the beginning, week 4, and week 6 of the study. After decapitation, aorta tissues were taken for the measurement of malondialdehyde, 8-hydroxy-2'-deoxyguanosine, glutathione levels, and myeloperoxidase and caspase-3 activity. Matrix metalloproteinase (MMP)-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were analyzed by Western blot technique. Aortic tissues were also examined by light microscopy. CaCl 2 caused an inflammatory response and oxidative damage indicated by rises in malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. Myeloperoxidase and caspase-3 activities were increased, but glutathione levels were reduced. On the one hand, MMP-2, MMP-9, tumor necrosis factor-α, and inducible nitric oxide synthase protein expressions were increased in the vehicle-treated <span class="hlt">AAA</span> group. On the other hand, melatonin treatment reversed all of these biochemical indices and histopathologic alterations. According to the data, although melatonin tended to reverse the biochemical parameters given on week 4, the preventive effect is more pronounced when given concomitantly with <span class="hlt">AAA</span> induction because values were closer to the control levels. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26371387','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26371387"><span>[Ultrasound screening of abdominal aortic aneurysm: Lessons from Vesale 2013].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Laroche, J P; Becker, F; Baud, J M; Miserey, G; Jaussent, A; Picot, M C; Bura-Rivière, A; Quéré, I</p> <p>2015-12-01</p> <p>Although aneurysm of the abdominal infra-renal aorta (<span class="hlt">AAA</span>) meets criteria warranting B mode ultrasound screening, the advantages of mass screening versus selective targeted opportunistic screening remain a subject of debate. In France, the French Society of Vascular Medicine (SFMV) and the Health Authority (HAS) published recommendations for targeted opportunistic screening in 2006 and 2013 respectively. The SFMV held a mainstream communication day on November 21, 2013 in France involving participants from metropolitan France and overseas departments that led to a proposal for free <span class="hlt">AAA</span> ultrasound screening: the Vesalius operation. Being a consumer operation, the selection criteria were limited to age (men and women between 60 and 75 years); the age limit was lowered to 50 years in case of direct family history of <span class="hlt">AAA</span>. More than 7000 people (as many women as men) were screened in 83 centers with a 1.70% prevalence of <span class="hlt">AAA</span> in the age-based target population (3.12% for men, 0.27% for women). The median diameter of detected <span class="hlt">AAA</span> was 33 mm (range 20 to 74 mm). The prevalence of <span class="hlt">AAA</span> was 1.7% in this population. Vesalius data are consistent with those of the literature both in terms of prevalence and for cardiovascular risk factors with the important role of smoking. Lessons from Vesalius to take into consideration are: screening is warranted in men 60 years and over, especially smokers, and in female smokers. Screening beyond 75 years should be discussed. Given the importance of screening, the SFMV set up a year of national screening for <span class="hlt">AAA</span> (Vesalius operation 2014/2015) in order to increase public and physician awareness about <span class="hlt">AAA</span> detection, therapeutic management, and monitoring. <span class="hlt">AAA</span> is a serious, common, disease that kills 6000 people each year. The goal of screening is cost-effective reduction in the death toll. Copyright © 2015 Elsevier Masson SAS. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28532922','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28532922"><span>Awake Craniotomy Anesthesia: A Comparison of the Monitored Anesthesia Care and Asleep-Awake-Asleep Techniques.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Eseonu, Chikezie I; ReFaey, Karim; Garcia, Oscar; John, Amballur; Quiñones-Hinojosa, Alfredo; Tripathi, Punita</p> <p>2017-08-01</p> <p>Commonly used sedation techniques for an awake craniotomy include monitored anesthesia care (MAC), using an unprotected airway, and the asleep-awake-asleep (<span class="hlt">AAA</span>) technique, using a partially or totally protected airway. We present a comparative analysis of the MAC and <span class="hlt">AAA</span> techniques, evaluating anesthetic management, perioperative outcomes, and complications in a consecutive series of patients undergoing the removal of an eloquent brain lesion. Eighty-one patients underwent awake craniotomy for an intracranial lesion over a 9-year period performed by a single-surgeon and a team of anesthesiologists. Fifty patients were treated using the MAC technique, and 31 were treated using the <span class="hlt">AAA</span> technique. A retrospective analysis evaluated anesthetic management, intraoperative complications, postoperative outcomes, pain management, and complications. The MAC and <span class="hlt">AAA</span> groups had similar preoperative patient and tumor characteristics. Mean operative time was shorter in the MAC group (283.5 minutes vs. 313.3 minutes; P = 0.038). Hypertension was the most common intraoperative complication seen (8% in the MAC group vs. 9.7% in the <span class="hlt">AAA</span> group; P = 0.794). Intraoperative seizure occurred at a rate of 4% in the MAC group and 3.2% in the <span class="hlt">AAA</span> group (P = 0.858). Awake cases were converted to general anesthesia in no patients in the MAC group and in 1 patient (3.2%) in the <span class="hlt">AAA</span> group (P = 0.201). No cases were aborted in either group. The mean hospital length of stay was 3.98 days in the MAC group and 3.84 days in the <span class="hlt">AAA</span> group (P = 0.833). Both the MAC and <span class="hlt">AAA</span> sedation techniques provide an efficacious and safe method for managing awake craniotomy cases and produce similar perioperative outcomes, with the MAC technique associated with shorter operative time. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17379201','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17379201"><span>Human serum cholinesterase from liver pathological samples exhibit highly elevated aryl acylamidase activity.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boopathy, Rathanam; Rajesh, Ramanna Valmiki; Darvesh, Sultan; Layer, Paul G</p> <p>2007-05-01</p> <p>Although aspartate aminotransferase (AST) and gamma-glutamyltransferase (gamma GT) enzymes are widely used as markers for liver disorders, the ubiquitous enzyme butyrylcholinesterase (BChE), synthesized in liver is also used as marker in the assessment of liver pathophysiology. This BChE enzyme in addition to its esterase activity has yet another enzymatic function designated as aryl acylamidase (<span class="hlt">AAA</span>) activity. It is determined in in vitro based on the hydrolysis of the synthetic substrate o-nitroacetanilide. In the present study, human serum cholinesterase (BChE) activity was studied with respect to its <span class="hlt">AAA</span> activity on the BChE protein (<span class="hlt">AAA</span>(BChE)) in patients with liver disorders. AST and gamma GT values were taken into account in this study as known markers for liver disorders. Blood samples were grouped into 3 based on esterase activity associated with BChE protein. They are normal, low, and very low BChE activity but with markedly increased AST and gamma GT levels. These samples were tested for their respective <span class="hlt">AAA</span> function. Association of <span class="hlt">AAA</span> with BChE from samples was proved using BChE monoclonal antibody precipitation experiment. The absolute levels of <span class="hlt">AAA</span> were increased as BChE activity decreased while deviating from normal samples and such deviation was directly proportional to the severity of the liver disorder. Differences between these groups became prominent after determining the ratios of <span class="hlt">AAA</span>(BChE) to BChE activities. Samples showing very high <span class="hlt">AAA</span>(BChE) to BChE ratio were also showing high to very high gamma GT values. These findings establish <span class="hlt">AAA</span>(BChE) as an independently regulated enzymatic activity on BChE especially in liver disorders. Moreover, since neither the low esterase activity of BChE by itself nor increased levels of AST/gamma GT are sufficient pathological indicators, this pilot study merits replication with large sample numbers.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29758327','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29758327"><span>Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lucas, Márcio L; Carraro, Cristina C; Belló-Klein, Adriane; Kalil, Antônio N; Aerts, Newton R; Carvalho, Fabiano B; Fernandes, Marilda C; Zettler, Claudio G</p> <p>2018-06-06</p> <p>Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (<span class="hlt">AAA</span>) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and <span class="hlt">AAA</span>. Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or <span class="hlt">AAA</span> (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas. There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and <span class="hlt">AAA</span> when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the <span class="hlt">AAA</span> group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the <span class="hlt">AAA</span> group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05). Oxidative stress is relevant in both AOD and <span class="hlt">AAA</span>, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and <span class="hlt">AAA</span>. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and <span class="hlt">AAA</span>. Copyright © 2018 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28699805','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28699805"><span>Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Yunpeng; Shen, Guanghui; Wang, Haiyang; Yao, Ye; Sun, Qingfeng; Jing, Bao; Liu, Gaoyan; Wu, Jia; Yuan, Chao; Liu, Siqi; Liu, Xinyu; Li, Shiyong; Li, Haocheng</p> <p>2017-12-01</p> <p>To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (<span class="hlt">AAA</span>). Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included. Twelve case-control studies were included in the meta-analysis with a total of 8345 patients (1977 in the <span class="hlt">AAA</span> group and 6368 in the control group). The pooled results showed that <span class="hlt">AAA</span> patients had higher hsCRP value than the control group (difference in means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found <span class="hlt">AAA</span> patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma levels than the control group (difference in means = 1.301, 95% CI = 0.821 to 1.781, p < .001). In patients with large aortic diameter (≥50 mm), no difference was observed in hsCRP levels between the <span class="hlt">AAA</span> and control groups (difference in means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis found the difference in means of hsCRP plasma levels between <span class="hlt">AAA</span> and control groups decreased as aortic diameter increased (slope = -0.04, p < .001), suggesting that hsCRP levels may be inversely associated with increasing aneurysm size. Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for <span class="hlt">AAA</span> patients with medium or small aortic diameter but not for <span class="hlt">AAA</span> patients with large aortic diameter. The correlation between serum hsCRP level and <span class="hlt">AAA</span> aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26941015','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26941015"><span>Role of Interleukin-1 Signaling in a Mouse Model of Kawasaki Disease-Associated Abdominal Aortic Aneurysm.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wakita, Daiko; Kurashima, Yosuke; Crother, Timothy R; Noval Rivas, Magali; Lee, Youngho; Chen, Shuang; Fury, Wen; Bai, Yu; Wagner, Shawn; Li, Debiao; Lehman, Thomas; Fishbein, Michael C; Hoffman, Hal M; Shah, Prediman K; Shimada, Kenichi; Arditi, Moshe</p> <p>2016-05-01</p> <p>Kawasaki disease (KD) is the most common cause of acquired cardiac disease in US children. In addition to coronary artery abnormalities and aneurysms, it can be associated with systemic arterial aneurysms. We evaluated the development of systemic arterial dilatation and aneurysms, including abdominal aortic aneurysm (<span class="hlt">AAA</span>) in the Lactobacillus casei cell-wall extract (LCWE)-induced KD vasculitis mouse model. We discovered that in addition to aortitis, coronary arteritis and myocarditis, the LCWE-induced KD mouse model is also associated with abdominal aorta dilatation and <span class="hlt">AAA</span>, as well as renal and iliac artery aneurysms. <span class="hlt">AAA</span> induced in KD mice was exclusively infrarenal, both fusiform and saccular, with intimal proliferation, myofibroblastic proliferation, break in the elastin layer, vascular smooth muscle cell loss, and inflammatory cell accumulation in the media and adventitia. Il1r(-/-), Il1a(-/-), and Il1b(-/-) mice were protected from KD associated <span class="hlt">AAA</span>. Infiltrating CD11c(+) macrophages produced active caspase-1, and caspase-1 or NLRP3 deficiency inhibited <span class="hlt">AAA</span> formation. Treatment with interleukin (IL)-1R antagonist (Anakinra), anti-IL-1α, or anti-IL-1β mAb blocked LCWE-induced <span class="hlt">AAA</span> formation. Similar to clinical KD, the LCWE-induced KD vasculitis mouse model can also be accompanied by <span class="hlt">AAA</span> formation. Both IL-1α and IL-1β play a key role, and use of an IL-1R blocking agent that inhibits both pathways may be a promising therapeutic target not only for KD coronary arteritis, but also for the other systemic arterial aneurysms including <span class="hlt">AAA</span> that maybe seen in severe cases of KD. The LCWE-induced vasculitis model may also represent an alternative model for <span class="hlt">AAA</span> disease. © 2016 American Heart Association, Inc.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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