The antimicrobial stewardship program in Gulf Cooperation Council (GCC) states: insights from a regional survey.

PubMed

Enani, Mushira A

2016-01-01

The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation. A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states. Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%). Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital-acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states.

The antimicrobial stewardship program in Gulf Cooperation Council (GCC) states: insights from a regional survey

PubMed Central

2015-01-01

Objectives: The purpose of the current study is to describe the prevalence and characteristics of antimicrobial stewardship programs (ASP) in Gulf Cooperation Council (GCC) states to explore opportunities and overcome barriers to effective ASP implementation. Methods: A cross-sectional questionnaire survey was used to evaluate the current status of ASP: major stewardship components, barriers of implementation and program impact in acute care hospitals of GCC states. Results: Forty-seven healthcare professionals responded from four GCC states, the majority from Saudi Arabia (81%). Twenty-nine (62%) participating hospitals had ASP in place. Of these established programs, 35 (75%) reported lack of funding and personnel as major barriers to program implementation. The top three objectives cited for the hospital ASP were to reduce resistance (72.3%), improve clinical outcomes (70.2%) and reduce costs (44.7%). The reported impact of existing ASP was reduction of inappropriate prescribing (68%), reduction of broad spectrum antibiotic use (63.8%), reduction of healthcare-associated infections (61.7%), reduction of length of stay or mortality metrics (59.6%), reduction in direct antibiotic cost (57.4%) and reduction of reported antibiotic resistance (55.3%). Conclusion: Survey participants from GCC states who have implemented ASP report significant impacts in the reduction of broad spectrum antibiotic use, hospital-acquired infection, inappropriate prescribing and antimicrobial resistance. These findings suggest a promising opportunity to enhance existing ASP through sharing of best practices and support the development of regional guidelines across GCC states. PMID:28989448

Compliance with the Healthy Eating Standards in YMCA afterschool programs

PubMed Central

Beets, Michael W.; Weaver, R. Glenn; Turner-McGrievy, Brie; Beighle, Aaron; Moore, Justin B.; Webster, Collin; Khan, Mahmud; Saunders, Ruth

2016-01-01

Objective In 2011, the YMCA of the USA adopted Healthy Eating (HE) Standards for all their afterschool programs (ASPs). The extent to which YMCA-ASPs comply with the standards is unknown. Methods Twenty ASPs from all YMCA-ASPs across SC (N=102) were invited to participate. Direct observation of the foods/beverages served and staff behaviors were collected on four non-consecutive days/ASP. Results One ASP did not serve a snack. Of the remaining, a total of 26% ASPs served a fruit/vegetable and 32% served water every day; 26% served sugar-sweetened beverages, 47% served sugar-added foods, and only 11% served whole grains, when grains were served. Staff were sitting with the children (65%) or verbally promoting healthy eating (15%) on at least one observation day. Staff where drinking non-approved drinks (25%) or foods (45%) on at least one observation day. No ASPs served snacks family-style every day. Conclusions/Implications Additional efforts are required to assist YMCA-operated ASPs in achieving these important nutrition standards. PMID:27372234

Answer Set Programming and Other Computing Paradigms

ERIC Educational Resources Information Center

Meng, Yunsong

2013-01-01

Answer Set Programming (ASP) is one of the most prominent and successful knowledge representation paradigms. The success of ASP is due to its expressive non-monotonic modeling language and its efficient computational methods originating from building propositional satisfiability solvers. The wide adoption of ASP has motivated several extensions to…

Defining Standards and Policies for Promoting Physical Activity in Afterschool Programs

ERIC Educational Resources Information Center

Beets, Michael W.; Wallner, Megan; Beighle, Aaron

2010-01-01

Background: National guidelines exist that define "quality" afterschool programs (3-6 pm, ASP). No widely adopted national standards/policies exist, however, for ASP providers for the promotion of physical activity (PA). To address this gap, state-level ASP organizations have developed or adopted standards/policies related to PA. The extent to…

Compliance With the Healthy Eating Standards in YMCA After-School Programs.

PubMed

Beets, Michael W; Weaver, R Glenn; Turner-McGrievy, Gabrielle; Beighle, Aaron; Moore, Justin B; Webster, Collin; Khan, Mahmud; Saunders, Ruth

2016-09-01

In 2011, the YMCA of the US adopted Healthy Eating standards for all of their after-school programs (ASPs). The extent to which YMCA ASPs comply with the standards is unknown. Twenty ASPs from all YMCA ASPs across South Carolina (N = 102) were invited to participate. Direct observation of the food and beverages served and staff behaviors were collected on 4 nonconsecutive days per ASP. One ASP did not serve a snack. Of the remaining ASPs, a total of 26% served a fruit or vegetable and 32% served water every day; 26% served sugar-sweetened beverages, 47% served sugar-added foods, and only 11% served whole grains when grains were served. Staff members sat with the children (65%) or verbally promoted healthy eating (15%) on at least 1 observation day. Staff drank non-approved drinks (25%) or foods (45%) on at least 1 observation day. No ASPs served snacks family-style every day. Additional efforts are required to assist YMCA-operated ASPs in achieving these important nutrition standards. Copyright © 2016 Society for Nutrition Education and Behavior. Published by Elsevier Inc. All rights reserved.

Uptake of Amino Acids and Their Metabolic Conversion into the Compatible Solute Proline Confers Osmoprotection to Bacillus subtilis

PubMed Central

Zaprasis, Adrienne; Bleisteiner, Monika; Kerres, Anne; Hoffmann, Tamara

2014-01-01

The data presented here reveal a new facet of the physiological adjustment processes through which Bacillus subtilis can derive osmostress protection. We found that the import of proteogenic (Glu, Gln, Asp, Asn, and Arg) and of nonproteogenic (Orn and Cit) amino acids and their metabolic conversion into proline enhances growth under otherwise osmotically unfavorable conditions. Osmoprotection by amino acids depends on the functioning of the ProJ-ProA-ProH enzymes, but different entry points into this biosynthetic route are used by different amino acids to finally yield the compatible solute proline. Glu, Gln, Asp, and Asn are used to replenish the cellular pool of glutamate, the precursor for proline production, whereas Arg, Orn, and Cit are converted into γ-glutamic semialdehyde/Δ1-pyrroline-5-carboxylate, an intermediate in proline biosynthesis. The import of Glu, Gln, Asp, Asn, Arg, Orn, and Cit did not lead to a further increase in the size of the proline pool that is already present in osmotically stressed cells. Hence, our data suggest that osmoprotection of B. subtilis by this group of amino acids rests on the savings in biosynthetic building blocks and energy that would otherwise have to be devoted either to the synthesis of the proline precursor glutamate or of proline itself. Since glutamate is the direct biosynthetic precursor for proline, we studied its uptake and found that GltT, an Na+-coupled symporter, is the main uptake system for both glutamate and aspartate in B. subtilis. Collectively, our data show how effectively B. subtilis can exploit environmental resources to derive osmotic-stress protection through physiological means. PMID:25344233

Salty or Sweet? Nutritional Quality, Consumption, and Cost of Snacks Served in Afterschool Programs

ERIC Educational Resources Information Center

Beets, Michael W.; Weaver, Robert G.; Tilley, Falon; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S.; Freedman, Darcy A.

2015-01-01

Background: Snacks served in afterschool programs (ASPs, 3-6?pm) represent an important opportunity to promote healthy eating. ASP policies suggest a fruit/vegetable is served daily, while sugar-sweetened foods/beverages and artificially flavored snacks are eliminated. Limited information exists on the types of snacks served in ASPs, if snacks…

Community Partnership to Address Snack Quality and Cost in After-School Programs

ERIC Educational Resources Information Center

Beets, Michael W.; Tilley, Falon; Turner-McGrievy, Gabrielle; Weaver, Robert G.; Jones, Sonya

2014-01-01

Background: Policies call on after-school programs (ASPs) to serve more nutritious snacks. A major barrier for improving snack quality is cost. This study describes the impact on snack quality and expenditures from a community partnership between ASPs and local grocery stores. Methods: Four large-scale ASPs (serving ~500 children, aged 6-12?years,…

Enhancing and Promoting Recovery In Attentionally Impaired People Diagnosed With Schizophrenia: Results From A Randomized Controlled Trial Of Attention Shaping In A Partial Hospital Program.

PubMed

Silverstein, Steven M; Roché, Matthew W; Khan, Zaynab; Carson, Sarah J; Malinovsky, Igor; Newbill, William A; Menditto, Anthony A; Wilkniss, Sandra M

2014-01-01

The attentional impairments associated with schizophrenia are well-documented and profound. Psychopharmacological and most psychosocial interventions have been shown to have limited effect in improving attentional capacity. That said, one form of psychosocial treatment, attention shaping procedures (ASP), has been repeatedly demonstrated to produce significant and meaningful change in various aspects of participant attentiveness behaviors. To date, studies of ASP have been limited in that they have been conducted primarily with inpatients, have not assessed the generalizability of ASP's effects, and have not explored whether reinforcement is required to be contingent on performance of attentive behaviors. To address these limitations we conducted the first randomized clinical trial of ASP with people diagnosed with schizophrenia who are being treated in a partial hospital program. Our results indicate that ASP is effective in improving attention in people with schizophrenia in these types of programs, the effects of ASP generalize outside of the immediate treatment context to both other treatment groups and real world functioning, and contingent reinforcement is a critical ingredient of ASP. This project provides further evidence for the benefits of use of ASP in the recovery-oriented treatment of people diagnosed with schizophrenia who have significant attentional impairments.

Adenosine diphosphate sugar pyrophosphatase prevents glycogen biosynthesis in Escherichia coli

PubMed Central

Moreno-Bruna, Beatriz; Baroja-Fernández, Edurne; Muñoz, Francisco José; Bastarrica-Berasategui, Ainara; Zandueta-Criado, Aitor; Rodríguez-López, Milagros; Lasa, Iñigo; Akazawa, Takashi; Pozueta-Romero, Javier

2001-01-01

An adenosine diphosphate sugar pyrophosphatase (ASPPase, EC 3.6.1.21) has been characterized by using Escherichia coli. This enzyme, whose activities in the cell are inversely correlated with the intracellular glycogen content and the glucose concentration in the culture medium, hydrolyzes ADP-glucose, the precursor molecule of glycogen biosynthesis. ASPPase was purified to apparent homogeneity (over 3,000-fold), and sequence analyses revealed that it is a member of the ubiquitously distributed group of nucleotide pyrophosphatases designated as “nudix” hydrolases. Insertional mutagenesis experiments leading to the inactivation of the ASPPase encoding gene, aspP, produced cells with marginally low enzymatic activities and higher glycogen content than wild-type bacteria. aspP was cloned into an expression vector and introduced into E. coli. Transformed cells were shown to contain a dramatically reduced amount of glycogen, as compared with the untransformed bacteria. No pleiotropic changes in the bacterial growth occurred in both the aspP-overexpressing and aspP-deficient strains. The overall results pinpoint the reaction catalyzed by ASPPase as a potential step of regulating glycogen biosynthesis in E. coli. PMID:11416161

Introduction of the ASP3D Computer Program for Unsteady Aerodynamic and Aeroelastic Analyses

NASA Technical Reports Server (NTRS)

Batina, John T.

2005-01-01

A new computer program has been developed called ASP3D (Advanced Small Perturbation 3D), which solves the small perturbation potential flow equation in an advanced form including mass-consistent surface and trailing wake boundary conditions, and entropy, vorticity, and viscous effects. The purpose of the program is for unsteady aerodynamic and aeroelastic analyses, especially in the nonlinear transonic flight regime. The program exploits the simplicity of stationary Cartesian meshes with the movement or deformation of the configuration under consideration incorporated into the solution algorithm through a planar surface boundary condition. The new ASP3D code is the result of a decade of developmental work on improvements to the small perturbation formulation, performed while the author was employed as a Senior Research Scientist in the Configuration Aerodynamics Branch at the NASA Langley Research Center. The ASP3D code is a significant improvement to the state-of-the-art for transonic aeroelastic analyses over the CAP-TSD code (Computational Aeroelasticity Program Transonic Small Disturbance), which was developed principally by the author in the mid-1980s. The author is in a unique position as the developer of both computer programs to compare, contrast, and ultimately make conclusions regarding the underlying formulations and utility of each code. The paper describes the salient features of the ASP3D code including the rationale for improvements in comparison with CAP-TSD. Numerous results are presented to demonstrate the ASP3D capability. The general conclusion is that the new ASP3D capability is superior to the older CAP-TSD code because of the myriad improvements developed and incorporated.

Internationalized and research-oriented photonics education: Abbe School of Photonics

NASA Astrophysics Data System (ADS)

Helgert, Christian; Nolte, Stefan; Pertsch, Thomas

2015-10-01

The Abbe School of Photonics (ASP) provides and coordinates the optics and photonics education of graduate and doctoral students at the Friedrich Schiller University in Jena, Germany. The internationalized Master's degree program is the key activity in training students in the optical sciences. The program is designed to provide them with the skills necessary to fill challenging positions in industry and academia. Here, an essential factor is ASP's close collaboration with more than 20 German photonics companies. To sustain these partners' future economic development, the availability of highly qualified employees is constantly required. Accordingly, these industrial partners, the European Union, the local state and the federal German government are strongly involved in the sustainable development of ASP's curriculum by both conceptual and financial engagements. The main goal is to promote the students' academic careers and job experience in the photonics industry as well as in academia. To open up the program to students from all over the world, all ASP lectures and courses are taught in English. Since 2009, more than 250 graduate students from more than 40 different countries have been enrolled at the School. Almost 90% of them of non-German nationality, fulfilling the essential ASP philosophy to locally establish an international education program. ASP's qualification strategy is fully research-oriented and based on the principles of academic freedom, competitive research conditions and internationalization at all levels. The education program is complemented by a structured doctoral student support and a prestigious guest professorship program.

FATE OF WATER SOLUBLE AZO DYES IN THE ACTIVATED SLUDGE PROCESS

EPA Science Inventory

The objective of this study was to determine the partitioning of water soluble azo dyes in the activated sludge process (ASP). Azo dyes are of concern because some of the dyes, dye precursors , and/or their degradation products such as aromatic amines (which are also dye precurso...

The proteolytic processing site of the precursor of lysyl oxidase.

PubMed Central

Cronshaw, A D; Fothergill-Gilmore, L A; Hulmes, D J

1995-01-01

The precise cleavage site of the N-terminal propeptide region of the precursor of lysyl oxidase has not yet been established, due to N-terminal blocking of the mature protein. Using a combination of peptide fragmentation, amino acid sequencing, time-of-flight m.s. and partial chemical unblocking procedures, it is shown that the mature form of lysyl oxidase begins at residue Asp-169 of the precursor protein (numbered according to the human sequence). The cleavage site is 28 residues to the C-terminal side of the site previously suggested on the basis of apparant molecular mass by SDS/PAGE, with the consequence that the two putative, N-linked glycosylation sites and the position of the Arg/Gln sequence polymorphism are now all in the precursor region. PMID:7864821

After-School Program Engagement: Links to Child Competence and Program Quality and Content

ERIC Educational Resources Information Center

Mahoney, Joseph L; Parente, Maria E.; Lord, Heather

2007-01-01

This 2-year study assessed program-level differences in after-school program (ASP) engagement in relation to child competencies (effectance motivation, social competence, school grades) and program quality and content. Participants were 141 children (M age = 8.4 years) who attended 9 ASPs in an urban, disadvantaged city in the United States.…

The ASP: Programs to Inspire Educators

NASA Astrophysics Data System (ADS)

Hurst, Anna; Gurton, S.; Bennett, M.; Berendson, M.; Gibbs, M.

2006-12-01

The Astronomical Society of the Pacific (ASP) provides educators with new approaches to hands-on astronomy and space science. Through interactive educational programs, our goal is to help more people understand, appreciate, and enjoy astronomy and science. Over the past several years, the ASP has re-dedicated itself to achieving this mission through an ever-expanding portfolio of programs. Our astronomy and education programs target educators of all descriptions classroom teachers, informal science educators (in science museums, planetariums, nature centers, etc.), college astronomy teachers, and amateur astronomers providing them with materials and training to capture the attention of their students and audiences and to introduce them to science via an initial engagement in astronomy. In this poster we provide an overview of current programs that include partnerships with the National Optical Astronomy Observatory, the Association of Science-Technology Centers, TERC, the Astronomical League, NASA, and the SETI Institute to address this broad range of formal and informal educators. Additionally, the poster will provide a summary of recently conducted research by the ASP regarding the Project ASTRO program, done in cooperation with our national partners, to gauge whether the program, as perceived by the teachers participating in Project ASTRO, a) assists in correcting common misconceptions in astronomy or science and b) improve students' attitudes towards science. Additional information regarding the ASP's educational programs can be found at: www.astrosociety.org/education.html

Impact of Implementing Antibiotic Stewardship Programs in 15 Small Hospitals: A Cluster-Randomized Intervention.

PubMed

Stenehjem, Edward; Hersh, Adam L; Buckel, Whitney R; Jones, Peter; Sheng, Xiaoming; Evans, R Scott; Burke, John P; Lopansri, Bert K; Srivastava, Rajendu; Greene, Tom; Pavia, Andrew T

2018-02-23

Studies on the implementation of antibiotic stewardship programs (ASPs) in small hospitals are limited. Accreditation organizations now require all hospitals to have ASPs. The objective of this cluster-randomized intervention was to assess the effectiveness of implementing ASPs in Intermountain Healthcare's 15 small hospitals. Each hospital was randomized to 1 of 3 ASPs of escalating intensity. Program 1 hospitals were provided basic antibiotic stewardship education and tools, access to an infectious disease hotline, and antibiotic utilization data. Program 2 hospitals received those interventions plus advanced education, audit and feedback for select antibiotics, and locally controlled antibiotic restrictions. Program 3 hospitals received program 2 interventions plus audit and feedback on the majority of antibiotics, and an infectious diseases-trained clinician approved restricted antibiotics and reviewed microbiology results. Changes in total and broad-spectrum antibiotic use within programs (intervention versus baseline) and the difference between programs in the magnitude of change in antibiotic use (eg, program 3 vs 1) were evaluated with mixed models. Program 3 hospitals showed reductions in total (rate ratio, 0.89; confidence interval, .80-.99) and broad-spectrum (0.76; .63-.91) antibiotic use when the intervention period was compared with the baseline period. Program 1 and 2 hospitals did not experience a reduction in antibiotic use. Comparison of the magnitude of effects between programs showed a similar trend favoring program 3, but this was not statistically significant. Only the most intensive ASP intervention was associated with reduction in total and broad-spectrum antibiotic use when compared with baseline. NCT03245879.

Pharmacist-driven antimicrobial stewardship program in an institution without infectious diseases physician support.

PubMed

Waters, C Dustin

2015-03-15

Improved drug-utilization and cost outcomes achieved by a pharmacist-led antimicrobial stewardship program (ASP) are described. Pharmacists may be tasked to lead ASP development and implementation with little or no support from an infectious diseases (ID) physician and other hospital personnel whose involvement on ASP teams is recommended (e.g., clinical microbiologists, infection control specialists, hospital epidemiologists). Several years ago, Intermountain Healthcare's 325-bed McKay-Dee Hospital in Utah implemented an ASP led by an antimicrobial stewardship pharmacist. In addition to reviewing patient profiles and meeting with physicians to discuss cases daily (Monday-Friday), the pharmacist was available to provide afterhours phone consultations; support was provided by an infection prevention nurse, two physician ASP champions, the pharmacy leadership, pharmacy informatics and hospital laboratory personnel, and the chief medical officer. In the program's first 33 months, the pharmacist made a total of 2,457 interventions or recommendations, with an acceptance rate of 91.8%. Comparison of selected outcomes during one-year periods before and after ASP implementation indicated substantial decreases in the utilization of four commonly used antimicrobial agents and classes (carbapenems, daptomycin, echinocandins, and levofloxacin) in the postimplementation period, with a significant decline in the average length of stay for community-acquired pneumonia (mean ± S.D., 2.69 ± 0.10 days versus 3.40 ± 0.23 days; p = 0.03). Two years after ASP implementation, annual cost savings attributed to the program were estimated at $355,000. In the absence of ID physician support and oversight, the pharmacist-led ASP achieved substantial reductions in antimicrobial utilization and associated expenditures. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Communicating with Facility Leadership; Metrics for Successful Antimicrobial Stewardship Programs (Asp) in Acute Care and Long-Term Care Facilities.

PubMed

Beganovic, Maya; LaPlante, Kerry L

2018-06-01

Up to 50% of hospital-administered and 70% of nursing home-administered antimicrobials are inappropriately prescribed. There is a great need to focus local, national and global efforts on appropriate antibiotic use. Formal programs dedicated to appropriate antibiotic use have been established in most US hospitals. These antimicrobial stewardship programs (ASP) exist to ensure that the correct drug, dose and duration of an antimicrobial is given, and only when there is a true bacterial infection (as opposed to bacterial colonization or a viral infection). These programs increase patient safety and reduce unintended consequences including Clostridium difficile infections, medication-related adverse effects, and antimicrobial resistance. Most of these programs are co-lead by an interdisciplinary team consisting of an infectious diseases (ID) pharmacist and an ID physician. However, consistent and meaningful metrics to study the impact of ASPs have not been elucidated. With the Joint Commission Standards for Acute Care facilities, and Centers for Medicare and Medicare (CMS) for long-term care facilities making antimicrobial stewardship (AMS) a condition of participation, both facilities will be scrambling to create appropriate quality care indicators to measure program success. One major theme across all healthcare settings is that ASPs must collaborate with facility leadership and key stakeholders at each institution in order to have an impactful benefit on patient quality of care, and safety. It is the purpose of this review to offer several economic, process, and patient-outcome measurements for ASP to optimally communicate with facility leadership. [Full article available at http://rimed.org/rimedicaljournal-2018-06.asp].

D-Aspartate drinking solution alleviates pain and cognitive impairment in neuropathic mice.

PubMed

Palazzo, Enza; Luongo, Livio; Guida, Francesca; Marabese, Ida; Romano, Rosaria; Iannotta, Monica; Rossi, Francesca; D'Aniello, Antimo; Stella, Luigi; Marmo, Federica; Usiello, Alessandro; de Bartolomeis, Andrea; Maione, Sabatino; de Novellis, Vito

2016-07-01

D-Aspartate (D-Asp) is a free D-amino acid detected in multiple brain regions and putative precursor of endogenous N-methyl-D-aspartate (NMDA) acting as agonist at NMDA receptors. In this study, we investigated whether D-Asp (20 mM) in drinking solution for 1 month affects pain responses and pain-related emotional, and cognitive behaviour in a model of neuropathic pain induced by the spared nerve injury (SNI) of the sciatic nerve in mice. SNI mice developed mechanical allodynia and motor coordination impairment 30 days after SNI surgery. SNI mice showed cognitive impairment, anxiety and depression-like behaviour, reduced sociability in the three chamber sociability paradigm, increased expression of NR2B subunit of NMDA receptor and Homer 1a in the medial prefrontal cortex (mPFC). The expression of (post synaptic density) PSD-95 and Shank 1was instead unaffected in the mPFC of the SNI mice. Treatment with D-Asp drinking solution, started right after the SNI (day 0), alleviated mechanical allodynia, improved cognition and motor coordination and increased social interaction. D-Asp also restored the levels of extracellular D-Asp, Homer 1a and NR2B subunit of the NMDA receptor to physiological levels and reduced Shank1 and PSD-95 protein levels in the mPFC. Amitriptyline, a tricyclic antidepressant used also to alleviate neuropathic pain in humans, reverted mechanical allodynia and cognitive impairment, and unlike D-Asp, was effective in reducing depression and anxiety-like behaviour in the SNI mice and increased PSD protein level. Altogether these findings demonstrate that D-Asp improves sensorial, motor and cognitive-like symptoms related to chronic pain possibly through glutamate neurotransmission normalization in neuropathic mice.

Education and Communication in an Interprofessional Antimicrobial Stewardship Program.

PubMed

Foral, Pamela A; Anthone, Jennifer M; Destache, Christopher J; Vivekanandan, Renuga; Preheim, Laurel C; Gorby, Gary L; Horne, John M; Dobronski, Leo A; Syed, Javeria J; Mindru, Cezarina; Ali, Mir A; Ali, Karim F; Neemann, Kari A; Bittner, Marvin J

2016-09-01

Interprofessional education/interprofessional practice (IPE/IPP) is an essential component in medical education and training. A collaborative interprofessional team environment ensures optimal patient-centered care. To describe the implementation of 2 interprofessional antimicrobial stewardship program (ASP) teams using IPE/IPP and to assess the acceptance rate by the primary medical and surgical teams of ASP recommendations for antimicrobial interventions. A business plan for the ASP was approved at 2 academic medical centers used for the present study. During a 3-year study period, 2 interprofessional ASP teams included an attending physician specializing in infectious disease (ID), an ID physician fellow, an ASP pharmacist, physician residents, medical students, pharmacy residents, and pharmacy students. Educational seminars were presented for all adult-admitting physicians to discuss the need for the ASP and the prospective audit and feedback process. Cases were presented for discussion during ASP/ID rounds and recommendations were agreed upon by the ASP team. A motivational interviewing face-to-face technique was frequently used to convey the ASP team recommendation to the primary medical or surgical team in a noncoercive and educational manner. The ASP team recommendations for ASP interventions were documented in the medical records. The overall acceptance rate of recommendations by the primary medical and surgical teams were greater than 90% (2051 of 2266). The most frequent interventions provided were streamline therapy (601), route of administration change (452), bug-drug mismatch (190), and discontinuation of therapy (179). Route of administration change was also the most frequently accepted intervention (96%). The motivational face-to-face communication technique was particularly useful in conveying ASP team member recommendations to the primary medical or surgical teams. Communicating recommendations as a multidisciplinary team in an educational manner seems to have resulted in to greater acceptance of recommendations.

Physical Activity and Energy Expenditure during an After-School Running Club: Laps versus Game Play

ERIC Educational Resources Information Center

Kahan, David; McKenzie, Thomas L.

2018-01-01

Background: After-school programs (ASPs) have the potential to contribute to student physical activity (PA), but there is limited empirical evidence to guide program development and implementation. Methods: We used pedometry to assess the overall effectiveness of an elementary school ASP running program relative to national and state PA…

After-School Programs: A Potential Partner to Support Urban Youth

ERIC Educational Resources Information Center

Evans, Ashley; Leung, Brian P.

2012-01-01

After-school programs (ASPs) are learning centers that provide enrichment opportunities after regular school hours. This article examines the value these programs can add to a child's educational day, especially for urban youth who are vulnerable during after-school hours. Quality ASPs can be part of the solution to help mitigate the effects of…

Impact of Antimicrobial Stewardship on Physician Practice in a Geriatric Facility

PubMed Central

Kassett, Nina; Sham, Rosalind; Aleong, Rosanne; Yang, Daisy; Kirzner, Michael; Craft, Aidlee

2016-01-01

Background There is a paucity of literature describing the implementation of antimicrobial stewardship programs (ASPs) in long-term care (LTC) facilities. The current study evaluated the impact of an ASP that was implemented across a geriatric facility, which included an inpatient specialty hospital and an LTC facility. The program included prospective audits with feedback, multidisciplinary education, information technology interventions, and guideline development. Objective To investigate the impact of the ASP on physicians’ prescribing practices in this geriatric facility. Methods Utilization data for antibiotics commonly used to treat urinary tract infections were retrieved for the period September 1, 2011, to August 31, 2013. The study examined whether there were significant changes in overall antibiotic use, ciprofloxacin use, and physician prescribing behaviour after program implementation in September 2012. Results There was no significant change in the total number of antibiotic prescriptions for urinary tract infections in the hospital or the LTC facility after ASP implementation. Significant reductions were seen in the average days of therapy initially prescribed and the actual days of therapy after ASP implementation in the LTC facility but not the hospital. Across both facilities, significant reductions were seen in the number of ciprofloxacin prescriptions. Conclusions The current study showed that an ASP can affect physicians’ antibiotic prescribing behaviour and antibiotic usage in an LTC environment. PMID:28123192

A Review of Quality Measures for Assessing the Impact of Antimicrobial Stewardship Programs in Hospitals

PubMed Central

Akpan, Mary Richard; Ahmad, Raheelah; Shebl, Nada Atef; Ashiru-Oredope, Diane

2016-01-01

The growing problem of antimicrobial resistance (AMR) has led to calls for antimicrobial stewardship programs (ASP) to control antibiotic use in healthcare settings. Key strategies include prospective audit with feedback and intervention, and formulary restriction and preauthorization. Education, guidelines, clinical pathways, de-escalation, and intravenous to oral conversion are also part of some programs. Impact and quality of ASP can be assessed using process or outcome measures. Outcome measures are categorized as microbiological, patient or financial outcomes. The objective of this review was to provide an overview of quality measures for assessing ASP and the reported impact of ASP in peer-reviewed studies, focusing particularly on patient outcomes. A literature search of papers published in English between 1990 and June 2015 was conducted in five databases using a combination of search terms. Primary studies of any design were included. A total of 63 studies were included in this review. Four studies defined quality metrics for evaluating ASP. Twenty-one studies assessed the impact of ASP on antimicrobial utilization and cost, 25 studies evaluated impact on resistance patterns and/or rate of Clostridium difficile infection (CDI). Thirteen studies assessed impact on patient outcomes including mortality, length of stay (LOS) and readmission rates. Six of these 13 studies reported non-significant difference in mortality between pre- and post-ASP intervention, and five reported reductions in mortality rate. On LOS, six studies reported shorter LOS post intervention; a significant reduction was reported in one of these studies. Of note, this latter study reported significantly (p < 0.001) higher unplanned readmissions related to infections post-ASP. Patient outcomes need to be a key component of ASP evaluation. The choice of metrics is influenced by data and resource availability. Controlling for confounders must be considered in the design of evaluation studies to adequately capture the impact of ASP and it is important for unintended consequences to be considered. This review provides a starting point toward compiling standard outcome metrics for assessing ASP. PMID:27025520

Structure and Deviancy Training in After-School Programs

ERIC Educational Resources Information Center

Rorie, Melissa; Gottfredson, Denise C.; Cross, Amanda; Wilson, Denise; Connell, Nadine M.

2011-01-01

Evidence regarding the effectiveness of after-school programs (ASPs) for reducing problem behaviors is mixed. Unstructured ASPs may increase antisocial behavior by increasing "deviancy training" opportunities, when peers reinforce deviant attitudes and behaviors. This research analyses approximately 3000 five-minute intervals from 398 observations…

Antimicrobial stewardship programs: how to start and steer a successful program.

PubMed

Drew, Richard H

2009-03-01

Antimicrobial stewardship programs (ASPs) promote the appropriate use of antimicrobials by selecting the appropriate dose, duration, and route of administration. The appropriate use of antimicrobials has the potential to improve efficacy, reduce treatment-related costs, minimize drug-related adverse events, and limit the potential for emergence of antimicrobial resistance. To summarize ASP tactics that can improve the appropriate use of antimicrobials in the hospital setting. Several measures can be used to implement such programs and gain multidisciplinary support while addressing common barriers. Implementation of an ASP requires a multidisciplinary approach with an infectious diseases physician and a clinical pharmacist with infectious diseases training as its core team members. As identified by recently published guidelines, 2 proactive strategies for promoting antimicrobial stewardship include: (1) formulary restriction and pre-authorization, and (2) prospective audit with intervention and feedback. Other supplemental strategies involve education, guidelines and clinical pathways, antimicrobial order forms, de-escalation of therapy, intravenous-to-oral (IV-to-PO) switch therapy, and dose optimization. Several barriers exist to successful implementation of ASPs. These include obtaining adequate administrative support and compensation for team members. Gaining physician acceptance can also be challenging if there is a perceived loss of autonomy in clinical decision making. ASPs have the potential to reduce antimicrobial resistance, health care costs, and drug-related adverse events while improving clinical outcomes. The efforts and expense required to implement and maintain ASPs are more than justified given their potential benefits to both the hospital and the patient.

Cultural Competence in Afterschool Programs

ERIC Educational Resources Information Center

Simpkins, Sandra D.; Riggs, Nathaniel R.

2014-01-01

Increasing ethnic diversity among American youth, in combination with funding priorities often targeting underserved populations, has increased the number of diverse youth attending afterschool programs (ASPs). At present, there is little guidance on how to best design ASPs and prepare staff to support the development of these diverse youth. The…

Making healthy eating and physical activity policy practice: the design and overview of a group randomized controlled trial in afterschool programs.

PubMed

Beets, Michael W; Glenn Weaver, R; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S; Freedman, Darcy A; Saunders, Ruth; Pate, Russell R; Beighle, Aaron; Hutto, Brent; Moore, Justin B

2014-07-01

National and state organizations have developed policies calling upon afterschool programs (ASPs, 3-6 pm) to serve a fruit or vegetable (FV) each day for snack, while eliminating foods and beverages high in added-sugars, and to ensure children accumulate a minimum of 30 min/d of moderate-to-vigorous physical activity (MVPA). Few efficacious and cost-effective strategies exist to assist ASP providers in achieving these important public health goals. This paper reports on the design and conceptual framework of Making Healthy Eating and Physical Activity (HEPA) Policy Practice in ASPs, a 3-year group randomized controlled trial testing the effectiveness of strategies designed to improve snacks served and increase MVPA in children attending community-based ASPs. Twenty ASPs, serving over 1800 children (6-12 years) will be enrolled and match-paired based on enrollment size, average daily min/d MVPA, and days/week FV served, with ASPs randomized after baseline data collection to immediate intervention or a 1-year delayed group. The framework employed, STEPs (Strategies To Enhance Practice), focuses on intentional programming of HEPA in each ASPs' daily schedule, and includes a grocery store partnership to reduce price barriers to purchasing FV, professional development training to promote physical activity to develop core physical activity competencies, as well as ongoing technical support/assistance. Primary outcome measures include children's accelerometry-derived MVPA and time spend sedentary while attending an ASP, direct observation of staff HEPA promoting and inhibiting behaviors, types of snacks served, and child consumption of snacks, as well as, cost of snacks via receipts and detailed accounting of intervention delivery costs to estimate cost-effectiveness. Copyright © 2014 Elsevier Inc. All rights reserved.

Impact of a Prospective Audit and Feedback Antimicrobial Stewardship Program at a Veterans Affairs Medical Center: A Six-Point Assessment

PubMed Central

Morrill, Haley J.; Caffrey, Aisling R.; Gaitanis, Melissa M.; LaPlante, Kerry L.

2016-01-01

Background Prospective audit and feedback is a core antimicrobial stewardship program (ASP) strategy; however its impact is difficult to measure. Methods Our quasi-experimental study measured the effect of an ASP on clinical outcomes, antimicrobial use, resistance, costs, patient safety (adverse drug events [ADE] and Clostridium difficile infection [CDI]), and process metrics pre- (9/10–10/11) and post-ASP (9/12–10/13) using propensity adjusted and matched Cox proportional-hazards regression models and interrupted time series (ITS) methods. Results Among our 2,696 patients, median length of stay was 1 day shorter post-ASP (5, interquartile range [IQR] 3–8 vs. 4, IQR 2–7 days, p<0.001). Mortality was similar in both periods. Mean broad-spectrum (-11.3%), fluoroquinolone (-27.0%), and anti-pseudomonal (-15.6%) use decreased significantly (p<0.05). ITS analyses demonstrated a significant increase in monthly carbapenem use post-ASP (trend: +1.5 days of therapy/1,000 patient days [1000PD] per month; 95% CI 0.1–3.0). Total antimicrobial costs decreased 14%. Resistance rates did not change in the one-year post-ASP period. Mean CDI rates/10,000PD were low pre- and post-ASP (14.2 ± 10.4 vs. 13.8 ± 10.0, p = 0.94). Fewer patients experienced ADEs post-ASP (6.0% vs. 4.4%, p = 0.06). Conclusions Prospective audit and feedback has the potential to improve antimicrobial use and outcomes, and contain bacterial resistance. Our program demonstrated a trend towards decreased length of stay, broad-spectrum antimicrobial use, antimicrobial costs, and adverse events. PMID:26978263

6 CFR 27.235 - Alternative security program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... submit an ASP in lieu of a Security Vulnerability Assessment, Site Security Plan, or both. (2) Tier 1... Tier 3 facilities may not submit an ASP in lieu of a Security Vulnerability Assessment. (b) The... Security Vulnerability Assessment or using the procedure specified in § 27.245 if the ASP is intended to...

Application of the ASP3D Computer Program to Unsteady Aerodynamic and Aeroelastic Analyses

NASA Technical Reports Server (NTRS)

Batina, John T.

2006-01-01

A new computer program has been developed called ASP3D (Advanced Small Perturbation - 3D), which solves the small perturbation potential flow equation in an advanced form including mass-consistent surface and trailing wake boundary conditions, and entropy, vorticity, and viscous effects. The purpose of the program is for unsteady aerodynamic and aeroelastic analyses, especially in the nonlinear transonic flight regime. The program exploits the simplicity of stationary Cartesian meshes with the movement or deformation of the configuration under consideration incorporated into the solution algorithm through a planar surface boundary condition. The paper presents unsteady aerodynamic and aeroelastic applications of ASP3D to assess the time dependent capability and demonstrate various features of the code.

Opposing effects of D-aspartic acid and nitric oxide on tuning of testosterone production in mallard testis during the reproductive cycle.

PubMed

Di Fiore, Maria M; Lamanna, Claudia; Assisi, Loredana; Botte, Virgilio

2008-07-04

D-Aspartic acid (D-Asp) and nitric oxide (NO) play an important role in tuning testosterone production in the gonads of male vertebrates. In particular, D-Asp promotes either the synthesis or the release of testosterone, whereas NO inhibits it. In this study, we have investigated for the first time in birds the putative effects of D-Asp and NO on testicular testosterone production in relation to two phases of the reproductive cycle of the adult captive wild-strain mallard (Anas platyrhynchos) drake. It is a typical seasonal breeder and its cycle consists of a short reproductive period (RP) in the spring (April-May) and a non reproductive period (NRP) in the summer (July), a time when the gonads are quiescent. The presence and the localization of D-Asp and NO in the testis and the trends of D-Asp, NO and testosterone levels were assessed during the main phases of the bird's reproductive cycle. Furthermore, in vitro experiments revealed the direct effect of exogenously administered D-Asp and NO on testosterone steroidogenesis. By using immunohistochemical (IHC) techniques, we studied the presence and the distributional pattern of D-Asp and NO in the testes of RP and NRP drakes. D-Asp levels were evaluated by an enzymatic method, whereas NO content, via nitrite, was assessed using biochemical measurements. Finally, immunoenzymatic techniques determined testicular testosterone levels. IHC analyses revealed the presence of D-Asp and NO in Leydig cells. The distributional pattern of both molecules was in some way correlated to the steroidogenic pathway, which is involved in autocrine testosterone production. Indeed, whereas NO was present only during the NRP, D-Asp was almost exclusively present during the RP. Consistently, the high testosterone testicular content occurring during RP was coupled to a high D-Asp level and a low NO content in the gonad. By contrast, in sexually inactive drakes (NRP), the low testosterone content in the gonad was coupled to a low D-Asp content and to a relatively high NO level. Consequently, to determine the exogenous effects of the two amino acids on testosterone synthesis, we carried out in vitro experiments using testis sections deriving from both the RP and NRP. When testis slices were incubated for 60 or 120 min with D-Asp, testosterone was enhanced, whereas in the presence of L-Arg, a precursor of NO, it was inhibited. Our results provide new insights into the involvement of D-Asp and NO in testicular testosterone production in the adult captive wild-strain mallard drake. The localization of these two molecules in the Leydig cells in different periods of the reproductive cycle demonstrates that they play a potential role in regulating local testosterone production.

Open innovation at the Abbe School of Photonics

NASA Astrophysics Data System (ADS)

Helgert, Christian; Geiss, Reinhard; Nolte, Stefan; Eilenberger, Falk; Zakoth, David; Mauroner, Oliver; Pertsch, Thomas

2017-08-01

The Abbe School of Photonics (ASP) provides and coordinates the optics and photonics education of graduate and doctoral students at the Friedrich Schiller University in Jena, Germany. The internationalized Master's degree program is the key activity in training students in the optical sciences. The program is designed to provide them with the skills necessary to fill challenging positions in industry and academia. Here, an essential factor is ASP's close collaboration with more than 20 German photonics companies. To sustain these partners' future economic development, the availability of highly qualified employees is constantly required. Accordingly, these industrial partners, the European Union, the local state and the federal German government are strongly involved in the sustainable development of ASP's curriculum by both conceptual and financial engagements. The main goal is to promote the students' academic careers and job experience in the photonics industry as well as in academia. To open up the program to students from all over the world, all ASP lectures and courses are taught in English. ASP's qualification strategy is fully research-oriented and based on the principles of academic freedom, competitive research conditions and internationalization at all levels. The education program is complemented by a structured doctoral student support and a prestigious guest professorship program. Recently, ASP and partners have started a project to build an open photonics laboratory in order to foster innovative and co-creative processes. The idea follows well-established open innovation schemes e.g. in electronics. This Photon Garage (German: "Lichtwerkstatt") will bring together professionals and interested laymen from different backgrounds to approach pertinent challenges in photonics. Here, we will share our latest insights into the potentials and opportunities offered by this novel educative approach.

Association of Inpatient Antimicrobial Utilization Measures with Antimicrobial Stewardship Activities and Facility Characteristics of Veterans Affairs Medical Centers.

PubMed

Graber, Christopher J; Jones, Makoto M; Chou, Ann F; Zhang, Yue; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew H; Glassman, Peter A

2017-05-01

Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. To determine associations between ASPs and facility characteristics, and inpatient antimicrobial utilization measures in the Veterans Affairs (VA) system in 2012. In 2012, VA administered a survey on antimicrobial stewardship practices to designated ASP contacts at VA acute care hospitals. From the survey, we identified 34 variables across 3 domains (evidence, organizational context, and facilitation) that were assessed using multivariable least absolute shrinkage and selection operator regression against 4 antimicrobial utilization measures from 2012: aggregate acute care antimicrobial use, antimicrobial use in patients with non-infectious primary discharge diagnoses, missed opportunities to convert from parenteral to oral antimicrobial therapy, and double anaerobic coverage. All 130 VA facilities with acute care services. Variables associated with at least 3 favorable changes in antimicrobial utilization included presence of postgraduate physician/pharmacy training programs, number of antimicrobial-specific order sets, frequency of systematic de-escalation review, presence of pharmacists and/or infectious diseases (ID) attendings on acute care ward teams, and formal ID training of the lead ASP pharmacist. Variables associated with 2 unfavorable measures included bed size, the level of engagement with VA Antimicrobial Stewardship Task Force online resources, and utilization of antimicrobial stop orders. Formalization of ASP processes and presence of pharmacy and ID expertise are associated with favorable utilization. Systematic de-escalation review and order set establishment may be high-yield interventions. Journal of Hospital Medicine 2017;12:301-309. © 2017 Society of Hospital Medicine

High-Precision Timing of Several Millisecond Pulsars

NASA Astrophysics Data System (ADS)

Ferdman, R. D.; Stairs, I. H.; Backer, D. C.; Ramachandran, R.; Demorest, P.; Nice, D. J.; Lyne, A. G.; Kramer, M.; Lorimer, D.; McLaughlin, M.; Manchester, D.; Camilo, F.; D'Amico, N.; Possenti, A.; Burgay, M.; Joshi, B. C.; Freire, P. C.

2004-12-01

The highest precision pulsar timing is achieved by reproducing as accurately as possible the pulse profile as emitted by the pulsar, in high signal-to-noise observations. The best profile reconstruction can be accomplished with several-bit voltage sampling and coherent removal of the dispersion suffered by pulsar signals as they traverse the interstellar medium. The Arecibo Signal Processor (ASP) and its counterpart the Green Bank Astronomical Signal Processor (GASP) are flexible, state-of-the-art wide-bandwidth observing systems, built primarily for high-precision long-term timing of millisecond and binary pulsars. ASP and GASP are in use at the 300-m Arecibo telescope in Puerto Rico and the 100-m Green Bank Telescope in Green Bank, West Virginia, respectively, taking advantage of the enormous sensitivities of these telescopes. These instruments result in high-precision science through 4 and 8-bit sampling and perform coherent dedispersion on the incoming data stream in real or near-real time. This is done using a network of personal computers, over an observing bandwidth of 64 to 128 MHz, in each of two polarizations. We present preliminary results of timing and polarimetric observations with ASP/GASP for several pulsars, including the recently-discovered relativistic double-pulsar binary J0737-3039. These data are compared to simultaneous observations with other pulsar instruments, such as the new "spigot card" spectrometer on the GBT and the Princeton Mark IV instrument at Arecibo, the precursor timing system to ASP. We also briefly discuss several upcoming observations with ASP/GASP.

Improving Science Literacy Though Engagement in Astronomy at the Astronomical Society of the Pacific

NASA Astrophysics Data System (ADS)

Manning, James; Gibbs, M.; Gurton, S.

2009-01-01

The Astronomical Society of the Pacific (ASP) increases the understanding and appreciation of astronomy by engaging scientists, educators, enthusiasts and the public to advance science and science literacy. The mission-based astronomy and space science education and public outreach programs provide hands-on resources for both formal and informal educators working with K-12 students and the general public. This poster both highlights the ASP's signature programs, such as Project ASTRO, the Night Sky Network, and Astronomy from the Ground Up, and provides updated information regarding the recent impact the programs are having throughout the United States. Information regarding the ASP can be located online at www.astrosociety.org.

Clinical and economic outcomes from a community hospital's antimicrobial stewardship program.

PubMed

Malani, Anurag N; Richards, Patrick G; Kapila, Shikha; Otto, Michael H; Czerwinski, Jennifer; Singal, Bonita

2013-02-01

Data from community antimicrobial stewardship programs (ASPs) are limited. We describe clinical and economic outcomes from the first year of our hospital's ASP. The ASP team comprised 2 infectious disease physicians and 3 intensive care unit pharmacists. The team prospectively audited the new starts and weekly use of 8 target antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. Using administrative data, outcomes from the first year of the program, including death within 30 days of hospitalization, readmission within 30 days of discharge, and development of Clostridium difficile infection (CDI), were compared with outcomes from a similar period before institution of the program. A total of 510 antimicrobial orders were reviewed, of which 323 (63%) were appropriate, 94 (18%) prompted deescalation, 61 (12%) were denied, and 27 (5%) led to formal consultation with an infectious disease physician. On multivariate analysis, implementation of the ASP was associated with an approximate 50% reduction in the odds of developing CDI (odds ratio, 0.46; 95% confidence interval, 0.25-0.82). The ASP was not associated with decreased mortality at 30 days after discharge or readmission rate. The antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81. The antimicrobial budget decreased by 15.2%, resulting in a total savings of $228,911. There was a 25.4% decrease in defined daily doses of the target antimicrobials. Implementation of the ASP was associated with significant reductions in CDI rate, antimicrobial use, and pharmacy costs. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

After-School Program Implementation in Urban Environments: Increasing Engagement among Adolescent Youth

ERIC Educational Resources Information Center

Pelcher, Allison; Rajan, Sonali

2016-01-01

Background: After-school programs (ASPs) play a crucial role in supplementing the present school day. However, implementing ASPs in the urban environment and among adolescents (grades 6-12) poses unique challenges. The purpose of this study was to conduct a systematic literature review to identify evidence-based barriers and facilitators to…

Impact of Policy Environment Characteristics on Physical Activity and Sedentary Behaviors of Children Attending Afterschool Programs

ERIC Educational Resources Information Center

Beets, Michael W.; Huberty, Jennifer; Beighle, Aaron; Moore, Justin B.; Webster, Collin; Ajja, Rahma; Weaver, Glenn

2013-01-01

State and national organizations recently developed policies focused on increasing physical activity (PA) in afterschool programs (ASPs). These policies emphasize "activity friendly" environment characteristics that, when present, should lead to higher levels of PA and reduce the amount of time children spend sedentary during an ASP.…

Strategies for improving antibiotic use in Qatar: a survey of pharmacists' perceptions and experiences.

PubMed

Pawluk, Shane; Black, Emily; El-Awaisi, Alla

2015-02-01

The objectives of this study were to identify antimicrobial stewardship activities in Qatar, identify pharmacist involvement in activities and summarize perceived barriers for implementation of antimicrobial stewardship programs (ASPs). A cross-sectional survey was developed based on study objectives and completed by pharmacists in Qatar. Most hospital settings have implemented components of ASP. Lack of infectious disease specialists and training of healthcare providers was the most common barrier to implementation or expansion of ASP identified in the hospital and community settings respectively. Pharmacists report some components of ASP have been implemented; however, barriers must be overcome to further expand ASPs. © 2014 Royal Pharmaceutical Society.

Antibiotic Stewardship Programs in U.S. Acute Care Hospitals: Findings From the 2014 National Healthcare Safety Network Annual Hospital Survey.

PubMed

Pollack, Lori A; van Santen, Katharina L; Weiner, Lindsey M; Dudeck, Margaret A; Edwards, Jonathan R; Srinivasan, Arjun

2016-08-15

The National Action Plan to Combat Antibiotic Resistant Bacteria calls for all US hospitals to improve antibiotic prescribing as a key prevention strategy for resistance and Clostridium difficile Antibiotic stewardship programs (ASPs) will be important in this effort but implementation is not well understood. We analyzed the 2014 National Healthcare Safety Network Annual Hospital Survey to describe ASPs in US acute care hospitals as defined by the Center for Disease Control and Prevention's (CDC) Core Elements for Hospital ASPs. Univariate analyses were used to assess stewardship infrastructure and practices by facility characteristics and a multivariate model determined factors associated with meeting all ASP core elements. Among 4184 US hospitals, 39% reported having an ASP that met all 7 core elements. Although hospitals with greater than 200 beds (59%) were more likely to have ASPs, 1 in 4 (25%) of hospitals with less than 50 beds reported achieving all 7 CDC-defined core elements of a comprehensive ASP. The percent of hospitals in each state that reported all seven elements ranged from 7% to 58%. In the multivariate model, written support (adjusted relative risk [RR] 7.2 [95% confidence interval [CI], 6.2-8.4]; P < .0001) or salary support (adjusted RR 1.5 [95% CI, 1.4-1.6]; P < .0001) were significantly associated with having a comprehensive ASP. Our findings show that ASP implementation varies across the United States and provide a baseline to monitor progress toward national goals. Comprehensive ASPs can be established in facilities of any size and hospital leadership support for antibiotic stewardship appears to drive the establishment of ASPs. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Controversies in Antimicrobial Stewardship: Focus on New Rapid Diagnostic Technologies and Antimicrobials

PubMed Central

Wenzler, Eric; Wong, Jordan R.; Goff, Debra A.; Jankowski, Christopher A.; Bauer, Karri A.

2016-01-01

Antimicrobial stewardship programs (ASPs) are challenged with ensuring appropriate antimicrobial use while minimizing expenditures. ASPs have consistently demonstrated improved patient outcomes and significant cost reductions but are continually required to justify the costs of their existence and interventions due to the silo mentality often adopted by hospital administrators. As new technologies and antimicrobials emerge, ASPs are in a constant tug-of-war between providing optimal clinical outcomes and ensuring cost containment. Additionally, robust data on cost-effectiveness of new rapid diagnostic technologies and antimicrobials with subsequent ASP interventions to provide justification are lacking. As the implementation of an ASP will soon be mandatory for acute care hospitals in the United States, ASPs must find ways to justify novel interventions to align themselves with healthcare administrators. This review provides a framework for the justification of implementing a rapid diagnostic test or adding a new antimicrobial to formulary with ASP intervention, reviews approaches to demonstrating cost-effectiveness, and proposes methods for which ASPs may reduce healthcare expenditures via alternative tactics. PMID:27025521

The Astronomical Society of the Pacific - Education and Public Outreach in the International Year of Astronomy

NASA Astrophysics Data System (ADS)

Gibbs, Michael; Manning, J.; Gurton, S.; Fraknoi, A.; Berendsen, M.; Hurst, A.; White, V.

2008-05-01

At the forefront of sharing the excitement of our exploration of the universe for 120 years, the Astronomical Society of the Pacific (ASP) is poised to use its networks and services to implement education and outreach programs for the 2009 International Year of Astronomy (IYA). The ASP is working with NASA, the AAS, NOAO, ASTC, and several other astronomical and educational organizations on IYA projects. The ASP will develop and implement four key signature programs, pending funding, for the IYA: a) "IYA Cosmic Calendar: A Year of Outreach Resources” with astronomy activities primarily for amateur astronomy clubs; b) "In the Footsteps of Galileo: A Teacher Training Program,” designed primarily for in-service teachers; c) an expanded "Astronomy from the Ground Up” program in IYA to bring astronomy into smaller museums and nature centers; and d) "The Cosmic Clearing-House,” an online educational resource for the best astronomy outreach resources and activities. The overarching goal for these programs is to bring together scientists, educators, and amateurs astronomers to improve science education and literacy through astronomy. The Society welcomes additional partners who seek to cooperate on IYA programs or work with the networks of formal and informal educators and amateur astronomers the ASP continues to support.

Physical and Social-Motivational Contextual Correlates of Youth Physical Activity in Underresourced Afterschool Programs

ERIC Educational Resources Information Center

Zarrett, Nicole; Sorensen, Carl; Cook, Brittany Skiles

2015-01-01

Afterschool programs (ASPs) have become increasingly recognized as a key context to support youth daily physical activity (PA) accrual. The purpose of the present study was to assess the physical and social-motivational climate characteristics of ASPs associated with youth PA, and variations in contextual correlates of PA by youth sex. Systematic…

Making Healthy Eating and Physical Activity Policy Practice: Process Evaluation of a Group Randomized Controlled Intervention in Afterschool Programs

ERIC Educational Resources Information Center

Weaver, R. Glenn; Beets, Michael W.; Hutto, Brent; Saunders, Ruth P.; Moore, Justin B.; Turner-McGrievy, Gabrielle; Huberty, Jennifer L.; Ward, Dianne S.; Pate, Russell R.; Beighle, Aaron; Freedman, Darcy

2015-01-01

This study describes the link between level of implementation and outcomes from an intervention to increase afterschool programs' (ASPs) achievement of healthy eating and physical activity (HE-PA) Standards. Ten intervention ASPs implemented the Strategies-To-Enhance-Practice (STEPs), a multi-component, adaptive intervention framework identifying…

Development of a Portfolio Management Approach with Case Study of the NASA Airspace Systems Program

NASA Technical Reports Server (NTRS)

Neitzke, Kurt W.; Hartman, Christopher L.

2012-01-01

A portfolio management approach was developed for the National Aeronautics and Space Administration s (NASA s) Airspace Systems Program (ASP). The purpose was to help inform ASP leadership regarding future investment decisions related to its existing portfolio of advanced technology concepts and capabilities (C/Cs) currently under development and to potentially identify new opportunities. The portfolio management approach is general in form and is extensible to other advanced technology development programs. It focuses on individual C/Cs and consists of three parts: 1) concept of operations (con-ops) development, 2) safety impact assessment, and 3) benefit-cost-risk (B-C-R) assessment. The first two parts are recommendations to ASP leaders and will be discussed only briefly, while the B-C-R part relates to the development of an assessment capability and will be discussed in greater detail. The B-C-R assessment capability enables estimation of the relative value of each C/C as compared with all other C/Cs in the ASP portfolio. Value is expressed in terms of a composite weighted utility function (WUF) rating, based on estimated benefits, costs, and risks. Benefit utility is estimated relative to achieving key NAS performance objectives, which are outlined in the ASP Strategic Plan.1 Risk utility focuses on C/C development and implementation risk, while cost utility focuses on the development and implementation portions of overall C/C life-cycle costs. Initial composite ratings of the ASP C/Cs were successfully generated; however, the limited availability of B-C-R information, which is used as inputs to the WUF model, reduced the meaningfulness of these initial investment ratings. Development of this approach, however, defined specific information-generation requirements for ASP C/C developers that will increase the meaningfulness of future B-C-R ratings.

Making Healthy Eating and Physical Activity Policy Practice: The Design and Overview of a Group Randomized Controlled Trial in Afterschool Programs

PubMed Central

Beets, Michael W.; Weaver, R. Glenn; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S.; Freedman, Darcy A.; Saunders, Ruth; Pate, Russell R.; Beighle, Aaron; Moore, Justin B.

2014-01-01

National and state organizations have developed policies calling upon afterschool programs (ASPs, 3-6pm) to serve a fruit or vegetable (FV) each day for snack, while eliminating foods and beverages high in added-sugars, and to ensure children accumulate a minimum of 30 min/d of moderate-to-vigorous physical activity (MVPA). Few efficacious and cost-effective strategies exist to assist ASP providers in achieving these important public health goals. This paper reports on the design and conceptual framework of Making Healthy Eating and Physical Activity (HEPA) Policy Practice in ASPs, a 3-year group randomized controlled trial testing the effectiveness of strategies designed to improve snacks served and increase MVPA in children attending community-based ASPs. Twenty ASPs, serving over 1,800 children (6-12yrs) will be enrolled and match-paired based on enrollment size, average daily min/d MVPA, and days/week FV served, with ASPs randomized after baseline data collection to immediate intervention or a 1-year delayed group. The framework employed, STEPs (Strategies To Enhance Practice), focuses on intentional programming of HEPA in each ASPs’ daily schedule, and includes a grocery store partnership to reduce price barriers to purchasing FV, professional development training to promote physical activity to develop core physical activity competencies, as well as ongoing technical support/assistance. Primary outcome measures include children’s accelerometry-derived MVPA and time spend sedentary while attending an ASP, direct observation of staff HEPA promoting and inhibiting behaviors, types of snacks served, and child consumption of snacks, as well as, cost of snacks via receipts and detailed accounting of intervention delivery costs to estimate cost-effectiveness. PMID:24893225

Ecological Forecasting Project Management with Examples

NASA Technical Reports Server (NTRS)

Skiles, J. W.; Schmidt, Cindy; Estes, Maury; Turner, Woody

2017-01-01

Once scientists publish results of their projects and studies, all too often they end up on the shelf and are not otherwise used. The NASA Earth Science Division established its Applied Sciences Program (ASP) to apply research findings to help solve and manage real-world problems and needs. ASP-funded projects generally produce decision support systems for operational applications which are expected to last beyond the end of the NASA funding. Because of NASAs unique perspective of looking down on the Earth from space, ASP studies involve the use of remotely sensed information consisting of satellite data and imagery as well as information from sub-orbital platforms. ASP regularly solicits Earth science proposals that address one or more focus areas; disasters mitigation, ecological forecasting, health and air quality, and water resources. Reporting requirements for ASP-funded projects are different from those typical for research grants from NASA and other granting agencies, requiring management approaches different from other programs. This presentation will address the foregoing in some detail and give examples of three ASP-funded ecological forecasting projects that include: 1) the detection and survey of chimpanzee habitat in Africa from space, 2) harmful algal blooms (HABs) in the California Current System affecting aquaculture facilities and marine mammal populations, and 3) a call for the public to identify North America wildlife in Wisconsin using trail camera photos. Contact information to propose to ASP solicitations for those PIs interested is also provided.

Salty or Sweet? Nutritional quality, consumption, and cost of snacks served in afterschool programs

PubMed Central

Beets, Michael W.; Weaver, R. Glenn; Tilley, Falon; Turner-McGrievy, Brie; Huberty, Jennifer; Ward, Dianne S.; Freedman, Darcy A.

2015-01-01

BACKGROUND Snacks served in afterschool programs (ASPs, 3–6pm) represent an important opportunity to promote healthy eating. ASP policies suggest a fruit/vegetable is served daily, while sugar-sweetened foods/beverages and artificially-flavored snacks are eliminated. Limited information exists on the types of snacks served in ASPs, if snacks meet existing nutrition policies, whether children eat the snacks, and their cost. METHODS Direct observation of snacks served and consumed was collected in 20 ASPs serving over 1,700 elementary-age children. The number of days snacks were served/week was evaluated for compliance with nutrition policies. Costs of snacks were collected via receipts. RESULTS Programs served desserts and artificially-flavored salty-snacks on 2.7 and 2.1 days/week. Fruits and vegetables were served 0.6 and 0.1 days/wk, respectively. Sugar-sweetened-beverages were served 1.8 days/wk. Of the children (N=383) observed, 75–100% consumed the snack served, with 95% and 100% of served fruits/vegetables consumed. No ASP served fruit/vegetables daily, 18 served sugar-sweetened foods, 16 served artificially-flavored snacks, and 14 served sugar-sweetened-beverages. Desserts and salty-snacks cost $0.27–$0.32/snack vs. $0.38–$0.40/snack for vegetables/fruits. CONCLUSIONS The quality of snacks failed to meet nutrition policies and consists of predominately high-sugar and artificially-flavored options. Strategies to improve snack offerings in ASPs while addressing price barriers are required. PMID:25564980

Salty or sweet? Nutritional quality, consumption, and cost of snacks served in afterschool programs.

PubMed

Beets, Michael W; Weaver, Robert G; Tilley, Falon; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S; Freedman, Darcy A

2015-02-01

Snacks served in afterschool programs (ASPs, 3-6 pm) represent an important opportunity to promote healthy eating. ASP policies suggest a fruit/vegetable is served daily, while sugar-sweetened foods/beverages and artificially flavored snacks are eliminated. Limited information exists on the types of snacks served in ASPs, if snacks meet existing nutrition policies, whether children eat the snacks, and their cost. Direct observation of snacks served and consumed was collected in 20 ASPs serving over 1700 elementary age children. The number of days that snacks were served/week was evaluated for compliance with nutrition policies. Costs of snacks were collected via receipts. Programs served desserts and artificially flavored salty snacks on 2.7 and 2.1 days/week. Fruits and vegetables were served 0.6 and 0.1 days/week, respectively. Sugar-sweetened beverages were served 1.8 days/week. Of the children (N = 383) observed, 75% to 100% consumed the snack served, with 95% and 100% of served fruits/vegetables consumed. No ASP served fruit/vegetables daily, 18 served sugar-sweetened foods, 16 served artificially flavored snacks, and 14 served sugar-sweetened beverages. Desserts and salty snacks cost $0.27-$0.32/snack vs $0.38-$0.40/snack for vegetables/fruits. The quality of snacks failed to meet nutrition policies and consists of predominately high-sugar and artificially flavored options. Strategies to improve snack offerings in ASPs while addressing price barriers are required. © 2015, American School Health Association.

Antimicrobial Stewardship: A Call to Action for Surgeons

PubMed Central

Duane, Therese M.; Catena, Fausto; Tessier, Jeffrey M.; Coccolini, Federico; Kao, Lillian S.; De Simone, Belinda; Labricciosa, Francesco M.; May, Addison K.; Ansaloni, Luca; Mazuski, John E.

2016-01-01

Abstract Despite current antimicrobial stewardship programs (ASPs) being advocated by infectious disease specialists and discussed by national and international policy makers, ASPs coverage remains limited to only certain hospitals as well as specific service lines within hospitals. The ASPs incorporate a variety of strategies to optimize antimicrobial agent use in the hospital, yet the exact set of interventions essential to ASP success remains unknown. Promotion of ASPs across clinical practice is crucial to their success to ensure standardization of antimicrobial agent use within an institution. To effectively accomplish this standardization, providers who actively engage in antimicrobial agent prescribing should participate in the establishment and support of these programs. Hence, surgeons need to play a major role in these collaborations. Surgeons must be aware that judicious antibiotic utilization is an integral part of any stewardship program and necessary to maximize clinical cure and minimize emergence of antimicrobial resistance. The battle against antibiotic resistance should be fought by all healthcare professionals. If surgeons around the world participate in this global fight and demonstrate awareness of the major problem of antimicrobial resistance, they will be pivotal leaders. If surgeons fail to actively engage and use antibiotics judiciously, they will find themselves deprived of the autonomy to treat their patients. PMID:27828764

Characterization of Fine Particulate Matter (PM) and Secondary PM Precursor Gases in the Mexico City Metropolitan Area

DOE R&D Accomplishments Database

Molina, Luisa T.; Volkamer, Rainer; de Foy, Benjamin; Lei, Wenfang; Zavala, Miguel; Velasco, Erik; Molina; Mario J.

2008-10-31

This project was one of three collaborating grants funded by DOE/ASP to characterize the fine particulate matter (PM) and secondary PM precursors in the Mexico City Metropolitan Area (MCMA) during the MILAGRO Campaign. The overall effort of MCMA-2006, one of the four components, focused on i) examination of the primary emissions of fine particles and precursor gases leading to photochemical production of atmospheric oxidants and secondary aerosol particles; ii) measurement and analysis of secondary oxidants and secondary fine PM production, with particular emphasis on secondary organic aerosol (SOA), and iii) evaluation of the photochemical and meteorological processes characteristic of the Mexico City Basin. The collaborative teams pursued the goals through three main tasks: i) analyses of fine PM and secondary PM precursor gaseous species data taken during the MCMA-2002/2003 campaigns and preparation of publications; ii) planning of the MILAGRO Campaign and deployment of the instrument around the MCMA; and iii) analysis of MCMA-2006 data and publication preparation.

Promoting Physical Activity within Under-Resourced Afterschool Programs: A Qualitative Investigation of Staff Experiences and Motivational Strategies for Engaging Youth

ERIC Educational Resources Information Center

Zarrett, Nicole; Abraczinskas, Michelle; Skiles Cook, Brittany; Wilson, Dawn K.; Ragaban, Faten

2018-01-01

Afterschool programs (ASPs) have become increasingly recognized as a key context to support youth daily physical activity (PA) accrual. Using Self-Determination Theory (SDT) as a framework, this study examined staff perspectives on the strengths and barriers within under-resourced ASPs for establishing a social-motivational climate for encouraging…

Characteristics of Pediatric Antimicrobial Stewardship Programs: Current Status of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative

PubMed Central

McPherson, Christopher; Lee, Brian R.; Terrill, Cindy; Hersh, Adam L.; Gerber, Jeffrey S.; Kronman, Matthew P.; Newland, Jason G.

2018-01-01

In response to the growing epidemic of antibiotic-resistant bacterial infections, antimicrobial stewardship programs (ASP) have been rapidly implemented in the United States (US). This study examines the prevalence of the Centers for Disease Control and Prevention’s (CDC) seven core elements of a successful ASP within a large subset of US Children’s Hospitals. In 2016, a survey was conducted of 52 pediatric hospitals assessing the presence of the seven core elements: leadership commitment, accountability, drug expertise, action, tracking, reporting, and education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%) included all seven core elements. Physician accountability (87%) and a dedicated ASP pharmacist or drug expert (88%) were present in the vast majority of hospitals. However, substantial variability existed in the financial support allotted to these positions. This variability did not predict program actions, tracking, reporting, and education. When compared with previous surveys, these results document a dramatic increase in the prevalence and resources of pediatric stewardship programs, although continued expansion is warranted. Further research is required to understand the feasibility of various core stewardship activities and the impact on patient outcomes in the setting of finite resources. PMID:29370071

Characteristics of Pediatric Antimicrobial Stewardship Programs: Current Status of the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) Collaborative.

PubMed

McPherson, Christopher; Lee, Brian R; Terrill, Cindy; Hersh, Adam L; Gerber, Jeffrey S; Kronman, Matthew P; Newland, Jason G

2018-01-25

In response to the growing epidemic of antibiotic-resistant bacterial infections, antimicrobial stewardship programs (ASP) have been rapidly implemented in the United States (US). This study examines the prevalence of the Centers for Disease Control and Prevention's (CDC) seven core elements of a successful ASP within a large subset of US Children's Hospitals. In 2016, a survey was conducted of 52 pediatric hospitals assessing the presence of the seven core elements: leadership commitment, accountability, drug expertise, action, tracking, reporting, and education. Forty-nine hospitals (94%) had established ASPs and 41 hospitals (79%) included all seven core elements. Physician accountability (87%) and a dedicated ASP pharmacist or drug expert (88%) were present in the vast majority of hospitals. However, substantial variability existed in the financial support allotted to these positions. This variability did not predict program actions, tracking, reporting, and education. When compared with previous surveys, these results document a dramatic increase in the prevalence and resources of pediatric stewardship programs, although continued expansion is warranted. Further research is required to understand the feasibility of various core stewardship activities and the impact on patient outcomes in the setting of finite resources.

Education and Public Outreach in the International Year of Astronomy at the Astronomical Society of the Pacific

NASA Astrophysics Data System (ADS)

Gibbs, M. G.; Manning, J. G.; Gurton, S.; Fraknoi, A.; Berendsen, M.; Hurst, A.; White, V.

2008-11-01

At the forefront of sharing the excitement of our exploration of the universe for 120 years, the Astronomical Society of the Pacific (ASP) is poised to use its networks and services to implement education and outreach programs for the 2009 International Year of Astronomy (IYA). The ASP is working with the National Aeronautics and Space Administration (NASA), the American Astronomical Society (AAS), National Optical Astronomy Observatory (NOAO), Association of Science---Technology Centers (ASTC), and several other astronomical and educational organizations on IYA projects. The ASP will develop and implement four key signature programs, pending funding, for the IYA: a) IYA 2009 Cosmic Companion, with astronomy activities primarily for amateur astronomy clubs; b) Galileo Teacher Training Program, designed primarily for in-service teachers; c) Expanding the Informal Universe, to bring astronomy into smaller museums and nature centers; and d) Cosmic Clearing-House, an online educational resource for the best astronomy outreach resources and activities. The overarching goal for these programs is to bring together scientists, educators, and amateurs astronomers to improve science education and literacy through astronomy. The Society welcomes additional partners who seek to cooperate on IYA programs or work with the networks of formal and informal educators and amateur astronomers the ASP continues to support.

Initiatives and resources to promote antimicrobial stewardship.

PubMed

Paño-Pardo, José Ramón; Campos, José; Natera Kindelán, Clara; Ramos, Antonio

2013-09-01

The development of an antimicrobial stewardship program (ASP) requires institutional support. However, obtaining sufficient institutional support is often a complex task that requires convincing the hospital's managers of the benefits of these programs. Additionally, in the design and implementation of an ASP, antimicrobial stewardship (AS) leaders need tools for diverse purposes, such as measuring antimicrobial consumption, education and training and designing protocols. In this review we provide useful information for AS promoters to facilitate the task of designing and implementing an ASP. First, we summarize information about various institutions that promote AS and include evidence that supports the need for and benefits of these programs. Then, several campaigns promoting AS are described. Finally, online resources for professionals dealing with AS are briefly summarized. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Use of computer decision support in an antimicrobial stewardship program (ASP).

PubMed

Evans, R S; Olson, J A; Stenehjem, E; Buckel, W R; Thorell, E A; Howe, S; Wu, X; Jones, P S; Lloyd, J F

2015-01-01

Document information needs, gaps within the current electronic applications and reports, and workflow interruptions requiring manual information searches that decreased the ability of our antimicrobial stewardship program (ASP) at Intermountain Healthcare (IH) to prospectively audit and provide feedback to clinicians to improve antimicrobial use. A framework was used to provide access to patient information contained in the electronic medical record, the enterprise-wide data warehouse, the data-driven alert file and the enterprise-wide encounter file to generate alerts and reports via pagers, emails and through the Centers for Diseases and Control's National Healthcare Surveillance Network. Four new applications were developed and used by ASPs at Intermountain Medical Center (IMC) and Primary Children's Hospital (PCH) based on the design and input from the pharmacists and infectious diseases physicians and the new Center for Diseases Control and Prevention/National Healthcare Safety Network (NHSN) antibiotic utilization specifications. Data from IMC and PCH now show a general decrease in the use of drugs initially targeted by the ASP at both facilities. To be effective, ASPs need an enormous amount of "timely" information. Members of the ASP at IH report these new applications help them improve antibiotic use by allowing efficient, timely review and effective prioritization of patients receiving antimicrobials in order to optimize patient care.

An Arg-Gly-Asp peptide stimulates Ca2+ efflux from osteoclast precursors through a novel mechanism

NASA Technical Reports Server (NTRS)

Yamakawa, K.; Duncan, R.; Hruska, K. A.

1994-01-01

We examined the effect of a peptide containing the Arg-Gly-Asp (RGD) sequence on 45Ca2+ efflux from osteoclast precursors. 45Ca(2+)-loaded osteoclast precursors were treated with GRGDSP (170 microM) for 10 min after 30 min of basal perfusion with a bicarbonate-containing buffer. GRGDSP significantly increased fractional efflux of Ca2+ from treated cells compared with vehicle-treated cells (P < 0.01) or cells treated with up to 200 micrograms/ml of a control peptide containing GRGESP. The effect of RGD was sustained for 15 min after the peptide was removed from the perfusate, but control levels of Ca2+ efflux returned by 1 h. The Ca2+ efflux effect of GRGDSP was most likely due to activation of the plasma membrane Ca(2+)-adenosinetriphosphatase (Ca(2+)-ATPase) pump, as indicated by its inhibition with vanadate and a calmodulin antagonist, N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide, and the absence of an effect of Na+/Ca2+ exchange inhibition. An inhibitor of cyclic nucleotide-dependent protein kinases, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (0.1 mM), failed to inhibit GRGDSP-stimulated Ca2+ efflux. However, genistein and herbimycin A, inhibitors of protein-tyrosine kinases, blocked Ca2+ efflux stimulated by GRGDSP. The results indicate that RGD sequences of matrix proteins may stimulate Ca2+ efflux from osteoclasts through activation of protein-tyrosine kinases and suggest that GRGDSP-stimulated Ca2+ efflux is mediated via the plasma membrane Ca(2+)-ATPase.

Effect of Communication Errors During Calls to an Antimicrobial Stewardship Program

PubMed Central

Linkin, Darren R.; Fishman, Neil O.; Landis, J. Richard; Barton, Todd D.; Gluckman, Steven; Kostman, Jay; Metlay, Joshua P.

2011-01-01

Objective To determine the effect of inaccurate communication of patient data—from clinicians caring for inpatients to prior-approval antimicrobial stewardship programs (ASP) staff (practitioners)—on the incidence of inappropriate antimicrobial recommendations by ASP practitioners Design A retrospective cohort design was utilized. The accuracy of communicated patient data was evaluated against patients’ medical records for pre-determined, clinically significant inaccuracies. Inappropriate antimicrobial recommendations were defined when an expert panel unanimously rated the actual recommendations as inappropriate after reviewing vignettes derived from inpatients’ medical records. Setting The setting was an academic medical center with a prior-approval ASP. Patients All inpatient subjects of ASP prior-approval calls were eligible for inclusion. Results The panel agreed on whether the antimicrobial recommendation was inappropriate or not in 163 (82%) of 200 ASP calls; the 163 calls were then the basis for further analyses. After controlling for confounders, inaccurate communications were associated with inappropriate antimicrobial recommendations with an odds ratio (OR) of 2.2 (p=0.03). In secondary analyses of specific data types, only inaccuracies of microbiological data were associated with the study outcome (OR 7.5, p=0.002). The most common reason given by panelists for an inappropriate rating was that antimicrobials were not indicated. Conclusions Inaccurate communication of patient data, particularly microbiological data, during prior-approval calls is associated with an increased risk of inappropriate antimicrobial recommendations from the ASP. Clinicians and ASP practitioners should work to confirm critical communicated data prior to use in prescribing decisions. PMID:17994518

Arizona's Application Service Provider.

ERIC Educational Resources Information Center

Jordan, Darla

2002-01-01

Describes the U.S.'s first statewide K-12 application service provider (ASP). The ASP, implemented by the Arizona School Facilities Board, provides access to productivity, communications, and education software programs from any Internet-enabled device, whether in the classroom or home. (EV)

Prevalence, Characteristics, and Perception of Nursery Antibiotic Stewardship Coverage in the United States.

PubMed

Cantey, Joseph B; Vora, Niraj; Sunkara, Mridula

2017-09-01

Prolonged or unnecessary antibiotic use is associated with adverse outcomes in infants. Antibiotic stewardship programs (ASPs) aim to prevent these adverse outcomes and optimize antibiotic prescribing. However, data evaluating ASP coverage of nurseries are limited. The objectives of this study were to describe the characteristics of nurseries with and without ASP coverage and to determine perceptions of and barriers to nursery ASP coverage. The 2014 American Hospital Association annual survey was used to randomly select a level III neonatal intensive care unit from all 50 states. A level I and level II nursery from the same city as the level III nursery were then randomly selected. Hospital, nursery, and ASP characteristics were collected. Nursery and ASP providers (pharmacists or infectious disease providers) were interviewed using a semistructured template. Transcribed interviews were analyzed for themes. One hundred forty-six centers responded; 104 (71%) provided nursery ASP coverage. In multivariate analysis, level of nursery, university affiliation, and number of full-time equivalent ASP staff were the main predictors of nursery ASP coverage. Several themes were identified from interviews: unwanted coverage, unnecessary coverage, jurisdiction issues, need for communication, and a focus on outcomes. Most providers had a favorable view of nursery ASP coverage. Larger, higher-acuity nurseries in university-affiliated hospitals are more likely to have ASP coverage. Low ASP staffing and a perceived lack of importance were frequently cited as barriers to nursery coverage. Most nursery ASP coverage is viewed favorably by providers, but nursery providers regard it as less important than ASP providers. © The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Evaluation of a statewide dissemination and implementation of physical activity intervention in afterschool programs: a nonrandomized trial.

PubMed

Beets, Michael W; Glenn Weaver, R; Turner-McGrievy, Gabrielle; Saunders, Ruth P; Webster, Collin A; Moore, Justin B; Brazendale, Keith; Chandler, Jessica

2017-12-01

In 2015, YMCA-operated afterschool programs (ASPs) across South Carolina pledged to achieve the national standard that calls for every child to accumulate 30 min/day of moderate-to-vigorous physical activity (MVPA) during program time. This study shares the first-year findings related to the dissemination, implementation, and outcomes associated with the statewide intervention to achieve the MVPA Standard. Twenty ASPs were sampled from all YMCA-operated ASPs (N = 97) and visited at baseline (spring 2015) and first-year follow-up (spring 2016). Programs were provided standardized professional development training to increase the MVPA children accumulated while attending ASPs. The training focused on extending the scheduled time for activity opportunities and modifying commonly played games to increase MVPA. The RE-AIM framework was used to evaluate the statewide intervention. Accelerometer-derived MVPA was the primary outcome. Implementation was evaluated via direct observation. Intent-to-treat (ITT) and as-treated comparisons were conducted in summer 2016. Reach/adoption was variable, with attendance at trainings ranging from 0 to 100% across ASPs. Effectiveness of the intervention using ITT models indicated no changes from baseline in the percentage of programs meeting the MVPA standard for boys or girls. Implementation levels also varied and were related to increases in both boys' and girls' MVPA for moderate and high implementers. Findings indicate improvements in MVPA can be made from attending the trainings and implementing some or all of the training components. Additional work is necessary to identify ways to ensure staff attend trainings to implement strategies and to identify which specific factors contributed to increases in MVPA.

ASP Celebrates IYA, One Month at a Time

NASA Astrophysics Data System (ADS)

Gurton, Suzanne; Berendsen, M.; Hurst, A.; White, V.

2008-05-01

Serving three major networks of educators, the ASP, in coordination with NASA and NOAO and others, is building a comprehensive program to celebrate the International Year of Astronomy (IYA) by featuring a different astronomy theme during each month of 2009. We will provide a rich array of themed resources, such as activities, tele-conferences, and news stories, to the variety of educators served by the ASP: amateur astronomers, museum educators and teachers. This poster will present our program of monthly themes, along with associated services and resources, to support the diverse public outreach efforts of the members of the NASA Night Sky Network, participants in Astronomy From the Ground Up, and Project ASTRO partners.

Analysis of the surface expression of c-kit and occurrence of the c-kit Asp816Val activating mutation in T cells, B cells, and myelomonocytic cells in patients with mastocytosis.

PubMed

Akin, C; Kirshenbaum, A S; Semere, T; Worobec, A S; Scott, L M; Metcalfe, D D

2000-02-01

The Asp816Val c-kit activating mutation is detectable in the peripheral blood cells of some patients with mastocytosis and in lesional skin biopsies obtained from adult patients with urticaria pigmentosa. These observations led to the conclusion that this mutation is present in mast cells and mast cell precursors that express c-kit. However, the distribution of the Asp816Val mutation among hematopoietic lineages is unknown. To determine the distribution of the Asp816Val mutation among hematopoietic lineages and to explore its relationship to clinical disease, we examined cells bearing differentiation markers for myelomonocytic cells as well as T and B lymphocytes, in both peripheral blood and bone marrow obtained from patients with mastocytosis. The presence of Asp816Val c-kit mutation in cells magnetically sorted from peripheral blood or bone marrow according to surface differentiation markers was studied by reverse transcriptase polymerase chain reaction (RT-PCR) restriction fragment length polymorphism (RFLP) analysis. The surface expression of c-kit was determined by flow cytometry. The mutation was detectable by RT-PCR in at least one cell lineage in the bone marrow in 7 of 7 patients examined and in the peripheral blood of 11 of 11 adult patients with urticaria pigmentosa and indolent disease. The mutation was identified most frequently in B cells and myeloid cells. Flow cytometric analysis demonstrated that the differentiated cells expressing mutated c-kit were negative for surface KIT. These results are consistent with the conclusion that the c-kit Asp816Val mutation occurs in an early progenitor cell and is carried by myelomonocytic cells, T cells, and B cells in addition to mast cells. However, unlike mast cells, these myelomonocytic cells, T cells, and B cells do not concomitantly express surface c-kit and thus may be less susceptible to the effects of this mutation.

Effects of After-School Programs on Attendance and Externalizing Behaviors with Primary and Secondary School Students: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Maynard, Brandy R.; Kremer, Kristen P.; Polanin, Joshua R.; Vaughn, Michael G.; Sarteschi, Christine M.

2015-01-01

Over the past two decades, the number and types of after-school programs (ASPs) have increased substantially as a result of increased federal and private spending and because ASPs are perceived to provide wide-ranging and far-reaching benefits to students, families, schools and the public. The purpose of this systematic review and meta-analysis is…

From policy to practice: strategies to meet physical activity standards in YMCA afterschool programs.

PubMed

Beets, Michael W; Weaver, Robert G; Moore, Justin B; Turner-McGrievy, Gabriel; Pate, Russell R; Webster, Collin; Beighle, Aaron

2014-03-01

In 2011, the U.S. Young Men's Christian Association (YMCA) adopted activity standards recommending that afterschool programs (ASPs) ensure all children engage in a minimum of 30 minutes of moderate to vigorous physical activity (MVPA) daily during the ASP. ASPs decide how to accomplish this standard, for which few effective strategies exist. To evaluate strategies designed to help ASPs meet the MVPA standard. Single group intervention with pretest and three follow-up measures repeated-cross-sectional design with a subsample cohort. Four large-scale YMCA ASPs, serving approximately 500 children each day. Community-based participatory development of strategies focused on modification of program schedules, professional development training, and weekly checklists to evaluate activity opportunities. Accelerometry-derived MVPA classified as meet or fail-to-meet the 30 minutes' MVPA/day standard collected over a minimum of 4 nonconsecutive days at baseline (fall 2011) and three follow-up assessments (spring 2012, fall 2012, spring 2013). Random intercept logistic regression models evaluated the probability of meeting the standard for boys and girls, separately (analyzed summer 2013). A total of 895 children (aged 5-12 years, 48.4% girls) representing 3654 daily measures were collected across the four assessments. The percentage of girls and boys meeting the MVPA standard at baseline was 13.3% and 28.0%, respectively. By spring 2013, this increased to 29.3% and 49.6%. These changes represented an increase in the odds of meeting the 30 minutes' MVPA/day standard by 1.5 (95% CI=1.1, 2.0) and 2.4 (95% CI=1.2, 4.8) for girls and boys, respectively. The strategies developed herein represent an effective approach to enhancing current practice within YMCA ASPs to achieve existing MVPA standards. Additional work is necessary to evaluate the scalability of the strategies in a larger sample of ASPs. © 2014 American Journal of Preventive Medicine Published by American Journal of Preventive Medicine All rights reserved.

A novel homodimeric geranyl diphosphate synthase from the orchid Phalaenopsis bellina lacking a DD(X)2-4D motif.

PubMed

Hsiao, Yu-Yun; Jeng, Mei-Fen; Tsai, Wen-Chieh; Chuang, Yu-Chen; Li, Chia-Ying; Wu, Tian-Shung; Kuoh, Chang-Sheng; Chen, Wen-Huei; Chen, Hong-Hwa

2008-09-01

Geranyl diphosphate (GDP) is the precursor of monoterpenes, which are the major floral scent compounds in Phalaenopsis bellina. The cDNA of P. bellina GDP synthase (PbGDPS) was cloned, and its sequence corresponds to the second Asp-rich motif (SARM), but not to any aspartate-rich (Asp-rich) motif. The recombinant PbGDPS enzyme exhibits dual prenyltransferase activity, producing both GDP and farnesyl diphosphate (FDP), and a yeast two-hybrid assay and gel filtration revealed that PbGDPS was able to form a homodimer. Spatial and temporal expression analyses showed that the expression of PbGDPS was flower specific, and that maximal PbGDPS expression was concomitant with maximal emission of monoterpenes on day 5 post-anthesis. Homology modelling of PbGDPS indicated that the Glu-rich motif might provide a binding site for Mg(2+) and catalyze the formation of prenyl products in a similar way to SARM. Replacement of the key Glu residues with alanine totally abolished enzyme activity, whereas their mutation to Asp resulted in a mutant with two-thirds of the activity of the wild-type protein. Phylogenetic analysis indicated that plant GDPS proteins formed four clades: members of both GDPS-a and GDPS-b clades contain Asp-rich motifs, and function as homodimers. In contrast, proteins in the GDPS-c and GDPS-d clades do not contain Asp-rich motifs, but although members of the GDPS-c clade function as heterodimers, PbGDPS, which is more closely related to the GDPS-c clade proteins than to GDPS-a and GDPS-b proteins, and is currently the sole member of the GDPS-d clade, functions as a homodimer.

Examining relational empowerment for elementary school students in a yPAR program.

PubMed

Langhout, Regina Day; Collins, Charles; Ellison, Erin Rose

2014-06-01

This paper joins relational empowerment, youth empowerment, and Bridging Multiple Worlds frameworks to examine forms of relational empowerment for children in two intermediary institutions-school and a youth participatory action research after-school program (yPAR ASP). Participants were twelve children, most of whom were Latina/o and from im/migrant families, enrolled in a yPAR ASP for 2 years. A mixed-method approach was utilized; we analyzed children's interviews, self-defined goals, and their social networks to examine their experiences of relational empowerment. We conclude that children experienced each of the five relational empowerment factors-collaborative competence, bridging social divisions, facilitating others' empowerment, mobilizing networks, and passing on a legacy-in the yPAR ASP setting, and some factors in school. These experiences, however, were more pronounced in the yPAR ASP setting. Additionally, social network analyses revealed that a small but meaningful percentage of actors bridged worlds, especially home and family, but by year 2, also school and the yPAR ASP. Finally, most helpers for school-based goals came from school, but a sizable number came from family, friends, and home worlds, and by year 2, also came from the yPAR ASP. Implications range from theoretical to methodological development, including the use of social network analysis as a tool to descriptively examine relational power in context.

Antimicrobial stewardship program in a Malaysian district hospital: First year experience

PubMed Central

Sing, Diana Yap Fui; Boo, Yang Liang; Mukhlis, Roshalina; Chin, Pek Woon; Hoo, Fan Kee

2016-01-01

Backgrounds & Objective: Antimicrobial resistance is an alarming public health threat that requires urgent global solution. Implementation of antimicrobial stewardship program (ASP) is an essential practice element for healthcare institutions in gate-keeping judicious antimicrobial use. This study highlighted the development, first year experience, and result of the implementation of ASP utilizing persuasive and restrictive approaches in a Malaysian district hospital. Methods: An observational study was conducted between January 2015 to December 2015 on implementation of ASP among hospitalized inpatients age 12 years old and above. Results: Recommendations were provided for 60% of cases (110 patients) with the average acceptance rate of 83.33%. Majority of the interventions were to stop the antimicrobial therapy (30.3%), and the most common audited antimicrobials was Piperacillin/Tazobactam (25.5%), followed by Meropenem (11.82%), Amoxicillin/Clavulanate and Vancomycin (8.18%) respectively. The concordance rate towards authorization policy was increased in 2015 (71.59% of cases) as compared before the implementation of ASP in 2014 (60.6% of cases). Restrictive enforcement under ASP had been shown to improve significantly adherence rate towards antimicrobials authorization policy (p-value: 0.004). Conclusion: ASP was successfully implemented in a district hospital. Future studies on its clinical outcomes are important to evaluate its effectiveness as well as focus on the improvement to the pre-existing strategies and measures. PMID:27648056

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

PubMed

Nguyen-Ha, Phuong-Tan; Howrie, Denise; Crowley, Kelli; Vetterly, Carol G; McGhee, William; Berry, Donald; Ferguson, Elizabeth; Polischuk, Emily; Brooks, Maria Mori; Goff, Jeffrey; Stillwell, Terri; Darville, Toni; Thompson, Ann E; Levin, James E; Michaels, Marian G; Green, Michael

2016-05-01

Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants. Copyright © 2016 by the American Academy of Pediatrics.

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study

PubMed Central

2014-01-01

Background Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. Methods We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. Results A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14–0.92). Conclusions Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting. PMID:24884397

Association between adherence to an antimicrobial stewardship program and mortality among hospitalised cancer patients with febrile neutropaenia: a prospective cohort study.

PubMed

Rosa, Regis G; Goldani, Luciano Z; dos Santos, Rodrigo P

2014-05-23

Initial management of chemotherapy-induced febrile neutropaenia (FN) comprises empirical therapy with a broad-spectrum antimicrobial. Currently, there is sufficient evidence to indicate which antibiotic regimen should be administered initially. However, no randomized trial has evaluated whether adherence to an antimicrobial stewardship program (ASP) results in lower rates of mortality in this setting. The present study sought to assess the association between adherence to an ASP and mortality among hospitalised cancer patients with FN. We conducted a prospective cohort study in a single tertiary hospital from October 2009 to August 2011. All adult patients who were admitted to the haematology ward with cancer and FN were followed up for 28 days. ASP adherence to the initial antimicrobial prescription was determined. The mortality rates of patients who were treated with antibiotics according to the ASP protocol were compared with those of patients treated with other antibiotic regimens. The multivariate Cox proportional hazards model and propensity score were used to estimate 28-day mortality risk. A total of 307 FN episodes in 169 subjects were evaluated. The rate of adherence to the ASP was 53%. In a Cox regression analysis, adjusted for propensity scores and other potential confounding factors, ASP adherence was independently associated with lower mortality (hazard ratio, 0.36; 95% confidence interval, 0.14-0.92). Antimicrobial selection is important for the initial management of patients with FN, and adherence to the ASP, which calls for the rational use of antibiotics, was associated with lower mortality rates in this setting.

Incorporating pharmacy student activities into an antimicrobial stewardship program in a long-term acute care hospital.

PubMed

Benson, John M

2014-02-01

The impact on antimicrobial costs of an antimicrobial stewardship program (ASP) that integrated pharmacy students as integral members was evaluated. Demographic and discharge disposition data and antimicrobial acquisition cost data were retrospectively collected for all patients admitted to Promise Hospital of Salt Lake between June 1, 2009, and May 31, 2012. During this study, the primary role of pharmacy students in the ASP was to monitor all infection-related patient problems in the facility and meet daily with the infectious diseases pharmacist and clinical pharmacist to develop recommendations for optimizing antimicrobial use. The primary outcome measure was the mean antimicrobial acquisition cost per patient per day, calculated before ASP implementation (baseline period) and two years after ASP implementation (intervention period). The acquisition costs of antimicrobial agents per patient day were compared before and two years after implementation of the ASP involving pharmacy students. Statistical significance was determined using Student's t test for continuous data and the chi-square test for nominal data. The rate of patient discharge to skilled nursing facilities was significantly higher during the intervention period versus the baseline period (p = 0.016); no other significant comparisons were found. The mean ± S.D. antimicrobial costs per patient day were $75.37 ± $11.85 in the baseline period and $64.13 ± $13.78 in the intervention period (p = 0.022). This difference represents a cost savings of $261,630 during the two-year intervention period. Decreased antimicrobial costs were observed over a two-year period after implementation of an ASP that incorporated pharmacy students as integral members of the program.

Making healthy eating policy practice: A group randomized controlled trial on changes in snack quality, costs, and consumption in after school programs

PubMed Central

Beets, Michael W.; Weaver, R. Glenn; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S.; Freedman, Darcy; Hutto, Brent; Moore, Justin B.; Beighle, Aaron

2017-01-01

Purpose The aim of this study was to evaluate an intervention designed to assist after school programs (ASPs) in meeting snack nutrition policies that specify that a fruit or vegetable (FV) be served daily, and sugar-sweetened beverages/foods and artificially flavored foods eliminated. Design One-year group randomized controlled trial Setting Afterschool programs operating in South Carolina, US. Subjects Twenty ASPs serving over 1,700 children were recruited, match-paired post-baseline on enrollment size and days FV were served/week (days/wk), and randomized to either an intervention (n=10) or control (n=10) groups. Intervention Strategies To Enhance Practice for Healthy Eating (STEPs-HE), a multi-step adaptive intervention framework, which assists ASP leaders and staff to serve snacks that meet nutrition policies while maintaining cost. Measures Direct observation of snacks served and consumed, and monthly snack expenditures via receipts. Analysis Nonparametric and mixed-model repeated-measures Results By post-assessment, intervention ASPs increased serving FV to 3.9±2.1 vs. 0.7±1.7days/wk and decreased serving sugar-sweetened beverages to 0.1±0.7 vs. 1.8±2.4days/wk and foods to 0.3±1.1 vs. 2.7±2.5days/wk compared to controls, respectively. Cost of snacks increased by $0.02/snack in the intervention ASPs ($0.36 to $0.38) compared to a $0.01/snack decrease in the control ($0.39 to $0.38). Across both assessments and groups 80–100% of children consumed FV. Conclusions The STEPs-HE intervention can assist ASPs in meeting nationally endorsed nutrition policies with marginal increases in cost. PMID:26158679

Identifying Strategies Programs Adopt to Meet Healthy Eating and Physical Activity Standards in Afterschool Programs.

PubMed

Weaver, Robert G; Moore, Justin B; Turner-McGrievy, Brie; Saunders, Ruth; Beighle, Aaron; Khan, M Mahmud; Chandler, Jessica; Brazendale, Keith; Randell, Allison; Webster, Collin; Beets, Michael W

2017-08-01

The YMCA of USA has adopted Healthy Eating and Physical Activity (HEPA) Standards for its afterschool programs (ASPs). Little is known about strategies YMCA ASPs are implementing to achieve Standards and these strategies' effectiveness. (1) Identify strategies implemented in YMCA ASPs and (2) evaluate the relationship between strategy implementation and meeting Standards. HEPA was measured via accelerometer (moderate-to-vigorous-physical-activity [MVPA]) and direct observation (snacks served) in 20 ASPs. Strategies were identified and mapped onto a capacity building framework ( Strategies To Enhance Practice [STEPs]). Mixed-effects regression estimated increases in HEPA outcomes as implementation increased. Model-implied estimates were calculated for high (i.e., highest implementation score achieved), moderate (median implementation score across programs), and low (lowest implementation score achieved) implementation for both HEPA separately. Programs implemented a variety of strategies identified in STEPs. For every 1-point increase in implementation score 1.45% (95% confidence interval = 0.33% to 2.55%, p ≤ .001) more girls accumulated 30 min/day of MVPA and fruits and/or vegetables were served on 0.11 more days (95% confidence interval = 0.11-0.45, p ≤ .01). Relationships between implementation and other HEPA outcomes did not reach statistical significance. Still regression estimates indicated that desserts are served on 1.94 fewer days (i.e., 0.40 vs. 2.34) in the highest implementing program than the lowest implementing program and water is served 0.73 more days (i.e., 2.37 vs. 1.64). Adopting HEPA Standards at the national level does not lead to changes in routine practice in all programs. Practical strategies that programs could adopt to more fully comply with the HEPA Standards are identified.

Communicable Astronomy for IYA: Using the Networks of the Astronomical Society of the Pacific for Education and Outreach

NASA Astrophysics Data System (ADS)

Manning, J.; Gibbs, M.; Gurton, S.; Fraknoi, A.

2008-12-01

At the forefront of sharing the excitement of the exploration of the universe for 120 years, the Astronomical Society of the Pacific (ASP) is poised to use its networks and services to implement education and outreach programs for the 2009 International Year of Astronomy (IYA). The ASP is partnering with NASA, the International Astronomical Union (IAU), the American Astronomical Society (AAS) and other organizations on IYA projects, and is developing signature programs for implementation--with the overarching goal of employing its networks of scientists, educators and amateur astronomers in efforts to improve science education and science literacy. This presentation will describe the ASP's efforts to make astronomy and science "communicable" through these astronomy intermediaries--to reach the larger public, to link astronomy to other sciences, and to create legacy programs that will continue beyond 2009.

ASP Celebrates IYA, One Month at a Time

NASA Astrophysics Data System (ADS)

Gurton, S.; Berendsen, M.; Hurst, A.; White, V.

2008-11-01

Serving three major networks of educators, the ASP is working with NASA, NOAO, ASTC and others to build a comprehensive program to celebrate the International Year of Astronomy (IYA2009). By featuring a different astronomy theme during each month of 2009, we will provide a rich array of themed resources, such as demonstrations and activities, teleconferences, and news stories to the variety of educators served by the ASP. This poster will present our program of monthly themes, along with associated services and resources, to support the diverse public outreach efforts of the members of the NASA Night Sky Network, museum educators in Astronomy From the Ground Up, and teachers in grades K--12 including Project ASTRO National Network partners and subscribers to Universe in the Classroom.

Gallium metal affinity capture tandem mass spectrometry for the selective detection of phosphopeptides in complex mixtures

PubMed Central

Blacken, Grady R.; Sadílek, Martin; Tureček, František

2008-01-01

Metal affinity capture tandem mass spectrometry (MAC-MSMS) is evaluated in a comparative study of a lysine-derived nitrilotriacetic acid (Nα, Nα-bis-(carboxymethyl)lysine, LysNTA) and an aspartic-acid-related iminodiacetic acid (N-(4-aminobutyl)aspartic acid, AspIDA) as selective phosphopeptide detection reagents. Both LysNTA and AspIDA spontaneously form ternary complexes with GaIII and phosphorylated amino acids and phosphopeptides upon mixing in solution. Collision-induced dissociation of positive complex ions produced by electrospray produces common fragments (LysNTA + H)+ or (AspIDA + H)+ at m/z 263 and 205, respectively. MSMS precursor scans using these fragments as reporter ions allow one to selectively detect multiple charge states of phosphopeptides in mixtures. It follows from this comparative study that LysNTA is superior to AspIDA in detecting phosphopeptides, possibly because of the higher coordination number and greater stability constant for GaIII – phosphopeptide complexation of the former reagent. In a continuing development of MAC-MSMS for proteomics applications, we demonstrate its utility in a post-column reaction format. Using a simple post-column-reaction ‘T’ and syringe pump to deliver our chelating reagents, α-casein tryptic phosphopeptides can be selectively analyzed from a solution containing a twofold molar excess of bovine serum albumin. The MAC-MSMS method is shown to be superior to the commonly used neutral loss scan for the common loss of phosphoric acid. PMID:18265438

Simultaneous determination of methocarbamol and aspirin by RP-HPLC using fluorescence detection with time programming: its application to pharmaceutical dosage form.

PubMed

El-Din, M Sharaf; Eid, M; Zeid, A M

2013-01-01

A new simple, rapid and sensitive reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of methocarbamol (MET) and aspirin (ASP) in their combined dosage form. The separation of these compounds was achieved within 6.0 min on a CLC Shim-pack C8 column (250 × 4.6 mm, 5 µm particle size) using isocratic mobile phase consisting of acetonitrile and 0.02 M dihydrogenphosphate buffer (30:70, v/v) at pH = 5.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence detection at 277/313 nm for MET and 298/410 nm for ASP using real-time programming. The selectivity, linearity of calibration, accuracy, inter- and intra-day precision and recovery were examined as parts of the method validation. The concentration-response relationship was linear over concentration ranges of 0.02-0.20 and 0.02-0.40 µg/mL for MET and ASP, respectively, with a limit of detection of 6 and 32 ng/mL for MET and ASP, respectively. The proposed method was successfully applied for the analysis of both MET and ASP in prepared tablets with average recoveries of 99.88 ± 0.65% for MET and 100.44 ± 0.78% for ASP. The results were favourably compared to those obtained by a reference method. Copyright © 2012 John Wiley & Sons, Ltd.

Conditions for Effective Application of Analysis of Symmetrically-Predicted Endogenous Subgroups

ERIC Educational Resources Information Center

Peck, Laura R.

2015-01-01

Several analytic strategies exist for opening up the "black box" to reveal more about what drives policy and program impacts. This article focuses on one of these strategies: the Analysis of Symmetrically-Predicted Endogenous Subgroups (ASPES). ASPES uses exogenous baseline data to identify endogenously-defined subgroups, keeping the…

Multifunctional role of osteopontin in directing intrafibrillar mineralization of collagen and activation of osteoclasts

PubMed Central

Rodriguez, Douglas E.; Thula-Mata, Taili; Toro, Edgardo J.; Yeh, Ya-Wen; Holt, Carl; Holliday, L. Shannon; Gower, Laurie B.

2013-01-01

Mineralized collagen composites are of interest because they have the potential to provide a bone-like scaffold that stimulates the natural processes of resorption and remodeling. Working toward this goal, our group has previously shown that the nanostructure of bone can be reproduced using a polymer-induced liquid-precursor (PILP) process, which enables intrafibrillar mineralization of collagen with hydroxyapatite (HA) to be achieved. This prior work used polyaspartic acid (pASP), a simple mimic for acidic non-collagenous proteins (NCPs), to generate nanodroplets/nanoparticles of an amorphous mineral precursor which can infiltrate the interstices of type-I collagen fibrils. In this study we show that osteopontin (OPN) can similarly serve as a process-directing agent for the intrafibrillar mineralization of collagen, even though OPN is generally considered a mineralization inhibitor. We also found that inclusion of OPN in the mineralization process promotes the interaction of mouse marrow-derived osteoclasts with PILP-remineralized bone that was previously demineralized, as measured by actin ring formation. While osteoclast activation occurred when pASP was used as the process-directing agent, using OPN resulted in a dramatic effect on osteoclast activation, presumably because of the inherent arginine-glycine-aspartate acid (RGD) ligands of OPN. By capitalizing on the multifunctionality of OPN, these studies may lead the way to producing biomimetic bone substitutes with the capability of tailorable bioresorption rates. PMID:24140612

A conceptual model for training after-school program staffers to promote physical activity and nutrition.

PubMed

Weaver, Robert Glenn; Beets, Michael W; Webster, Collin; Beighle, Aaron; Huberty, Jennifer

2012-04-01

After-school programs (ASPs, 3 pm to 6 pm) have been called upon to increase the amount of daily physical activity children accumulate and improve the nutritional quality of the snacks served. To this end, state and national physical activity and nutrition (PAaN) policies have been proposed. Frontline staff who directly interact with children on a daily basis are charged with the responsibility to meet policy goals. Without appropriate skills, staffers' ability to achieve such goals is limited. The gap between policies and improvements in PAaN must be bridged through professional development training. This article describes the development of an ASP staff professional development training program. A systematic review was performed to identify relevant theoretical perspectives, empirical evidence, and recommended best practices relating to promoting PAaN of children. A comprehensive professional development framework was developed that incorporated the key elements identified from the review. These elements were distilled into 5 primary categories and conceptually referred to as the 5 Ms: mission-clearly defined policy/standards for PAaN; motivate-providing choices, developmentally appropriate activities, feedback, and encouragement; manage-structuring and managing the environment for safety, routines, and discipline; monitor-ongoing evaluation of PAaN; and maximize-incorporating all former Ms. The application of this training framework should lead to improved implementation and eventual achievement of policy goals for PAaN in ASPs. These competencies need to be developed in all ASPs if widespread improvements in PAaN within the ASP setting are to be realized. © 2012, American School Health Association.

The Daniel K. Inouye College of Pharmacy Scripts

PubMed Central

Goo, Roy Alan SH; Chu, Cherie HL; Yoneda, Melissa K; Ma, Carolyn SJ

2016-01-01

In recent years the misuse of antimicrobials has contributed to the growing problem of antimicrobial resistance. Antimicrobial Stewardship Programs (ASP) decrease the misuse of antimicrobials by supporting a rational, systematic approach. ASP strategies vary from broad-ranging policies and other decision support tools to prospective audit review of patients on antimicrobials. Many healthcare facilities, however, have been slow to adopt stewardship attributable to the fact that early ASP models required individuals with specialized training, and a significant amount of time and infrastructural investment from facilities. In response to the increasing need for ASPs in Hawai‘i, the Hawai‘i Department of Health (HDOH) partnered with the Daniel K. Inouye College of Pharmacy (DKICP) to develop the Hawai‘i Antimicrobial Stewardship Collaborative (HASC), a voluntary collaboration whose main objective is to assist hospital institutions in the implementation of a simplified model of the Centers for Disease Control and Prevention's Core Elements of Hospital Antimicrobial Stewardship Programs. The work of HASC places Hawai‘i's health care institutions in an advantageous position to be able to comply with impending accreditation standards relating to antibiotics and infections. PMID:27437167

ASP Programs and IYA

NASA Astrophysics Data System (ADS)

Manning, James G.

2009-01-01

At the forefront of sharing the excitement of the exploration of the universe for 120 years, the Astronomical Society of the Pacific is poised to use its networks and services to implement education and outreach programs for the 2009 International Year of Astronomy (IYA2009). The ASP is partnering with NASA, the AAS and other astronomy and education organizations on IYA2009 projects, and is developing signature programs for implementation-with the overarching goal of bringing together scientists, educators and amateur astronomers in efforts to improve science education and science literacy through astronomy. The presentation will outline five major thrusts designed to serve the amateur astronomy community, formal educators, informal educators, the online community, and these communities in combination through IYA-related professional development, resources, and the facilitation of connections. The use of the proceedings of the IYA2009 Symposium in St. Louis in June, 2008 as an IYA2009 resource will be mentioned, and the ASP will encourage partners to work with the Society to help reach mutual goals and objectives for IYA2009 and beyond.

Canavan disease. Analysis of the nature of the metabolic lesions responsible for development of the observed clinical symptoms.

PubMed

Baslow, M H; Resnik, T R

1997-10-01

Canavan disease (CD), a rare recessive autosomal genetic disorder, is characterized by early onset and a progressive spongy degeneration of the brain involving loss of the axon's myelin sheath. After a relatively normal birth, homozygous individuals generally develop clinical symptoms within months, and usually die within several years of the onset of the disease. A biochemical defect associated with this disease results in reduced activity of the enzyme N-acetyl-L-aspartate amidohydrolase (aspartoacylase) and affected individuals have less ability to hydrolyze N-acetyl-L-asparate (NAA) in brain and other tissues. As a result of aspartoacylase deficiency, NAA builds up in extracellular fluids (ECF) and is excreted in urine. From an analysis of the NAA biochemical cycle in various tissues of many vertebrate species, evidence is presented that there may be two distinct NAA circulation patterns related to aspartoacylase activity. These include near-field circulations in the brain and the eye, and a far-field systemic circulation involving the liver and kidney, the purpose of which in each case is apparently to regenerate aspartate (Asp) in order for it to be recycled into NAA as part of the still unknown function of the NAA cycle. Based on the authors' analysis, they have also identified several metabolic outcomes of the genetic biochemical aspartoacylase lesion. First, there is a daily induced Asp deficit in the central nervous system (CNS) that is at least six times the static level of available free Asp. Second, there is up to a 50-fold drop in the intercompartmental NAA gradient, and third, the ability of the brain to perform its normal intercompartmental cycling of NAA to Asp is terminated, and as a result, the only remaining long-term source of Asp for NAA synthesis is via nutritional supplementation of Asp or its metabolic precursors. Finally, the authors identify a potential maternal-fetal interaction that may be responsible for observed normal fetal development in utero, and that provides a rationale for, and suggests how, CD might respond to far-field nutritional, transplantation, or genetic engineering techniques to alter the course of the disease.

Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention.

PubMed

Pollack, Loria A; Srinivasan, Arjun

2014-10-15

The proven benefits of antibiotic stewardship programs (ASPs) for optimizing antibiotic use and minimizing adverse events, such as Clostridium difficile and antibiotic resistance, have prompted the Centers for Disease Control and Prevention (CDC) to recommend that all hospitals have an ASP. This article summarizes Core Elements of Hospital Antibiotic Stewardship Programs, a recently released CDC document focused on defining the infrastructure and practices of coordinated multidisciplinary programs to improve antibiotic use and patient care in US hospitals. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Metrics for the NASA Airspace Systems Program

NASA Technical Reports Server (NTRS)

Smith, Jeremy C.; Neitzke, Kurt W.

2009-01-01

This document defines an initial set of metrics for use by the NASA Airspace Systems Program (ASP). ASP consists of the NextGen-Airspace Project and the NextGen-Airportal Project. The work in each project is organized along multiple, discipline-level Research Focus Areas (RFAs). Each RFA is developing future concept elements in support of the Next Generation Air Transportation System (NextGen), as defined by the Joint Planning and Development Office (JPDO). In addition, a single, system-level RFA is responsible for integrating concept elements across RFAs in both projects and for assessing system-wide benefits. The primary purpose of this document is to define a common set of metrics for measuring National Airspace System (NAS) performance before and after the introduction of ASP-developed concepts for NextGen as the system handles increasing traffic. The metrics are directly traceable to NextGen goals and objectives as defined by the JPDO and hence will be used to measure the progress of ASP research toward reaching those goals. The scope of this document is focused on defining a common set of metrics for measuring NAS capacity, efficiency, robustness, and safety at the system-level and at the RFA-level. Use of common metrics will focus ASP research toward achieving system-level performance goals and objectives and enable the discipline-level RFAs to evaluate the impact of their concepts at the system level.

Effects of Daily Physical Education on Physical Fitness and Weight Status in Middle School Adolescents

ERIC Educational Resources Information Center

Erfle, Stephen E.; Gamble, Abigail

2014-01-01

Background: In 2009, the Pennsylvania Department of Health developed the Active Schools Program (ASP) which required 30?minutes of daily physical education (PE) in middle schools to reduce childhood obesity. This investigation evaluated the ASP effects on physical fitness and weight status in middle school adolescents throughout 1 academic year.…

Antimicrobial Stewardship Programs: Appropriate Measures and Metrics to Study their Impact.

PubMed

Morris, Andrew M

Antimicrobial stewardship is a new field that struggles to find the right balance between meaningful and useful metrics to study the impact of antimicrobial stewardship programs (ASPs). ASP metrics primarily measure antimicrobial use, although microbiological resistance and clinical outcomes are also important measures of the impact an ASP has on a hospital and its patient population. Antimicrobial measures looking at consumption are the most commonly used measures, and are focused on defined daily doses, days of therapy, and costs, usually standardized per 1,000 patient-days. Each measure provides slightly different information, with their own upsides and downfalls. Point prevalence measurement of antimicrobial use is an increasingly used approach to understanding consumption that does not entirely rely on sophisticated electronic information systems, and is also replicable. Appropriateness measures hold appeal and promise, but have not been developed to the degree that makes them useful and widely applicable. The primary reason why antimicrobial stewardship is necessary is the growth of antimicrobial resistance. Accordingly, antimicrobial resistance is an important metric of the impact of an ASP. The most common approach to measuring resistance for ASP purposes is to report rates of common or important community- or nosocomial-acquired antimicrobial-resistant organisms, such as methicillin-resistant Staphylococcus aureus and Clostridium difficile. Such an approach is dependent on detection methods, community rates of resistance, and co-interventions, and therefore may not be the most accurate or reflective measure of antimicrobial stewardship interventions. Development of an index to reflect the net burden of resistance holds theoretical promise, but has yet to be realized. Finally, programs must consider patient outcome measures. Mortality is the most objective and reliable method, but has several drawbacks. Disease- or organism-specific mortality, or cure, are increasingly used metrics.

Physical and Social-Motivational Contextual Correlates of Youth Physical Activity in Underresourced Afterschool Programs.

PubMed

Zarrett, Nicole; Sorensen, Carl; Cook, Brittany Skiles

2015-08-01

Afterschool programs (ASPs) have become increasingly recognized as a key context to support youth daily physical activity (PA) accrual. The purpose of the present study was to assess the physical and social-motivational climate characteristics of ASPs associated with youth PA, and variations in contextual correlates of PA by youth sex. Systematic observations of 7 ASPs serving underserved youth (minority, low income) was conducted using the System for Observing Play and Leisure Activity in Youth and a social-motivational climate observation tool founded on self-determination theory. For five program days at each site, teams of two coders conducted continuous observations of youth PA (sedentary, moderate, vigorous), five physical features (e.g., equipment availability), eight staff interactions (e.g., encourage PA), and seven motivational climate components (e.g., inclusive). Aligned with previous research, regressions controlling for variations by site indicated that organized PA, provision of portable equipment, and staff PA participation and supervision are key correlates of youth PA. Moreover, as the first study to systematically observe motivational-context characteristics of ASPs, we identified several key modifiable motivational features that are necessary to address in order to increase youth engagement in PA during the out-of-school hours. Among motivational features assessed, "relatedness" components (positive peer relations, inclusive/cooperative activities) were primary correlates of girls' PA. In contrast, all three motivational features specified by self-determination theory (support for autonomy, mastery/competence, and inclusion/relatedness) were correlated with boys' PA. Findings are discussed in terms of policy and practice for understanding strengths and needs of ASPs to effectively engage youth in PA. © 2015 Society for Public Health Education.

Framework for the design and delivery of organized physical activity sessions for children and adolescents: rationale and description of the 'SAAFE' teaching principles.

PubMed

Lubans, David R; Lonsdale, Chris; Cohen, Kristen; Eather, Narelle; Beauchamp, Mark R; Morgan, Philip J; Sylvester, Benjamin D; Smith, Jordan J

2017-02-23

The economic burden of inactivity is substantial, with conservative estimates suggesting the global cost to health care systems is more than US$50 billion. School-based programs, including physical education and school sport, have been recommended as important components of a multi-sector, multi-system approach to address physical inactivity. Additionally, community sporting clubs and after-school programs (ASPs) offer further opportunities for young people to be physically active outside of school. Despite demonstrating promise, current evidence suggests school-based physical activity programs, community sporting clubs and ASPs are not achieving their full potential. For example, physical activity levels in physical education (PE) and ASP sessions are typically much lower than recommended. For these sessions to have the strongest effects on young people's physical activity levels and their on-going physical literacy, they need to improve in quality and should be highly active and engaging. This paper presents the Supportive, Active, Autonomous, Fair, Enjoyable (SAAFE) principles, which represent an evidence-based framework designed to guide the planning, delivery and evaluation of organized physical activity sessions in school, community sport and ASPs. In this paper we provide a narrative and integrative review of the conceptual and empirical bases that underpin this framework and highlight implications for knowledge translation and application.

Making Healthy Eating Policy Practice: A Group Randomized Controlled Trial on Changes in Snack Quality, Costs, and Consumption in After-School Programs.

PubMed

Beets, Michael W; Weaver, R Glenn; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Ward, Dianne S; Freedman, Darcy; Hutto, Brent; Moore, Justin B; Beighle, Aaron

2016-09-01

The aim of this study was to evaluate an intervention designed to assist after-school programs (ASPs) in meeting snack nutrition policies that specify that a fruit or vegetable be served daily and sugar-sweetened beverages/foods and artificially flavored foods eliminated. The study used a 1-year group-randomized controlled trial. The study took place in ASPs operating in South Carolina, United States. Twenty ASPs serving over 1700 children were recruited, match-paired postbaseline on enrollment size and days fruits/vegetables were served per week, and randomized to either intervention (n = 10) or control (n = 10) groups. The study used Strategies To Enhance Practice for Healthy Eating (STEPs-HE), a multistep adaptive intervention framework that assists ASP leaders and staff to serve snacks that meet nutrition policies while maintaining cost. Direct observation of snacks served and consumed and monthly snack expenditures as determined by receipts were used. The study used nonparametric and mixed-model repeated measures. By postassessment, intervention ASPs increased serving of fruits/vegetables to 3.9 ± 2.1 vs. 0.7 ± 1.7 d/wk and decreased serving sugar-sweetened beverages to 0.1 ± 0.7 vs. 1.8 ± 2.4 d/wk and sugar-sweetened foods to 0.3 ± 1.1 vs. 2.7 ± 2.5 d/wk compared to controls, respectively. Cost of snacks increased by $0.02/snack in the intervention ASPs ($0.36 to $0.38) compared to a $0.01 per snack decrease in the control group ($0.39 to $0.38). Across both assessments and groups, 80% to 100% of children consumed FVs. The STEPs-HE intervention can assist ASPs in meeting nationally endorsed nutrition policies with marginal increases in cost. © 2016 by American Journal of Health Promotion, Inc.

Dramatic effects of a new antimicrobial stewardship program in a rural community hospital.

PubMed

Libertin, Claudia R; Watson, Stephanie H; Tillett, William L; Peterson, Joy H

2017-09-01

New Joint Commission antimicrobial stewardship requirements took effect on January 1, 2017, promoted as a central strategy for coping with the emerging problems of antimicrobial resistance and Clostridium difficile infection. Our objective was to measure the effects of a new antimicrobial stewardship program (ASP) in a rural community hospital with no prior ASP, in the context of having a new infectious disease specialist on staff. An ASP team was formed to implement a prospective audit with health care provider feedback and targeting 12 antimicrobial agents in a rural hospital in Georgia. An educational grand rounds lecture series was provided before implementation of the ASP to all prescribers. After implementation, algorithms to aid the selection of empirical antibiotics for specific infectious disease syndromes based on local antibiograms were provided to prescribers to improve this selection. Rates of C difficile infections, total targeted antimicrobial costs, and drug utilization rates were calculated for 1 year pre-ASP implementation (2013) and 1 year post-ASP implementation (October 2014-December 2015). The patient safety metric of C difficile infections decreased from 3.35 cases per 1,000 occupied bed days (OBDs) in 2013 to 1.35 cases per 1,000 OBDs in 2015. Total targeted antimicrobial costs decreased 50% from $16.93 per patient day in 2013 to $8.44 per patient day in 2015. Overall antimicrobial use decreased 10% from before the ASP initiative to 1 year after it. Annualized savings were $280,000 in 1 year, based on drug savings only. Judicious use of antimicrobials and resources can improve a patient safety metric and decrease costs dramatically in rural institutions where the average hospital census is <100 patients per day. The savings would allow the institutions to spend better while improving the use of antimicrobials. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

The volitional inhibition of anticipatory ocular pursuit using a stop signal.

PubMed

Jarrett, Christian Beresford; Barnes, Graham R

2003-10-01

Unlike limb movements, smooth pursuit eye movements cannot normally be performed in the absence of a target. However, when subjects have a high expectancy of an imminent target appearance, the situation changes, and anticipatory smooth pursuit (ASP) tends to precede target onset by several hundred milliseconds. The velocity of this ASP is scaled predictively according to expected target velocity. And when an upcoming target is unexpectedly altered, or fails to appear, ASP continues regardless for approximately 150-200 ms before modification by visual feedback begins [J. Neurophysiol., 84 (2000) 2340]. These and other observations led to the earlier suggestion that ASP might be ballistic, being pre-programmed from start to finish. Two experiments with different timing parameters were therefore performed to test this hypothesis using a version of Logan's [Psychol. Rev., 91 (1984) 295] stop signal task. The aim was to test whether ASP could be stopped at will, and if so, whether the time taken to stop varied as a function of the time since ASP onset. Results showed that in response to a stop signal, ASP can be inhibited at any point in its trajectory, and for the majority of subjects in experiment 1, and all the subjects in experiment 2, with a latency that does not change significantly with target speed or time since ASP onset. These results provide the first demonstration that anticipatory movements can be stopped volitionally in response to a stop signal. Possible cognitive and neurophysiological mechanisms underlying this process are discussed.

Two types of amorphous protein particles facilitate crystal nucleation.

PubMed

Yamazaki, Tomoya; Kimura, Yuki; Vekilov, Peter G; Furukawa, Erika; Shirai, Manabu; Matsumoto, Hiroaki; Van Driessche, Alexander E S; Tsukamoto, Katsuo

2017-02-28

Nucleation, the primary step in crystallization, dictates the number of crystals, the distribution of their sizes, the polymorph selection, and other crucial properties of the crystal population. We used time-resolved liquid-cell transmission electron microscopy (TEM) to perform an in situ examination of the nucleation of lysozyme crystals. Our TEM images revealed that mesoscopic clusters, which are similar to those previously assumed to consist of a dense liquid and serve as nucleation precursors, are actually amorphous solid particles (ASPs) and act only as heterogeneous nucleation sites. Crystalline phases never form inside them. We demonstrate that a crystal appears within a noncrystalline particle assembling lysozyme on an ASP or a container wall, highlighting the role of heterogeneous nucleation. These findings represent a significant departure from the existing formulation of the two-step nucleation mechanism while reaffirming the role of noncrystalline particles. The insights gained may have significant implications in areas that rely on the production of protein crystals, such as structural biology, pharmacy, and biophysics, and for the fundamental understanding of crystallization mechanisms.

42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...

42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...

42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Submission of...

42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Submission of...

42 CFR 414.806 - Penalties associated with the failure to submit timely and accurate ASP data.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Penalties associated with the failure to submit timely and accurate ASP data. 414.806 Section 414.806 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES...

Connecting NASA Airborne Scientists, Engineers, and Pilots to K-12 Classrooms

NASA Astrophysics Data System (ADS)

Schaller, E. L.

2015-12-01

The NASA Airborne Science Program (ASP) conducts Earth system science research missions with NASA aircraft all over the world. During ASP missions, NASA scientists, engineers and pilots are deployed to remote parts of the world such as Greenland, Antarctica, Chile, and Guam. These ASP mission personnel often have a strong desire to share the excitement of their mission with local classrooms near their deployment locations as well as classrooms back home in the United States. Here we discuss ongoing efforts to connect NASA scientists, engineers and pilots in the field directly with K-12 classrooms through both in-person interactions and remotely via live web-based chats.

Social media as a tool for antimicrobial stewardship.

PubMed

Pisano, Jennifer; Pettit, Natasha; Bartlett, Allison; Bhagat, Palak; Han, Zhe; Liao, Chuanhong; Landon, Emily

2016-11-01

To increase the reach of our antimicrobial stewardship program (ASP), social media platforms, Facebook and Twitter, were used to increase internal medicine residents' (IMRs') antibiotic (Abx) knowledge and awareness of ASP resources. Fifty-five of 110 (50%) IMRs consented to participate; 39 (71%) completed both pre- and postintervention surveys and followed our ASP on social media. Along with 20 basic Abx and infectious diseases (IDs) questions, this survey assessed IMR awareness of ASP initiatives, social media usage, and attitudes and beliefs surrounding Abx resistance. Over 6 months, IMRs received posts and Tweets of basic Abx/IDs trivia while promoting use of educational tools and clinical pathways on our ASP Web site. To compare pre- and postsurvey responses, McNemar test or Stuart-Maxwell test was used for categorical variables, and paired t test or Wilcoxon signed-rank test was used for continuous variables, as appropriate. Of the IMRs, 98% and 58% use Facebook and Twitter, respectively. To compare pre- and postintervention, median scores for Abx knowledge increased from 12 (interquartile range, 8-13) to 13 (interquartile range, 11-15; P = .048); IMRs knowing how to access the ASP Web site increased from 70% to 94%. More IMRs indicated that they used the clinical pathways "sometimes, frequently, or always" after the intervention (33% vs 61%, P = .004). Social media is a valuable tool to reinforce ASP initiatives while encouraging the use of ASP resources to promote antimicrobial mindfulness. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Intercomparison of SOUP, ASP, LPSP, and MDI magnetograms

NASA Astrophysics Data System (ADS)

Berger, T.; Lites, B.; Martinez-Pillet, V.; Tarbell, T.; Title, A.

2001-05-01

We compare simultaneous magnetograms of a solar active region taken by the Advanced Stokes Polarimeter (ASP) and the Solar Optical Universal Polimeter (SOUP) in 1998. In addition we compare magnetograms taken by the La Palma Stokes Polarimeter (LPSP), the Michelson Doppler Imager (MDI) on SOHO, and the SOUP instrument in 2000. The SOUP instrument on the Swedish Vacuum Solar Telescope (SVST) attains the highest spatial resolution but has the least understood calibration; the ASP on the Dunn Solar Telescope (DST) at Sacramento Peak attains the highest magnetic field precision. The goal of the program is to better quantify the SOUP magnetograms and thereby study magnetic element dynamics in the photosphere with higher precision.

Physical activity opportunities in afterschool programs.

PubMed

Weaver, R Glenn; Beets, Michael W; Huberty, Jennifer; Freedman, Darcy; Turner-Mcgrievy, Gabrielle; Ward, Diane

2015-05-01

Afterschool programs (ASPs) have potential to provide children moderate to vigorous physical activity (MVPA). The availability and types (e.g., free play or organized activities) of physical activity opportunities, their structure (e.g., presence of lines, elimination games), and staff behaviors (e.g., encouragement, engaged) can influence children's MVPA. This study explored these factors in 20 ASPs serving over 1,700 elementary-age children. The occurrence, types, and structure of physical activity opportunities, and staff behaviors were collected via the SOSPAN (System for Observing Staff Promotion of Physical Activity and Nutrition). A total of 4,660 SOSPAN scans were completed across 63 complete program days (1,733 during physical activity opportunities). Physical activity opportunities were observed on 60 program days across all 20 sites, with 73% of those opportunities classified as free play. ASPs scheduled an average of 66.3 minutes (range 15-150 minutes) of physical activity opportunities daily. Games played included basketball, tag, soccer, and football. Staff rarely engaged in physical activity promotion behaviors, and the structure of organized games discouraged MVPA. For example, staff verbally promoted physical activity in just 6.1% of scans, while organized games were more likely to involve lines and elimination. Professional development training may enhance staffs' physical activity promotion and the structure of activity opportunities. © 2015 Society for Public Health Education.

Physical activity opportunities in afterschool programs

PubMed Central

Weaver, R. Glenn; Beets, Michael W.; Huberty, Jennifer; Freedman, Darcy; Turner-Mcgrievy, Gabrielle; Ward, Diane

2015-01-01

Afterschool programs (ASPs) have potential to provide children moderate-to-vigorous physical activity (MVPA). The availability and types (e.g., free play or organized activities) of physical activity opportunities, their structure (e.g., presence of lines, elimination games), and staff behaviors (e.g., encouragement, engaged) can influence children’s MVPA. This study explored these factors in 20 ASPs serving over 1,700 elementary-age children. The occurrence, types and structure of physical activity opportunities, and staff behaviors were collected via the System for Observing Staff Promotion of Physical Activity and Nutrition (SOSPAN). A total of 4,660 SOSPAN scans were completed across 63 complete program days (1733 during physical activity opportunities). Physical activity opportunities were observed on 60 program days across all 20 sites, with 73% of those opportunities classified as free play. ASPs scheduled an average of 66.3 minutes (range 15-150min) of physical activity opportunities daily. Games played included basketball, tag, soccer and football. Staff rarely engaged in physical activity promotion behaviors, and the structure of organized games discouraged MVPA. For example, staff verbally promoted physical activity in just 6.1% of scans, while organized games were more likely to involve lines and elimination. Professional development training may enhance staffs’ physical activity promotion and the structure of activity opportunities. PMID:25586132

Antimicrobial Stewardship in Inpatient Settings in the Asia Pacific Region: A Systematic Review and Meta-analysis.

PubMed

Honda, Hitoshi; Ohmagari, Norio; Tokuda, Yasuharu; Mattar, Caline; Warren, David K

2017-05-15

An antimicrobial stewardship program (ASP) is one of the core elements needed to optimize antimicrobial use. Although collaboration at the national level to address the importance of ASPs and antimicrobial resistance has occurred in the Asia Pacific region, hospital-level ASP implementation in this region has not been comprehensively evaluated. We conducted a systematic review and meta-analysis to assess the efficacy of ASPs in inpatient settings in the Asia Pacific region from January 2005 through March 2016. The impact of ASPs on various outcomes, including patient clinical outcomes, antimicrobial prescription outcomes, microbiological outcomes, and expenditure were assessed. Forty-six studies were included for a systematic review and meta-analysis. The pooled risk ratio for mortality from ASP before-after trials and 2-group comparative studies were 1.03 (95% confidence interval [CI], .88-1.19) and 0.69 (95% CI, .56-.86), respectively. The pooled effect size for change in overall antimicrobial and carbapenem consumption (% difference) was -9.74% (95% CI, -18.93% to -.99%) and -10.56% (95% CI, -19.99% to -3.03%), respectively. Trends toward decreases in the incidence of multidrug-resistant organisms and antimicrobial expenditure (range, 9.7%-58.1% reduction in cost in the intervention period/arm) were also observed. ASPs in inpatient settings in the Asia Pacific region appear to be safe and effective to reduce antimicrobial consumption and improve outcomes. However, given the significant variations in assessing the efficacy of ASPs, high-quality studies using standardized surveillance methodology for antimicrobial consumption and similar metrics for outcome measurement are needed to further promote antimicrobial stewardship in this region. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation.

PubMed

Steinhardt, Alberto Penas; Aranguren, Florencia; Tellechea, Mariana L; Gómez Rosso, Leonardo A; Brites, Fernando D; Martínez-Larrad, Maria T; Serrano-Ríos, Manuel; Frechtel, Gustavo D; Taverna, Mariano J

2010-05-01

Toll-like receptor 4 (TLR4) plays a key role in the activation of innate immune responses. Loss-of-function mutations in TLR4 prevent diet-induced obesity and insulin resistance (IR). We conducted a population cross-sectional study to evaluate whether Asp299Gly (rs4986790) TLR4 gene polymorphism is associated with metabolic syndrome (MS), surrogates of IR, and syndromes of lipid accumulation (SLAs) in Argentinean healthy male subjects. rs4986790 was genotyped in 621 healthy unrelated male blood donors. National Cholesterol Education Program/Adult Treatment Panel III-MS (NCEP/ATP III-MS); SLAs such as enlarged waist elevated triglyceride syndrome (EWET), hypertriglyceridemic waist (HW), and overweight-lipid syndrome (OLS); and surrogates of IR were assessed. The prevalence of MS, OLS, and EWET was significantly higher among Asp299Asp carriers (P < .05). These findings were confirmed using 32 000 bootstrap samples. Surrogate markers of IR were also significantly higher in Asp299Asp carriers (P < .05). Most findings were especially strengthened among individuals with C-reactive protein below the 95th percentile and/or total cholesterol to high-density lipoprotein cholesterol ratio >or=5. This is the first report to find, in Argentinean healthy male blood donors, associations between the Asp299Asp genotype of rs4986790 TLR4 gene polymorphism and high risk for NCEP/ATP III-MS, SLAs, and surrogates of IR. These findings are consistent with previous functional and observational studies showing that Asp299 allele, in comparison with Gly299, is associated with increased TLR4 activation, higher levels of inflammatory cytokines, acute-phase reactants and soluble adhesion molecules, and higher risk of atherosclerosis.

NOS3 Glu298Asp genotype and blood pressure response to endurance training: the HERITAGE family study.

PubMed

Rankinen, T; Rice, T; Pérusse, L; Chagnon, Y C; Gagnon, J; Leon, A S; Skinner, J S; Wilmore, J H; Rao, D C; Bouchard, C

2000-11-01

Endothelium-dependent vasodilation is a mechanism that may affect blood pressure response to endurance training. Because NO plays a central role in this process, the endothelial NO synthase gene is a good candidate for the regulation of exercise blood pressure. We investigated the associations between an endothelial NO synthase gene polymorphism (Glu298Asp) and endurance training-induced changes in resting and submaximal exercise blood pressure in 471 white subjects of the HERITAGE Family Study. Two submaximal exercise tests at 50 W were conducted both before and after a 20-week endurance training program. Steady-state exercise blood pressure was measured twice in each test with an automated unit. The Glu298Asp polymorphism was typed with a PCR-based method and digestion with BAN:II. Both systolic and diastolic blood pressure at 50 W decreased in response to the training program, whereas resting blood pressure remained unchanged. The decrease in diastolic blood pressure at 50 W was greater (P=0.0005, adjusted for age, gender, baseline body mass index, and baseline diastolic blood pressure at 50 W) in the Glu/Glu homozygotes (4.4 [SEM 0.4] mm Hg, n=187) than in the heterozygotes (3.1 [0.4] mm Hg, n=213) and the Asp/Asp homozygotes (1.3 [0.7] mm Hg, n=71). The genotype accounted for 2.3% of the variance in diastolic blood pressure at 50 W training response. Both the Glu298 homozygotes and the heterozygotes had a greater (P=0.013) training-induced reduction in rate-pressure product at 50 W than the Asp298 homozygotes. These data suggest that DNA sequence variation in the endothelial NO synthase gene locus is associated with the endurance training-induced decreases in submaximal exercise diastolic blood pressure and rate-pressure product in sedentary normotensive white subjects.

The O/OREOS Mission - Astrobiology in Low Earth Orbit. [Astrobiology in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Ehrenfreund, P.; Ricco, A. J.; Squires, D.; Kitts, C.; Agasid, E.; Bramall, N.; Bryson, K.; Chittenden, J.; Conley, C.; Cook, A.;

The O/OREOS mission—Astrobiology in low Earth orbit

NASA Astrophysics Data System (ADS)

Ehrenfreund, P.; Ricco, A. J.; Squires, D.; Kitts, C.; Agasid, E.; Bramall, N.; Bryson, K.; Chittenden, J.; Conley, C.; Cook, A.; Mancinelli, R.; Mattioda, A.; Nicholson, W.; Quinn, R.; Santos, O.; Tahu, G.; Voytek, M.; Beasley, C.; Bica, L.; Diaz-Aguado, M.; Friedericks, C.; Henschke, M.; Landis, D.; Luzzi, E.; Ly, D.; Mai, N.; Minelli, G.; McIntyre, M.; Neumann, M.; Parra, M.; Piccini, M.; Rasay, R.; Ricks, R.; Schooley, A.; Stackpole, E.; Timucin, L.; Yost, B.; Young, A.

2014-01-01

The O/OREOS (Organism/Organic Exposure to Orbital Stresses) nanosatellite is the first science demonstration spacecraft and flight mission of the NASA Astrobiology Small-Payloads Program (ASP). O/OREOS was launched successfully on November 19, 2010, to a high-inclination (72°), 650-km Earth orbit aboard a US Air Force Minotaur IV rocket from Kodiak, Alaska. O/OREOS consists of 3 conjoined cubesat (each 1000 cm3) modules: (i) a control bus; (ii) the Space Environment Survivability of Living Organisms (SESLO) experiment; and (iii) the Space Environment Viability of Organics (SEVO) experiment. Among the innovative aspects of the O/OREOS mission are a real-time analysis of the photostability of organics and biomarkers and the collection of data on the survival and metabolic activity for microorganisms at 3 times during the 6-month mission. We report on the spacecraft characteristics, payload capabilities, and present operational phase and flight data from the O/OREOS mission. The science and technology rationale of O/OREOS supports NASA's scientific exploration program by investigating the local space environment as well as space biology relevant to Moon and Mars missions. It also serves as a precursor for experiments on small satellites, the International Space Station (ISS), future free-flyers and lunar surface exposure facilities.

Characteristics of Antimicrobial Stewardship Programs at Veterans Affairs Hospitals: Results of a Nationwide Survey.

PubMed

Chou, Ann F; Graber, Christopher J; Jones, Makoto; Zhang, Yue; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew; Kelly, Allison; Glassman, Peter A

2016-06-01

BACKGROUND Antimicrobial stewardship programs (ASPs) are variably implemented. OBJECTIVE To characterize variations of antimicrobial stewardship structure and practices across all inpatient Veterans Affairs facilities in 2012 and correlate key characteristics with antimicrobial usage. DESIGN A web-based survey regarding stewardship activities was administered to each facility's designated contact. Bivariate associations between facility characteristics and inpatient antimicrobial use during 2012 were determined. SETTING Total of 130 Veterans Affairs facilities with inpatient services. RESULTS Of 130 responding facilities, 29 (22%) had a formal policy establishing an ASP, and 12 (9%) had an approved ASP business plan. Antimicrobial stewardship teams were present in 49 facilities (38%); 34 teams included a clinical pharmacist with formal infectious diseases (ID) training. Stewardship activities varied across facilities, including development of yearly antibiograms (122 [94%]), formulary restrictions (120 [92%]), stop orders for antimicrobial duration (98 [75%]), and written clinical pathways for specific conditions (96 [74%]). Decreased antimicrobial usage was associated with having at least 1 full-time ID physician (P=.03), an ID fellowship program (P=.003), and a clinical pharmacist with formal ID training (P=.006) as well as frequency of systematic patient-level reviews of antimicrobial use (P=.01) and having a policy to address antimicrobial use in the context of Clostridium difficile infection (P=.01). Stop orders for antimicrobial duration were associated with increased use (P=.03). CONCLUSIONS ASP-related activities varied considerably. Decreased antibiotic use appeared related to ID presence and certain select practices. Further statistical assessments may help optimize antimicrobial practices. Infect Control Hosp Epidemiol 2016;37:647-654.

An increase level of acylation stimulating protein is correlated with metabolic risk markers in North Indian obese women.

PubMed

Mishra, Supriya; Gupta, Vani; Mishra, Sameeksha; Gupta, Vandana; Mahdi, Abbas Ali; Sachan, Rekha

2017-12-01

The present study was to investigate the association between serum acylation stimulating protein (ASP) level with metabolic risk factors in North Indian obese women. This is a case control study, total n=322 women aged between 20 and 45 years (n=162 with metabolic syndrome & n=160 without metabolic syndrome) were recruited for the study according to National Cholesterol Education Program Treatment Panel (NCEPATP) guidelines. Serum ASP level were determined by enzyme linked immunosorbent assay. Results indicated that circulating ASP and other metabolic risk factors (waist circumference, triglycerides, fasting plasma glucose etc) were significantly higher in women with metabolic syndrome (WmetS) than in women without syndrome (WometS) (p<0.001). Furthermore circulating ASP was significantly higher possitively correlated with waist circumference (r=0.51, p<0.001), triglyceride (r=0.56, p<0.001), glucose (r=0.70, p<0.001), and negatively correlated with high density lipoprotein(r=-0.56, p<0.001) in women with metabolic syndrome. Conclusively circulating ASP was found to be significantly associated with hyperlipidemia, obesity and obesity related disorders in North Indian obese women. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

76 FR 21325 - Notice of Funds Availability: Inviting Applications for the Market Access Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... for the 2012 Market Access Program (MAP). The intended effect of this notice is to solicit... INFORMATION CONTACT: Entities wishing to apply for funding assistance should contact the Program Operations....gov/mos/programs/map.asp . SUPPLEMENTARY INFORMATION: I. Funding Opportunity Description Authority...

Direct assessment of the metabolic origin of carbon atoms in glutamate from illuminated leaves using 13 C-NMR.

PubMed

Abadie, Cyril; Lothier, Jérémy; Boex-Fontvieille, Edouard; Carroll, Adam; Tcherkez, Guillaume

2017-12-01

Glutamate (Glu) is the cornerstone of nitrogen assimilation and photorespiration in illuminated leaves. Despite this crucial role, our knowledge of the flux to Glu de novo synthesis is rather limited. Here, we used isotopic labelling with 13 CO 2 and 13 C-NMR analyses to examine the labelling pattern and the appearance of multi-labelled species of Glu molecules to trace the origin of C-atoms found in Glu. We also compared this with 13 C-labelling patterns in Ala and Asp, which reflect citrate (and thus Glu) precursors, that is, pyruvate and oxaloacetate. Glu appeared to be less 13 C-labelled than Asp and Ala, showing that the Glu pool was mostly formed by 'old' carbon atoms. There were modest differences in intramolecular 13 C- 13 C couplings between Glu C-2 and Asp C-3, showing that oxaloacetate metabolism to Glu biosynthesis did not involve C-atom redistribution by the Krebs cycle. The apparent carbon allocation increased with carbon net photosynthesis. However, when expressed relative to CO 2 fixation, it was clearly higher at low CO 2 while it did not change in 2% O 2 , as compared to standard conditions. We conclude that Glu production from current photosynthetic carbon represents a small flux that is controlled by the gaseous environment, typically upregulated at low CO 2 . © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Putting The "Yee-Hah!" In Astronomy Outreach: Professional Development Through The ASP "Sky Rangers" Project

NASA Astrophysics Data System (ADS)

Manning, Jim; Gurton, S.; Hurst, A.

2010-05-01

The Astronomical Society of the Pacific is conducting a NASA-funded professional development program to help increase astronomy education and outreach capacity at national parks, nature centers, and other outdoor and environmental centers--venues that still have a dark night sky as a natural resource and a yen to interpret it for their visitors. Through online workshops and on-site workshops at national parks, the ASP staff, working in conjunction with partners from the National Park Service, National Association for Interpretation, and the Association of Science and Technology Centers, provides materials and training focusing on the sky. Participants become part of ASP's "Astronomy from the Ground Up" informational education community of practice, with ongoing options to hone their new skills. The presenter will report on early progress and lessons learned, as well as future plans, as the ASP and its partners work to help wilderness and nature interpreters put a little more "yee-hah!" in their visitor presentations aimed at the sky.

Antibiotic Stewardship in Small Hospitals: Barriers and Potential Solutions.

PubMed

Stenehjem, Edward; Hyun, David Y; Septimus, Ed; Yu, Kalvin C; Meyer, Marc; Raj, Deepa; Srinivasan, Arjun

2017-08-15

Antibiotic stewardship programs (ASPs) improve antibiotic prescribing. Seventy-three percent of US hospitals have <200 beds. Small hospitals (<200 beds) have similar rates of antibiotic prescribing compared to large hospitals, but the majority of small hospitals lack ASPs that satisfy the Centers for Disease Control and Prevention's core elements. All hospitals, regardless of size, are now required to have ASPs by The Joint Commission, and the Centers for Medicare and Medicaid Services has proposed a similar requirement. Very few studies have described the successful implementation of ASPs in small hospitals. We describe barriers commonly encountered in small hospitals when constructing an antibiotic stewardship team, obtaining appropriate metrics of antibiotic prescribing, implementing antibiotic stewardship interventions, obtaining financial resources, and utilizing the microbiology laboratory. We propose potential solutions that tailor stewardship activities to the needs of the facility and the resources typically available. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

The Networks and Services of the Astronomical Society of the Pacific

NASA Astrophysics Data System (ADS)

Manning, J. G.; Fraknoi, A.; Gibbs, M. G.; Gurton, S.; Hurst, A.; Berendesen, M.; Deans, P.; White, V.

2008-11-01

Founded in 1889, the Astronomical Society of the Pacific (ASP) is an international organization dedicated to advancing science literacy through engagement in astronomy. Its programs, many with sponsorship from the National Science Foundation, NASA, and astronomical institutions around the world, are particularly designed to assist those who work to improve the public understanding of science. In recent years, the ASP has been expanding the impact of its diverse projects through a variety of networks and services.

Planning for Multiagent Using ASP-Prolog

NASA Astrophysics Data System (ADS)

Son, Tran Cao; Pontelli, Enrico; Nguyen, Ngoc-Hieu

This paper presents an Answer Set Programming based approach to multiagent planning. The proposed methodology extends the action language \\cal B in [12] to represent and reason about plans with cooperative actions of an individual agent operating in a multiagent environment. This language is used to formalize multiagent planning problems and the notion of a joint plan for multiagent in the presence of cooperative actions. Finally, the paper presents a system for computing joint plans based on the ASP-Prolog system.

Community partnership to address snack quality and cost in after-school programs.

PubMed

Beets, Michael W; Tilley, Falon; Turner-McGrievy, Gabrielle; Weaver, Robert G; Jones, Sonya

2014-08-01

Policies call on after-school programs (ASPs) to serve more nutritious snacks. A major barrier for improving snack quality is cost. This study describes the impact on snack quality and expenditures from a community partnership between ASPs and local grocery stores. Four large-scale ASPs (serving ˜500 children, aged 6-12 years, each day) and a single local grocery store chain participated in this study. The nutritional quality of snacks served was recorded preintervention (18 weeks spring/fall 2011) and postintervention (7 weeks spring 2012) via direct observation, along with cost/child/snack/day. Preintervention snacks were low-nutrient-density salty snacks (eg, chips, 3.0 servings/week), sugar-sweetened beverages (eg, powdered-lemonade, 1.9 servings/week), and desserts (eg, cookies, 2.1 servings/week), with only 0.4 servings/week of fruits and no vegetables. By postintervention, fruits (3.5 servings/week) and vegetables (1.2 servings/week) were increased, whereas sugar-sweetened beverages and desserts were eliminated. Snack expenditures were $0.26 versus $0.24 from preintervention to postintervention. Partnership savings versus purchasing snacks at full retail cost was 24.5% or $0.25/serving versus $0.34/serving. This innovative partnership can serve as a model in communities where ASPs seek to identify low-cost alternatives to providing nutritious snacks. © 2014, American School Health Association.

Community Partnership to Address Snack Quality and Cost in Afterschool Programs

PubMed Central

Tilley, Falon; Turner-McGrievy, Gabrielle; Weaver, Robert Glenn; Jones, Sonya

2014-01-01

Background Policies call on afterschool programs (ASPs) to serve more nutritious snacks. A major barrier for improving snack quality is cost. This study describes the impact on snack quality and expenditures from a community-partnership between ASPs and local grocery stores. Methods Four large-scale ASPs (serving ∼500 children aged 6-12 years each day) and a single local grocery store chain participated in the study. The nutritional quality of snacks served was recorded pre-intervention (18 weeks spring/fall 2011) and post-intervention (7 weeks spring 2012) via direct observation, along with cost/child/snack/day. Results Pre-intervention snacks were low-nutrient-density salty snacks (eg, chips, 3.0 servings/week), sugar-sweetened beverages (eg, powdered-lemonade, 1.9 servings/week), and desserts (eg, cookies, 2.1servings/week), with only 0.4 servings/week of fruits and no vegetables. By post-intervention, fruits (3.5 servings/week) and vegetables (1.2 servings/week) increased, while sugar-sweetened beverages and desserts were eliminated. Snack expenditures were $0.26 versus $0.24 from pre-intervention to post-intervention. Partnership savings versus purchasing snacks at full retail cost was 24.5% or $0.25/serving versus $0.34/serving. Conclusions This innovative partnership can serve as a model in communities where ASPs seek to identify low-cost alternatives to providing nutritious snacks. PMID:25040123

Long-term outcomes of an antimicrobial stewardship program implemented in a hospital with low baseline antibiotic use.

PubMed

Jenkins, Timothy C; Knepper, Bryan C; Shihadeh, Katherine; Haas, Michelle K; Sabel, Allison L; Steele, Andrew W; Wilson, Michael L; Price, Connie S; Burman, William J; Mehler, Philip S

2015-06-01

To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use. Quasi-experimental, interrupted time-series study. Public safety net hospital with 525 beds. Implementation of a formal ASP in July 2008. We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008-September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005-June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1,000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset Clostridium difficile infection, and other patient-centered measures. During the preintervention period, total antibacterial and antipseudomonal use were declining (-9.2 and -5.5 DOT/1,000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (-3.7 and -2.2 DOT/1,000 PD, respectively), resulting in a slope change of 5.5 DOT/1,000 PD per quarter for total antibacterial use (P=.10) and 3.3 DOT/1,000 PD per quarter for antipseudomonal use (P=.01). Antibiotic expenditures declined markedly during the stewardship period (-$295.42/1,000 PD per quarter, P=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures. Common ASP outcome measures have limitations.

Point-of-care Beta-lactam Allergy Skin Testing by Antimicrobial Stewardship Programs: A Pragmatic Multicenter Prospective Evaluation.

PubMed

Leis, Jerome A; Palmay, Lesley; Ho, Grace; Raybardhan, Sumit; Gill, Suzanne; Kan, Tiffany; Campbell, Jackie; Kiss, Alex; McCready, Janine B; Das, Pavani; Minnema, Brian; Powis, Jeff E; Walker, Sandra A N; Ferguson, Heather; Wong, Benny; Weber, Elizabeth

2017-06-01

Beta-lactam allergy skin testing (BLAST) is recommended by antimicrobial stewardship program (ASP) guidelines, yet few studies have systematically evaluated its impact when delivered at point-of-care. We conducted a pragmatic multicenter prospective evaluation of the use of point-of-care BLAST by ASPs. In staggered 3-month intervals, ASP teams at three hospitals received training by allergists to offer BLAST for eligible patients with infectious diseases receiving non-preferred beta-lactam therapy due to severity of their allergy. The primary outcome was the proportion of patients receiving the preferred beta-lactam therapy. Of 827 patients with reported beta-lactam allergy over 15-months, beta-lactam therapy was preferred among 632(76%). During baseline periods, 50% (124/246) received preferred beta-lactam therapy based on history, compared with 60% (232/386) during the intervention periods (p=0.02), which improved further to 81% (313/386) upon provision of BLAST (p<0.001) without any increase in incidence of adverse drug reactions (4% vs. 3%; p=0.4). After adjusting for patient variables and the correlation between hospitals, the intervention period was associated with a 4.5-fold greater odds of receiving preferred beta-lactam therapy (95% CI, 2.4-8.2; p<0.0001). The use of BLAST at the point-of-care across three hospital ASPs resulted in greater use of preferred beta-lactam therapy without increasing the risk of adverse drug reactions. Longer term studies are needed to better assess the safety and clinical impact of this ASP intervention. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Impact of formulary restriction with prior authorization by an antimicrobial stewardship program

PubMed Central

Reed, Erica E.; Stevenson, Kurt B.; West, Jessica E.; Bauer, Karri A.; Goff, Debra A.

2013-01-01

In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come. PMID:23154323

Impact of formulary restriction with prior authorization by an antimicrobial stewardship program.

PubMed

Reed, Erica E; Stevenson, Kurt B; West, Jessica E; Bauer, Karri A; Goff, Debra A

2013-02-15

In an era of increasing antimicrobial resistance and few antimicrobials in the developmental pipeline, many institutions have developed antimicrobial stewardship programs (ASPs) to help implement evidence-based (EB) strategies for ensuring appropriate utilization of these agents. EB strategies for accomplishing this include formulary restriction with prior authorization. Potential limitations to this particular strategy include delays in therapy, prescriber pushback, and unintended increases in use of un-restricted antimicrobials; however, our ASP found that implementing prior authorization for select antimicrobials along with making a significant effort to educate clinicians on criteria for use ensured more appropriate prescribing of these agents, hopefully helping to preserve their utility for years to come.

Simulating Aerosol Optical Properties With the Aerosol Simulation Program (ASP): Closure Studies Using ARCTAS Data

NASA Astrophysics Data System (ADS)

Alvarado, M. J.; Macintyre, H. L.; Bian, H.; Chin, M.; Wang, C.

2012-12-01

The scattering and absorption of ultraviolet and visible radiation by aerosols can significantly alter actinic fluxes and photolysis rates. Accurate modeling of aerosol optical properties is thus essential to simulating atmospheric chemistry, air quality, and climate. Here we evaluate the aerosol optical property predictions of the Aerosol Simulation Program (ASP) with in situ data on aerosol scattering and absorption gathered during the Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) campaign. The model simulations are initialized with in situ data on the aerosol size distribution and composition. We perform a set of sensitivity studies (e.g., internal vs. external mixture, core-in-shell versus Maxwell-Garnett, fraction of the organic carbon mass that is light-absorbing "brown carbon," etc.) to determine the model framework and parameters most consistent with the observations. We compare the ASP results to the aerosol optical property lookup tables in FAST-JX and suggest improvements that will better enable FAST-JX to simulate the impact of aerosols on photolysis rates and atmospheric chemistry.

From policy to practice: Addressing snack quality, consumption, and price in afterschool programs

PubMed Central

Beets, Michael W.; Tilley, Falon; Weaver, Robert G.; Turner-McGrievy, Brie; Moore, Justin B.; Webster, Collin

2013-01-01

Objective To evaluate a community partnership between afterschool programs (ASPs) and grocery store to provide discounted pricing on snacks to meet the National Afterschool Association Healthy Eating Standards that call for serving a fruit/vegetable (FV) daily, while eliminating sugar-based foods/beverages. Methods A single-group, pre- with multiple post-test design (Spring 2011–2013) in four large-scale ASPs serving 500 children/day was used along with direct observation of snacks served, consumed, and cost. Results At baseline FV, sugar-sweetened beverages (SSB), and desserts were served 0.1±0.5, 1.7±2.0, and 2.0±1.4 days/wk. By Spring 2013, FV increased to 5.0±0.0 days/wk, while SSB and desserts were eliminated. Eighty-four percent of children consumed the fruit; 59% consumed the vegetables. Cost associated with purchasing snacks resulted in a $2,000–$3,000 savings over a standard 180day school year. Conclusions and Implications This partnership can serve as a model for successfully meeting nutrition policies established for ASP snacks. PMID:24268299

77 FR 24169 - Notice of Funds Availability: Inviting Applications for the Market Access Program

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

... for the 2013 Market Access Program (MAP). The intended effect of this notice is to solicit... not be considered. FOR FURTHER INFORMATION CONTACT: Entities wishing to apply for funding assistance... at http://www.fas.usda.gov/mos/programs/map.asp . SUPPLEMENTARY INFORMATION: I. Funding Opportunity...

ASP Strategies and Appropriate Antibiotic Use

PubMed Central

Lee, Brian R; Tribble, Alison; Handy, Lori; Gerber, Jeffrey S; Hersh, Adam L; Kronman, Matthew; Terrill, Cindy; Newland, Jason

2017-01-01

Abstract Background The Infectious Diseases Society of America (IDSA) recommends hospitals implement antimicrobial stewardship programs (ASP) in order to decrease inappropriate antibiotic use due to the rise in antibiotic-resistant infections. Data are limited on the extent to which different ASP strategies influence appropriate antibiotic use. Methods We conducted an online survey in 2016 of U.S. Children’s Hospitals to collect hospital-level information on dedicated ASP effort, ASP monitoring activities, use of audit-feedback, formulary restrictions, rapid diagnostics, etc. During the same period the ASP teams at these hospitals completed 3 point prevalence surveys that documented details on all admitted patients 0–17 years receiving any antibiotics, determined what ASP modifications could be made, and if the antibiotic was appropriate. We employed hierarchical, multivariable logit models to examine which ASP-related, hospital-level strategies were associated with appropriate antibiotic use. Results Thirty hospitals participated. A total of 6,921 patients were included, representing 10,068 total antibiotics. Of these orders, 8,554 (85.0%) were categorized as appropriate, though this varied across sites (range: 68-92%). Additionally, 78.2% of antibiotics did not have recommended modifications. Appropriate antibiotic use was significantly higher for hospitals that relied on rapid diagnostics (aOR: 1.6; P < 0.001) or monitored their days of therapy (DOT) rate (aOR: 1.4; P < 0.001), whereas the presence of either audit-feedback (aOR: 1.04; P = 0.75) or formulary restrictions (aOR: 0.83; P = 0.059) were not associated. Having annual education for all prescribers had increased likelihood of antibiotics having no modification recommendations (aOR: 1.45; P = 0.037). Total ASP FTE was not correlated with hospital-level percent appropriate use (corr: −0.05; P = 0.79) or antibiotic modification recommendations (corr: −0.08; P = 0.67). Conclusion Routine monitoring of DOT rates and utilization of rapid diagnostics were associated with appropriate antibiotic use. Additional analysis is needed to understand additional factors that can aid hospitals in developing and maintaining ASPs to reduce inappropriate antibiotic use. Disclosures B. R. Lee, Merck: Grant Investigator, Grant recipient. PCORI: Grant Investigator, Grant recipient. C. Terrill, Merck: Grant Investigator, Research grant Allergan: Grant Investigator, Research grant. J. Newland, Merck: Grant Investigator, Research grant. Allergan: Grant Investigator, Research grant

Effects of Participation in after-School Programs for Middle School Students: A Randomized Trial

ERIC Educational Resources Information Center

Gottfredson, Denise; Cross, Amanda Brown; Wilson, Denise; Rorie, Melissa; Connell, Nadine

2010-01-01

This study assessed the effects of attending an after-school program (ASP) on a range of outcomes for middle school youths. The program operated for 9 hr per week for 30 weeks and included attendance monitoring and reinforcement, academic assistance, a prevention curriculum, and recreational programming. Participants were 447 students randomly…

Implementation of an antimicrobial stewardship program targeting residents with urinary tract infections in three community long-term care facilities: a quasi-experimental study using time-series analysis.

PubMed

Doernberg, Sarah B; Dudas, Victoria; Trivedi, Kavita K

2015-01-01

Asymptomatic bacteriuria in the elderly commonly results in antibiotic administration and, in turn, contributes to antimicrobial resistance, adverse drug events, and increased costs. This is a major problem in the long-term care facility (LTCF) setting, where residents frequently transition to and from the acute-care setting, often transporting drug-resistant organisms across the continuum of care. The goal of this study was to assess the feasibility and efficacy of antimicrobial stewardship programs (ASPs) targeting urinary tract infections (UTIs) at community LTCFs. This was a quasi-experimental study targeting antibiotic prescriptions for UTI using time-series analysis with 6-month retrospective pre-intervention and 6-month intervention period at three community LTCFs. The ASP team (infectious diseases (ID) pharmacist and ID physician) performed weekly prospective audit and feedback of consecutive prescriptions for UTI. Loeb clinical consensus criteria were used to assess appropriateness of antibiotics; recommendations were communicated to the primary treating provider by the ID pharmacist. Resident outcomes were recorded at subsequent visits. Generalized estimating equations using segmented regression were used to evaluate the impact of the ASP intervention on rates of antibiotic prescribing and antibiotic resistance. One-hundred and four antibiotic prescriptions for UTI were evaluated during the intervention, and recommendations were made for change in therapy in 40 (38 %), out of which 10 (25 %) were implemented. Only eight (8 %) residents started on antibiotics for UTI met clinical criteria for antibiotic initiation. An immediate 26 % decrease in antibiotic prescriptions for UTI during the ASP was identified with a 6 % reduction continuing through the intervention period (95 % Confidence Interval ([CI)] for the difference: -8 to -3 %). Similarly, a 25 % immediate decrease in all antibiotic prescriptions was noted after introduction of the ASP with a 5 % reduction continuing throughout the intervention period (95 % CI: -8 to -2 %). No significant effect was noted on resistant organisms or Clostridium difficile. Weekly prospective audit and feedback ASP in three community LTCFs over 6 months resulted in antibiotic utilization decreases but many lost opportunities for intervention.

Filamentous fungal-specific septin AspE is phosphorylated in vivo and interacts with actin, tubulin and other septins in the human pathogen Aspergillus fumigatus

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

Juvvadi, Praveen Rao; Belina, Detti; Soderblom, Erik J.

2013-02-15

Highlights: ► In vivo interactions of the novel septin AspE were identified by GFP-Trap® affinity purification. ► Septins AspA, AspB, AspC and AspD interacted with AspE in vivo. ► Actin and tubulin interacted with AspE in vivo. ► AspE is phosphorylated at six serine residues in vivo. -- Abstract: We previously analyzed the differential localization patterns of five septins (AspA–E), including a filamentous fungal-specific septin, AspE, in the human pathogen Aspergillus fumigatus. Here we utilized the A. fumigatus strain expressing an AspE–EGFP fusion protein and show that this novel septin with a tubular localization pattern in hyphae is phosphorylated inmore » vivo and interacts with the other septins, AspA, AspB, AspC and AspD. The other major proteins interacting with AspE included the cytoskeletal proteins, actin and tubulin, which may be involved in the organization and transport of the septins. This is the first report analyzing the phosphorylation of AspE and localizing the sites of phosphorylation, and opens opportunities for further analysis on the role of post-translational modifications in the assembly and organization of A. fumigatus septins. This study also describes the previously unknown interaction of AspE with the actin-microtubule network. Furthermore, the novel GFP-Trap® affinity purification method used here complements widely-used GFP localization studies in fungal systems.« less

Aqueous Phase Synthesis of CuIn Alloy Nanoparticles and Their Application for a CIS (CuInSe2)-Based Printable Solar Battery

PubMed Central

Takahashi, Hideyuki; Fujiki, Hironari; Yokoyama, Shun; Kai, Takayuki; Tohji, Kazuyuki

2018-01-01

To apply CuInSe2 (CIS)-based printable solar batteries; an aqueous phase synthesis method of Cu-In (CI) alloy nanoparticles is studied. Metal complexes in the original solution are restricted to homogenized species by utilizing calculations. For example; [(Cu2+)(ASP2−)2] [ASP: the “body (C4H5O4N)” of aspartic acid (C4H7O4N)] is predominant in the pH 6–13 region (CASP/CCu > 6); while In complexes can be restricted to [(In3+)(OH−)(EDTA4−)] (pH 10–12; CEDTA/CIn = 2) and/or [(In3+)(ASP2−)2] (pH 7–9; CASP/CIn = 5). These results indicate that the added amount of complex reagents should be determined by calculations and not the stoichiometric ratio. The reduction potential of homogenized metal complex is measured by cyclic voltammetry (CV) measurements and evaluated by Nernst’s equation using the overall stability constants. CuIn alloy nanoparticles with a small amount of byproduct (In nanoparticles) are successfully synthesized. The CI precursor films are spin-coated onto the substrate using a 2-propanol dispersion. Then the films are converted into CIS solar cells; which show a maximum conversion efficiency of 2.30%. The relationship between the open circuit potential; short circuit current density; and fill factor indicate that smoothing of the CIS films and improving the crystallinity and thickness increase the solar cell conversion efficiency. PMID:29642413

The Relationships among Group Size, Participation, and Performance of Programming Language Learning Supported with Online Forums

ERIC Educational Resources Information Center

Shaw, Ruey-Shiang

2013-01-01

This study examined the relationships among group size, participation, and learning performance factors when learning a programming language in a computer-supported collaborative learning (CSCL) context. An online forum was used as the CSCL environment for learning the Microsoft ASP.NET programming language. The collaborative-learning experiment…

Aquatic Species Program Review: Proceedings of the March 1983 Principal Investigators Meeting

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

Not Available

1983-06-01

The Aquatic Species Program (ASP) addresses the utilization of plant biomass that naturally occurs in wetland or submerged areas. Processes are being developed through this program to make use of such aquatic species, capitalizing on their inherent capacity for rapid growth as well as their extraordinary chemical compositions.

ASP: Gearing Up for the Next 120

NASA Astrophysics Data System (ADS)

Manning, J. G.

2010-08-01

In 2009, the Astronomical Society of the Pacific celebrates 120 years of serving the cause of astronomy, with a membership of professional and amateur astronomers, educators, and interested public; professional and popular publications; and increasingly, a variety of education and professional development programs and dissemination networks serving our various constituencies. As the Society begins a new strategic planning phase and looks forward to the next 120 years of service, with a re-articulated mission ("Advancing science literacy through engagement in astronomy") and a continuing commitment to science, education and outreach, in which direction(s) shall it head? The presenter will offer a few thoughts and conference participants will be surveyed for theirs in their role as continuing or newly minted ASP members. Outcomes: The audience will gain insight into ASP's future planning and will be surveyed for their input in the process.

A Pilot Study for Antimicrobial Stewardship Post-Discharge: Avoiding Pitfalls at the Transitions of Care.

PubMed

Jones, Justin M; Leedahl, Nathan D; Losing, Ashley; Carson, Paul J; Leedahl, David D

2018-04-01

Lack of patient follow-up is a major concern during care transitions, and the role of an antimicrobial stewardship program (ASP) in assessing antimicrobial regimens after hospital discharge is not well described. We implemented an expanded ASP to include patients recently discharged from the hospital and measured its impact on inappropriate antimicrobial therapy 72 hours after inpatient culture data were finalized. A prospective cohort study was conducted at a 583-bed tertiary care center in the Upper Midwest of America. All patients discharged from our facility on antimicrobial therapy with pending culture results between February 3, 2016, and March 2, 2016, were included for review. If a pathogen nonsusceptible to all prescribed antimicrobials was identified post-discharge, a recommendation for therapy modification was communicated to the prescriber. Thirty-eight patients discharged from our hospital on antimicrobial therapy with pending culture results were evaluated for intervention. When final culture susceptibilities were considered, 5 of 38 patients had been prescribed an inappropriate antimicrobial agent. An ASP pharmacist intervened on 4 of 5 patients, resulting in 3 of 5 patients transitioning to appropriate antimicrobial therapy. When compared to a historical cohort, our transitions-of-care ASP yielded a 3.6-fold increase in antimicrobial-related interventions among discharged patients while reducing inappropriate outpatient antimicrobial therapy by 39%. We believe this is the first pharmacist-driven ASP represented in the medical literature which evaluated all available inpatient culture data to serve patients discharged from the hospital. Antimicrobial stewardship for patients in care transitions may provide an opportunity to increase ASP interventions and reduce inappropriate antimicrobial therapy.

From policy to practice: addressing snack quality, consumption, and price in after-school programs.

PubMed

Beets, Michael W; Tilley, Falon; Weaver, Robert G; Turner-McGrievy, Gabrielle; Moore, Justin B; Webster, Collin

2014-01-01

To evaluate a community partnership between after-school programs (ASPs) and grocery stores to provide discounted pricing on snacks to meet the National Afterschool Association Healthy Eating Standards that call for serving a fruit or vegetable (FV) daily while eliminating sugar-based foods and beverages. A single-group, pretest with multiple posttest design (spring, 2011-2013) in 4 large-scale ASPs serving 500 children/d was used, along with direct observation of snacks served, consumed, and cost. At baseline, FV, sugar-sweetened beverages, and desserts were served 0.1 ± 0.5, 1.7 ± 2.0, and 2.0 ± 1.4 d/wk. By spring, 2013, FV increased to 5.0 ± 0.0 d/wk, whereas sugar-sweetened beverages and desserts were eliminated. A total of 84% of children consumed the fruit; 59% consumed the vegetables. Cost associated with purchasing snacks resulted in a $2,000-$3,000 savings over a standard 180-day school year. This partnership can serve as a model for successfully meeting nutrition policies established for ASP snacks. Copyright © 2014 Society for Nutrition Education and Behavior. All rights reserved.

Effects of Annotations and Homework on Learning Achievement: An Empirical Study of Scratch Programming Pedagogy

ERIC Educational Resources Information Center

Su, Addison Y. S.; Huang, Chester S. J.; Yang, Stephen J. H.; Ding, T. J.; Hsieh, Y. Z.

2015-01-01

In Taiwan elementary schools, Scratch programming has been taught for more than four years. Previous studies have shown that personal annotations is a useful learning method that improve learning performance. An annotation-based Scratch programming (ASP) system provides for the creation, share, and review of annotations and homework solutions in…

Using Lagrangian Chemical Transport Modeling to Assess the Impact of Biomass Burning on Ozone and PM2.5

NASA Astrophysics Data System (ADS)

Alvarado, M. J.; Lonsdale, C. R.; Brodowski, C. M.

2017-12-01

One of the challenges of using in situ measurements to study the air quality and climate impacts of biomass burning is correctly determining the contribution of biomass burning sources to the measured ambient concentrations. This is especially important for policy purposes, as the ozone (O3) and fine particulate matter (PM2.5) from natural wildfires should not be confused with that from controllable anthropogenic sources. We have developed a Lagrangian chemical transport model called STILT-ASP that is able to quantify the impact of wildfire events on O3 and PM2.5 measurements made at surface monitoring sites, by mobile laboratories, or by aircraft. STILT-ASP is built by coupling the Stochastic Time Inverted Lagrangian Transport (STILT) model with AER's Aerosol Simulation Program (ASP), which has been used in many studies of the gas and aerosol chemistry of biomass burning smoke. Here we present recent revisions made in STILT-ASP v2.0, including the use of more detailed chemical speciation of fire emissions and biogenic emissions calculated using the MEGAN model with meteorological inputs consistent with those used to drive STILT. We will present the results of an evaluation of the performance of STILT-ASP v2.0 using surface, mobile lab, and aircraft data from the 2013 Houston DISCOVER-AQ campaign. STILT-ASP v2.0 showed good average performance for O3 during the peak of the high O3 episodes on Sept. 25-26, 2013, with a mean bias of -4 ppbv. We will also demonstrate the use of STILT-ASP to evaluate the impact of biomass burning on O3 and PM2.5 in urban areas and to assess the impact of remote fires on the boundary conditions used in Eulerian chemical transport models like CAMx.

A Status Report on the AAS Astronomy Ambassadors Program

NASA Astrophysics Data System (ADS)

Fienberg, Richard Tresch; Fraknoi, Andrew; Gurton, Suzanne; Hurst, Anna; Schatz, Dennis L.

2014-06-01

The American Astronomical Society, in partnership with the Astronomical Society of the Pacific (ASP), has launched a series of professional-development workshops and a community of practice designed to improve early-career astronomers’ ability to communicate effectively with students and the public. Called AAS Astronomy Ambassadors, the program provides training and mentoring for young astronomers, from advanced undergraduates to beginning faculty; it also provides them access to resources and a network of contacts within the astronomy education and public outreach (EPO) community. Ambassadors are provided with a library of outreach activities and resource materials suitable for a range of venues and audiences. For much of this library we are using resources developed by organizations such as the ASP, the Pacific Science Center, and the Center for Astronomy Education for other outreach programs, though some resources have been created by one of us (AF) specifically for this program. After a period of evaluation and revision, the program’s “Menu of Outreach Opportunities for Science Education” (MOOSE) is now posted on the AAS website at http://aas.org/outreach/moose-menu-outreach-opportunities-science-education.The first two Astronomy Ambassadors workshops were held at AAS meetings in January 2013 and January 2014; each served 30 young astronomers chosen from about twice that many applicants. Web-based follow-up activities are being provided through a website at the ASP designed to keep cohorts of educators trained in their programs in touch with one another. The AAS is exploring ways to fund additional workshops at future winter meetings; suggestions are most welcome. Meanwhile, the Astronomy Ambassadors trained to date have logged more than 150 outreach events, reaching many thousands of children and adults across the U.S. and Canada.

Physical Activity and Psychological Correlates during an After-School Running Club

ERIC Educational Resources Information Center

Kahan, David; McKenzie, Thomas L.

2018-01-01

Background: After-school programs (ASPs) have the potential to contribute to moderate-to-vigorous physical activity (MVPA), but there is limited empirical evidence to guide their development and implementation. Purpose: This study assessed the replication of an elementary school running program and identified psychological correlates of children's…

Modeling the Complex Photochemistry of Biomass Burning Plumes in Plume-Scale, Regional, and Global Air Quality Models

NASA Astrophysics Data System (ADS)

Alvarado, M. J.; Lonsdale, C. R.; Yokelson, R. J.; Travis, K.; Fischer, E. V.; Lin, J. C.

2014-12-01

Forecasting the impacts of biomass burning (BB) plumes on air quality is difficult due to the complex photochemistry that takes place in the concentrated young BB plumes. The spatial grid of global and regional scale Eulerian models is generally too large to resolve BB photochemistry, which can lead to errors in predicting the formation of secondary organic aerosol (SOA) and O3, as well as the partitioning of NOyspecies. AER's Aerosol Simulation Program (ASP v2.1) can be used within plume-scale Lagrangian models to simulate this complex photochemistry. We will present results of validation studies of the ASP model against aircraft observations of young BB smoke plumes. We will also present initial results from the coupling of ASP v2.1 into the Lagrangian particle dispersion model STILT-Chem in order to better examine the interactions between BB plume chemistry and dispersion. In addition, we have used ASP to develop a sub-grid scale parameterization of the near-source chemistry of BB plumes for use in regional and global air quality models. The parameterization takes inputs from the host model, such as solar zenith angle, temperature, and fire fuel type, and calculates enhancement ratios of O3, NOx, PAN, aerosol nitrate, and other NOy species, as well as organic aerosol (OA). We will present results from the ASP-based BB parameterization as well as its implementation into the global atmospheric composition model GEOS-Chem for the SEAC4RS campaign.

β-Lactam Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins.

PubMed

Li, Julius; Echevarria, Kelly L; Traugott, Kristi A

2017-03-01

Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia is associated with high morbidity and mortality. Traditionally, antistaphylococcal penicillins (ASPs) have been considered the agents of choice for the treatment of MSSA bacteremia. Vancomycin has been demonstrated to have poorer outcomes in several studies and is only recommended for patients with severe penicillin allergies. Although cefazolin is considered as an alternative to the ASPs for patients with nonsevere penicillin allergies, cefazolin offers several pharmacologic advantages over ASPs, such as more convenient dosing regimens, and antimicrobial stewardship programs are increasingly using cefazolin as the preferential agent for MSSA infections as part of cost-saving initiatives. Concerns about susceptibility to hydrolysis by type A β-lactamases, particularly at high inocula seen in deep-seated infections such as endocarditis; selective pressures from unnecessary gram-negative coverage; and lack of comparative clinical data have precluded recommending cefazolin as a first-line therapy for MSSA bacteremia. Recent clinical studies, however, have suggested similar clinical efficacy but better tolerability, with lower rates of discontinuation due to adverse drug reactions, of cefazolin compared with ASPs. Other variables, such as adequate source control (e.g., intravascular catheter removal, debridement, or drainage) and enhanced pharmacodynamics through aggressive cefazolin dosing, may mitigate the role of cefazolin inoculum effect and factor into determining improved clinical outcomes. In this review, we highlight the utility of cefazolin versus ASPs in the treatment of MSSA bacteremia with a focus on clinical efficacy and safety. © 2017 Pharmacotherapy Publications, Inc.

Academic Support Program in the Faculty of Agricultural and Forestry Engineering of the University of Cordoba (Spain)

NASA Astrophysics Data System (ADS)

Castro, Sergio; Navarro, Rafael M.; Camacho, Emilio; Gallardo, Rosa; García-Ferrer, Alfonso; Pérez-Marín, M. Dolores; Peña, Adolfo; Taguas, Encarnación V.

2014-05-01

The incorporation of new students to undergraduate degrees is performed in different stages through a long, sequential enrollment process. The student integration to the new context of higher education including group work and new teaching methodologies lead to notable adaptation difficulties to this new educational environment. In fact, the highest rate of student failure in the Bachelor degree usually happens during the first courses. The Unit of Quality Evaluation/Monitoring of School of Agricultural and Forest Engineering (ETSIAM) has detected that these failure rates at first and second degree course may be reduced through the involvement of students in a support learning process, by increasing their skills and motivation as well as the contact with the University environment in the context of their future professional horizon. In order to establish a program of this type, it has been launched an Academic Support Program (ASP) at the ETSIAM. This program aims to achieve and reinforce the basic academic and personal skills/competences require by the Bologna's process (BC) and specific competences of the engineers on the area of Agriculture and Forestry in the European context. The ASP includes diferent bloks of seminars, lectures, collaborative work and discussion groups among students, professionals, professors and researchers and it has been designed based on these competences and tranversal contents in both degrees. These activities are planned in a common time for both degrees, out of teaching classes. In addition, a virtual space in Moodle has been created for discussion forums and preparation activities. Additional information about schedules, speakers and companies, presentations and other material are also provided. In the preliminary implementation of the ASP, we will present the results corresponding to the first year of this academic support program. We have conducted a survey among the students in order to have a first feedback about the impact of the ASP on their integration to University. As a general opinion, the students considered that the seminars were useful and interesting. Moreover, they appreciated that activities were open and attendance was not required. Student proposed new topics related with their professional development. This type of activities not only allows improving the satisfaction of the students but also connecting professors of different subjects and areas of knowledge with student and professional sector.

Considering a new domain for antimicrobial stewardship: Topical antibiotics in the open surgical wound.

PubMed

Edmiston, Charles E; Leaper, David; Spencer, Maureen; Truitt, Karen; Litz Fauerbach, Loretta; Graham, Denise; Johnson, Helen Boehm

2017-11-01

The global push to combat the problem of antimicrobial resistance has led to the development of antimicrobial stewardship programs (ASPs), which were recently mandated by The Joint Commission and the Centers for Medicare and Medicaid Services. However, the use of topical antibiotics in the open surgical wound is often not monitored by these programs nor is it subject to any evidence-based standardization of care. Survey results indicate that the practice of using topical antibiotics intraoperatively, in both irrigation fluids and powders, is widespread. Given the risks inherent in their use and the lack of evidence supporting it, the practice should be monitored as a core part of ASPs, and alternative agents, such as antiseptics, should be considered. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Impact of an antimicrobial stewardship program with multidisciplinary cooperation in a community public teaching hospital in Taiwan.

PubMed

Lin, Yu-Shiuan; Lin, I-Fen; Yen, Yung-Feng; Lin, Pei-Ching; Shiu, Yu-Chih; Hu, Hsing-Yi; Yang, Ying-Pi

2013-11-01

Reports of antimicrobial stewardship programs (ASPs) in community hospitals are limited, with the major focus on specific agents, small settings, or short time periods. Here we present the outcomes of cost control, consumption restraint, and quality of care after a 3-year multidisciplinary ASP in a 415-bed community public teaching hospital. Three strategies for improving antimicrobial stewardship were implemented: education, clinical pharmacists-based intervention, and regular outcome announcement. The steering panel of the program was a committee composed of infection specialists, attending physicians, clinical pharmacists, nurses, and medical laboratorists. Semiannual data from July 2009 to June 2012 was analyzed. Antibiotic costs declined from $21,464 to $12,146 per 1,000 patient-days (-43.4%). Approximately $2.5 million was saved in 3 years, and estimated labor cost was $3,935 per month. Defined daily dose per 1,000 patient-days were diminished from 906.7 to 717.5 (-20.9%). Significant reductions were found in the consumption of aminoglycosides, first-generation cephalosporins, and aminopenicillins. However, through comprehensive auditing, increasing consumption of fourth-generation cephalosporins and fluoroquinolones was noticed. No significant difference in the quality of care (ie, length of stay, incidence of health care associated infections, and mortality) was observed. The multidisciplinary ASP was beneficial to reduce antibiotic cost and consumption. The strategies were practical and worthy to be recommended to community health care settings. Copyright © 2013 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Airspace Systems Program: Next Generation Air Transportation System, NextGen Systems Analysis, Integration and Evaluation Project. Version 1.0; Project Plan

NASA Technical Reports Server (NTRS)

Quon, Leighton

2010-01-01

The key objectives of the NASA ASP are to: Improve mobility, capacity efficiency and access of the airspace system. Improve collaboration, predictability, and flexibility for the airspace users. Enable accurate modeling and simulation of air transportation systems. Accommodate operations of all classes of aircraft. Maintain system safety and environmental protection. In support of these program objectives, the major goal of the NextGen-SAIE Project is to enable the transition of key capacity and efficiency improvements to the NAS. Since many aspects of the NAS are unique to specific airport or airspace environments, demand on various parts of the NAS is not expected to increase equally as system demand grows. SAIE will provide systems level analysis of the NAS characteristics, constraints, and demands such that a suite of capacity-increasing concepts and technologies for system solutions are enabled and facilitated. The technical objectives in support of this goal are the following: Integration, evaluation, and transition of more mature concepts and technologies in an environment that faithfully emulates real-world complexities. Interoperability research and analysis of ASP technologies across ATM functions is performed to facilitate integration and take ASP concepts and technologies to higher Technology Readiness Level (TRL). Analyses are conducted on the program s concepts to identify the system benefits or impacts. System level analysis is conducted to increase understanding of the characteristics and constraints of airspace system and its domains.

Seven Steps for Implementing Afterschool Programs: Strategies for Physical Educators

ERIC Educational Resources Information Center

Price-Shingles, June N.; Place, Greg

2016-01-01

After-school programs (ASP) are a long-standing activity historically facilitated by organizations such as the YMCA, Boys and Girls Club, social service/community centers and, in the past decade, an increasing number of municipal park districts. Staffing usually consist of recreation professionals, social and youth workers, and volunteers. In…

Afterschool Program Participation and the Development of Child Obesity and Peer Acceptance

ERIC Educational Resources Information Center

Mahoney, Joseph L.; Lord, Heather; Carryl, Erica

2005-01-01

This longitudinal study assessed the role of afterschool program (ASP) participation in the development of child obesity and peer acceptance in a sample of 439 children. Most participants lived in poverty and were Hispanic or African American. Measurements of height and weight determined obesity status and peer acceptance was assessed through…

76 FR 45221 - Notice of Funding Availability: Inviting Applications for the Food for Progress Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-28

...://www.fas.usda.gov/excredits/FoodAid/FFP/FrameworkGuidance.asp . VI. Proposal Review Criteria A. Review... beneficiaries realistic for the proposed activities? (f) Are the beneficiaries and criteria for selection... Applications for the Food for Progress Program Announcement Type: New. Catalog of Federal Domestic Assistance...

Purification and characterisation of a new hypothalamic satiety peptide, cocaine and amphetamine regulated transcript (CART), produced in yeast.

PubMed

Thim, L; Nielsen, P F; Judge, M E; Andersen, A S; Diers, I; Egel-Mitani, M; Hastrup, S

1998-05-29

Cocaine and amphetamine regulated transcript (CART) is a newly discovered hypothalamic peptide with a potent appetite suppressing activity following intracerebroventricular administration. When the mature rat CART sequence encoding CART(1-102) was inserted in the yeast expression plasmid three CART peptides could be purified from the fermentation broth reflecting processing at dibasic sequences. None of these corresponded to the naturally occurring CART(55-102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102) has been produced and CART(55-102) was generated by digestion of the precursor with dipeptidylaminopeptidase-1. All four generated CART peptides have been characterised by N-terminal amino acid sequencing and mass spectrometry. The CART peptides contain six cysteine residues and using the yeast expressed CART(62-102) the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to 2.0 microg) they all produced a dose dependent inhibition of food intake.

Prediction of binding modes between protein L-isoaspartyl (D-aspartyl) O-methyltransferase and peptide substrates including isomerized aspartic acid residues using in silico analytic methods for the substrate screening.

PubMed

Oda, Akifumi; Noji, Ikuhiko; Fukuyoshi, Shuichi; Takahashi, Ohgi

2015-12-10

Because the aspartic acid (Asp) residues in proteins are occasionally isomerized in the human body, not only l-α-Asp but also l-β-Asp, D-α-Asp and D-β-Asp are found in human proteins. In these isomerized aspartic acids, the proportion of D-β-Asp is the largest and the proportions of l-β-Asp and D-α-Asp found in human proteins are comparatively small. To explain the proportions of aspartic acid isomers, the possibility of an enzyme able to repair l-β-Asp and D-α-Asp is frequently considered. The protein L-isoaspartyl (D-aspartyl) O-methyltransferase (PIMT) is considered one of the possible repair enzymes for l-β-Asp and D-α-Asp. Human PIMT is an enzyme that recognizes both l-β-Asp and D-α-Asp, and catalyzes the methylation of their side chains. In this study, the binding modes between PIMT and peptide substrates containing l-β-Asp or D-α-Asp residues were investigated using computational protein-ligand docking and molecular dynamics simulations. The results indicate that carboxyl groups of both l-β-Asp and D-α-Asp were recognized in similar modes by PIMT and that the C-terminal regions of substrate peptides were located in similar positions on PIMT for both the l-β-Asp and D-α-Asp peptides. In contrast, for peptides containing l-α-Asp or D-β-Asp residues, which are not substrates of PIMT, the computationally constructed binding modes between PIMT and peptides greatly differed from those between PIMT and substrates. In the nonsubstrate peptides, not inter- but intra-molecular hydrogen bonds were observed, and the conformations of peptides were more rigid than those of substrates. Thus, the in silico analytical methods were able to distinguish substrates from nonsubstrates and the computational methods are expected to complement experimental analytical methods. Copyright © 2015 Elsevier B.V. All rights reserved.

The efficacy of the direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in the pediatric ward of a tertiary medical facility without a pediatric antimicrobial stewardship program.

PubMed

Hoshina, T; Yamamoto, N; Ogawa, M; Nakamoto, T; Kusuhara, K

2017-08-01

Antimicrobial stewardship programs (ASPs) have been introduced in most hospital complexes; however, they are not always useful for pediatric patients. The aim of this study is to investigate the efficacy of direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in a tertiary medical facility without pediatric ASP. This retrospective study included 1,821 patients who were hospitalized in the pediatric ward of a large metropolitan hospital from 2010 to 2015. The clinical course, the use of intravenous antimicrobial agents and the results of a microbiological analysis were compared between the period after the beginning of direct intervention by the specialist (post-intervention period) and the previous period (pre-intervention period). In the post-intervention period, the proportion of the patients who received intravenous antimicrobial agents, the number of antimicrobial agents used for each episode, and the proportion of episodes in which an antimicrobial agent was re-administrated were significantly lower (P = 0.006, P = 0.004, P = 0.036, respectively), and the duration of antimicrobial treatment was significantly shorter (P < 0.001). In addition, narrower spectrum antimicrobial agents were used, and the incidence of meropenem-sensitive Pseudomonas aeruginosa significantly increased (P = 0.037) in the post-intervention period. There was no change of mortality between the two periods. Direct clinical intervention by a pediatric infectious diseases specialist is useful for the treatment of infectious diseases in the pediatric ward of a tertiary medical facility without a pediatric ASP. The creation of a pediatric ASP is recommended in hospital complexes.

Longitudinal evaluation of a World Wide Web-based antimicrobial stewardship program: assessing factors associated with approval patterns and trends over time.

PubMed

Venugopal, Vidya; Lehmann, Christoph U; Diener-West, Marie; Agwu, Allison L

2014-02-01

The Johns Hopkins Children's Medical and Surgery Center developed a Web-based Antimicrobial Stewardship Program (ASP) in 2005. The present study aimed to assess longitudinal antimicrobial request and approval patterns for this ASP. We analyzed a total of 16,229 antimicrobial requests for 3,542 patients between June 1, 2005, and June 30, 2009. Antimicrobial approval was the outcome of interest. We assessed gaming by studying trends in automatically approved requests. Nonparametric tests for trend were performed to detect changes in approval patterns. Multiple logistic regression was used to identify factors associated with approval. The vast majority (91.3%) of antimicrobial requests were approved, with an increase of 6.1% over time (P < .01). Renewal requests were more likely than primary requests (adjusted odds ratio [aOR], 1.72; 95% confidence interval [CI], 1.45-2.04) to be approved. Antiviral requests had higher odds of approval than antibiotic requests (aOR, 1.27; 95% CI, 1.04-1.56). Compared with requests by medical services, requests by surgical services had lower odds of approval (aOR, 0.70; 95% CI, 0.59-0.83), whereas pediatric intensive care requests had higher odds of approval (aOR, 1.18; 95% CI, 1.00-1.40). The number of auto-approved requests remained consistent. The Web-based ASP allows management of a large number of antimicrobial requests, without apparent gaming. Observed differences in approval patterns based on patient, requestor, and antimicrobial factors may inform the development of ASPs and evaluation of provider education and training. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

Long-Term Outcomes of an Antimicrobial Stewardship Program Implemented in a Hospital with Low Baseline Antibiotic Use

PubMed Central

Jenkins, Timothy C.; Knepper, Bryan C.; Shihadeh, Katherine; Haas, Michelle K.; Sabel, Allison L.; Steele, Andrew W.; Wilson, Michael L.; Price, Connie S.; Burman, William J.; Mehler, Philip S.

2016-01-01

Objective To evaluate the long-term outcomes of an antimicrobial stewardship program (ASP) implemented in a hospital with low baseline antibiotic use Design Quasi-experimental, interrupted-time series study Setting 525-bed public safety-net hospital Intervention Implementation of a formal ASP in July 2008 Methods We conducted a time-series analysis to evaluate the impact of the ASP over a 6.25-year period (July 1, 2008 – September 30, 2014) while controlling for trends during a 3-year preintervention period (July 1, 2005 – June 30, 2008). The primary outcome measures were total antibacterial and antipseudomonal use in days of therapy (DOT) per 1000 patient-days (PD). Secondary outcomes included antimicrobial costs and resistance, hospital-onset C. difficile infection, and other patient-centered measures. Results During the preintervention period, total antibacterial and antipseudomonal use were declining (−9.2 and −5.5 DOT/1000 PD per quarter, respectively). During the stewardship period, both continued to decline, although at lower rates (−3.7 and −2.2 DOT/1000 PD, respectively), resulting in a slope change of 5.5 DOT/1000 PD per quarter for total antibacterial use (P = .10) and 3.3 DOT/100 PD per quarter for antipseudomonal use (P = .01). Antibiotic expenditures declined markedly during the stewardship period (−$295.42/1000PD per quarter, p=.002). There were variable changes in antimicrobial resistance and few apparent changes in C. difficile infection and other patient-centered outcomes. Conclusion In a hospital with low baseline antibiotic use, implementation of an ASP was associated with sustained reductions in total antibacterial and antipseudomonal use and declining antibiotic expenditures; however, this study highlights limitations of commonly used stewardship outcome measures. PMID:25740560

The Highly Conserved Asp23 Family Protein YqhY Plays a Role in Lipid Biosynthesis in Bacillus subtilis

PubMed Central

Tödter, Dominik; Gunka, Katrin; Stülke, Jörg

2017-01-01

In most bacteria, fatty acid biosynthesis is an essential process that must be controlled by the availability of precursors and by the needs of cell division. So far, no mechanisms controlling synthesis of malonyl-coenzyme A (CoA), the committed step in fatty acid synthesis, have been identified in the Gram-positive model bacterium Bacillus subtilis. We have studied the localization and function of two highly expressed proteins of unknown function, YqhY and YloU. Both proteins are members of the conserved and widespread Asp23 family. While the deletion of yloU had no effect, loss of the yqhY gene induced the rapid acquisition of suppressor mutations. The vast majority of these mutations affect subunits of the acetyl-CoA carboxylase (ACCase) complex, the enzyme that catalyzes the formation of malonyl-CoA. Moreover, lack of yqhY is accompanied by the formation of lipophilic clusters in the polar regions of the cells indicating an increased activity of ACCase. Our results suggest that YqhY controls the activity of ACCase and that this control results in inhibition of ACCase activity. Hyperactivity of the enzyme complex in the absence of YqhY does then provoke mutations that cause reduced ACCase activity. PMID:28579978

Evaluation of Ga-DOTA-(D-Asp)n as bone imaging agents: D-aspartic acid peptides as carriers to bone.

PubMed

Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Makino, Akira; Kozaka, Takashi; Kiyono, Yasushi; Shiba, Kazuhiro; Odani, Akira

2017-10-25

67 Ga-DOTA-(L-Asp) 11 and 67 Ga-DOTA-(L-Asp) 14 , which have been developed as bone imaging agents, showed a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, 67 Ga-DOTA-(D-Asp) n (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of 67 Ga-DOTA-(D-Asp) n tended to increase with increasing length of the amino acid chain. 67 Ga-DOTA-(D-Asp) 11 and 67 Ga-DOTA-(D-Asp) 14 caused a high accumulation of radioactivity in the bones of the mice. However, the results for 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n were comparable. In urine analyses, the proportion of intact complex after injection of 67 Ga-DOTA-(D-Asp) 14 was significantly higher than that of 67 Ga-DOTA-(L-Asp) 14 . Although 67 Ga-DOTA-(D-Asp) 14 was more stable than 67 Ga-DOTA-(L-Asp) 14 , the properties of 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n as bone imaging agents may be comparable.

Quantitative determination of free D-Asp, L-Asp and N-methyl-D-aspartate in mouse brain tissues by chiral separation and Multiple Reaction Monitoring tandem mass spectrometry.

PubMed

Fontanarosa, Carolina; Pane, Francesca; Sepe, Nunzio; Pinto, Gabriella; Trifuoggi, Marco; Squillace, Marta; Errico, Francesco; Usiello, Alessandro; Pucci, Piero; Amoresano, Angela

2017-01-01

Several studies have suggested that free d-Asp has a crucial role in N-methyl d-Asp receptor-mediated neurotransmission playing very important functions in physiological and pathological processes. This paper describes the development of an analytical procedure for the direct and simultaneous determination of free d-Asp, l-Asp and N-methyl d-Asp in specimens of different mouse brain tissues using chiral LC-MS/MS in Multiple Reaction Monitoring scan mode. After comparing three procedures and different buffers and extraction solvents, a simple preparation procedure was selected the analytes of extraction. The method was validated by analyzing l-Asp, d-Asp and N-methyl d-Asp recovery at different spiked concentrations (50, 100 and 200 pg/μl) yielding satisfactory recoveries (75-110%), and good repeatability. Limits of detection (LOD) resulted to be 0.52 pg/μl for d-Asp, 0.46 pg/μl for l-Asp and 0.54 pg/μl for NMDA, respectively. Limits of quantification (LOQ) were 1.57 pg/μl for d-Asp, 1.41 pg/μl for l-Asp and 1.64 pg/μl for NMDA, respectively. Different concentration levels were used for constructing the calibration curves which showed good linearity. The validated method was then successfully applied to the simultaneous detection of d-Asp, l-Asp and NMDA in mouse brain tissues. The concurrent, sensitive, fast, and reproducible measurement of these metabolites in brain tissues will be useful to correlate the amount of free d-Asp with relevant neurological processes, making the LC-MS/MS MRM method well suited, not only for research work but also for clinical analyses.

Associations between XPD Asp312Asn Polymorphism and Risk of Head and Neck Cancer: A Meta-Analysis Based on 7,122 Subjects

PubMed Central

Hu, Yuan Yuan; Yuan, Hua; Jiang, Guang Bing; Chen, Ning; Wen, Li; Leng, Wei Dong; Zeng, Xian Tao; Niu, Yu Ming

2012-01-01

Background To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis. Methods We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk. Results Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P heterogeneity = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P heterogeneity = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P heterogeneity = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P heterogeneity = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models. Conclusions This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer. PMID:22536360

Antimicrobial Therapy for Legionnaire's Disease: Antibiotic Stewardship Implications.

PubMed

Cunha, Cheston B; Cunha, Burke A

2017-03-01

Legionnaire's disease is a common cause of community-acquired pneumonia (CAP). Although no single clinical feature is diagnostic, if characteristic extrapulmonary findings are present a presumptive clinical syndromic diagnosis is possible. Depending on geographic location, season, and physician awareness, Legionnaire's disease may be included in the differential diagnosis of CAP. Some antibiotics effective against Legionella sp are also effective in treating the typical bacterial causes of CAP. From an antimicrobial stewardship program (ASP) perspective, monotherapy is preferred to double-drug therapy. From an ASP and pharmacoeconomic standpoint, monotherapy with doxycycline or a respiratory quinolone provides optimal cost effective therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Lauroyl-L-aspartate decreased food intake and body temperature in neonatal chicks.

PubMed

Erwan, E; Chowdhury, V S; Ito, K; Furuse, M

2013-11-15

We hypothesized that the effects of L- and D-amino acids might be influenced when conjugated with fatty acid. Thus, the effects of oral administration of lauroyl-L-aspartate (Lau-L-Asp) as well as lauroyl-D-aspartate (Lau-D-Asp) were examined. In Experiment 1, oral administration of both Lau-L-Asp and Lau-D-Asp decreased food intake while L- or D-Asp did not influence food intake. Interestingly, only Lau-L-Asp decreased body temperature. Experiment 2 was conducted to determine whether non-conjugated mixture of L-Asp plus lauric acid has same effects under ad libitum feeding conditions. Lau-L-Asp decreased food intake and body temperature, but L-Asp plus lauric acid did not show any effect studied. In Experiment 3, we found that Lau-L-Asp declined food intake as well as time-dependently suppressed the body temperature in fasted chicks. However, L-Asp plus lauric acid did not show any effect. These results suggest that Lau-L-Asp may exert anorexigenic and hypothermic actions in chicks. © 2013.

Working at the intersection of context, culture, and technology: Provider perspectives on antimicrobial stewardship in the emergency department using electronic health record clinical decision support.

PubMed

Chung, Phillip; Scandlyn, Jean; Dayan, Peter S; Mistry, Rakesh D

2017-11-01

Antibiotic stewardship programs (ASPs) have not been fully developed for the emergency department (ED), in part the result of the barriers characteristic of this setting. Electronic health record-based clinical decision support (EHR CDS) represents a promising strategy to implement ASPs in the ED. We aimed to determine the cultural beliefs and structural barriers and facilitators to implementation of antimicrobial stewardship in the pediatric ED using EHR CDS. Interviews and focus groups were conducted with hospital and ED leadership, attending ED physicians, nurse practitioners, physician assistants, and residents at a single health system in Colorado. We reviewed and coded the data using constant comparative analysis and framework analysis until a final set of themes emerged. Two dominant perceptions shaped providers' perspectives on ASPs in the ED and EHR CDS: (1) maintaining workflow efficiency and (2) constrained decision-making autonomy. Clinicians identified structural barriers to ASPs, such as pace of the ED, and various beliefs that shaped patterns of practice, including accommodating the prescribing decisions of other providers and managing parental expectations. Recommendations to enhance uptake focused on designing a simple yet flexible user interface, providing clinicians with performance data, and on-boarding clinicians to enhance buy-in. Developing a successful ED-based ASP using EHR CDS should attend to technologic needs, the institutional context, and the cultural beliefs of practice associated with providers' antibiotic prescribing. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Expert Consensus on Metrics to Assess the Impact of Patient-Level Antimicrobial Stewardship Interventions in Acute-Care Settings

PubMed Central

Anderson, Deverick J.; Cochran, Ronda L.; Hicks, Lauri A.; Srinivasan, Arjun; Dodds Ashley, Elizabeth S.

2017-01-01

Antimicrobial stewardship programs (ASPs) positively impact patient care, but metrics to assess ASP impact are poorly defined. We used a modified Delphi approach to select relevant metrics for assessing patient-level interventions in acute-care settings for the purposes of internal program decision making. An expert panel rated 90 candidate metrics on a 9-point Likert scale for association with 4 criteria: improved antimicrobial prescribing, improved patient care, utility in targeting stewardship efforts, and feasibility in hospitals with electronic health records. Experts further refined, added, or removed metrics during structured teleconferences and re-rated the retained metrics. Six metrics were rated >6 in all criteria: 2 measures of Clostridium difficile incidence, incidence of drug-resistant pathogens, days of therapy over admissions, days of therapy over patient days, and redundant therapy events. Fourteen metrics rated >6 in all criteria except feasibility were identified as targets for future development. PMID:27927866

Web-based UMLS concept retrieval by automatic text scanning: a comparison of two methods.

PubMed

Brandt, C; Nadkarni, P

2001-01-01

The Web is increasingly the medium of choice for multi-user application program delivery. Yet selection of an appropriate programming environment for rapid prototyping, code portability, and maintainability remain issues. We summarize our experience on the conversion of a LISP Web application, Search/SR to a new, functionally identical application, Search/SR-ASP using a relational database and active server pages (ASP) technology. Our results indicate that provision of easy access to database engines and external objects is almost essential for a development environment to be considered viable for rapid and robust application delivery. While LISP itself is a robust language, its use in Web applications may be hard to justify given that current vendor implementations do not provide such functionality. Alternative, currently available scripting environments for Web development appear to have most of LISP's advantages and few of its disadvantages.

The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice.

PubMed

Paglialunga, Sabina; Fisette, Alexandre; Munkonda, Mercedes; Gao, Ying; Richard, Denis; Cianflone, Katherine

2010-04-23

Acylation stimulating protein (ASP) is an adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP) and human recombinant ASP (rASP) were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD) to examine their effects on body weight, food intake and energy expenditure. In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P < 0.05) while Anti-ASP neutralized the rASP response. Mice treated with Anti-ASP showed elevated energy expenditure (P < 0.0001), increased skeletal muscle glucose oxidation (+141%, P < 0.001), reduced liver glycogen (-34%, P < 0.05) and glucose-6-phosphate content (-64%, P = 0.08) compared to control mice. There was no change in body weight, food intake, fasting insulin, adiponectin, CRP or TG levels compared to controls. Interestingly, HFD mice treated with rASP showed the opposite phenotype with reduced energy expenditure (P < 0.0001) and increased body weight (P < 0.05), cumulative food intake (P < 0.0001) and liver glycogen content (+59%, P < 0.05). Again, there was no change in circulating insulin, adiponectin, CRP or TG levels, however, plasma free fatty acids were reduced (-48%, P < 0.05). In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

Dansylated octapeptide Dns-Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn inhibits the proliferation rate of HL-60 cells.

PubMed

Marsili, V; Nardicchi, V; Lupidi, G; Brozzetti, A; Gianfranceschi, G L

1996-12-01

Small acidic phosphorylated chromatin peptides show regulatory activity on gene expression. The peptide pyroGlu-Asp-Asp-Ser-Asp-Glu-Glu-Asn, synthesized on the basis of structural and biochemical studies, shows functional properties in vitro (phosphorylation by casein kinase II, control of DNA transcription by RNA polymerase II, inhibition of proliferation and promotion of differentiation in some cell lines) very similar to those of native chromatin peptides. In this report we show that the dansylated octapeptide Dns-Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn remarkably inhibits cell growth of the HL-60 cell line. The biological effect of the peptide seems to be considerably higher than that shown by the nondansylated peptide, and it cannot be attributed to a toxic effect of the Dns group. The measurement of uptake of 3H-labelled Glu-Asp-Asp-Ser-Asp-Glu-Glu-Asn demonstrates that it is unable to pass through the HL-60 cell membrane. It is our considered opinion that the addition of hydrophobic groups to the peptide N-terminus should increase the biological activity by improving its transport through the cellular membrane.

Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells.

PubMed

van de Water, B; Tijdens, I B; Verbrugge, A; Huigsloot, M; Dihal, A A; Stevens, J L; Jaken, S; Mulder, G J

2000-08-18

Decreased phosphorylation of focal adhesion kinase and paxillin is associated with loss of focal adhesions and stress fibers and precedes the onset of apoptosis (van de Water, B., Nagelkerke, J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The cortical actin cytoskeletal network is also lost during apoptosis, yet little is known about the temporal relationship between altered phosphorylation of proteins that are critical in the regulation of this network and their potential cleavage by caspases during apoptosis. Adducins are central in the cortical actin network organization. Cisplatin caused apoptosis of renal proximal tubular epithelial cells, which was associated with the cleavage of alpha-adducin into a 74-kDa fragment; this was blocked by a general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk). Hemagglutinin-tagged human alpha-adducin was cleaved into a similar 74-kDa fragment by caspase-3 in vitro but not by caspase-6 or -7. Asp-Arg-Val-Asp(29)-Glu, Asp-Ile-Val-Asp(208)-Arg, and Asp-Asp-Ser-Asp(633)-Ala were identified as the principal caspase-3 cleavage sites; Asp-Asp-Ser-Asp(633)-Ala was key in the formation of the 74-kDa fragment. Cisplatin also caused an increased phosphorylation of alpha-adducin and gamma-adducin in the MARCKS domain that preceded alpha-adducin cleavage and was associated with loss of adducins from adherens junctions; this was not affected by z-VAD-fmk. In conclusion, the data support a model in which increased phosphorylation of alpha-adducin due to cisplatin leads to dissociation from the cytoskeleton, a situation rendered irreversible by caspase-3-mediated cleavage of alpha-adducin at Asp-Asp-Ser-Asp(633)-Ala.

Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation.

PubMed

Dias, Rodrigo G; Alves, Maria-Janieire N N; Pereira, Alexandre C; Rondon, Maria Urbana P B; Dos Santos, Marcelo R; Krieger, José E; Krieger, Marta H; Negrão, Carlos E

2009-04-10

The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not sympathetic vasoconstriction.

TREATMENT INTENSIFICATION WITH INSULIN DEGLUDEC/INSULIN ASPART TWICE DAILY: RANDOMIZED STUDY TO COMPARE SIMPLE AND STEP-WISE TITRATION ALGORITHMS.

PubMed

Gerety, Gregg; Bebakar, Wan Mohamad Wan; Chaykin, Louis; Ozkaya, Mesut; Macura, Stanislava; Hersløv, Malene Lundgren; Behnke, Thomas

2016-05-01

This 26-week, multicenter, randomized, open-label, parallel-group, treat-to-target trial in adults with type 2 diabetes compared the efficacy and safety of treatment intensification algorithms with twice-daily (BID) insulin degludec/insulin aspart (IDegAsp). Patients randomized 1:1 to IDegAsp BID used either a 'Simple' algorithm (twice-weekly dose adjustments based on a single prebreakfast and pre-evening meal self-monitored plasma glucose [SMPG] measurement; IDegAsp[BIDSimple], n = 136) or a 'Stepwise' algorithm (once-weekly dose adjustments based on the lowest of 3 pre-breakfast and 3 pre-evening meal SMPG values; IDegAsp[BIDStep-wise], n = 136). After 26 weeks, mean change from baseline in glycated hemoglobin (HbA1c) with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise] (-15 mmol/mol versus -14 mmol/mol; 95% confidence interval [CI] upper limit, <4 mmol/mol) (baseline HbA1c: 66.3 mmol/mol IDegAsp[BIDSimple] and 66.6 mmol/mol IDegAsp[BIDStep-wise]). The proportion of patients who achieved HbA1c <7.0% (<53 mmol/mol) at the end of the trial was 66.9% with IDegAsp[BIDSimple] and 62.5% with IDegAsp[BIDStep-wise]. Fasting plasma glucose levels were reduced with each titration algorithm (-1.51 mmol/L IDegAsp[BIDSimple] versus -1.95 mmol/L IDegAsp[BIDStep-wise]). Weight gain was 3.8 kg IDegAsp[BIDSimple] versus 2.6 kg IDegAsp[BIDStep-wise], and rates of overall confirmed hypoglycemia (5.16 episodes per patient-year of exposure [PYE] versus 8.93 PYE) and nocturnal confirmed hypoglycemia (0.78 PYE versus 1.33 PYE) were significantly lower with IDegAsp[BIDStep-wise] versus IDegAsp[BIDSimple]. There were no significant differences in insulin dose increments between groups. Treatment intensification with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise]. Both titration algorithms were well tolerated; however, the more conservative step-wise algorithm led to less weight gain and fewer hypoglycemic episodes. Clinicaltrials.gov: NCT01680341.

The Aspergillus fumigatus septins play pleiotropic roles in septation, conidiation, and cell wall stress, but are dispensable for virulence.

PubMed

Vargas-Muñiz, José M; Renshaw, Hilary; Richards, Amber D; Lamoth, Frédéric; Soderblom, Erik J; Moseley, M Arthur; Juvvadi, Praveen R; Steinbach, William J

2015-08-01

Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the human pathogenic yeasts Candida albicans and Cryptococcus neoformans, as well as the plant pathogen Magnaporthe oryzae. Aspergillus spp. contains five genes encoding for septins (aspA-E). While the importance of septins AspA, AspB, AspC, and AspE for growth and conidiation has been elucidated in the filamentous fungal model Aspergillus nidulans, nothing is known on the role of septins in growth and virulence in the human pathogen Aspergillus fumigatus. Here we deleted all five A. fumigatus septins, and generated certain double and triple septin deletion strains. Phenotypic analyses revealed that while all the septins are dispensable in normal growth conditions, AspA, AspB, AspC and AspE are required for regular septation. Furthermore, deletion of only the core septin genes significantly reduced conidiation. Concomitant with the absence of an electron-dense outer conidial wall, the ΔaspB strain was also sensitive to anti-cell wall agents. Infection with the ΔaspB strain in a Galleria mellonella model of invasive aspergillosis showed hypervirulence, but no virulence difference was noted when compared to the wild-type strain in a murine model of invasive aspergillosis. Although the deletion of aspB resulted in increased release of TNF-α from the macrophages, no significant inflammation differences in lung histology was noted between the ΔaspB strain and the wild-type strain. Taken together, these results point to the importance of septins in A. fumigatus growth, but not virulence in a murine model. Copyright © 2015 Elsevier Inc. All rights reserved.

An Ecological Analysis of After-School Program Participation and the Development of Academic Performance and Motivational Attributes for Disadvantaged Children

ERIC Educational Resources Information Center

Mahoney, Joseph L.; Lord, Heather; Carryl, Erica

2005-01-01

This longitudinal study evaluated after-school program (ASP) participation and the development of academic performance (school grades, reading achievement) and teacher-rated motivational attributes (expectancy of success, effectance motivation) over a school year. Participants were 599 boys and girls (6.3 to 10.6 years) from an urban,…

Bodily Play in the After-School Program: Fulfillment of Intentionality in Interaction between Body and Place

ERIC Educational Resources Information Center

Londal, Knut

2011-01-01

This article investigates the relationship between children in an after-school program (ASP) and the places where they play. It focuses on the kind of bodily play the children themselves choose and control. The author applies a life-world approach to this study, and his theoretical perspective is based on phenomenological philosophy. The…

Influence of a Science-Focused After-School Program on Underrepresented High-School Students' Science Attitudes and Trajectory: A Survey Validation Study

ERIC Educational Resources Information Center

Puvirajah, Anton; Verma, Geeta; Li, Hongli; Martin-Hansen, Lisa

2015-01-01

As engagement with science, technology, engineering, and mathematics (STEM) increases in after-school programs (ASPs), it is important to examine the impact of this engagement on students' academic achievement, STEM participation, and affinity toward STEM. Results of these examinations can offer insights into both best practices that could be…

A Conceptual Model for Training After-School Program Staffers to Promote Physical Activity and Nutrition

ERIC Educational Resources Information Center

Weaver, Robert Glenn; Beets, Michael W.; Webster, Collin; Beighle, Aaron; Huberty, Jennifer

2012-01-01

Background: After-school programs (ASPs, 3 pm to 6 pm) have been called upon to increase the amount of daily physical activity children accumulate and improve the nutritional quality of the snacks served. To this end, state and national physical activity and nutrition (PAaN) policies have been proposed. Frontline staff who directly interact with…

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

Colantonio, Patrizia; Leboffe, Loris; Bolli, Alessandro

Caspase-3 is responsible for the cleavage of several proteins including the nuclear enzyme poly(ADP-ribose) polymerase (PARP). Designed on the cleavage site of PARP, Ac-Asp-Glu-Val-Asp-H has been reported as a highly specific inhibitor. To overcome the susceptibility to proteolysis, the intrinsic instability, and the scarce membrane permeability of tetra-peptidyl aldehydes, di- and tri-peptidyl caspase-3 inhibitors have been synthesized. Here, the synthesis and the inhibition properties of peptidyl aldehydes Z-tLeu-Asp-H, Z-tLeu-Val-Asp-H, and Z-Val-tLeu-Asp-H are reported. Z-tLeu-Asp-H, Z-tLeu-Val-Asp-H, and Z-Val-tLeu-Asp-H inhibit competitively human caspase-3 activity in vitro with K{sub i}{sup 0} = 3.6 nM, 18.2 nM, and 109 nM, respectively (pH 7.4 andmore » 25 deg. C). Moreover, Z-tLeu-Asp-H impairs apoptosis in human DLD-1 colon adenocarcinoma cells without affecting caspase-8. Therefore, Ac-Asp-Glu-Val-Asp-H can be truncated to Z-tLeu-Asp-H retaining nanomolar inhibitory activity in vitro and displaying action in whole cells, these properties reflect the unprecedented introduction of the bulky and lipophilic tLeu residue at the P{sub 2} position.« less

In vitro activity of almond skin polyphenols for scavenging free radicals and inducing quinone reductase.

PubMed

Chen, C-Y Oliver; Blumberg, Jeffrey B

2008-06-25

Observational studies and clinical trials suggest nut intake, including almonds, is associated with an enhancement in antioxidant defense and a reduction in the risk of cancer and cardiovascular disease. Almond skins are rich in polyphenols (ASP) that may contribute to these putative benefits. To assess their potential mechanisms of action, we tested the in vitro effect of ASP extracted with methanol (M) or a gastrointestinal juice mimic (GI) alone or in combination with vitamins C (VC) or E (VE) (1-10 micromol/L) on scavenging free radicals and inducing quinone reductase (QR). Flavonoid profiles from ASP-M and -GI extracts were different from one another. ASP-GI was more potent in scavenging HOCl and ONOO (-) radicals than ASP-M. In contrast, ASP-M increased and ASP-GI decreased QR activity in Hepa1c1c7 cells. Adding VC or VE to ASP produced a combination- and dose-dependent action on radical scavenging and QR induction. In comparison to their independent actions, ASP-M plus VC were less potent in scavenging DPPH, HOCl, ONOO (-), and O 2 (-) (*). However, the interaction between ASP-GI plus VC promoted their radical scavenging activity. Combining ASP-M plus VC resulted in a synergistic interaction, inducing QR activity, but ASP-GI plus VC had an antagonistic effect. On the basis of their total phenolic content, the measures of total antioxidant activity of ASP-M and -GI were comparable. Thus, in vitro, ASP act as antioxidants and induce QR activity, but these actions are dependent upon their dose, method of extraction, and interaction with antioxidant vitamins.

Conformational Change in the Active Site of Streptococcal Unsaturated Glucuronyl Hydrolase Through Site-Directed Mutagenesis at Asp-115.

PubMed

Nakamichi, Yusuke; Oiki, Sayoko; Mikami, Bunzo; Murata, Kousaku; Hashimoto, Wataru

2016-08-01

Bacterial unsaturated glucuronyl hydrolase (UGL) degrades unsaturated disaccharides generated from mammalian extracellular matrices, glycosaminoglycans, by polysaccharide lyases. Two Asp residues, Asp-115 and Asp-175 of Streptococcus agalactiae UGL (SagUGL), are completely conserved in other bacterial UGLs, one of which (Asp-175 of SagUGL) acts as a general acid and base catalyst. The other Asp (Asp-115 of SagUGL) also affects the enzyme activity, although its role in the enzyme reaction has not been well understood. Here, we show substitution of Asp-115 in SagUGL with Asn caused a conformational change in the active site. Tertiary structures of SagUGL mutants D115N and D115N/K370S with negligible enzyme activity were determined at 2.00 and 1.79 Å resolution, respectively, by X-ray crystallography. The side chain of Asn-115 is drastically shifted in both mutants owing to the interaction with several residues, including Asp-175, by formation of hydrogen bonds. This interaction between Asn-115 and Asp-175 probably prevents the mutants from triggering the enzyme reaction using Asp-175 as an acid catalyst.

IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

PubMed

Chung, Si-Yin; Reed, Shawndrika

2015-01-01

The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. Published by Elsevier Ltd.

Terbium-Aspartic Acid Nanocrystals with Chirality-Dependent Tunable Fluorescent Properties.

PubMed

Ma, Baojin; Wu, Yu; Zhang, Shan; Wang, Shicai; Qiu, Jichuan; Zhao, Lili; Guo, Daidong; Duan, Jiazhi; Sang, Yuanhua; Li, Linlin; Jiang, Huaidong; Liu, Hong

2017-02-28

Terbium-aspartic acid (Tb-Asp) nanocrystals with chirality-dependent tunable fluorescent properties can be synthesized through a facile synthesis method through the coordination between Tb and Asp. Asp with different chirality (dextrorotation/d and levogyration/l) changes the stability of the coordination center following fluorescent absorption/emission ability differences. Compared with l-Asp, d-Asp can coordinate Tb to form a more stable center, following the higher quantum yield and longer fluorescence life. Fluorescence intensity of Tb-Asp linearly increases with increase ratio of d-Asp in the mixed chirality Tb-Asp system, and the fluorescent properties of Tb-Asp nanocrystals can be tuned by adjusting the chirality ratio. Tb-Asp nanocrystals possess many advantage, such as high biocompatibility, without any color in visible light irradiation, monodispersion with very small size, and long fluorescent life. Those characteristics will give them great potential in many application fields, such as low-cost antifake markers and advertisements using inkjet printers or for molds when dispersed in polydimethylsiloxane. In addition, europium can also be used to synthesize Eu-Asp nanoparticles. Importantly, the facile, low-cost, high-yield, mass-productive "green" process provides enormous advantages for synthesis and application of fluorescent nanocrystals, which will have great impact in nanomaterial technology.

Substitution of amino acids Asp-85, Asp-212, and Arg-82 in bacteriorhodopsin affects the proton release phase of the pump and the pK of the Schiff base.

PubMed

Otto, H; Marti, T; Holz, M; Mogi, T; Stern, L J; Engel, F; Khorana, H G; Heyn, M P

1990-02-01

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-[(3-cholamidopropyl)dimethylammonio]-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting a role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early (less than 0.2 microseconds) reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base. In the Arg-82----Gln mutant, no net transient proton release was observed, whereas, in the Arg-82----Ala mutant, uptake and release were reversed. The pK shift of the purple-to-blue transition in the Asp-85----Glu, Arg-82----Ala, and Arg-82----Gln mutants and the similarity in the photocycle and photoelectrical signals of the Asp-85----Ala, Asp-85----Asn, and Asp-212----Asn mutants suggest the interaction between Asp-85, Arg-82, Asp-212, and the Schiff base as essential for proton release.

Synthesis and research of benzylamides of some isocyclic and heterocyclic acids as potential anticonvulsants.

PubMed

Strupińska, Marzanna; Rostafińska-Suchar, Grazyna; Pirianowicz-Chaber, Elzbieta; Stables, James P; Jiang, Jeff; Paruszewski, Ryszard

2013-01-01

A series of benzylamides of isocyclic and heterocyclic acids was synthesized and tested in Anticonvulsant Screening Project (ASP) of Antiepileptic Drug Development Program (ADDP) of NIH. Near all synthesized derivatives of heterocyclic acids showed activity. All obtained derivatives of mono- and bicyclic isocyclic acids were inactive. The power of action of heterocyclic acids derivatives seems does not depend upon kind of heteroatom (N, O or S). One of the compounds (2-furoic acid benzylamide (4)) appeared most promising. It showed in minimal clonic seizure (6Hz) test (ASP) in rats after i. p. administration: MES ED50 = 36.5 mg/kg, TOX TD50 = 269.75 mg/kg, and PI = 7.39.

The Networks Of The Astronomical Society Of The Pacific And The International Year Of Astronomy

NASA Astrophysics Data System (ADS)

Fraknoi, Andrew; Manning, J.; Gurton, S.; Gibbs, M.; Hurst, A.; White, V.; Berendsen, M.

2007-12-01

Serious planning has begun for the International Year of Astronomy (IYA) in 2009, which will also be the 120th anniversary of the Astronomical Society of the Pacific (ASP). A key element required for IYA's success in reaching the maximum number of people in the U.S. will be to find effective ways of disseminating the programs and materials that are being developed. The ASP's national networks of educational intermediaries can play a major role in training, dissemination, and organization for IYA. These networks include: the Project ASTRO National Site Network (13 regional sites training professional and amateur astronomers to work with local teachers and families), the Night Sky Network (over 200 amateur astronomy clubs engaged in active outreach), the Astronomy from the Ground Up Network (smaller science and nature centers increasing their offerings in astronomy), and the Cosmos in the Classroom Network (hundreds of instructors of introductory astronomy in community, state, and liberal arts colleges). The ASP also offers "The Universe in the Classroom", a quarterly newsletter for those teaching astronomy in grades 3-12, an extensive web site of educational resources, podcasts, workshops, national conferences, and awards to help improve the public understanding of astronomy. At the Summer 2008 AAS meeting, the ASP will sponsor a major symposium and workshops on preparing for IYA (and working with a range of different audiences.)

Does mental illness stigma contribute to adolescent standardized patients' discomfort with simulations of mental illness and adverse psychosocial experiences?

PubMed

Hanson, Mark D; Johnson, Samantha; Niec, Anne; Pietrantonio, Anna Marie; High, Bradley; MacMillan, Harriet; Eva, Kevin W

2008-01-01

Adolescent mental illness stigma-related factors may contribute to adolescent standardized patients' (ASP) discomfort with simulations of psychiatric conditions/adverse psychosocial experiences. Paradoxically, however, ASP involvement may provide a stigma-reduction strategy. This article reports an investigation of this hypothetical association between simulation discomfort and mental illness stigma. ASPs were randomly assigned to one of two simulation conditions: one was associated with mental illness stigma and one was not. ASP training methods included carefully written case simulations, educational materials, and active teaching methods. After training, ASPs completed the adapted Project Role Questionnaire to rate anticipated role discomfort with hypothetical adolescent psychiatric conditions/adverse psychosocial experiences and to respond to open-ended questions regarding this discomfort. A mixed design ANOVA was used to compare comfort levels across simulation conditions. Narrative responses to an open-ended question were reviewed for relevant themes. Twenty-four ASPs participated. A significant effect of simulation was observed, indicating that ASPs participating in the simulation associated with mental illness stigma anticipated greater comfort with portraying subsequent stigma-associated roles than did ASPs in the simulation not associated with stigma. ASPs' narrative responses regarding their reasons for anticipating discomfort focused upon the role of knowledge-related factors. ASPs' work with a psychiatric case simulation was associated with greater anticipated comfort with hypothetical simulations of psychiatric/adverse psychosocial conditions in comparison to ASPs lacking a similar work experience. The ASPs provided explanations for this anticipated discomfort that were suggestive of stigma-related knowledge factors. This preliminary research suggests an association between ASP anticipated role discomfort and mental illness stigma, and that ASP work may contribute to stigma reduction.

Human mass balance, metabolite profile and identification of metabolic enzymes of [¹⁴C]ASP015K, a novel oral janus kinase inhibitor.

PubMed

Oda, Kazuo; Cao, Ying J; Sawamoto, Taiji; Nakada, Naoyuki; Fisniku, Ogert; Nagasaka, Yasuhisa; Sohda, Kin-Ya

2015-01-01

1. The human mass balance of (14)C-labelled ASP015K ([(14)C]ASP015K), an orally bioavailable Janus kinase (JAK) inhibitor, was characterized in six healthy male subjects after a single oral dose of [(14)C]ASP015K (100 mg, 3.7 MBq) in solution. [(14)C]ASP015K was rapidly absorbed with tmax of 1.6 and 1.8 h for ASP015K and total radioactivity in plasma, respectively. Mean recovery in urine and feces amounted to 36.8% and 56.6% of the administered dose, respectively. The main components of radioactivity in plasma and urine were ASP015K and M2 (5'-O-sulfo ASP015K). In feces, ASP015K and M4 (7-N-methyl ASP015K) were the main components. 2. In vitro study of ASP015K metabolism showed that the major isozyme contributing to the formation of M2 was human sulfotransferase (SULT) 2A1 and of M4 was nicotinamide N-methyltransferase (NNMT). 3. The in vitro intrinsic clearance (CLint_in vitro) of M4 formation from ASP015K in human liver cytosol (HLC) was 11-fold higher than that of M2. The competitive inhibitory effect of nicotinamide on M4 formation in the human liver was considered the reason for high CLint_in vitro of M4 formation, while each metabolic pathway made a near equal contribution to the in vivo elimination of ASP015K. ASP015K was cleared by multiple mechanisms.

Aversive Startle Potentiation and Fear Pathology: Mediating Role of Threat Sensitivity and Moderating Impact of Depression

PubMed Central

Yancey, James R.; Vaidyanathan, Uma; Patrick, Christopher J.

2015-01-01

Enhanced startle during exposure to unpleasant cues (aversive startle potentiation; ASP) appears in the RDoC matrix as a physiological index of acute threat response. Increased ASP has been linked to focal fear disorders and to scale measures of dispositional fearfulness (i.e., threat sensitivity; THT+). However, some studies have reported reduced ASP for fear pathology accompanied by major depressive disorder (MDD) or pervasive distress. The current study evaluated whether (a) THT+ as indexed by reported dispositional fearfulness mediates the relationship between fear disorders (when unaccompanied by depression) and ASP, and (b) depression moderates relations of THT+ and fear disorders with ASP. Fear disorder participants without MDD showed enhanced ASP whereas those with MDD (or other distress conditions) showed evidence of reduced ASP. Continuous THT+ scores also predicted ASP, and this association: (a) was likewise moderated by depression/distress, and (b) accounted for the relationship between ASP and fear pathology without MDD. These findings point to a role for the RDoC construct of acute threat, operationalized dispositionally, in enhanced ASP shown by individuals with fear pathology unaccompanied by distress pathology. PMID:25448265

The role of collagen charge clusters in the modulation of matrix metalloproteinase activity.

PubMed

Lauer, Janelle L; Bhowmick, Manishabrata; Tokmina-Roszyk, Dorota; Lin, Yan; Van Doren, Steven R; Fields, Gregg B

2014-01-24

Members of the matrix metalloproteinase (MMP) family selectively cleave collagens in vivo. Several substrate structural features that direct MMP collagenolysis have been identified. The present study evaluated the role of charged residue clusters in the regulation of MMP collagenolysis. A series of 10 triple-helical peptide (THP) substrates were constructed in which either Lys-Gly-Asp or Gly-Asp-Lys motifs replaced Gly-Pro-Hyp (where Hyp is 4-hydroxy-L-proline) repeats. The stabilities of THPs containing the two different motifs were analyzed, and kinetic parameters for substrate hydrolysis by six MMPs were determined. A general trend for virtually all enzymes was that, as Gly-Asp-Lys motifs were moved from the extreme N and C termini to the interior next to the cleavage site sequence, kcat/Km values increased. Additionally, all Gly-Asp-Lys THPs were as good or better substrates than the parent THP in which Gly-Asp-Lys was not present. In turn, the Lys-Gly-Asp THPs were also always better substrates than the parent THP, but the magnitude of the difference was considerably less compared with the Gly-Asp-Lys series. Of the MMPs tested, MMP-2 and MMP-9 most greatly favored the presence of charged residues with preference for the Gly-Asp-Lys series. Lys-Gly-(Asp/Glu) motifs are more commonly found near potential MMP cleavage sites than Gly-(Asp/Glu)-Lys motifs. As Lys-Gly-Asp is not as favored by MMPs as Gly-Asp-Lys, the Lys-Gly-Asp motif appears advantageous over the Gly-Asp-Lys motif by preventing unwanted MMP hydrolysis. More specifically, the lack of Gly-Asp-Lys clusters may diminish potential MMP-2 and MMP-9 collagenolytic activity. The present study indicates that MMPs have interactions spanning the P23-P23' subsites of collagenous substrates.

78 FR 27408 - Revised OIG's Provider Self-Disclosure Protocol

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-10

... programs (as defined in section 1128B(f) of the Social Security Act (the Act), 42 U.S.C. 1320a-7b(f)). The... on its Web site: http://oig.hhs.gov/compliance/self-disclosure-info/index.asp . FOR FURTHER...

Aeromonas sobria serine protease (ASP): a subtilisin family endopeptidase with multiple virulence activities.

PubMed

Imamura, Takahisa; Murakami, Yoji; Nitta, Hidetoshi

2017-09-26

Aeromonas sobria serine protease (ASP) is secreted from Aeromonas sobria, a pathogen causing gastroenteritis and sepsis. ASP resembles Saccharomyces cerevisiae Kex2, a member of the subtilisin family, and preferentially cleaves peptide bonds at the C-terminal side of paired basic amino acid residues; also accepting unpaired arginine at the P1 site. Unlike Kex2, however, ASP lacks an intramolecular chaperone N-terminal propeptide, instead utilizes the external chaperone ORF2 for proper folding, therefore, ASP and its homologues constitute a new subfamily in the subtilisin family. Through activation of the kallikrein/kinin system, ASP induces vascular leakage, and presumably causes edema and septic shock. ASP accelerates plasma clotting by α-thrombin generation from prothrombin, whereas it impairs plasma clottability by fibrinogen degradation, together bringing about blood coagulation disorder that occurs in disseminated intravascular coagulation, a major complication of sepsis. From complement C5 ASP liberates C5a that induces neutrophil recruitment and superoxide release, and mast cell degranulation, which are associated with pus formation, tissue injury and diarrhea, respectively. Nicked two-chain ASP also secreted from A. sobria is more resistant to inactivation by α2-macroglobulin than single-chain ASP, thereby raising virulence activities. Thus, ASP is a potent virulence factor and may participate in the pathogenesis of A. sobria infection.

Polyamine is a critical determinant of Pseudomonas chlororaphis O6 for GacS-dependent bacterial cell growth and biocontrol capacity.

PubMed

Park, Ju Yeon; Kang, Beom Ryong; Ryu, Choong-Min; Anderson, Anne J; Kim, Young Cheol

2018-05-01

The Gac/Rsm network regulates, at the transcriptional level, many beneficial traits in biocontrol-active pseudomonads. In this study, we used Phenotype MicroArrays, followed by specific growth studies and mutational analysis, to understand how catabolism is regulated by this sensor kinase system in the biocontrol isolate Pseudomonas chlororaphis O6. The growth of a gacS mutant was decreased significantly relative to that of the wild-type on ornithine and arginine, and on the precursor of these amino acids, N-acetyl-l-glutamic acid. The gacS mutant also showed reduced production of polyamines. Expression of the genes encoding arginine decarboxylase (speA) and ornithine decarboxylases (speC) was controlled at the transcriptional level by the GacS sensor of P. chlororaphis O6. Polyamine production was reduced in the speC mutant, and was eliminated in the speAspeC mutant. The addition of exogenous polyamines to the speAspeC mutant restored the in vitro growth inhibition of two fungal pathogens, as well as the secretion of three biological control-related factors: pyrrolnitrin, protease and siderophore. These results extend our knowledge of the regulation by the Gac/Rsm network in a biocontrol pseudomonad to include polyamine synthesis. Collectively, our studies demonstrate that bacterial polyamines act as important regulators of bacterial cell growth and biocontrol potential. © 2017 BSPP AND JOHN WILEY & SONS LTD.

Evidence for association of a common variant of the endothelial nitric oxide synthase gene (Glu298→Asp polymorphism) to the presence, extent, and severity of coronary artery disease

PubMed Central

Colombo, M G; Andreassi, M G; Paradossi, U; Botto, N; Manfredi, S; Masetti, S; Rossi, G; Clerico, A; Biagini, A

2002-01-01

Background: Genetic variants of endothelial nitric oxide synthase (eNOS) could influence individual susceptibility to coronary artery disease. Objective: To assess whether Glu298→Asp polymorphism of the eNOS gene is associated with the occurrence and severity of angiographically defined coronary artery disease in the Italian population. Methods: Polymerase chain reaction/restriction fragment length polymorphism analysis was done to detect the Glu298→Asp variant of the eNOS gene in 201 patients with coronary artery disease and 114 controls. The severity of coronary artery disease was expressed by the number of affected vessels and by the Duke scoring system. Results: The frequencies of the eNOS Glu/Glu, Glu/Asp, and Asp/Asp genotypes in the coronary artery disease group were significantly different from those of controls (45.3%, 38.8%, and 15.9% v 42.1%, 51.8%, and 6.1%, respectively; χ2 = 8.589, p = 0.0136). In comparison with subjects who had a Glu298 allele in the eNOS gene, the risk of coronary artery disease was increased among Asp/Asp carriers (odds ratio 2.9, 95% confidence interval 1.2 to 6.8, p = 0.01) and was independent of the other common risk factors (p = 0.04). There was a significant association between the eNOS Glu298→Asp variant and both the number of stenosed vessels (mean (SEM), 2.3 (0.1) for Asp/Asp v 1.9 (0.1) and 1.8 (0.1) for Glu/Glu and Glu/Asp, respectively; p = 0.01) and the Duke score (56.1 (3.1) for Asp/Asp v 46.7 (2.0) and 46.1 (1.9) for Glu/Glu and Glu/Asp, respectively; p = 0.02). Conclusions: Glu298→Asp polymorphism of the eNOS gene appears to be associated with the presence, extent, and severity of angiographically assessed coronary artery disease. PMID:12010932

Change in plasma acylation stimulating protein during euglycaemic-hyperinsulinaemic clamp in overweight and obese postmenopausal women: a MONET study.

PubMed

St-Pierre, David H; Cianflone, Katherine; Smith, Jessica; Coderre, Lise; Karelis, Antony D; Imbeault, Pascal; Lavoie, Jean-Marc; Rabasa-Lhoret, Rémi

2009-04-01

Acylation-stimulating protein (ASP) has been shown to positively stimulate fatty acid esterification and glucose uptake in adipocytes. In vitro studies demonstrate that insulin stimulates ASP secretion from adipocytes. Individuals with obesity and/or metabolic disturbances (insulin resistance and type 2 diabetes) have increased plasma ASP. The present study was designed to evaluate whether ASP levels are influenced by the metabolic profiles of overweight and obese postmenopausal women during a euglycaemic/hyperinsulinaemic clamp (EHC). Patients The study population consisted of 76 overweight and obese sedentary postmenopausal women. We evaluated insulin sensitivity, plasma ASP levels, body composition including visceral adipose tissue area, blood lipid profiles, liver enzymes, peak aerobic capacity, resting metabolic rate (RMR) and total energy expenditure (TEE). We observed wide interindividual variations of ASP levels during the EHC. Therefore, subjects were divided into three groups based on ASP changes. Negative ASP Responders (NAR; n = 24) showed a -20% or greater decrease in ASP levels while Positive ASP Responders (PAR; n = 42) displayed ASP fluctuations superior to +20%. Ten subjects had little or no ASP change and were considered as Zero ASP responders (ZAR). PAR women displayed a worse metabolic profile than NAR women, including higher BMI, visceral adipose tissue, fasting insulin levels, lean body mass, and alanine aminotransferase (ALT), a marker of impaired liver function. After adjustment for BMI, only ALT remained significantly different, while lean body mass (P = 0.08) and visceral adipose tissue (P = 0.07) remained marginally higher. Correlation analysis of all subjects demonstrated that fasting ASP levels correlated positively with albumin and VO(2 peak) and this association remained significant after adjustments for the effect of BMI. In addition, the percentage maximal change in ASP levels during the EHC was positively associated with BMI, lean body mass, visceral adipose tissue, fasting insulin, HOMA, TEE, RMR, ALT and AST. Overall these results suggest that an elevated ASP response during the EHC is associated with metabolic disturbances in overweight and obese postmenopausal women.

Can After-School Programs and Private Tutoring Help Improve Students' Achievement? Revisiting the Effects in Korean Secondary Schools

ERIC Educational Resources Information Center

Ha, Yeojin; Park, Hyun-Jeong

2017-01-01

The purpose of this study is to examine the causal effects of after-school programs (ASPs) and private tutoring on Korean secondary school students' academic achievement. The students' data from the Gyeonggi Education Panel Study were used in this study for the actual data analysis. The study attempted to adjust for possible selection bias toward…

Competitive formation of b(2) and c(2)-H2O ions from b(3) ions containing Asp residue during tandem mass spectrometry: the influence of neighboring Arg.

PubMed

Guo, Mengzhe; Guo, Cheng; Pan, Yuanjiang

2014-08-01

The fragmentation of b3 ions derived from protonated Arg-Xxx-Asp-Ala-Ala (Xxx = Ala, Asp, Glu, Cys) and Arg-Xxx-Glu-Ala-Ala was investigated by electrospray ionization tandem mass spectrometry (MS (n) ) with collision-induced dissociation. A particular ion, which is 1 Da less than b2 ion, is shown to be the c2-H2O ion. The mechanism for its formation involved the aspartic acid in the third position easily losing anhydride to form a c2 ion, which then lost water to form an eight-membered ring of azacyclooctane derivative under the participation of the guanidine of the N-terminal arginine. However, this phenomenon was not observed when the aspartic acid was replaced by glutamic acid. The Amber program was used to determine the conformation of the original c2 residue from the dynamic energy perspective, and then density functional theory-based calculations and changing N-terminal amino acid from arginine to phenylalanine supported this mechanism.

Implementation of an Antimicrobial Stewardship Program in a Neonatal Intensive Care Unit.

PubMed

Nzegwu, Nneka I; Rychalsky, Michelle R; Nallu, Loren A; Song, Xuemei; Deng, Yanhong; Natusch, Amber M; Baltimore, Robert S; Paci, George R; Bizzarro, Matthew J

2017-10-01

OBJECTIVE To evaluate antimicrobial utilization and prescription practices in a neonatal intensive care unit (NICU) after implementation of an antimicrobial stewardship program (ASP). DESIGN Quasi-experimental, interrupted time-series study. SETTING A 54-bed, level IV NICU in a regional academic and tertiary referral center. PATIENTS AND PARTICIPANTS All neonates prescribed antimicrobials from January 1, 2011, to June 30, 2016, were eligible for inclusion. INTERVENTION Implementation of a NICU-specific ASP beginning July 2012. METHODS We convened a multidisciplinary team and developed guidelines for common infections, with a focus on prescriber audit and feedback. We conducted an interrupted time-series analysis to evaluate the effects of our ASP. Our primary outcome measure was days of antibiotic therapy (DOT) per 1,000 patient days for all and for select antimicrobials. Secondary outcomes included provider-specific antimicrobial prescription events for suspected late-onset sepsis (blood or cerebrospinal fluid infection at >72 hours of life) and guideline compliance. RESULTS Antibiotic utilization decreased by 14.7 DOT per 1,000 patient days during the stewardship period, although this decrease was not statistically significant (P=.669). Use of ampicillin, the most commonly antimicrobial prescribed in our NICU, decreased significantly, declining by 22.5 DOT per 1,000 patient days (P=.037). Late-onset sepsis evaluation and prescription events per 100 NICU days of clinical service decreased significantly (P<.0001), with an average reduction of 2.65 evaluations per year per provider. Clinical guidelines were adhered to 98.75% of the time. CONCLUSIONS Implementation of a NICU-specific antimicrobial stewardship program is feasible and can improve antibiotic prescribing practices. Infect Control Hosp Epidemiol 2017;38:1137-1143.

Combined effects of ankylosing spondylitis-associated ERAP1 polymorphisms outside the catalytic and peptide-binding sites on the processing of natural HLA-B27 ligands.

PubMed

Martín-Esteban, Adrian; Gómez-Molina, Patricia; Sanz-Bravo, Alejandro; López de Castro, José A

2014-02-14

ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys-528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575, but the difference depended on residue 528. The same hierarchy was observed with synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent. Sometimes the epitope yields were variant-specific at all times. For other peptides, concomitant generation and destruction led to similar epitope amounts with all the variants at long, but not at short, digestion times. The generation/destruction balance of two related HLA-B27 ligands was analyzed in vitro and in live cells. Their relative yields at long digestion times were comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis.

Combined Effects of Ankylosing Spondylitis-associated ERAP1 Polymorphisms Outside the Catalytic and Peptide-binding Sites on the Processing of Natural HLA-B27 Ligands*

PubMed Central

Martín-Esteban, Adrian; Gómez-Molina, Patricia; Sanz-Bravo, Alejandro; López de Castro, José A.

2014-01-01

ERAP1 polymorphism involving residues 528 and 575/725 is associated with ankylosing spondylitis among HLA-B27-positive individuals. We used four recombinant variants to address the combined effects of the K528R and D575N polymorphism on the processing of HLA-B27 ligands. The hydrolysis of a fluorogenic substrate, Arg-528/Asp-575 < Lys-528/Asp-575 < Arg-528/Asn-575 < Lys-528/Asn-575, indicated that the relative activity of variants carrying Arg-528 or Lys-528 depends on residue 575. Asp-575 conferred lower activity than Asn-575, but the difference depended on residue 528. The same hierarchy was observed with synthetic precursors of HLA-B27 ligands, but the effects were peptide-dependent. Sometimes the epitope yields were variant-specific at all times. For other peptides, concomitant generation and destruction led to similar epitope amounts with all the variants at long, but not at short, digestion times. The generation/destruction balance of two related HLA-B27 ligands was analyzed in vitro and in live cells. Their relative yields at long digestion times were comparable with those from HLA-B27-positive cells, suggesting that ERAP1 was a major determinant of the abundance of these peptides in vivo. The hydrolysis of fluorogenic and peptide substrates by an HLA-B27 ligand or a shorter peptide, respectively, was increasingly inhibited as a function of ERAP1 activity, indicating that residues 528 and 575 affect substrate inhibition of ERAP1 trimming. The significant and complex effects of co-occurring ERAP1 polymorphisms on multiple HLA-B27 ligands, and their potential to alter the immunological and pathogenetic features of HLA-B27 as a function of the ERAP1 context, explain the epistatic association of both molecules in ankylosing spondylitis. PMID:24352655

The modeling and design of the Annular Suspension and Pointing System /ASPS/. [for Space Shuttle

NASA Technical Reports Server (NTRS)

Kuo, B. C.; Lin, W. C. W.

1979-01-01

The Annular Suspension and Pointing System (ASPS) is a payload auxiliary pointing device of the Space Shuttle. The ASPS is comprised of two major subassemblies, a vernier and a coarse pointing subsystem. The three functions provided by the ASPS are related to the pointing of the payload, centering the payload in the magnetic actuator assembly, and tracking the payload mounting plate and shuttle motions by the coarse gimbals. The equations of motion of a simplified planar model of the ASPS are derived. Attention is given to a state diagram of the dynamics of the ASPS with position-plus-rate controller, the nonlinear spring characteristic for the wire-cable torque of the ASPS, the design of the analog ASPS through decoupling and pole placement, and the time response of different components of the continuous control system.

ASP archiving solution of regional HUSpacs.

PubMed

Pohjonen, Hanna; Kauppinen, Tomi; Ahovuo, Juhani

2004-09-01

The application service provider (ASP) model is not novel, but widely used in several non-health care-related business areas. In this article, ASP is described as a potential solution for long-term and back-up archiving of the picture archiving and communication system (PACS) of the Hospital District of Helsinki and Uusimaa (HUS). HUSpacs is a regional PACS for 21 HUS hospitals serving altogether 1.4 million citizens. The ultimate goal of this study was to define the specifications for the ASP archiving service and to compare different commercial options for archiving solutions (costs derived by unofficial requests for proposal): in-house PACS components, the regional ASP concept and the hospital-based ASP concept. In conclusion, the large scale of the HUS installation enables a cost-effective regional ASP archiving, resulting in a four to five times more economical solution than hospital-based ASP.

The ASP3 locus in Saccharomyces cerevisiae originated by horizontal gene transfer from Wickerhamomyces.

PubMed

League, Garrett P; Slot, Jason C; Rokas, Antonis

2012-11-01

The asparagine degradation pathway in the S288c laboratory strain of Saccharomyces cerevisiae is comprised of genes located at two separate loci. ASP1 is located on chromosome IV and encodes for cytosolic l-asparaginase I, whereas ASP3 contains a gene cluster located on chromosome XII comprised of four identical genes, ASP3-1, ASP3-2, ASP3-3, and ASP3-4, which encode for cell wall-associated l-asparaginase II. Interestingly, the ASP3 locus appears to be only present, in variable copy number, in S. cerevisiae strains isolated from laboratory or industrial environments and is completely absent from the genomes of 128 diverse fungal species. Investigation of the evolutionary history of ASP3 across these 128 genomes as well as across the genomes of 43 S. cerevisiae strains shows that ASP3 likely arose in a S. cerevisiae strain via horizontal gene transfer (HGT) from, or a close relative of, the wine yeast Wickerhamomyces anomalus, which co-occurs with S. cerevisiae in several biotechnological processes. Thus, because the ASP3 present in the S288c laboratory strain of S. cerevisiae is induced in response to nitrogen starvation, its acquisition may have aided yeast adaptation to artificial environments. Our finding that the ASP3 locus in S. cerevisiae originated via HGT further highlights the importance of gene sharing between yeasts in the evolution of their remarkable metabolic diversity. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Oral administration of D-aspartate, but not L-aspartate, depresses rectal temperature and alters plasma metabolites in chicks.

PubMed

Erwan, Edi; Chowdhury, Vishwajit Sur; Nagasawa, Mao; Goda, Ryosei; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

2014-07-25

L-Aspartate (L-Asp) and D-aspartate (D-Asp) are physiologically important amino acids in mammals and birds. However, the functions of these amino acids have not yet been fully understood. In this study, we therefore examined the effects of L-Asp and D-Asp in terms of regulating body temperature, plasma metabolites and catecholamines in chicks. Chicks were first orally administered with different doses (0, 3.75, 7.5 and 15 mmol/kg body weight) of L- or D-Asp to monitor the effects of these amino acids on rectal temperature during 120 min of the experimental period. Oral administration of D-Asp, but not of L-Asp, linearly decreased the rectal temperature in chicks. Importantly, orally administered D-Asp led to a significant reduction in body temperature in chicks even under high ambient temperature (HT) conditions. However, centrally administered D-Asp did not significantly influence the body temperature in chicks. As for plasma metabolites and catecholamines, orally administered D-Asp led to decreased triacylglycerol and uric acid concentrations and increased glucose and chlorine concentrations but did not alter plasma catecholamines. These results suggest that oral administration of D-Asp may play a potent role in reducing body temperature under both normal and HT conditions. The alteration of plasma metabolites further indicates that D-Asp may contribute to the regulation of metabolic activity in chicks. Copyright © 2014 Elsevier Inc. All rights reserved.

Two-Year Healthy Eating Outcomes: An RCT in Afterschool Programs.

PubMed

Beets, Michael W; Weaver, R Glenn; Turner-McGrievy, Gabrielle; Huberty, Jennifer; Moore, Justin B; Ward, Dianne S; Freedman, Darcy A; Beighle, Aaron

2017-09-01

Across the U.S., afterschool programs (ASPs, 3:00pm-6:00pm) are trying to achieve nationally endorsed nutrition standards (Healthy Eating Standards) calling for fruits/vegetables and water to be served every day, while eliminating sugar-sweetened beverages and foods. The purpose of this study was to evaluate the 2-year changes in the types of foods and beverages served during a community-based intervention designed to achieve the Healthy Eating Standards. Randomized delayed treatment trial with an immediate (1-year baseline and 2-year intervention) or delayed (2-year baseline and 1-year intervention) group. Twenty ASPs serving 1,700 children (aged 5-12 years) were recruited, with baseline occurring spring 2013, and outcome assessment occurring spring 2014 and 2015. The multistep intervention, Strategies To Enhance Practice for Healthy Eating, assisted ASP leaders/staff to serve foods/beverages that meet the nutrition standards. The foods and beverages served for snack were observed directly. Compared with non-intervention years, both the immediate and delayed groups increased the number of days/week that fruits/vegetables (0.6 vs 1.7 days/week and 0.6 vs 4.4 days/week, OR=3.80, 95% CI=1.45, 9.95) and water (2.3 vs 3.7 days/week and 2.7 vs 4.8 days/week, OR=4.65, 95% CI=1.69, 12.79) were served. Sugar-sweetened beverages were almost eliminated by post-assessment (1.2 vs 0.2 days/week and 3.2 vs 0.0 days/week, OR=0.05, 95% CI=0.02, 0.13). Only the immediate group decreased the number of days/week desserts were served (2.9 vs 0.6 days/week, OR=0.10, 95% CI=0.03, 0.33). Implementation barriers for the delayed group included once/month delivery schedules for fruits/vegetables and limited storage space for foods meeting the Healthy Eating Standards. Improvements in the foods/beverages served in ASPs can be made, yet were hindered by structural barriers related to procurement and storage of perishable foods. Additional efforts are needed to support ASPs as they work toward fully achieving the Healthy Eating Standards. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Assembly of the Type II Secretion System such as Found in Vibrio cholerae Depends on the Novel Pilotin AspS

PubMed Central

Dunstan, Rhys A.; Heinz, Eva; Wijeyewickrema, Lakshmi C.; Pike, Robert N.; Purcell, Anthony W.; Evans, Timothy J.; Praszkier, Judyta; Robins-Browne, Roy M.; Strugnell, Richard A.; Korotkov, Konstantin V.; Lithgow, Trevor

2013-01-01

The Type II Secretion System (T2SS) is a molecular machine that drives the secretion of fully-folded protein substrates across the bacterial outer membrane. A key element in the machinery is the secretin: an integral, multimeric outer membrane protein that forms the secretion pore. We show that three distinct forms of T2SSs can be distinguished based on the sequence characteristics of their secretin pores. Detailed comparative analysis of two of these, the Klebsiella-type and Vibrio-type, showed them to be further distinguished by the pilotin that mediates their transport and assembly into the outer membrane. We have determined the crystal structure of the novel pilotin AspS from Vibrio cholerae, demonstrating convergent evolution wherein AspS is functionally equivalent and yet structurally unrelated to the pilotins found in Klebsiella and other bacteria. AspS binds to a specific targeting sequence in the Vibrio-type secretins, enhances the kinetics of secretin assembly, and homologs of AspS are found in all species of Vibrio as well those few strains of Escherichia and Shigella that have acquired a Vibrio-type T2SS. PMID:23326233

Effects of long-term administration of aspartame on biochemical indices, lipid profile and redox status of cellular system of male rats.

PubMed

Adaramoye, Oluwatosin A; Akanni, Olubukola O

2016-01-01

Aspartame (N-L-α-aspartyl-L-phenylalanine-1-methyl ester) (ASP) is a synthetic sweetener used in foods and its safety remains controversial. The study was designed to investigate the effects of long-term administration of aspartame on redox status, lipid profile and biochemical indices in tissues of male Wistar rats. Rats were assigned into four groups and given distilled water (control), aspartame at doses of 15 mg/kg (ASP 1), 35 mg/kg (ASP 2) and 70 mg/kg (ASP 3) daily by oral gavage for consecutive 9 weeks. Administration of ASP 2 and ASP 3 significantly increased the weight of liver and brain, and relative weight of liver of rats. Lipid peroxidation products significantly increased in the kidney, liver and brain of rats at all doses of ASP with concomitant depletion of antioxidant parameters, viz. glutathione-s-transferase, glutathione peroxidase, superoxide dismutase, catalase and reduced glutathione. Furthermore, ASP 2 and ASP 3 significantly increased the levels of gamma glutamyl transferase by 70% and 85%; alanine aminotransferase by 66% and 117%; aspartate aminotransferase by 21% and 48%; urea by 72% and 58% and conjugated bilirubin by 63% and 64%, respectively. Also, ASP 2 and ASP 3 significantly increased the levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the rats. Histological findings showed that ASP 2 and ASP 3 caused cyto-architectural changes such as degeneration, monocytes infiltration and necrotic lesions in brain, kidney and liver of rats. Aspartame may induce redox and lipid imbalance in rats via mechanism that involves oxidative stress and depletion of glutathione-dependent system.

Characterization of the functional role of Asp141, Asp194, and Asp464 residues in the Mn2+-L-malate binding of pigeon liver malic enzyme.

PubMed

Chou, W Y; Chang, H P; Huang, C H; Kuo, C C; Tong, L; Chang, G G

2000-02-01

Pigeon liver malic enzyme was inactivated and cleaved at Asp141, Asp194, and Asp464 by the Cu2+-ascorbate system in acidic environment. Site-specific mutagenesis was performed at these putative metal-binding sites. Three point mutants, D141N, D194N, and D464N; three double mutants, D(141,194)N, D(194,464)N, and D(141,464)N; and a triple mutant, D(141,194,464)N; as well as the wild-type malic enzyme (WT) were successfully cloned and expressed in Escherichia coli cells. All recombinant enzymes, except the triple mutant, were purified to apparent homogeneity by successive Q-Sepharose and adenosine-2',5'-bisphosphate-agarose columns. The mutants showed similar apparent Km,NADP values to that of the WT. The Km,Mal value was increased in the D141N and D194N mutants. The Km,Mn value, on the other hand, was increased only in the D141N mutant by 14-fold, corresponding to approximately 1.6 kcal/mol for the Asp141-Mn2+ binding energy. Substrate inhibition by L-malate was only observed in WT, D464N, and D(141,464)N. Initial velocity experiments were performed to derive the various kinetic parameters. The possible interactions between Asp141, Asp194, and Asp464 were analyzed by the double-mutation cycles and triple-mutation box. There are synergistic weakening interactions between Asp141 and Asp194 in the metal binding that impel the D(141,194)N double mutant to an overall specificity constant [k(cat)/(Kd,Mn Km,Mal Km,NADP)] at least four orders of magnitude smaller than the WT value. This difference corresponds to an increase of 6.38 kcal/mol energy barrier for the catalytic efficiency. Mutation at Asp464, on the other hand, has partial additivity on the mutations at Asp141 and Asp194. The overall specificity constants for the double mutants D(194,464)N and D(141,464)N or the triple mutant D(141,194,464)N were decreased by only 10- to 100-fold compared to the WT. These results strongly suggest the involvement of Asp141 in the Mn2+-L-malate binding for the pigeon liver malic enzyme. The Asp194 and Asp464, which may be oxidized by nonspecific binding of Cu2+, are involved in the Mn2+-L-malate binding or catalysis indirectly by modulating the binding affinity of Asp141 with the Mn2+.

eNOS Glu298Asp polymorphism and hypertension in a cohort study in Japanese.

PubMed

Kishimoto, Takuji; Misawa, Yumiko; Kaetu, Akihiko; Nagai, Maria; Osaki, Yoneatsu; Okamoto, Mikizoh; Yoshida, Soiti; Kurosawa, Yoichi; Fukumoto, Soji

2004-11-01

Some recent case-control association studies have suggested negative and positive relationship between Glu298Asp (the substitution of aspartic acid for glutamic acid at amino acid position 298) polymorphism of the endothelial nitric oxide synthase (eNOS) gene and hypertension. To investigate whether the Glu298Asp polymorphism of the eNOS gene affects the incidence of hypertension, a retrospective cohort study was performed. The baseline data among Japanese workers in Shimane Prefecture, Japan, were obtained at regular health examination in 1992, and a retrospective cohort study was performed to analyze the influence of Glu298Asp polymorphism on the incidence of hypertension in 1998. The incidences of Glu298Glu, Glu298Asp, and Asp298Asp genotypes in the subjects were 86.4%, 12.6% and 1.1%, respectively. The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by single variance analysis were 0.830 in total subjects [95% confidence interval (CI) 0.474-1.452], 0.596 in subjects 20-39 years old (95% CI; 0.207-1.717), and 0.915 in subjects 40-59 years old (95% CI; 0.464-1.805). The risk ratios of Glu298Asp and Asp298Asp against Glu298Glu for the incidence of hypertension by multiple variance analysis adjusted for sex, BMI, serum total cholesterol, serum high-density lipoprotein (HDL) cholesterol, fasting glucose, cigarette smoking, drinking habits, eating habits, and exercise in 1992 were 0.750 in total subjects (95% CI; 0.421-1.335), 0.505 in subjects 20-39 years old (95% CI; 0.170-1.496), and 0.873 in subjects 40-59 years old (95% CI; 0.434-1.757). These results suggested no association between the Glu298Asp gene polymorphism and the incidence of hypertension in this selected population.

A conserved hydrogen-bond network in the catalytic centre of animal glutaminyl cyclases is critical for catalysis.

PubMed

Huang, Kai-Fa; Wang, Yu-Ruei; Chang, En-Cheng; Chou, Tsung-Lin; Wang, Andrew H-J

2008-04-01

QCs (glutaminyl cyclases; glutaminyl-peptide cyclotransferases, EC 2.3.2.5) catalyse N-terminal pyroglutamate formation in numerous bioactive peptides and proteins. The enzymes were reported to be involved in several pathological conditions such as amyloidotic disease, osteoporosis, rheumatoid arthritis and melanoma. The crystal structure of human QC revealed an unusual H-bond (hydrogen-bond) network in the active site, formed by several highly conserved residues (Ser(160), Glu(201), Asp(248), Asp(305) and His(319)), within which Glu(201) and Asp(248) were found to bind to substrate. In the present study we combined steady-state enzyme kinetic and X-ray structural analyses of 11 single-mutation human QCs to investigate the roles of the H-bond network in catalysis. Our results showed that disrupting one or both of the central H-bonds, i.e., Glu(201)...Asp(305) and Asp(248)...Asp(305), reduced the steady-state catalysis dramatically. The roles of these two COOH...COOH bonds on catalysis could be partly replaced by COOH...water bonds, but not by COOH...CONH(2) bonds, reminiscent of the low-barrier Asp...Asp H-bond in the active site of pepsin-like aspartic peptidases. Mutations on Asp(305), a residue located at the centre of the H-bond network, raised the K(m) value of the enzyme by 4.4-19-fold, but decreased the k(cat) value by 79-2842-fold, indicating that Asp(305) primarily plays a catalytic role. In addition, results from mutational studies on Ser(160) and His(319) suggest that these two residues might help to stabilize the conformations of Asp(248) and Asp(305) respectively. These data allow us to propose an essential proton transfer between Glu(201), Asp(305) and Asp(248) during the catalysis by animal QCs.

Clinical Utility of Ammonia Concentration as a Diagnostic Test in Monitoring of the Treatment with L-Asparaginase in Children with Acute Lymphoblastic Leukemia

PubMed Central

Czogała, Małgorzata; Balwierz, Walentyna; Sztefko, Krystyna; Rogatko, Iwona

2014-01-01

L-asparaginase (ASP) is an enzyme used as one of the basic regimens in the acute lymphoblastic leukemia (ALL) therapy. Because of the possibility of the enzyme inactivation by antibodies, monitoring of ASP activity is essential. The aim of the study was to examine if plasma concentration of ammonia, a direct product of the reaction catalyzed by ASP, can be used in the assessment of ASP activity. A group of 87 patients with acute lymphoblastic leukemia treated in the Department of Pediatric Oncology and Hematology in Krakow was enrolled to the study. ASP activity and ammonia concentration were measured after ASP administrations during induction. A positive correlation was found between the ammonia concentration and ASP activity (R = 0.44; P < 0.0001) and between the medium values of ammonia concentration and ASP activity (R = 0.56; P < 0.0001). The analysis of ROC curves revealed the moderate accuracy of the ammonia concentration values in the ASP activity assessment. It was also found that the medium value of ammonia concentrations can be useful in identification of the patients with low (<100 IU/L) and undetectable (<30 IU/L) ASP activity. The plasma ammonia concentration may reflect ASP activity and can be useful when a direct measurement of the activity is unavailable. PMID:25157375

Structural elucidation of the DFG-Asp in and DFG-Asp out states of TAM kinases and insight into the selectivity of their inhibitors.

PubMed

Messoussi, Abdellah; Peyronnet, Lucile; Feneyrolles, Clémence; Chevé, Gwénaël; Bougrin, Khalid; Yasri, Aziz

2014-10-10

Structural elucidation of the active (DFG-Asp in) and inactive (DFG-Asp out) states of the TAM family of receptor tyrosine kinases is required for future development of TAM inhibitors as drugs. Herein we report a computational study on each of the three TAM members Tyro-3, Axl and Mer. DFG-Asp in and DFG-Asp out homology models of each one were built based on the X-ray structure of c-Met kinase, an enzyme with a closely related sequence. Structural validation and in silico screening enabled identification of critical amino acids for ligand binding within the active site of each DFG-Asp in and DFG-Asp out model. The position and nature of amino acids that differ among Tyro-3, Axl and Mer, and the potential role of these residues in the design of selective TAM ligands, are discussed.

De novo mutations of the ATP6V1A gene cause developmental encephalopathy with epilepsy.

PubMed

Fassio, Anna; Esposito, Alessandro; Kato, Mitsuhiro; Saitsu, Hirotomo; Mei, Davide; Marini, Carla; Conti, Valerio; Nakashima, Mitsuko; Okamoto, Nobuhiko; Olmez Turker, Akgun; Albuz, Burcu; Semerci Gündüz, C Nur; Yanagihara, Keiko; Belmonte, Elisa; Maragliano, Luca; Ramsey, Keri; Balak, Chris; Siniard, Ashley; Narayanan, Vinodh; Ohba, Chihiro; Shiina, Masaaki; Ogata, Kazuhiro; Matsumoto, Naomichi; Benfenati, Fabio; Guerrini, Renzo

2018-06-01

V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p.Pro27Arg, p.Asp100Tyr), and to moderate delay with milder epilepsy in the other two (p.Asp349Asn, p.Asp371Gly). Modelling performed on the available prokaryotic and eukaryotic structures of v-ATPase predicted p.Pro27Arg to perturb subunit interaction, p.Asp100Tyr to cause steric hindrance and destabilize protein folding, p.Asp349Asn to affect the catalytic function and p.Asp371Gly to impair the rotation process, necessary for proton transport. We addressed the impact of p.Asp349Asn and p.Asp100Tyr mutations on ATP6V1A expression and function by analysing ATP6V1A-overexpressing HEK293T cells and patients' lymphoblasts. The p.Asp100Tyr mutant was characterized by reduced expression due to increased degradation. Conversely, no decrease in expression and clearance was observed for p.Asp349Asn. In HEK293T cells overexpressing either pathogenic or control variants, p.Asp349Asn significantly increased LysoTracker® fluorescence with no effects on EEA1 and LAMP1 expression. Conversely, p.Asp100Tyr decreased both LysoTracker® fluorescence and LAMP1 levels, leaving EEA1 expression unaffected. Both mutations decreased v-ATPase recruitment to autophagosomes, with no major impact on autophagy. Experiments performed on patients' lymphoblasts using the LysoSensor™ probe revealed lower pH of endocytic organelles for p.Asp349Asn and a reduced expression of LAMP1 with no effect on the pH for p.Asp100Tyr. These data demonstrate gain of function for p.Asp349Asn characterized by an increased proton pumping in intracellular organelles, and loss of function for p.Asp100Tyr with decreased expression of ATP6V1A and reduced levels of lysosomal markers. We expressed p.Asp349Asn and p.Asp100Tyr in rat hippocampal neurons and confirmed significant and opposite effects in lysosomal labelling. However, both mutations caused a similar defect in neurite elongation accompanied by loss of excitatory inputs, revealing that altered lysosomal homeostasis markedly affects neurite development and synaptic connectivity. This study provides evidence that de novo heterozygous ATP6V1A mutations cause a developmental encephalopathy with a pathomechanism that involves perturbations of lysosomal homeostasis and neuronal connectivity, uncovering a novel role for v-ATPase in neuronal development.

Research Related to Multi Degree of Freedom Magnetic Suspensions. Degree awarded by Old Dominion Univ. Aug. 1997

NASA Technical Reports Server (NTRS)

Britcher, Colin; Yang, Yan

1997-01-01

This thesis covers the activities associated with (1) recommissioning of the 6-inch Magnetic Suspension and Balance System (MSBS) and (2) enhancing the Annular Suspension and Pointing System (ASPS). These activities continue the program of research in the multi degree of freedom magnetic suspension program at Old Dominion University. The 6-inch MSBS is a large gap magnetic suspension system used as a model support and balance system in wind tunnels. The first stage of recommissioning of the 6-inch MSBS for the 6-inch subsonic wind tunnel is performed. Experimental data and computational results for the magnetic field distribution of the MSBS are given and compared with the estimated magnetic field strength. The comparison indicates that the magnet system is still operating as designed. The Electromagnetic Position Sensor used in the 6-inch MSBS is analyzed before its find reinstatement. The ASPS is a small gap magnetic suspension system providing orientation, mechanical isolation and fine pointing of space payloads. The control system of the ASPS is improved by designing a new code to realize red time control over the system. The original Proportional-Derivative controller is upgraded to a Proportional-Integral-Derivative controller. This progress leads to a system which is more stable and robust with less noise. This new controller is generic and can be adapted to the 6-inch MSBS. Finally, future work on these two systems is proposed.

The relationship of Asperger's syndrome to autism: a preliminary EEG coherence study.

PubMed

Duffy, Frank H; Shankardass, Aditi; McAnulty, Gloria B; Als, Heidelise

2013-07-31

It has long been debated whether Asperger's Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD. Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other. Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed. Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The ASP population appears to constitute a neurophysiologically identifiable, normally distributed entity within the higher functioning tail of the ASD population distribution. These results must be replicated with a larger sample given their potentially immense clinical, emotional and financial implications for affected individuals, their families and their caregivers.

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

PubMed Central

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp)8, has a strong affinity to bone surface. The aim of this study was to synthesize (Asp)8-PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp)8-PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp)8-PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp)8-PEG-PCL nanoparticles by cancer cells. (Asp)8-PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10–800 μg/mL. (Asp)8-PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp)8-PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp)8-PEG-PCL. (Asp)8-PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp)8-PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp)8-PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp)8-PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone. PMID:28507436

Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori.

PubMed

Luo, Xiao-Feng; Jiao, Jian-Hua; Zhang, Wen-Yue; Pu, Han-Ming; Qu, Bao-Jin; Yang, Bing-Ya; Hou, Min; Ji, Min-Jun

2016-07-07

To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori.

The relationship of Asperger’s syndrome to autism: a preliminary EEG coherence study

PubMed Central

2013-01-01

Background It has long been debated whether Asperger’s Syndrome (ASP) should be considered part of the Autism Spectrum Disorders (ASD) or whether it constitutes a unique entity. The Diagnostic and Statistical Manual, fourth edition (DSM-IV) differentiated ASP from high functioning autism. However, the new DSM-5 umbrellas ASP within ASD, thus eliminating the ASP diagnosis. To date, no clear biomarkers have reliably distinguished ASP and ASD populations. This study uses EEG coherence, a measure of brain connectivity, to explore possible neurophysiological differences between ASP and ASD. Methods Voluminous coherence data derived from all possible electrode pairs and frequencies were previously reduced by principal components analysis (PCA) to produce a smaller number of unbiased, data-driven coherence factors. In a previous study, these factors significantly and reliably differentiated neurotypical controls from ASD subjects by discriminant function analysis (DFA). These previous DFA rules are now applied to an ASP population to determine if ASP subjects classify as control or ASD subjects. Additionally, a new set of coherence based DFA rules are used to determine whether ASP and ASD subjects can be differentiated from each other. Results Using prior EEG coherence based DFA rules that successfully classified subjects as either controls or ASD, 96.2% of ASP subjects are classified as ASD. However, when ASP subjects are directly compared to ASD subjects using new DFA rules, 92.3% ASP subjects are identified as separate from the ASD population. By contrast, five randomly selected subsamples of ASD subjects fail to reach significance when compared to the remaining ASD populations. When represented by the discriminant variable, both the ASD and ASD populations are normally distributed. Conclusions Within a control-ASD dichotomy, an ASP population falls closer to ASD than controls. However, when compared directly with ASD, an ASP population is distinctly separate. The ASP population appears to constitute a neurophysiologically identifiable, normally distributed entity within the higher functioning tail of the ASD population distribution. These results must be replicated with a larger sample given their potentially immense clinical, emotional and financial implications for affected individuals, their families and their caregivers. PMID:23902729

Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone.

PubMed

Liu, Jinsong; Zeng, Youyun; Shi, Shuai; Xu, Lihua; Zhang, Hualin; Pathak, Janak L; Pan, Yihuai

2017-01-01

Treatment of cancer metastasized to bone is still a challenge due to hydrophobicity, instability, and lack of target specificity of anticancer drugs. Poly (ethylene glycol)-poly (ε-caprolactone) polymer (PEG-PCL) is an effective, biodegradable, and biocompatible hydrophobic drug carrier, but lacks bone specificity. Polyaspartic acid with eight peptide sequences, that is, (Asp) 8 , has a strong affinity to bone surface. The aim of this study was to synthesize (Asp) 8 -PEG-PCL nanoparticles as a bone-specific carrier of hydrophobic drugs to treat cancer metastasized to bone. 1 H nuclear magnetic resonance, Fourier transform infrared spectroscopy, and transmission electron microscopy data showed that (Asp) 8 -PEG-PCL nanoparticles (size 100 nm) were synthesized successfully. (Asp) 8 -PEG-PCL nanoparticles did not promote erythrocyte aggregation. Fluorescence microscopy showed clear uptake of Nile red-loaded (Asp) 8 -PEG-PCL nanoparticles by cancer cells. (Asp) 8 -PEG-PCL nanoparticles did not show cytotoxic effect on MG63 and human umbilical vein endothelial cells at the concentration of 10-800 μg/mL. (Asp) 8 -PEG-PCL nanoparticles bound with hydroxyapatite 2-fold more than PEG-PCL. Intravenously injected (Asp) 8 -PEG-PCL nanoparticles accumulated 2.7-fold more on mice tibial bone, in comparison to PEG-PCL. Curcumin is a hydrophobic anticancer drug with bone anabolic properties. Curcumin was loaded in the (Asp) 8 -PEG-PCL. (Asp) 8 -PEG-PCL showed 11.07% loading capacity and 95.91% encapsulation efficiency of curcumin. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles gave sustained release of curcumin in high dose for >8 days. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic effect on MG63, MCF7, and HeLa cancer cells. In conclusion, (Asp) 8 -PEG-PCL nanoparticles were biocompatible, permeable in cells, a potent carrier, and an efficient releaser of hydrophobic anticancer drug and were bone specific. The curcumin-loaded (Asp) 8 -PEG-PCL nanoparticles showed strong antitumorigenic ability in vitro. Therefore, (Asp) 8 -PEG-PCL nanoparticles could be a potent carrier of hydrophobic anticancer drugs to treat the cancer metastasized to bone.

Establishment of a nested-ASP-PCR method to determine the clarithromycin resistance of Helicobacter pylori

PubMed Central

Luo, Xiao-Feng; Jiao, Jian-Hua; Zhang, Wen-Yue; Pu, Han-Ming; Qu, Bao-Jin; Yang, Bing-Ya; Hou, Min; Ji, Min-Jun

2016-01-01

AIM: To investigate clarithromycin resistance positions 2142, 2143 and 2144 of the 23SrRNA gene in Helicobacter pylori (H. pylori) by nested-allele specific primer-polymerase chain reaction (nested-ASP-PCR). METHODS: The gastric tissue and saliva samples from 99 patients with positive results of the rapid urease test (RUT) were collected. The nested-ASP-PCR method was carried out with the external primers and inner allele-specific primers corresponding to the reference strain and clinical strains. Thirty gastric tissue and saliva samples were tested to determine the sensitivity of nested-ASP-PCR and ASP-PCR methods. Then, clarithromycin resistance was detected for 99 clinical samples by using different methods, including nested-ASP-PCR, bacterial culture and disk diffusion. RESULTS: The nested-ASP-PCR method was successfully established to test the resistance mutation points 2142, 2143 and 2144 of the 23SrRNA gene of H. pylori. Among 30 samples of gastric tissue and saliva, the H. pylori detection rate of nested-ASP-PCR was 90% and 83.33%, while the detection rate of ASP-PCR was just 63% and 56.67%. Especially in the saliva samples, nested-ASP-PCR showed much higher sensitivity in H. pylori detection and resistance mutation rates than ASP-PCR. In the 99 RUT-positive gastric tissue and saliva samples, the H. pylori-positive detection rate by nested-ASP-PCR was 87 (87.88%) and 67 (67.68%), in which there were 30 wild-type and 57 mutated strains in gastric tissue and 22 wild-type and 45 mutated strains in saliva. Genotype analysis showed that three-points mixed mutations were quite common, but different resistant strains were present in gastric mucosa and saliva. Compared to the high sensitivity shown by nested-ASP-PCR, the positive detection of bacterial culture with gastric tissue samples was 50 cases, in which only 26 drug-resistant strains were found through analyzing minimum inhibitory zone of clarithromycin. CONCLUSION: The nested-ASP-PCR assay showed higher detection sensitivity than ASP-PCR and drug sensitivity testing, which could be performed to evaluate clarithromycin resistance of H. pylori. PMID:27433095

Automated Sequence Processor: Something Old, Something New

NASA Technical Reports Server (NTRS)

Streiffert, Barbara; Schrock, Mitchell; Fisher, Forest; Himes, Terry

2012-01-01

High productivity required for operations teams to meet schedules Risk must be minimized. Scripting used to automate processes. Scripts perform essential operations functions. Automated Sequence Processor (ASP) was a grass-roots task built to automate the command uplink process System engineering task for ASP revitalization organized. ASP is a set of approximately 200 scripts written in Perl, C Shell, AWK and other scripting languages.. ASP processes/checks/packages non-interactive commands automatically.. Non-interactive commands are guaranteed to be safe and have been checked by hardware or software simulators.. ASP checks that commands are non-interactive.. ASP processes the commands through a command. simulator and then packages them if there are no errors.. ASP must be active 24 hours/day, 7 days/week..

Prevention and Control of Multidrug-Resistant Gram-Negative Bacteria in Adult Intensive Care Units: A Systematic Review and Network Meta-analysis.

PubMed

Teerawattanapong, Nattawat; Kengkla, Kirati; Dilokthornsakul, Piyameth; Saokaew, Surasak; Apisarnthanarak, Anucha; Chaiyakunapruk, Nathorn

2017-05-15

This study evaluated the relative efficacy of strategies for the prevention of multidrug-resistant gram-negative bacteria (MDR-GNB) in adult intensive care units (ICUs). A systematic review and network meta-analysis was performed; searches of the Cochrane Library, PubMed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) included all randomized controlled trials and observational studies conducted in adult patients hospitalized in ICUs and evaluating standard care (STD), antimicrobial stewardship program (ASP), environmental cleaning (ENV), decolonization methods (DCL), or source control (SCT), simultaneously. The primary outcomes were MDR-GNB acquisition, colonization, and infection; secondary outcome was ICU mortality. Of 3805 publications retrieved, 42 met inclusion criteria (5 randomized controlled trials and 37 observational studies), involving 62068 patients (median age, 58.8 years; median APACHE [Acute Physiology and Chronic Health Evaluation] II score, 18.9). The majority of studies reported extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and MDR Acinetobacter baumannii. Compared with STD, a 4-component strategy composed of STD, ASP, ENV, and SCT was the most effective intervention (rate ratio [RR], 0.05 [95% confidence interval {CI}, .01-.38]). When ENV was added to STD+ASP or SCT was added to STD+ENV, there was a significant reduction in the acquisition of MDR A. baumannii (RR, 0.28 [95% CI, .18-.43] and 0.48 [95% CI, .35-.66], respectively). Strategies with ASP as a core component showed a statistically significant reduction the acquisition of ESBL-producing Enterobacteriaceae (RR, 0.28 [95% CI, .11-.69] for STD+ASP+ENV and 0.23 [95% CI, .07-.80] for STD+ASP+DCL). A 4-component strategy was the most effective intervention to prevent MDR-GNB acquisition. As some strategies were differential for certain bacteria, our study highlighted the need for further evaluation of the most effective prevention strategies. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Appropriateness of Antibiotic Prescribing in U. S. Children’s Hospitals: A National Point Prevalence Survey

PubMed Central

Tribble, Alison; Lee, Brian; Handy, Lori; Gerber, Jeffrey S; Hersh, Adam L; Kronman, Matthew; Terrill, Cindy; Newland, Jason

2017-01-01

Abstract Background Multiple studies estimate that inappropriate antibiotic prescribing ranges from 30–50% in hospitalized patients, but few have included pediatric patients. Pediatric studies characterizing inappropriate prescribing are needed to target and improve antimicrobial stewardship program (ASP) efforts. Methods Cross-sectional analysis of antimicrobial prescribing at 30 U.S. children’s hospitals. Participating hospitals were academic, tertiary care hospitals in the Sharing Antimicrobial Reports for Pediatric Stewardship (SHARPS) collaborative. Subjects were children 0–17 years with an active antibiotic order at 0800 on a single day during three consecutive calendar quarters (Q3 2016 – Q1 2017). Each hospital’s ASP used a standardized survey to collect data on antibiotic orders and evaluate appropriateness. Data were pooled from the three surveys. The primary outcome was the pooled estimate for the percentage of prescriptions classified as inappropriate. Secondary outcomes were pooled estimates for indication, reason for inappropriate use, and ASP review status for each antibiotic. Results Of 19,598 children hospitalized on survey days, 6,922 (35%) had ≥1 active antibiotic order. Median age of children receiving antibiotics was 3.7 years (0.5, 10.9). Figures 1 and 2 show the most common antibiotics and indications. Of all antibiotic orders, 1,514 (15%) were classified as inappropriate, and 19% of patients with antibiotic orders had at least one inappropriate order. The most common reasons for inappropriate use were bug-drug mismatch (26%), surgical prophylaxis > 24 hours (18%) and unnecessary duplicate therapy (12%). ASPs would not have routinely reviewed 50% of all inappropriate orders. An additional 22% of inappropriate orders were for antibiotics typically reviewed by ASPs, but were yet to be reviewed at the time of the survey. Conclusion Across 30 children’s hospitals, approximately 1 in 3 hospitalized children is receiving an antibiotic at any given time. Almost 20% of these children are receiving inappropriate therapy, and a substantial portion of inappropriate use is not captured by current ASP practices. Figures 1 and 2: Disclosures C. Terrill, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant; J. Newland, Merck: Grant Investigator, Research grant; Allergan: Grant Investigator, Research grant.

NSWC-NADC interactive communication links for AN/UYS-1 loadtape creation and retrieval

NASA Astrophysics Data System (ADS)

Greathouse, D. M.

1984-09-01

This report contains an alternative method of communication (interactive vs. remote batch) with the Naval Air Development Center for the creation and retrieval of AN/UYS-1 Advanced Signal Processor (ASP) operational software loadtapes. Operational software for the Digital Acoustic Sensor Simulator (DASS) program is developed and maintained at the Naval Air Development Center (NADC). The Facility for Automated Software Production (FASP), an NADC-resident software generation facility, provides the support tools necessary for data base creation, software development and maintenance, and loadtape generation. Once a loadtape file is generated at NADC, it must be retrieved via telephone transmission and placed in a format suitable for loading into the AN/UYS-1 Advanced Signal Processor (ASP).

The Relationship between Intensity and Breadth of After-School Program Participation and Academic Achievement: Evidence from a Short-Term Longitudinal Study

ERIC Educational Resources Information Center

Springer, Ken; Diffily, Deborah

2012-01-01

We explored the extent to which intensity and breadth of participation in an after-school program (ASP) predicted academic achievement, as measured by changes in grades and attendance. The sample comprised 719 2nd-grade through 8th-grade Boys and Girls Clubs of Greater Dallas members during the 2009-2010 academic year. With respect to intensity,…

Molecular characterization of 45 kDa aspartic protease of Trichinella spiralis.

PubMed

Park, Jong Nam; Park, Sang Kyun; Cho, Min Kyoung; Park, Mi-Kyung; Kang, Shin Ae; Kim, Dong-Hee; Yu, Hak Sun

2012-12-21

In a previous study, we identified an aspartic protease gene (Ts-Asp) from the Trichinella spiralis muscle stage larva cDNA library. The gene sequence of Ts-Asp was 1281 bp long and was found to encode a protein consisting of 405 amino acids, with a molecular mass of 45.248 kD and a pI of 5.95. The deduced Ts-Asp has a conserved catalytic motif with catalytic aspartic acid residues in the active site, a common characteristic of aspartic proteases. In addition, the deduced amino acid sequence of Ts-Asp was found to possess significant homology (above 50%) with aspartic proteases from nematode parasites. Results of phylogenetic analysis indicated a close relationship of Ts-Asp with cathepsin D aspartic proteases. For production of recombinant Ts-Asp (rTs-Asp), the pGEX4T expression system was used. Like other proteases, the purified rTs-Asp was able to digest collagen matrix in vitro. Abundant expression of Ts-Asp was observed in muscle stage larva. Ts-Asp was detected in ES proteins, and was able to elicit the production of specific antibodies. It is the first report of molecular characterization of aspartic protease isolated from T. spiralis. Copyright © 2012 Elsevier B.V. All rights reserved.

The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in non-discriminating aspartyl-tRNA synthetase safeguards the genetic code.

PubMed

Fischer, Frédéric; Huot, Jonathan L; Lorber, Bernard; Diss, Guillaume; Hendrickson, Tamara L; Becker, Hubert D; Lapointe, Jacques; Kern, Daniel

2012-06-01

Helicobacter pylori catalyzes Asn-tRNA(Asn) formation by use of the indirect pathway that involves charging of Asp onto tRNA(Asn) by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp into Asn by the GatCAB amidotransferase. We show that the partners of asparaginylation assemble into a dynamic Asn-transamidosome, which uses a different strategy than the Gln-transamidosome to prevent the release of the mischarged aminoacyl-tRNA intermediate. The complex is described by gel-filtration, dynamic light scattering and kinetic measurements. Two strategies for asparaginylation are shown: (i) tRNA(Asn) binds GatCAB first, allowing aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii) tRNA(Asn) is bound by ND-AspRS which releases the Asp-tRNA(Asn) product much slower than the cognate Asp-tRNA(Asp); this kinetic peculiarity allows GatCAB to bind and transamidate Asp-tRNA(Asn) before its release by the ND-AspRS. These results are discussed in the context of the interrelation between the Asn and Gln-transamidosomes which use the same GatCAB in H. pylori, and shed light on a kinetic mechanism that ensures faithful codon reassignment for Asn.

76 FR 81942 - Agency Information Collection Request 30-Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-29

... the control group. This information will enable us to describe each implemented program and the... and Evaluation (ASPE), the Centers for Disease Control and Prevention (CDC), and the Administration... Evaluation). The TPP Replication Evaluation will be an experimental evaluation which will determine the...

Different HIV-1 env frames: gp120 and ASP (antisense protein) biosynthesis, and theirs co-variation tropic amino acid signatures in X4- and R5-viruses.

PubMed

Dimonte, Salvatore

2017-01-01

Antisense protein (ASP) is the new actor of viral life of Human Immunodeficiency Virus type 1 (HIV-1) although proposed above 20 years ago. The asp ORF is into complementary strand of the gp120/gp41 junction of env gene. The ASP biological role remains little known. Knowing the Env markers of viral tropism, a dataset of sequences (660 strains) was used to analyze the hypothetical ASP involvement in CCR5 (R5) and/or CXCR4 (X4) co-receptor interaction. Preliminarily, prevalence of ASP and gp120 V3 mutations was performed; following association among mutations were elaborate. The classical V3 tropic-signatures were confirmed, and 36 R5- and 22 X4-tropic ASP mutations were found. Moreover, by analyzing the ASP sequences, 36 out of 179 amino acid positions significantly associated with different co-receptor usage were found. Several statistically significant associations between gp120 V3 and ASP mutations were observed. The dendrogram showed the existence of a cluster associated with R5-usage and a large cluster associated with X4-usage. These results show that gp120 V3 and specific amino acid changes in ASP are associated together with CXCR4 and/or CCR5-usage. These findings implement previous observations on unclear ASP functions. J. Med. Virol. 89:112-122, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparative Effectiveness of After-School Programs to Increase Physical Activity

PubMed Central

Gesell, Sabina B.; Sommer, Evan C.; Lambert, E. Warren; Vides de Andrade, Ana Regina; Davis, Lauren; Beech, Bettina M.; Mitchell, Stephanie J.; Neloms, Stevon; Ryan, Colleen K.

2013-01-01

Background. We conducted a comparative effectiveness analysis to evaluate the difference in the amount of physical activity children engaged in when enrolled in a physical activity-enhanced after-school program based in a community recreation center versus a standard school-based after-school program. Methods. The study was a natural experiment with 54 elementary school children attending the community ASP and 37 attending the school-based ASP. Accelerometry was used to measure physical activity. Data were collected at baseline, 6 weeks, and 12 weeks, with 91% retention. Results. At baseline, 43% of the multiethnic sample was overweight/obese, and the mean age was 7.9 years (SD = 1.7). Linear latent growth models suggested that the average difference between the two groups of children at Week 12 was 14.7 percentage points in moderate-vigorous physical activity (P < .001). Cost analysis suggested that children attending traditional school-based ASPs—at an average cost of $17.67 per day—would need an additional daily investment of $1.59 per child for 12 weeks to increase their moderate-vigorous physical activity by a model-implied 14.7 percentage points. Conclusions. A low-cost, alternative after-school program featuring adult-led physical activities in a community recreation center was associated with increased physical activity compared to standard-of-care school-based after-school program. PMID:23984052

[Experimental study on aging effect of Angelica sinensis polysaccharides combined with cytarabine on human leukemia KG1alpha cell lines].

PubMed

Xu, Chun-Yan; Geng, Shan; Liu, Jun; Zhu, Jia-Hong; Zhang, Xian-Ping; Jiang, Rong; Wang, Ya-Ping

2014-04-01

The latest findings of our laboratory showed that Angelica sinensis polysaccharide (ASP) showed a definite effect in regulating the aging of hematopoietic stem cells. Leukemia is a type of malignant hematopoietic tumor in hematopoietic stem cells. There have been no relevant reports about ASP's effect in regulating the aging of leukemia cells. In this study, human acute myeloid leukemia (AML) KG1alpha cell lines in logarithmic growth phase were taken as the study object, and were divided into the ASP group, the cytarabine (Ara-C) group, the ASP + Ara-C group and the control group. The groups were respectively treated with different concentration of ASP, Ara-C and ASP + Ara-C for different periods, with the aim to study the effect of ASP combined with Ara-C in regulating the aging of human acute myeloid leukemia KG1alpha cell lines and its relevant mechanism. The results showed that ASP, Ara-C and ASP + Ara-C could obviously inhibit KG1alpha cell proliferation in vitro, block the cells in G0/G1 phase. The cells showed the aging morphological feature. The percentage of positive stained aging cells was dramatically increased, and could significantly up-regulate the expression of aging-related proteins P16 and RB, which were more obvious in the ASP + Ara-C group. In conclusion, the aging mechanism of KG1alpha cell induced by ASP and Ara-C may be related to the regulation of the expression of aging-related proteins, suggesting that the combined administration of ASP and anticancer drugs plays a better role in the treatment of leukemia .

Structural Effect of the Asp345a Insertion in Penicillin-Binding Protein 2 from Penicillin-Resistant Strains of Neisseria gonorrhoeae

PubMed Central

2015-01-01

A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well-established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the β2c−β2d loop. The crystal structure resolves the ambiguity of whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the β-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower the rate of acylation by sterically impeding binding of the antibiotic or by hindering breakage of the β-lactam ring during acylation because of the negative charge of its side chain. PMID:25403720

Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae.

PubMed

Fedarovich, Alena; Cook, Edward; Tomberg, Joshua; Nicholas, Robert A; Davies, Christopher

2014-12-09

A hallmark of penicillin-binding protein 2 (PBP2) from penicillin-resistant strains of Neisseria gonorrhoeae is insertion of an aspartate after position 345. The insertion resides on a loop near the active site and is immediately adjacent to an existing aspartate (Asp346) that forms a functionally important hydrogen bond with Ser363 of the SxN conserved motif. Insertion of other amino acids, including Glu and Asn, can also lower the rate of acylation by penicillin, but these insertions abolish transpeptidase function. Although the kinetic consequences of the Asp insertion are well-established, how it impacts the structure of PBP2 is unknown. Here, we report the 2.2 Å resolution crystal structure of a truncated construct of PBP2 containing all five mutations present in PBP2 from the penicillin-resistant strain 6140, including the Asp insertion. Commensurate with the strict specificity for the Asp insertion over similar amino acids, the insertion does not cause disordering of the structure, but rather induces localized flexibility in the β2c-β2d loop. The crystal structure resolves the ambiguity of whether the insertion is Asp345a or Asp346a (due to the adjacent Asp) because the hydrogen bond between Asp346 and Ser362 is preserved and the insertion is therefore Asp346a. The side chain of Asp346a projects directly toward the β-lactam-binding site near Asn364 of the SxN motif. The Asp insertion may lower the rate of acylation by sterically impeding binding of the antibiotic or by hindering breakage of the β-lactam ring during acylation because of the negative charge of its side chain.

Experimental and Theoretical Investigations of Infrared Multiple Photon Dissociation Spectra of Aspartic Acid Complexes with Zn2+ and Cd2.

PubMed

Boles, Georgia C; Hightower, Randy L; Coates, Rebecca A; McNary, Christopher P; Berden, Giel; Oomens, Jos; Armentrout, P B

2018-04-12

Complexes of aspartic acid (Asp) cationized with Zn 2+ : Zn(Asp-H) + , Zn(Asp-H) + (ACN) where ACN = acetonitrile, and Zn(Asp-H) + (Asp); as well as with Cd 2+ , CdCl + (Asp), were examined by infrared multiple photon dissociation (IRMPD) action spectroscopy using light generated from a free electron laser. A series of low-energy conformers for each complex was found using quantum chemical calculations to identify the structures formed experimentally. The main binding motif observed for the heavy-metal complex, CdCl + (Asp)[N,CO,CO s ], is a charge-solvated, tridentate structure, where the metal center binds to the backbone amino group and carbonyl oxygens of the backbone and side-chain carboxylic acids. Likewise, the deprotonated Zn(Asp-H) + (ACN) and Zn(Asp-H) + (Asp) complexes show comparable [N,CO - ,CO s ](ACN) and [N,CO - ,CO s ][N,CO,CO s ] coordinations, respectively. Interestingly, there was only minor spectral evidence for the analogous Zn(Asp-H) + [N,CO - ,CO s ] binding motif, even though this species is predicted to be the lowest-energy conformer. Instead, rearrangement and partial dissociation of the amino acid are observed, as spectral features most consistent with the experimental spectrum are exhibited by a four-coordinate Zn(Asp-NH 4 ) + [CO 2 - ,CO s ](NH 3 ) complex. Analysis of the mechanistic pathway leading from the predicted lowest-energy conformer to the isobaric deaminated complex is explored theoretically. Further, comparison of the current work to that of Zn 2+ and Cd 2+ complexes of asparagine (Asn) allows additional conclusions regarding populated conformers and effects of carboxamide versus carboxylic acid binding to be drawn.

Role of four conserved aspartic acid residues of EF-loops in the metal ion binding and in the self-assembly of ciliate Euplotes octocarinatus centrin.

PubMed

Liu, Wen; Duan, Lian; Sun, Tijian; Yang, Binsheng

2016-12-01

Ciliate Euplotes octocarinatus centrin (EoCen) is an EF-hand calcium-binding protein closely related to the prototypical calcium sensor protein calmodulin. Four mutants (D37K, D73K, D110K and D146K) were created firstly to elucidate the importance of the first aspartic acid residues (Asp37, Asp73, Asp110 and Asp146) in the beginning of the four EF-loops of EoCen. Aromatic-sensitized Tb 3+ fluorescence indicates that the aspartic acid residues are very important for the metal-binding of EoCen, except for Asp73 (in EF-loop II). Resonance light scattering (RLS) measurements for different metal ions (Ca 2+ and Tb 3+ ) binding proteins suggest that the order of four conserved aspartic acid residues for contributing to the self-assembly of EoCen is Asp37 > Asp146 > Asp110 > Asp73. Cross-linking experiment also exhibits that Asp37 and Asp146 play critical role in the self-assembly of EoCen. Asp37, in site I, which is located in the N-terminal domain, plays the most important role in the metal ion-dependent self-assembly of EoCen, and there is cooperativity between N-terminal and C-terminal domain (especially the site IV). In addition, the dependence of Tb 3+ induced self-assembly of EoCen and the mutants on various factors, including ionic strength and pH, were characterized using RLS. Finally, 2-p-toluidinylnaphthalene-6-sulfonate (TNS) binding, ionic strength and pH control experiments indicate that in the process of EoCen self-assembly, molecular interactions are mediated by both electrostatic and hydrophobic forces, and the hydrophobic interaction has the important status.

Amateur Astronomers: Secret Agents of EPO

NASA Astrophysics Data System (ADS)

Berendsen, M.; White, V.; Devore, E.; Reynolds, M.

2008-06-01

Amateur astronomers prime the public to be more interested, receptive, and excited about space science, missions, and programs. Through recent research and targeted programs, amateur astronomy outreach is being increasingly recognized by professional astronomers, educators, and other amateurs as a valued and important service. The Night Sky Network program, administered by the ASP, is the first nationwide research-based program specifically targeted to support outreach by amateur astronomers. This Network of trained and informed amateur astronomers can provide a stimulating introduction to your EPO programs as Network members share the night sky with families, students, and youth groups.

The L76V Drug Resistance Mutation Decreases the Dimer Stability and Rate of Autoprocessing of HIV-1 Protease by Reducing Internal Hydrophobic Contacts

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

Louis, John M.; Zhang, Ying; Sayer, Jane M.

2011-09-06

The mature HIV-1 protease (PR) bearing the L76V drug resistance mutation (PR{sub L76V}) is significantly less stable, with a >7-fold higher dimer dissociation constant (K{sub d}) of 71 {+-} 24 nM and twice the sensitivity to urea denaturation (UC{sub 50} = 0.85 M) relative to those of PR. Differential scanning calorimetry showed decreases in T{sub m} of 12 C for PR{sub L76V} in the absence of inhibitors and 5-7 C in the presence of inhibitors darunavir (DRV), saquinavir (SQV), and lopinavir (LPV), relative to that of PR. Isothermal titration calorimetry gave a ligand dissociation constant of 0.8 nM for DRV,more » {approx}160-fold higher than that of PR, consistent with DRV resistance. Crystal structures of PR{sub L76V} in complexes with DRV and SQV were determined at resolutions of 1.45-1.46 {angstrom}. Compared to the corresponding PR complexes, the mutated Val76 lacks hydrophobic interactions with Asp30, Lys45, Ile47, and Thr74 and exhibits closer interactions with Val32 and Val56. The bound DRV lacks one hydrogen bond with the main chain of Asp30 in PR{sub L76V} relative to PR, possibly accounting for the resistance to DRV. SQV shows slightly improved polar interactions with PR{sub L76V} compared to those with PR. Although the L76V mutation significantly slows the N-terminal autoprocessing of the precursor TFR-PR{sub L76V} to give rise to the mature PR{sub L76V}, the coselected M46I mutation counteracts the effect by enhancing this rate but renders the TFR-PRM46I/L76V precursor less responsive to inhibition by 6 {micro}M LPV while preserving inhibition by SQV and DRV. The correlation of lowered stability, higher K{sub d}, and impaired autoprocessing with reduced internal hydrophobic contacts suggests a novel molecular mechanism for drug resistance.« less

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

Otto, H.; Marti, T.; Holz, M.

Photocycle and flash-induced proton release and uptake were investigated for bacteriorhodopsin mutants in which Asp-85 was replaced by Ala, Asn, or Glu; Asp-212 was replaced by Asn or Glu; Asp-115 was replaced by Ala, Asn, or Glu; Asp-96 was replaced by Ala, Asn, or Glu; and Arg-82 was replaced by Ala or Gln in dimyristoylphosphatidylcholine/3-((3-cholamidopropyl)dimethylammonio)-1- propanesulfonate micelles at pH 7.3. In the Asp-85----Ala and Asp-85----Asn mutants, the absence of the charged carboxyl group leads to a blue chromophore at 600 and 595 nm, respectively, and lowers the pK of the Schiff base deprotonation to 8.2 and 7, respectively, suggesting amore » role for Asp-85 as counterion to the Schiff base. The early part of the photocycles of the Asp-85----Ala and Asp-85----Asn mutants is strongly perturbed; the formation of a weak M-like intermediate is slowed down about 100-fold over wild type. In both mutants, proton release is also slower but clearly precedes the rise of M. The amplitude of the early reversed photovoltage component in the Asp-85----Asn mutant is very large, and the net charge displacement is close to zero, indicating proton release and uptake on the cytoplasmic side of the membrane. The data suggest an obligatory role for Asp-85 in the efficient deprotonation of the Schiff base and in the proton release phase, probably as proton acceptor. In the Asp-212----Asn mutant, the rise of the absorbance change at 410 nm is slowed down to 220 microsecond, its amplitude is small, and the release of protons is delayed to 1.9 ms. The absorbance changes at 650 nm indicate perturbations in the early time range with a slow K intermediate. Thus Asp-212 also participates in the early events of charge translocation and deprotonation of the Schiff base.« less

Structural basis of potassium activation in plant asparaginases.

PubMed

Ajewole, Ebenezer; Santamaria-Kisiel, Liliana; Pajak, Agnieszka; Jaskolski, Mariusz; Marsolais, Frédéric

2018-04-01

l-asparaginases (EC 3.5.1.1) play an important role in nitrogen mobilization in plants. Here, we investigated the biochemical and biophysical properties of potassium-dependent (PvAspG1) and potassium-independent (PvAspG-T2) l-asparaginases from Phaseolus vulgaris. Our previous studies revealed that PvAspG1 requires potassium for catalytic activation and its crystal structure suggested that Ser-118 in the activation loop plays a critical role in coordinating the metal cation. This amino acid residue is replaced by isoleucine in PvAspG-T2. Reciprocal mutants of the enzymes were produced and the effect of the amino acid substitution on the kinetic parameters, allosteric effector binding, secondary structure conformation, and pH profile were studied. Introduction of the serine residue conferred potassium activation in PvAspG-T2. Conversely, the PvAspG1-S118I mutant could no longer be activated by potassium. PvAspG1 and the PvAspG-T2-I117S mutant had a similar half-maximal effective concentration (EC 50 ) value for potassium activation, between 0.1 and 0.3 mm. Potassium binding elicited a similar conformational change in PvAspG1 and PvAspG-T2-I117S, as studied by circular dichroism. However, no change in conformation was observed for PvAspG-T2 and PvAspG1-S118I. Analysis of kinetic parameters in function of pH indicated that potassium activation mediated by Ser-118 influences the ionization of specific functional groups in the enzyme-substrate complex. Together, the results indicate that Ser-118 of PvAspG1 is essential and sufficient for potassium activation in plant l-asparaginases. ENZYME: l-Asparaginase (EC 3.5.1.1). © 2018 Federation of European Biochemical Societies.

Influence of the magnesium aspartate hydrochloride administration to the maternal circuit on the aspartate concentration of the fetal circuit under in vitro perfusion of human placenta.

PubMed

Malek, A; Leiser, R

2009-01-01

Magnesium aspartate hydrochloride (Magnesiocard, Mg-Asp-HCl) is proposed as a substitute of magnesium sulfate for the treatment of preeclampsia and premature labor. After an i.v. administration of a dose equivalent to that used in the treatment of preeclampsia to nonpregnant volunteers, a 10-fold increase of aspartic acid (Asp) over the physiological level was observed. Animal experiments have demonstrated that highly increased fetal levels of acidic amino acids such as Asp could be associated with neurotoxic damage in the fetal brain. The influence of such an elevation of Asp concentration in the maternal circuit on the fetal level, using the in vitro perfusion model of human placenta, was investigated. After a control phase (2h), a therapeutic dose of Mg combined with Asp (Magnesiocard, Mg-Asp-HCl) was applied to the maternal circuit approaching 10 times the physiological level of Asp. The administration was performed in two different phases simulating either a peak of maximum concentration (bolus application, 2h) or a steady state level (initially added, 4h). In four experiments, during experimental phases (6h) a slow increase in concentration in the fetal circuit was seen for Mg, AIB (alpha-aminoisobutyric acid, artificial amino acid) and creatinine confirming previous observations. In contrast, no net transfer of Asp across the placenta was seen. A continuous decrease in the concentration of Asp on both maternal and fetal side suggests active uptake and metabolization by the placenta. Viability control parameters remained stable indicating the absence of an effect on placental metabolism, permeability and morphology. Elevation of Asp concentration up to 10 times the physiological level by the administration of Mg-Asp-HCl to the maternal circuit under in vitro perfusion conditions of human placenta has no influence on the fetal level of Asp suggesting no transfer of Asp from the maternal to fetal compartment. Therefore, the administration of Mg-Asp-HCl to preeclamptic patients would be beneficial for the patients without any impact on placental or fetal physiology.

L-Asp is a useful tool in the purification of the ionotropic glutamate receptor A2 ligand-binding domain.

PubMed

Krintel, Christian; Frydenvang, Karla; Ceravalls de Rabassa, Anna; Kaern, Anne M; Gajhede, Michael; Pickering, Darryl S; Kastrup, Jette S

2014-05-01

In purification of the ionotropic glutamate receptor A2 (GluA2) ligand-binding domain (LBD), L-Glu-supplemented buffers have previously been used for protein stabilization during the procedure. This sometimes hampers structural studies of low-affinity ligands, because L-Glu is difficult to displace, despite extensive dialysis. Here, we show that L-Asp binds to full-length GluA2 with low affinity (Ki = 0.63 mM) and to the GluA2 LBD with even lower affinity (Ki = 2.6 mM), and we use differential scanning fluorimetry to show that L-Asp is able to stabilize the isolated GluA2 LBD. We also show that L-Asp can replace L-Glu during purification, providing both equal yields and purity of the resulting protein sample. Furthermore, we solved three structures of the GluA2 LBD in the presence of 7.5, 50 and 250 mM L-Asp. Surprisingly, with 7.5 mM L-Asp, the GluA2 LBD crystallized as a mixed dimer, with L-Glu being present in one subunit, and neither L-Asp nor L-Glu being present in the other subunit. Thus, residual L-Glu is retained from the expression medium. On the other hand, only L-Asp was found at the binding site when 50 or 250 mM L-Asp was used for crystallization. The binding mode observed for L-Asp at the GluA2 LBD is very similar to that described for L-Glu. Taking our findings together, we have shown that L-Asp can be used instead of L-Glu for ligand-dependent stabilization of the GluA2 LBD during purification. This will enable structural studies of low-affinity ligands for lead optimization in structure-based drug design. Structural data are available in the Protein Data Bank under accession numbers 4O3B (7.5 mM L-Asp), 4O3C (50 mM L-Asp), and 4O3A (250 mM L-Asp). © 2014 FEBS.

Determination of ASPS performance for large payloads in the shuttle orbiter disturbance environment. [digital simulation

NASA Technical Reports Server (NTRS)

Keckler, C. R.; Kibler, K. S.; Powell, L. F.

1979-01-01

A high fidelity simulation of the annular suspension and pointing system (ASPS), its payload, and the shuttle orbiter was used to define the worst case orientations of the ASPS and its payload for the various vehicle disturbances, and to determine the performance capability of the ASPS under these conditions. The most demanding and largest proposed payload, the Solar Optical Telescope was selected for study. It was found that, in all cases, the ASPS more than satisfied the payload's requirements. It is concluded that, to satisfy facility class payload requirements, the ASPS or a shuttle orbiter free-drift mode (control system off) should be utilized.

Characterization of chicken antisera raised against Aspergillus spp. by enzyme linked immunosorbent assay.

PubMed

Chen, F S; Chen, J W; Zhao, S; Gan, Z B; Luo, X C; Zhou, Q

2000-10-01

Enzyme linked immunosorbent assays of three Aspergillus species have been developed. Laying hens were immunized with the exoantigens from Asp. flavus, Asp. ochreaus and Asp. versicolor. All test chickens except for one produced antisera raised against the exoantigens. The antisera production process and ELISA titer were analysed. Fourteen days after the first injection, the antisera began to produce largely, on the 35th day reached to the peak, and maintained a stable level until the 42nd day. The maximum ELISA titer of the antisera to the exoantigens from Asp. flavus, Asp. ochreaus and Asp. versicolor was 1:8,000, 1:10,000 and 1:10,000, respectively. The cross-reactivities of antisera were determined with seventeen species of Aspergillus, ten species of fungi from other genera and the buffer-extracts of grain. The antisera did not cross-react with the exoantigens from other genera and the buffer-extracts of grain. The antiserum to exoantigen from Asp. ochreaus was species-specific, whereas the antisera against Asp. flavus and Asp. versicolor tended to cross-react with other Aspergillus species to varying degrees. The results suggest that exoantigens immunoassays can be developed to indentify and detect Aspergillus genus in grains.

Effects of aspartic acid and potassium chloride on arginine kinase from shrimp.

PubMed

Tang, Hong-min; Yang, Yin-ye; Zhang, Song-fu

2006-12-15

The aspartic acid (Asp)-induced unfolding and the salt-induced folding of arginine kinase (AK) were studied in terms of enzyme activity, intrinsic fluorescence emission spectra, 1-anilino-8-naphthalenesulfonate (ANS) fluorescence spectra and far-UV circular dichroism (CD) spectra. The results showed that Asp caused inactivation and unfolding of AK with no aggregation during AK denaturation. The unfolding of the whole molecule and the inactivation of AK in different Asp concentrations were compared. Much lower Asp concentration was required to induce inactivation than to produce significant conformational changes of the enzyme molecule. However, with further addition of Asp, the molar ellipticity at 222 and 208 nm, the wavelength shift and the emission intensity of ANS hardly changed. Asp denatured AK was reactivated by dilution. In addition, potassium chloride (KCl) induced the molten globule state with a compact structure after AK was denatured with 7.5 mM Asp. These results collectively elucidate the osmotic effect of Asp anions for the molten globule formed during unfolding process. They also suggest that the effect of Asp differed from that of other denaturants such as guanidine hydrochloride or urea during AK folding. The molten globule state indicates that intermediates exist during AK folding.

Comparison of subcutaneous soluble human insulin and insulin analogues (AspB9, GluB27; AspB10; AspB28) on meal-related plasma glucose excursions in type I diabetic subjects.

PubMed

Kang, S; Creagh, F M; Peters, J R; Brange, J; Vølund, A; Owens, D R

1991-07-01

To compare postprandial glucose excursions and plasma free insulin-analogue levels after subcutaneous injection of three novel human insulin analogues (AspB10; AspB9, GluB27; and AspB28) with those after injection of soluble human insulin (Actrapid HM U-100). Six male subjects with insulin-dependent diabetes, at least 1 wk apart and after an overnight fast and basal insulin infusion, received 72 nmol (approximately 12 U) s.c. of soluble human insulin 30 min before, or 72 nmol of each of the three analogues immediately before, a standard 500-kcal meal. Mean basal glucoses were similar on the 4 study days. Compared to human insulin (6.3 +/- 0.8 mM), mean +/- SE peak incremental glucose rises were similar after analogues AspB10 (5.4 +/- 0.8 mM) and AspB9, GluB27 (5.4 +/- 0.7 mM) and significantly lower after analogue AspB28 (3.6 +/- 1.2 mM, P less than 0.02). Relative to soluble human insulin (100% +/- SE21), incremental areas under the glucose curve between 0 and 240 min were 79% +/- 34 (AspB10, NS), 70% +/- 29 (AspB9, GluB27, NS), and 43% +/- 23 (AspB28, P less than 0.02). Basal plasma free insulin levels were similar on the 4 study days. Plasma free insulin-analogue levels rose rapidly to peak 30 min after injection at 308 +/- 44 pM (AspB10); 1231 +/- 190 pM (AspB9, GluB27) and 414 +/- 42 pM (AspB28) and were significantly higher than corresponding (i.e., 30 min postmeal) plasma free insulin levels of 157 +/- 15 pM (P less than 0.02 in each case). Plasma profiles of the insulin analogues were more physiological than that of human insulin after subcutaneous injection. All three analogues given immediately before the meal are at least as effective as soluble human insulin given 30 min earlier. These analogues are promising potential candidates for short-acting insulins of the future.

Xeroderma pigmentosum group D polymorphisms and esophageal cancer susceptibility: a meta-analysis based on case-control studies.

PubMed

Yang, Rong; Zhang, Chong; Malik, Armah; Shen, Zhi-Da; Hu, Jian; Wu, Yi-He

2014-11-28

To clarify the effects of the xeroderma pigmentosum group D (XPD) Asp312Asn and Lys751Gln gene polymorphisms on the risk of esophageal cancer (EC). A computerised literature search was conducted to identify the relevant studies from the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the associations between the XPD Asp312Asn and/or Lys751Gln polymorphisms and EC susceptibility. Statistical analyses were performed using the software Stata 12.0. A fixed or random effects model was selected based on a heterogeneity test. Publication bias was estimated using funnel plots and Egger's linear regression method. Subgroup analyses were performed based on histological type and ethnicity. Thirteen case-control studies with a total of 10 comparisons for the Asp312Asn polymorphism, including 2373 cases and 3175 controls, and 15 comparisons for the Lys751Gln polymorphism, including 3226 cases and 5237 controls, were recruited for the meta-analysis. In terms of the XPD Asp312Asn polymorphism, significantly increased EC risks were identified in the Asp/Asn vs Asp/Asp comparison (OR = 1.17, 95%CI: 1.02-1.33, P = 0.03) and in the dominant-model comparison (Asn/Asn+Asp/Asn vs Asp/Asp: OR = 1.18, 95%CI: 1.04-1.34, P = 0.01). However, no significant associations were found in the Asn/Asn vs Asp/Asp comparison (OR = 1.30, 95%CI: 1.00-1.70, P = 0.05) or in the recessive-model comparison (Asn/Asn vs Asp/Asn + Asp/Asp: OR = 1.17, 95%CI: 0.91-1.50, P = 0.22). In terms of the XPD Lys751Gln polymorphism, a significant association with EC susceptibility was found under the recessive model (Gln/Gln vs Lys/Gln+Lys/Lys: OR = 1.21, 95%CI: 1.02-1.43, P = 0.03). However, no associations were identified in the other comparisons (co-dominant model: Lys/Gln vs Lys/Lys: OR = 1.11, 95%CI: 0.94-1.31, P = 0.20; Gln/Gln vs Lys/Lys: OR = 1.31, 95%CI: 0.98-1.75, P = 0.07; dominant model: OR = 1.14, 95%CI: 0.96-1.35, P = 0.14). The results of this meta-analysis suggest that the XPD Asp312Asn and Lys751Gln gene polymorphisms are associated with a significantly increased risk for EC.

76 FR 21327 - Notice of Funds Availability: Inviting Applications for the Foreign Market Development Cooperator...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-15

... intended effect of this notice is to solicit applications from eligible applicants for 2012 and to award... to apply for funding assistance should contact the Program Operations Division, Office of Trade.../fmdprogram.asp . SUPPLEMENTARY INFORMATION: I. Funding Opportunity Description Authority: The Cooperator...

Ingested d-Aspartate Facilitates the Functional Connectivity and Modifies Dendritic Spine Morphology in Rat Hippocampus.

PubMed

Kitamura, Akihiko; Hojo, Yasushi; Ikeda, Muneki; Karakawa, Sachise; Kuwahara, Tomomi; Kim, Jonghyuk; Soma, Mika; Kawato, Suguru; Tsurugizawa, Tomokazu

2018-05-30

d-Aspartate (d-Asp), the stereoisomer of l-aspartate, has a role in memory function in rodents. However, the mechanism of the effect of d-Asp has not been fully understood. In this study, we hypothesized that ingested d-Asp directly reaches the hippocampal tissues via the blood circulation and modifies the functional connectivity between hippocampus and other regions through spinogenesis in hippocampal CA1 neurons. The spinogenesis induced by the application of d-Asp was investigated using rat acute hippocampal slices. The density of CA1 spines was increased following 21 and 100 μM d-Asp application. The nongenomic spine increase pathway involved LIM kinase. In parallel to the acute slice study, brain activation was investigated in awake rats using functional MRI following the intragastric administration of 5 mM d-Asp. Furthermore, the concentration of d-Asp in the blood serum and hippocampus was significantly increased 15 min after intragastric administration of d-Asp. A functional connectivity by awake rat fMRI demonstrated increased slow-frequency synchronization in the hippocampus and other regions, including the somatosensory cortex, striatum, and the nucleus accumbens, 10-20 min after the start of d-Asp administration. These results suggest that ingested d-Asp reaches the brain through the blood circulation and modulates hippocampal neural networks through the modulation of spines.

The Crystal Structure of Peroxiredoxin Asp f3 Provides Mechanistic Insight into Oxidative Stress Resistance and Virulence of Aspergillus fumigatus.

PubMed

Hillmann, Falk; Bagramyan, Karine; Straßburger, Maria; Heinekamp, Thorsten; Hong, Teresa B; Bzymek, Krzysztof P; Williams, John C; Brakhage, Axel A; Kalkum, Markus

2016-09-14

Invasive aspergillosis and other fungal infections occur in immunocompromised individuals, including patients who received blood-building stem cell transplants, patients with chronic granulomatous disease (CGD), and others. Production of reactive oxygen species (ROS) by immune cells, which incidentally is defective in CGD patients, is considered to be a fundamental process in inflammation and antifungal immune response. Here we show that the peroxiredoxin Asp f3 of Aspergillus fumigatus inactivates ROS. We report the crystal structure and the catalytic mechanism of Asp f3, a two-cysteine type peroxiredoxin. The latter exhibits a thioredoxin fold and a homodimeric structure with two intermolecular disulfide bonds in its oxidized state. Replacement of the Asp f3 cysteines with serine residues retained its dimeric structure, but diminished Asp f3's peroxidase activity, and extended the alpha-helix with the former peroxidatic cysteine residue C61 by six residues. The asp f3 deletion mutant was sensitive to ROS, and this phenotype was rescued by ectopic expression of Asp f3. Furthermore, we showed that deletion of asp f3 rendered A. fumigatus avirulent in a mouse model of pulmonary aspergillosis. The conserved expression of Asp f3 homologs in medically relevant molds and yeasts prompts future evaluation of Asp f3 as a potential therapeutic target.

C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

PubMed

Nsaiba, Mohamed Jalloul; Lapointe, Marc; Mabrouk, Hajer; Douki, Wahiba; Gaha, Lotfi; Pérusse, Louis; Bouchard, Claude; Jrad, Besma Bel Hadj; Cianflone, Katherine

2015-05-01

Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.

Additive antithrombotic effect of ASP6537, a selective cyclooxygenase (COX)-1 inhibitor, in combination with clopidogrel in guinea pigs.

PubMed

Sakata, Chinatsu; Suzuki, Ken-Ichi; Morita, Yoshiaki; Kawasaki, Tomihisa

2017-03-05

Clopidogrel (Plavix ® , Sanofi-Aventis), the adenosine diphosphate P2Y 12 receptor antagonist, is reported to be effective in the prevention of cardiovascular events and is often used in combination with aspirin, particularly in high-risk patients. ASP6537 is a reversible cyclooxygenase (COX)-1 inhibitor that is under investigation as an anti-platelet agent. First, we investigated the reversibility of the antiplatelet effect of ASP6537 and its interaction with ibuprofen to compare the usability of ASP6537 with that of aspirin. We then evaluated the antithrombotic effect of ASP6537 in combination with clopidogrel using a FeCl 3 -induced thrombosis model in guinea pigs. ASP6537 exerted reversible antiplatelet activity, and no pharmacodynamic interaction with ibuprofen was noted. When administered as monotherapy, ASP6537 exerted a significant antithrombotic effect at ≥3mg/kg, while aspirin inhibited thrombosis at 100mg/kg. ASP6537 exerted significant additive effects in combination with clopidogrel, and the minimum antithrombotic dose was reduced by concomitant administration of clopidogrel. Our study showed that ASP6537 did not interact with ibuprofen and has clear additive effects in combination with clopidogrel. ASP6537 may therefore represent a promising antiplatelet agent for use in clinical settings in combination with clopidogrel. Copyright © 2017 Elsevier B.V. All rights reserved.

Mechanism research on starting residual oil migration in ASP flooding with different Alkali concentration

NASA Astrophysics Data System (ADS)

Xia, Huifen; Pan, Junliang; Niu, Lijuan; Xu, Tianhan

2018-02-01

The results illustrate that under the condition of the same viscosity of ASP system, oil displacement efficiency is different while the ASP system with different alkali concentration has the same order of magnitude as the interfacial tension of oil. In this paper, the microscopic simulation visual model is used to study the mechanism of starting migration of residual oil by doing ASP flooding experiments with different alkali concentration. The results indicate that the migration of residual oil is different from that in the ASP systems with different alkali concentration. ASP system with high alkali concentration can start the migration by means of emulsifying residual oil into oil droplets and oil threads, on this account, increasing the alkali concentration can make the recovery degree of ASP system higher, which will finally be beneficial to the oil recovery.

Low temperature effects on nitrification and nitrifier community structure in V-ASP for decentralized wastewater treatment and its improvement by bio-augmentation.

PubMed

Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Zhao, Ke

2018-03-01

The vegetation-activated sludge process (V-ASP) has been proved to be an environment-friendly decentralized wastewater treatment system with extra esthetic function and less footprint. However, the effects of low temperature on the treatment performance of V-ASP and related improvement methods are rarely investigated, up to now. In this work, the effect of low temperature on nitrification in V-ASP was comprehensively investigated from overall nitrification performance, substrate utilization kinetics, functional enzymatic activities, and microbial community structure shift by comparison with conventional ASP. Bio-augmentation methods in terms of single-time nitrifier-enriched biomass dosage were employed to improve nitrification efficiency in bench- and full-scale systems. The experiment results demonstrated that the NH 4 + -N removal efficiency in V-ASP system decreased when the operational temperature decreased from 30 to 15 °C, and the decreasing extent was rather smaller compared to ASP, as well as ammonium and nitrite oxidation rates and enzymatic activities, which indicated the V-ASP system possesses high resistance to low temperature. With direct dosage of 1.6 mg nitrifier/gSS sludge, the nitrification efficiency in V-ASP was enhanced dramatically from below 50% to above 90%, implying that bio-augmentation was effective for V-ASP whose enzymatic activities and microbial communities were both also improved. The feasibility and effectiveness of bio-augmentation was further confirmed in a full-scale V-ASP system after a long-term experiment which is instructive for the practical application.

America’s Holy War

DTIC Science & Technology

2006-04-14

Journal. 24 April 2002. http://www.mepc.org/public_asp/journal/ vol10 /0306_alqaeda.asp accessed on 21 Sept 05. 21 “Translation of April 24, 2002 al...Qaeda document”. Middle East Policy Council Journal. 24 April 2002. http://www.mepc.org/public_asp/journal/ vol10 /0306_alqaeda.asp accessed on 21 Sept... vol10 /0306_alqaeda.asp accessed on 21 Sept 05. 23 “Osama bin Laden’s Speech on the Eve of the 2004 US Elections”. The Middle East Media Research

Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antimicrobial Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children.

PubMed

Malcolmson, Caroline; Ng, Karen; Hughes, Shevaun; Kissoon, Niranjan; Schina, Jillian; Tilley, Peter A; Roberts, Ashley

2017-06-01

Early definitive identification of infectious pathogens coupled with antimicrobial stewardship interventions allow for targeted and timely administration of antimicrobials. We investigated the combined impact of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) technology and an antimicrobial stewardship program (ASP) in pediatric patients with blood stream infections (BSIs). This is a single-center study comparing a control group of patients from October 2009 to July 2010 with BSIs to a cohort of patients postimplementation of MALDI-TOF and an ASP, from October 2013 to July 2014. Primary outcome was time to optimal therapy. Secondary outcomes included time to effective therapy, 30-day all-cause mortality, 30-day readmission rate, hospital length of stay, and intensive care admission. One hundred episodes of BSIs were identified in the preintervention period, and 121 episodes were identified in the postintervention period. Time from blood culture collection to organism identification was significantly reduced in the prospective cohort compared with historical controls (18.8 vs 43.7 hours, respectively). A total of 73 ASP interventions were made on the treatment of BSIs in the postintervention period. Combined use of MALDI-TOF and ASP significantly reduced time to optimal therapy (77.0 to 54.2 hours, P < .001). In the subgroup analysis of Gram-negative bacteremia, time to effective and optimal therapy were significantly reduced (2.0 vs 0.7 hours and 146.8 vs 48.0 hours, respectively). There were no significant differences in clinical outcomes. The combined use of MALDI-TOF and ASP allows early optimization of antimicrobial therapy in pediatric inpatients with BSIs. © The Author 2016. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

DETERMINATION OF C1 AND Cx CELLULOLYTIC ACTIVITIES IN ENZYME PREPARATIONS OF MOLD FUNGI (Opredelenie C1 i Cx Tsellyuloliticheskikh Aktivnostei v Fermentnykh Preparatakh iz Plesnevykh Gribov),

DTIC Science & Technology

Trichotecium roseum, Aspergillus awamory, Asp. niger , Asp. flavus. Differences in the distribution of C1 - and Cx - activities in the preparations of various strains of the same fungus (Asp. awamory, Asp. oryzae) are shown. (Author)

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

Metz, G.; Siebert, F.; Engelhard, M.

Solid state {sup 13}C nuclear magnetic resonance measurements of bacteriorhodopsin labeled with (4-{sup 13}C)Asp show that resonances of single amino acids can be resolved. In order to assign and characterize the resonances of specific Asp residues, three different approaches were used. (1) Determination of the chemical shift anisotropy from side-band intensities provides information about the protonation state of Asp residues; (2) relaxation studies and T{sub 1} filtering allow one to discriminate between resonances with different mobility; (3) a comparison of the spectra of light- and dark-adapted bacteriorhodopsin provides evidence for resonances from aspartic acid residues in close neighborhood of themore » chromophore. In agreement with other investigations, four resonances are assigned to internal residues. Two of them are protonated in the ground state up to pH 10 (Asp{sub 96} and Asp{sub 115}). All other detected resonance, including Asp{sub 85} and Asp{sub 212}, are due to deprotonated aspartic acid. Two lines due to the two internal deprotonated groups change upon dark and light adaptation, whereas the protonated Asp residues are unaffected.« less

Biodegradation of phenanthrene in bioaugmented microcosm by consortium ASP developed from coastal sediment of Alang-Sosiya ship breaking yard.

PubMed

Patel, Vilas; Patel, Janki; Madamwar, Datta

2013-09-15

A phenanthrene-degrading bacterial consortium (ASP) was developed using sediment from the Alang-Sosiya shipbreaking yard at Gujarat, India. 16S rRNA gene-based molecular analyses revealed that the bacterial consortium consisted of six bacterial strains: Bacillus sp. ASP1, Pseudomonas sp. ASP2, Stenotrophomonas maltophilia strain ASP3, Staphylococcus sp. ASP4, Geobacillus sp. ASP5 and Alcaligenes sp. ASP6. The consortium was able to degrade 300 ppm of phenanthrene and 1000 ppm of naphthalene within 120 h and 48 h, respectively. Tween 80 showed a positive effect on phenanthrene degradation. The consortium was able to consume maximum phenanthrene at the rate of 46 mg/h/l and degrade phenanthrene in the presence of other petroleum hydrocarbons. A microcosm study was conducted to test the consortium's bioremediation potential. Phenanthrene degradation increased from 61% to 94% in sediment bioaugmented with the consortium. Simultaneously, bacterial counts and dehydrogenase activities also increased in the bioaugmented sediment. These results suggest that microbial consortium bioaugmentation may be a promising technology for bioremediation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coordination ability determined transition metal ions substitution of Tb in Tb-Asp fluorescent nanocrystals and a facile ions-detection approach.

PubMed

Duan, Jiazhi; Ma, Baojin; Liu, Feng; Zhang, Shan; Wang, Shicai; Kong, Ying; Du, Min; Han, Lin; Wang, Jianjun; Sang, Yuanhua; Liu, Hong

2018-04-26

Although the synthesis and fluorescent properties of lanthanide-amino acid complex nanostructures have been investigated extensively, limited studies have been reported on metal ions' substitution ability for the lanthanide ions in the complex and their effect on the fluorescent property. In this study, taking biocompatible Tb-aspartic acid (Tb-Asp) complex nanocrystals as a model, the substitution mechanism of metal ions, particularly transition metals, for Tb ions in Tb-Asp nanocrystals and the change in the fluorescent property of the Tb-Asp nanocrystals after substitution were systematically investigated. The experimental results illustrated that metal ions with higher electronegativity, higher valence, and smaller radius possess stronger ability for Tb ions' substitution in Tb-Asp nanocrystals. Based on the effect of substituting ions' concentration on the fluorescent property of Tb-Asp, a facile method for copper ions detection with high sensitivity was proposed by measuring the fluorescent intensity of Tb-Asp nanocrystals' suspensions containing different concentrations of copper ions. The good biocompatibility, great convenience of synthesis and sensitive detection ability make Tb-Asp nanocrystals a very low cost and effective material for metal ions detection, which also opens a new door for practical applications of metal-Asp coordinated nanocrystals.

The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in non-discriminating aspartyl-tRNA synthetase safeguards the genetic code

PubMed Central

Fischer, Frédéric; Huot, Jonathan L.; Lorber, Bernard; Diss, Guillaume; Hendrickson, Tamara L.; Becker, Hubert D.; Lapointe, Jacques; Kern, Daniel

2012-01-01

Helicobacter pylori catalyzes Asn-tRNAAsn formation by use of the indirect pathway that involves charging of Asp onto tRNAAsn by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp into Asn by the GatCAB amidotransferase. We show that the partners of asparaginylation assemble into a dynamic Asn-transamidosome, which uses a different strategy than the Gln-transamidosome to prevent the release of the mischarged aminoacyl-tRNA intermediate. The complex is described by gel-filtration, dynamic light scattering and kinetic measurements. Two strategies for asparaginylation are shown: (i) tRNAAsn binds GatCAB first, allowing aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii) tRNAAsn is bound by ND-AspRS which releases the Asp-tRNAAsn product much slower than the cognate Asp-tRNAAsp; this kinetic peculiarity allows GatCAB to bind and transamidate Asp-tRNAAsn before its release by the ND-AspRS. These results are discussed in the context of the interrelation between the Asn and Gln-transamidosomes which use the same GatCAB in H. pylori, and shed light on a kinetic mechanism that ensures faithful codon reassignment for Asn. PMID:22362756

Host protective ASP-based vaccine against the parasitic nematode Ostertagia ostertagi triggers NK cell activation and mixed IgG1-IgG2 response.

PubMed

González-Hernández, Ana; Van Coppernolle, Stefanie; Borloo, Jimmy; Van Meulder, Frederik; Paerewijck, Oonagh; Peelaers, Iris; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

2016-07-11

The mucus-dwelling parasite Ostertagia ostertagi is one of the most important gastrointestinal nematodes in cattle. Our group has previously demonstrated the protective capacity of a vaccine against this parasite based on a native activation-associated secreted protein ASP1 (nASP) in combination with the saponin adjuvant QuilA. The aim of the current study was to analyse the effect of both antigen and adjuvant on the cellular and humoral vaccine-induced immune responses by comparing the native ASP to a recombinant version expressed in Pichia pastoris (pASP) and replacing QuilA by Al(OH)3. Immunization of cattle with the protective nASP+QuilA vaccine was associated with antigen-induced proliferation of natural killer (NK) cells combined with IFN-γ secretion and the induction of a mixed IgG1/IgG2 antibody response. ASP-specific activation and proliferation of NK cells was also observed in mice following the same vaccination regime. Replacing QuilA by Al(OH)3 or nASP by pASP significantly decreased the capacity of the vaccines to trigger both NK cell activation and antibody responses and failed to induce protection against a challenge infection. Reduction of the structurally anchoring disulphide bonds of the nASP completely abolished its ability to induce NK cell activation and antibody responses, highlighting the importance of protein conformation for the immunostimulatory activity.

Racemization at the Asp 58 residue in αA-crystallin from the lens of high myopic cataract patients.

PubMed

Zhu, Xiang-Jia; Zhang, Ke-Ke; He, Wen-Wen; Du, Yu; Hooi, Michelle; Lu, Yi

2018-02-01

Post-translational modifications in lens proteins are key causal factors in cataract. As the most abundant post-translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA-crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l-Asp 58 to d-isoAsp58 in αA-crystallin has been found in age-related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l-Asp 58 to d-Asp 58 in αA-crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l-Asp 58 to d-isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l-Asp 58 to d-Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA-crystallin. The different trend in the conversion of αA-crystallin by racemization, especially the elevated level of d-Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Fungal extracellular polysaccharides in house dust as a marker for exposure to fungi: relations with culturable fungi, reported home dampness, and respiratory symptoms.

PubMed

Douwes, J; van der Sluis, B; Doekes, G; van Leusden, F; Wijnands, L; van Strien, R; Verhoeff, A; Brunekreef, B

1999-03-01

Epidemiologic studies have demonstrated an association between indoor fungal growth and respiratory symptoms. However, in only a few studies was fungal exposure actually measured. The purpose of this study was to evaluate the measurement by enzyme immunoassay of extracellular polysaccharides of Aspergillus and Penicillium species (EPS-Asp/Pen ) in house dust as a marker for fungal exposure and to study the relations between EPS-Asp/Pen levels and home dampness and respiratory symptoms in children. Extracts of house dust samples from bedroom and living room floors and mattresses from homes of 31 children with chronic respiratory symptoms and 29 children with no chronic respiratory symptoms were analyzed for EPS-Asp/Pen. EPS-Asp/Pen were readily detectable (40 to 46,513 nanogram equivalent/g dust) in 161 house dust extracts, with highest concentrations in living room floor dust. EPS-Asp/Pen levels were 2 to 3 times higher on carpeted floors than on smooth floors. EPS-Asp/Pen were significantly correlated with total culturable fungi (r = 0.3 to 0.5) and with house dust mite allergens (r = 0.3 to 0.5). EPS-Asp/Pen levels in living room floor dust were positively associated with occupant-reported home dampness. This was not observed for EPS-Asp/Pen in bedroom floor and mattress dust. EPS-Asp/Pen levels in living room floor dust were positively associated with respiratory symptoms. EPS-Asp/Pen in bedroom floor and mattress dust showed a reversed association with respiratory symptoms, possibly because of allergen-avoidance measures taken in the bedroom. The enzyme immunoassay for fungal EPS-Asp/Pen may be a useful method for exposure assessment of indoor fungi.

Correlation between cervical lordosis and adjacent segment pathology after anterior cervical spinal surgery.

PubMed

Lee, Soo Eon; Jahng, Tae-Ahn; Kim, Hyun Jib

2015-12-01

To evaluate the incidence and risk factors for adjacent segment pathology (ASP) after anterior cervical spinal surgery. Fourteen patients (12 male, mean age 47.1 years) who underwent single-level cervical disk arthroplasty (CDA group) and 28 case-matched patients (24 male, mean age 53.6 years) who underwent single-level anterior cervical discectomy and fusion (ACDF group) were included. Presence of radiologic ASP (RASP) was based on observed changes in anterior osteophytes, disks, and calcification of the anterior longitudinal ligament on lateral radiographs. The mean follow-up period was 43.4 months in the CDA group and 44.6 months in the ACDF group. At final follow-up, ASP was observed in 5 (35.7%) CDA patients and 16 (57.1%) ACDF patients (p = 0.272). The interval between surgery and ASP development was 33.8 months in the CDA group and 16.3 months in the ACDF group (p = 0.046). The ASP risk factor analysis indicated postoperative cervical angle at C3-7 being more lordotic in non-ASP patients in both groups. Restoration of lordosis occurred in the CDA group regardless of the presence of ASP, but heterotopic ossification development was associated with the presence of ASP in the CDA group. And the CDA group had significantly greater clinical improvements than those in the ACDF group when ASP was present. In both CDA and ACDF patients, RASP developed, but CDA was associated with a delay in ASP development. A good clinical outcome was expected in CDA group, even when ASP developed. Restoration of cervical lordosis was an important factor in anterior cervical spine surgery.

Insulin degludec/insulin aspart once daily in Type 2 diabetes: a comparison of simple or stepwise titration algorithms (BOOST® : SIMPLE USE).

PubMed

Park, S W; Bebakar, W M W; Hernandez, P G; Macura, S; Hersløv, M L; de la Rosa, R

2017-02-01

To compare the efficacy and safety of two titration algorithms for insulin degludec/insulin aspart (IDegAsp) administered once daily with metformin in participants with insulin-naïve Type 2 diabetes mellitus. This open-label, parallel-group, 26-week, multicentre, treat-to-target trial, randomly allocated participants (1:1) to two titration arms. The Simple algorithm titrated IDegAsp twice weekly based on a single pre-breakfast self-monitored plasma glucose (SMPG) measurement. The Stepwise algorithm titrated IDegAsp once weekly based on the lowest of three consecutive pre-breakfast SMPG measurements. In both groups, IDegAsp once daily was titrated to pre-breakfast plasma glucose values of 4.0-5.0 mmol/l. Primary endpoint was change from baseline in HbA 1c (%) after 26 weeks. Change in HbA 1c at Week 26 was IDegAsp Simple -14.6 mmol/mol (-1.3%) (to 52.4 mmol/mol; 6.9%) and IDegAsp Stepwise -11.9 mmol/mol (-1.1%) (to 54.7 mmol/mol; 7.2%). The estimated between-group treatment difference was -1.97 mmol/mol [95% confidence interval (CI) -4.1, 0.2] (-0.2%, 95% CI -0.4, 0.02), confirming the non-inferiority of IDegAsp Simple to IDegAsp Stepwise (non-inferiority limit of ≤ 0.4%). Mean reduction in fasting plasma glucose and 8-point SMPG profiles were similar between groups. Rates of confirmed hypoglycaemia were lower for IDegAsp Stepwise [2.1 per patient years of exposure (PYE)] vs. IDegAsp Simple (3.3 PYE) (estimated rate ratio IDegAsp Simple /IDegAsp Stepwise 1.8; 95% CI 1.1, 2.9). Nocturnal hypoglycaemia rates were similar between groups. No severe hypoglycaemic events were reported. In participants with insulin-naïve Type 2 diabetes mellitus, the IDegAsp Simple titration algorithm improved HbA 1c levels as effectively as a Stepwise titration algorithm. Hypoglycaemia rates were lower in the Stepwise arm. © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

[Comparison of the Effectiveness and Safety of Combined Chemotherapy with PEG-Asp for Treatment of ALL and T-NHL Patients].

PubMed

Xu, Yan; Wang, Jin; Yang, Nan; Bai, Ju; Zhang, Peng-Yu; Gu, Liu-Fang; Lei, Bo; Liu, Jie; Wang, Fang-Xia; Huang, Bing-Qiao; Zhang, Wang-Gang; He, Ai-Li; Cao, Xing-Mei; Chen, Yin-Xia; Ma, Xiao-Rong

2016-04-01

To explore the effectiveness and safety of combined chemotherapy with pegasparaginase (PEG-Asp) for treatment of patients with acute lymphoblastic leukemia (ALL) and T cell non-Hodgkin's lymphoma (T-NHL) patients. A total of 62 ALL or T-NHL patients were diagnosed and treated in our department and were enrolled in this study. Among them, 22 patients received the combined chemotherapy with PEG-Asp, while the other 40 patients received the standard chemotherapy with L-asparaginase (L-Asp) as the control. Therapeutic effectiveness, adverse effects, duration and expense of hospitalization, treatment-related mortality and survival were evaluated and compared in 2 different groups. In group of combined chemotherapy with PEG-Asp, the overall response rate was 90.91% (20 cases), among them CR rate and PR rate are 77.27% (17 cases) and 13.64% (3 cases), respectively. In the group of standard chemotherapy with L-Asp, the overall response rate was 87.5% (35 cases), among them CR rate and PR rate were 72.5% (29 cases) and 15% (6 cases), respectively. The difference neither between PEG-Asp and L-Asp chemotherapy groups nor between ALL and T-NHL subgroups was significant (P > 0.05). The 6-month and 12-month overall survival rates were not significantly different between the PEG-Asp and L-Asp chemotherapy groups, respectively (P > 0.05). The adverse effects were identified as degree 1-2 according to the WHO criteria of drug toxicity. Neither the adverse effects identified as degree 3-4 nor the treatment-related death were observed. Expect for allergy and hyperglycaemia, the difference of side-effect incidence between the two groups were not significant (P > 0.05). The treatment for all the patients in PEG-Asp chemotherapy group was completed, while the treatment with L-Asp was completed only in 29 cases. Moreover, both average duration and expense of hospitalization after the combined chemotherapy were less than the control. With higher response rate, lower drug toxicity and allergy incidence, the combined chemotherapy with PEG-Asp can replace the standard chemotherapy with L-Asp in the treatment of ALL and T-NHL. The optimization of the combined chemotheropeutic protocols for more cases and long-term survival rates need to further and deeply explorate.

Colloidal aggregation and structural assembly of aspect ratio variant goethite (α-FeOOH) with nC60 fullerene in environmental media.

PubMed

Ghosh, Saikat; Pradhan, Nihar R; Mashayekhi, Hamid; Zhang, Qiu; Pan, Bo; Xing, Baoshan

2016-12-01

Environmental mobility of C 60 fullerene can be significantly affected in the presence of naturally abundant α-FeOOH. However, α-FeOOH vary significantly in sizes, shapes and associated properties that can greatly influence the fate and transport of C 60 fullerene in environmental media. Therefore, colloidal hetero-association between well crystallized low aspect (L Asp ) α-FeOOH and nC 60 fullerene may differ substantially to weakly crystallized high-aspect (H Asp ) counterpart. In contrast to L Asp α-FeOOH, inherent crystal defects and surface charge generation in H Asp α-FeOOH facilitated strong Coulombic attraction and aggregation with fullerene in acidic pH. However, L Asp α-FeOOH demonstrated subtle entropic depletion mediated interaction with fullerene prevalent in hard rods. Humic acid (HA) encapsulation of H Asp α-FeOOH substantially blocked fullerene attachment. Minute enhancement in colloidal stability was detected for HA-coated H Asp α-FeOOH and fullerene mixture to HA-coated H Asp α-FeOOH alone. To investigate the interfacial assembly of α-FeOOH with fullerene "in situ" differential interference contrast (DIC) microscopic investigations were employed. This study showed significantly different interface behavior of the binary mixtures of fullerene and H Asp α-FeOOH NPs, and L Asp particles. On air-water interface, bare H Asp α-FeOOH displayed liquid crystalline packing. However, addition of fullerene to H Asp α-FeOOH suspension at pH5 produced closed-loop polygonal and circular ring structures. Head-to-tail alignment of magnetic dipoles as well as fullerene hydrophobicity facilitated such assembly formation. "Ex situ" AFM investigation revealed further the presence of magnetically derived ring structure which asserts that the formed "in situ" ensembles were not transient, hence, may abate fullerene transport through environmental interfaces. Barring hydrophobicity assisted attachment of fullerene to L Asp α-FeOOHs, the absence of any close-packed structures may unlikely abate fullerene transport as envisaged in case of H Asp α-FeOOH. Thus, aspect ratio variation and associated material properties of naturally abundant α-FeOOH may significantly impact fullerene transport through environmental media. Copyright © 2016 Elsevier Ltd. All rights reserved.

Absorption kinetics and action profiles of subcutaneously administered insulin analogues (AspB9GluB27, AspB10, AspB28) in healthy subjects.

PubMed

Kang, S; Brange, J; Burch, A; Vølund, A; Owens, D R

1991-11-01

The subcutaneous absorption and resulting changes in plasma insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations after subcutaneous bolus injection of three soluble human insulin analogues (AspB9GluB27, monomeric; AspB28, mixture of monomers and dimers; and AspB10, dimeric) and soluble human insulin were evaluated. Fasting healthy male volunteers (n = 7) were studied on five occasions 1 wk apart randomly receiving 0.6 nmol.kg-1 s.c. 125I-labeled AspB10 or soluble human insulin (Novolin R, Novo, Copenhagen); 1st study and 0.6 nmol.kg-1 s.c. 125I-labeled AspB28, AspB9GluB27 or soluble human insulin (2nd study). Residual radioactivity at the injection site was measured over 8 h with frequent venous sampling for plasma immunoreactive insulin or analogue, glucose, C-peptide, and blood intermediary metabolite concentrations. The three analogues were absorbed 2-3 times faster than human insulin. The mean +/- SE time to 50% residual radioactivity was 94 +/- 6 min for AspB10 compared with 184 +/- 10 min for human insulin (P less than 0.001), 83 +/- 8 min for AspB28 (P less than 0.005), and 63 +/- 9 min for AspB9GluB27 (P less than 0.001) compared with 182 +/- 21 min for human insulin. delta Peak plasma insulin analogue levels were significantly higher after each analogue than after human insulin (P less than 0.005). With all three analogues, the mean hypoglycemic nadir occurred earlier at 61-65 min postinjection compared with 201-210 min for the reference human insulins (P less than 0.005). The magnitude of the hypoglycemic nadir was greater after AspB9GluB27 (P less than 0.05) and AspB28 (P less than 0.001) compared with human insulin. There was a significantly faster onset and offset of responses in C-peptide and intermediary metabolite levels after the analogues than after human insulin (P less than 0.05). The rapid absorption and biological actions of these analogues offer potential therapeutic advantages over the current short-acting neutral soluble insulins.

Introducing an antibiotic stewardship program in a pediatric center in China.

PubMed

Zhang, Zhi-Gang; Chen, Fei; Chen, Jian-Zhong

2018-06-01

This study aimed to investigate the effect of antibiotic stewardship programs (ASP) on reducing antimicrobial resistance rate, antibiotics consumption and multi-drug resistance bacterial infections in the pediatric patients. This study was carried out in the Pediatric Center of a tertiary hospital of Shandong Province, China. The study duration was separated into two periods according to introduction of ASP (began from April 2011). Before intervention: from April 2009 to March 2011; after intervention: from April 2012 to March 2014. The consumption of antibiotics, defined daily dose (DDD), isolation of multidrug-resistant organisms (MDRO) and resistance rate of antibiotics were analyzed and compared between the two study periods. Total antibiotics consumption (DDDs) reduced from 56,725 in 2011 to 31,380 in 2014; antibiotic use density (AUD) reduced from 93.8 to 43.5; mean (± SD) antibiotic costs per patient (per quarter) decreased from 637 (± 29) RMB to 462 (± 49) RMB; and the mean total drug consumption (g)/DDD (DDDs) for inpatients decreased from 90.4 (± 3.3) to 56.4 (± 9.5). Multidrug-resistant microorganisms isolation reduced significantly from 463 (20.0) to 216 (6.9%). Resistance rate of general spectrum antibiotics reduced remarkably after intervention. The proportion of patients colonized or infected with Carbapenems-resistant Acinetobacter baumannii was correlated with DDDs of carbapenem. Implementation of ASP leads to reduced medical expense, decrease of improper and abuse of antibiotics, and reduced antibiotics resistance rate and MDRO isolation. Continuous efforts to improve antibiotic use are required.

β-secretase inhibitors for Alzheimer's disease: identification using pharmacoinformatics.

PubMed

Islam, Md Ataul; Pillay, Tahir S

2018-02-01

In this study we searched for potential β-site amyloid precursor protein cleaving enzyme1 (BACE1) inhibitors using pharmacoinformatics. A large dataset containing 7155 known BACE1 inhibitors was evaluated for pharmacophore model generation. The final model (R = 0.950, RMSD = 1.094, Q 2  = 0.901, se = 0.332, [Formula: see text] = 0.901, [Formula: see text] = 0.756, sp = 0.468, [Formula: see text] = 0.667) was revealed with the importance of spatial arrangement of hydrogen bond acceptor and donor, hydrophobicity and aromatic ring features. The validated model was then used to search NCI and InterBioscreen databases for promising BACE1 inhibitors. The initial hits from both databases were sorted using a number of criteria and finally three molecules from each database were considered for further validation using molecular docking and molecular dynamics studies. Different protonation states of Asp32 and Asp228 dyad were analysed and best protonated form used for molecular docking study. Observation of the number of binding interactions in the molecular docking study supported the potential of these molecules being promising inhibitors. Values of RMSD, RMSF, Rg in molecular dynamics study and binding energies unquestionably explained that final screened molecules formed stable complexes inside the receptor cavity of BACE1. Hence, it can be concluded that the final screened six compounds may be potential therapeutic agents for Alzheimer's disease.

Nonequilibrium radiation and chemistry models for aerocapture vehicle flowfields, volume 3

NASA Technical Reports Server (NTRS)

Carlson, Leland A.

1991-01-01

The computer programs developed to calculate the shock wave precursor and the method of using them are described. This method calculated the precursor flow field in a nitrogen gas including the effects of emission and absorption of radiation on the energy and composition of gas. The radiative transfer is calculated including the effects of absorption and emission through the line as well as the continuum process in the shock layer and through the continuum processes only in the precursor. The effects of local thermodynamic nonequilibrium in the shock layer and precursor regions are also included in the radiative transfer calculations. Three computer programs utilized by this computational scheme to calculate the precursor flow field solution for a given shock layer flow field are discussed.

Anisotropic Dispersion and Partial Localization of Acoustic Surface Plasmons on an Atomically Stepped Surface: Au(788)

NASA Astrophysics Data System (ADS)

Smerieri, M.; Vattuone, L.; Savio, L.; Langer, T.; Tegenkamp, C.; Pfnür, H.; Silkin, V. M.; Rocca, M.

2014-10-01

Understanding acoustic surface plasmons (ASPs) in the presence of nanosized gratings is necessary for the development of future devices that couple light with ASPs. We show here by experiment and theory that two ASPs exist on Au(788), a vicinal surface with an ordered array of monoatomic steps. The ASPs propagate across the steps as long as their wavelength exceeds the terrace width, thereafter becoming localized. Our investigation identifies, for the first time, ASPs coupled with intersubband transitions involving multiple surface-state subbands.

Effect of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the morphology of the thymus in hypophysectomized young and old birds.

PubMed

Pateyk, A V; Baranchugova, L M; Rusaeva, N S; Obydenko, V I; Kuznik, B I

2013-03-01

Investigations were carried out on chicks of different age. It was found that the most pronounced changes in the morphology of the thymus occurred after neonatal hypophysectomy. These changes are least pronounced in old chicks. Peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis of amino acid composition of peptide complexes of the anterior and posterior pituitary lobes administered to hypophysectomized birds regardless of age promoted recovery of the morphological structures of the thymus. The anterior pituitary peptide (Lys-Glu-Asp-Gly) had more pronounced effect on the recovery of thymic structure than posterior pituitary peptide (Ala-Glu-Asp-Gly).

3D Bioprinting of Developmentally Inspired Templates for Whole Bone Organ Engineering.

PubMed

Daly, Andrew C; Cunniffe, Gráinne M; Sathy, Binulal N; Jeon, Oju; Alsberg, Eben; Kelly, Daniel J

2016-09-01

The ability to print defined patterns of cells and extracellular-matrix components in three dimensions has enabled the engineering of simple biological tissues; however, bioprinting functional solid organs is beyond the capabilities of current biofabrication technologies. An alternative approach would be to bioprint the developmental precursor to an adult organ, using this engineered rudiment as a template for subsequent organogenesis in vivo. This study demonstrates that developmentally inspired hypertrophic cartilage templates can be engineered in vitro using stem cells within a supporting gamma-irradiated alginate bioink incorporating Arg-Gly-Asp adhesion peptides. Furthermore, these soft tissue templates can be reinforced with a network of printed polycaprolactone fibers, resulting in a ≈350 fold increase in construct compressive modulus providing the necessary stiffness to implant such immature cartilaginous rudiments into load bearing locations. As a proof-of-principal, multiple-tool biofabrication is used to engineer a mechanically reinforced cartilaginous template mimicking the geometry of a vertebral body, which in vivo supported the development of a vascularized bone organ containing trabecular-like endochondral bone with a supporting marrow structure. Such developmental engineering approaches could be applied to the biofabrication of other solid organs by bioprinting precursors that have the capacity to mature into their adult counterparts over time in vivo. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Triazole RGD antagonist reverts TGFβ1-induced endothelial-to-mesenchymal transition in endothelial precursor cells.

PubMed

Bianchini, Francesca; Peppicelli, Silvia; Fabbrizzi, Pierangelo; Biagioni, Alessio; Mazzanti, Benedetta; Menchi, Gloria; Calorini, Lido; Pupi, Alberto; Trabocchi, Andrea

2017-01-01

Fibrosis is the dramatic consequence of a dysregulated reparative process in which activated fibroblasts (myofibroblasts) and Transforming Growth Factor β1 (TGFβ1) play a central role. When exposed to TGFβ1, fibroblast and epithelial cells differentiate in myofibroblasts; in addition, endothelial cells may undergo endothelial-to-mesenchymal transition (EndoMT) and actively participate to the progression of fibrosis. Recently, the role of αv integrins, which recognize the Arg-Gly-Asp (RGD) tripeptide, in the release and signal transduction activation of TGFβ1 became evident. In this study, we present a class of triazole-derived RGD antagonists that interact with αvβ3 integrin. Above different compounds, the RGD-2 specifically interferes with integrin-dependent TGFβ1 EndoMT in Endothelial Colony-Forming Cells (ECPCs) derived from circulating Endothelial Precursor Cells (ECPCs). The RGD-2 decreases the amount of membrane-associated TGFβ1, and reduces both ALK5/TGFβ1 type I receptor expression and Smad2 phosphorylation in ECPCs. We found that RGD-2 antagonist reverts EndoMT, reducing α-smooth muscle actin (α-SMA) and vimentin expression in differentiated ECPCs. Our results outline the critical role of integrin in fibrosis progression and account for the opportunity of using integrins as target for anti-fibrotic therapeutic treatment.

Liquid chromatography-high resolution mass spectrometric methods for the surveillance monitoring of cyanotoxins in freshwaters.

PubMed

Bogialli, Sara; Bortolini, Claudio; Di Gangi, Iole Maria; Di Gregorio, Federica Nigro; Lucentini, Luca; Favaro, Gabriella; Pastore, Paolo

2017-08-01

A comprehensive risk management on human exposure to cyanotoxins, whose production is actually unpredictable, is limited by reliable analytical tools for monitoring as many toxic algal metabolites as possible. Two analytical approaches based on a LC-QTOF system for target analysis and suspect screening of cyanotoxins in freshwater were presented. A database with 369 compounds belonging to cyanobacterial metabolites was developed and used for a retrospective data analysis based on high resolution mass spectrometry (HRMS). HRMS fragmentation of the suspect cyanotoxin precursor ions was subsequently performed for correctly identifying the specific variants. Alternatively, an automatic tandem HRMS analysis tailored for cyanotoxins was performed in a single chromatographic run, using the developed database as a preferred precursor ions list. Twenty-five extracts of surface and drinking waters contaminated by cyanobacteria were processed. The identification of seven uncommon microcystins (M(O)R, MC-FR, MSer 7 -YR, D-Asp 3 MSer 7 -LR, MSer 7 -LR, dmAdda-LR and dmAdda-YR) and 6 anabaenopeptins (A, B, F, MM850, MM864, oscyllamide Y) was reported. Several isobaric variants, fully separated by chromatography, were pointed out. The developed methods are proposed to be used by environmental and health agencies for strengthening the surveillance monitoring of cyanotoxins in water. Copyright © 2017 Elsevier B.V. All rights reserved.

The Apollo Program and Amino Acids

ERIC Educational Resources Information Center

Fox, Sidney W.

1973-01-01

Discusses the determination of hydrolyzable amino acid precursors and a group of six amino acids in the returned lunar samples of the Apollo programs. Indicates that molecular evolution is arrested at the precursor stage on the Moon because of lack of water. (CC)

77 FR 24171 - Notice of Funds Availability: Inviting Applications for the Foreign Market Development Cooperator...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-23

... intended effect of this notice is to solicit applications from eligible applicants for 2013 and to set out... considered. FOR FURTHER INFORMATION CONTACT: Entities wishing to apply for funding assistance should contact...://www.fas.usda.gov/mos/programs/fmdprogram.asp . SUPPLEMENTARY INFORMATION: I. Funding Opportunity...

Securing Voice over IP Conferencing with Decentralized Group Encryption

DTIC Science & Technology

2007-09-04

media stream. Call data can then be encrypted and decrypted. Zfone is available as a plug-in for a number of VoIP programs, including Gizmo [13...Terminal. http://www.l- 3com.com/csw/product/specs/Airborne/TCDLAir.asp. [13] The Gizmo Project. http://gizmoproject.com. [14] The OpenSSL

Core Intervention Components: Identifying and Operationalizing What Makes Programs Work. ASPE Research Brief

ERIC Educational Resources Information Center

Blase, Karen; Fixsen, Dean

2013-01-01

This brief is part of a series that explores key implementation considerations. It focuses on the importance of identifying, operationalizing, and implementing the "core components" of evidence-based and evidence-informed interventions that likely are critical to producing positive outcomes. The brief offers a definition of "core components",…

76 FR 59701 - Agency Information Collection Request. 30 Day Public Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-27

... and Medicaid programs for children. To answer these questions, ASPE will draw on three new primary... notice directly to the OS OMB Desk Officer; faxed to OMB at 202-395-5806. Proposed Project: The Children... collection to provide the federal government with new and detailed insights into how the Children's Health...

Studies on Aspirin Crystals Generated by a Modified Vapor Diffusion Method.

PubMed

Mittal, Amit; Malhotra, Deepak; Jain, Preeti; Kalia, Anupama; Shunmugaperumal, Tamilvanan

2016-08-01

The objectives of the current investigation were (1) to study the influence of selected two different non-solvents (diethylether and dichloromethane) on the drug crystal formation of a model drug, aspirin (ASP-I) by the modified vapor diffusion method and (2) to characterize and compare the generated crystals (ASP-II and ASP-III) using different analytical techniques with that of unprocessed ASP-I. When compared to the classical vapor diffusion method which consumes about 15 days to generate drug crystals, the modified method needs only 12 h to get the same. Fourier transform-infrared spectroscopy (FT-IR) reveals that the internal structures of ASP-II and ASP-III crystals were identical when compared with ASP-I. Although the drug crystals showed a close similarity in X-ray diffraction patterns, the difference in the relative intensities of some of the diffraction peaks (especially at 2θ values of around 7.7 and 15.5) could be attributed to the crystal habit or crystal size modification. Similarly, the differential scanning calorimetry (DSC) study speculates that only the crystal habit modifications might occur but without involving any change in internal structure of the generated drug polymorphic form I. This is further substantiated from the scanning electron microscopy (SEM) pictures that indicated the formation of platy shape for the ASP-II crystals and needle shape for the ASP-III crystals. In addition, the observed slow dissolution of ASP crystals should indicate polymorph form I formation. Thus, the modified vapor diffusion method could routinely be used to screen and legally secure all possible forms of other drug entities too.

Comparative analysis of the immune responses induced by native versus recombinant versions of the ASP-based vaccine against the bovine intestinal parasite Cooperia oncophora.

PubMed

González-Hernández, Ana; Borloo, Jimmy; Peelaers, Iris; Casaert, Stijn; Leclercq, Georges; Claerebout, Edwin; Geldhof, Peter

2018-01-01

The protective capacities of a native double-domain activation-associated secreted protein (ndd-ASP)-based vaccine against the cattle intestinal nematode Cooperia oncophora has previously been demonstrated. However, protection analysis upon vaccination with a recombinantly produced antigen has never been performed. Therefore, the aim of the current study was to test the protective potential of a Pichia-produced double-domain ASP (pdd-ASP)-based vaccine against C. oncophora. Additionally, we aimed to compare the cellular and humoral mechanisms underlying the vaccine-induced responses by the native (ndd-ASP) and recombinant vaccines. Immunisation of cattle with the native C. oncophora vaccine conferred significant levels of protection after an experimental challenge infection, whereas the recombinant vaccine did not. Moreover, vaccination with ndd-ASP resulted in a higher proliferation of CD4-T cells both systemically and in the small intestinal mucosa when compared with animals vaccinated with the recombinant antigen. In terms of humoral response, although both native and recombinant vaccines induced similar levels of antibodies, animals vaccinated with the native vaccine were able to raise antibodies with greater specificity towards ndd-ASP in comparison with antibodies raised by vaccination with the recombinant vaccine, suggesting a differential immune recognition towards the ndd-ASP and pdd-ASP. Finally, the observation that animals displaying antibodies with higher percentages of recognition towards ndd-ASP also exhibited the lowest egg counts suggests a potential relationship between antibody specificity and protection. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Structures of aspartic acid-96 in the L and N intermediates of bacteriorhodopsin: analysis by Fourier transform infrared spectroscopy

NASA Technical Reports Server (NTRS)

Maeda, A.; Sasaki, J.; Shichida, Y.; Yoshizawa, T.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.

1992-01-01

The light-induced difference Fourier transform infrared spectrum between the L or N intermediate minus light-adapted bacteriorhodopsin (BR) was measured in order to examine the protonated states and the changes in the interactions of carboxylic acids of Asp-96 and Asp-115 in these intermediates. Vibrational bands due to the protonated and unprotonated carboxylic acid were identified by isotope shift and band depletion upon substitution of Asp-96 or -115 by asparagine. While the signal due to the deprotonation of Asp-96 was clearly observed in the N intermediate, this residue remained protonated in L. Asp-115 was partially deprotonated in L. The C = O stretching vibration of protonated Asp-96 of L showed almost no shift upon 2H2O substitution, in contrast to the corresponding band of Asp-96 or Asp-115 of BR, which shifted by 9-12 cm-1 under the same conditions. In the model system of acetic acid in organic solvents, such an absence of the shift of the C = O stretching vibration of the protonated carboxylic acid upon 2H2O substitution was seen only when the O-H of acetic acid is hydrogen-bonded. The non-hydrogen-bonded monomer showed the 2H2O-dependent shift. Thus, the O-H bond of Asp-96 enters into hydrogen bonding upon conversion of BR to L. Its increased hydrogen bonding in L is consistent with the observed downshift of the O-H stretching vibration of the carboxylic acid of Asp-96.

GLU298ASP and 4G/5G Polymorphisms and the Risk of Ischemic Stroke in Young Individuals.

PubMed

Esparza-García, Juan Carlos; Santiago-Germán, David; Guadalupe Valades-Mejía, María; Hernández-Juárez, Jesus; Aguilar-Sosa, Eberth; Leaños-Miranda, Alfredo; Alvarado-Moreno, Antonio; Majluf-Cruz, Abraham; Isordia-Salas, Irma

2015-09-01

Polymorphisms in the endothelial nitric oxide synthase (eNOS) and in the plasminogen activator inhibitor -1 (PAI-1) genes have been implicated in stroke pathogenesis but results are still controversial. The aim of this study was to examine the possible contribution of Glu298Asp in the eNOS and 4G/5G in the PAI-1polymorphisms with ischemic stroke in a young Mexican population. In a case-control study, conducted between January 2006 and June 2010, 204 patients ≤45 years of age with ischemic stroke and 204 controls matched by age and gender, were recruited. The Glu298Asp and 4G/5G polymorphisms were determined in all participants by polymerase chain reaction-restriction fragment length polymorphism. There was a significant difference in the Glu298Asp genotype distribution (P=0.001) and allele frequency between the two groups (P=0.001). The 4G/5G genotype distribution (P=0.40) and the allele frequency was similar between groups; (P=0.13). There were independent factors for ischemic stroke: Asp carriage (GluAsp+AspAsp) (P=0.02); smoking (P=0.01); hypertension (P=0.03), and familial history of atherothrombotic disease (P=0.04). The Asp allele from the Gu298Asp gene represents an independent risk factor for ischemic stroke in a young Mexican population. In contrast, the 4G/5G was not associated with an increased risk for this disease in the same group of patients, as previously has been demonstrated in other populations.

Antimicrobial Stewardship Program Using Plan-Do-Study-Act Cycles to Reduce Unjustified Antibiotic Prescribing in Children Admitted With an Asthma Exacerbation

PubMed Central

Dorzin, Sasha E.; Halaby, Claudia; Quintos, Maria Lyn; Noor, Asif

2017-01-01

OBJECTIVE Antimicrobial stewardship programs (ASPs) ensure appropriate antibiotic use, reduce health care costs, and minimize antibiotic resistance. National asthma guidelines do not recommend antibiotics during an exacerbation unless the child has an infection or comorbidities. The American Academy of Pediatrics (AAP) established a benchmark for unjustified antibiotic use at 6.6%.9 A retrospective study at our institution showed that 7.8% of antibiotics were prescribed without justification in children admitted for asthma. The purpose of this study was to reduce unjustified antibiotic use at our institution by 25% in children through an ASP directed toward asthma. METHODS The study period lasted from November 2015 to March 2016. Children 6 months to 17 years of age, admitted for an asthma exacerbation, were included while those with comorbidities were excluded. A multidisciplinary team from pediatric pharmacotherapy, pulmonology, emergency department (ED), infectious diseases, and quality improvement was formed to focus on process improvement. Interventions were executed in a series of Plan-Do-Study-Act cycles. In cycle 1, our asthma guidelines on appropriate antibiotic use were disseminated to pediatric house staff and posted in pediatric units. Cycle 2 encompassed presenting the ASP and guidelines to the pediatric ED staff. Cycle 3 consisted of a journal club with the pulmonary division to discuss the role of azithromycin in an asthma exacerbation. RESULTS In cycle 1, twenty-four patients were reviewed in November 2015. Antibiotics were prescribed in 8/24 (33%) children, with an unjustified rate of 2/24 (8.3%). In cycle 2, twenty-three patients were reviewed in December and January with 8/23 (35%) prescribed antibiotics and an unjustified rate of 2/23 (8.7%). For cycle 3, in February and March 2016, twenty-one children were reviewed. Antibiotics were prescribed in 6/21 (27%) children and all were justified. In total, 68 patients were included in our study and had an unjustified antibiotic prescribing rate of 4/68 (5.9%), a reduction of 25%. CONCLUSION Our ASP surpassed the benchmark set by AAP guidelines, by reducing the percentage of unjustified antibiotics in children with asthma to 5.9%. PMID:29290744

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

Loew, G.H.; Axe, F.U.; Collins, J.R.

In this study, we have investigated the plausibility of a key postulated transformation of the proximal imidazole ligand (His 175) to an imidazolate by proton transfer to a nearby aspartate (Asp 235) absent in Mb. The proton relay system studied included not only models for the His 175 and Asp 235 residues but also for a nearby Trp 191 residue that could also interact with Asp 235 through hydrogen bonding and polarization. Two semiempirical quantum mechanical methods, Am1 and MNDO/H, with improved capabilities of describing H-bonded systems, were used to calculate the enthalpies of the three tautomeric forms of themore » proton relay system corresponding to the proton on the His, Asp, and Trp, respectively. These calculations were made for several models of the effect of the iron. Relative tautomeric enthalpies were calculated both with H-atom only optimization, keeping the heavy atoms fixed in their X-ray positions, and additional optimization that allowed the model Asp residue to relax. Transition-state enthalpies for the proton transfer from His to Asp were also calculated. The results of these studies suggest that the crucial postulated proton transfer from His to Asp is energetically favored, but only in the presence of the interaction of the iron with the imidazole ligand. Another stable form of the cluster, with competing proton transfer from the Trp to the Asp, was found only when the Asp position was allowed to optimize.« less

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

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu; Loukas, Alex; Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Brisbane, QLD 4006

In order to clarify the structural basis of the pathogenesis-related-1 domain, Na-ASP-1, the first multi-domain ASP from the human hookworm parasite N. americanus, has been crystallized. 2.2 Å resolution data have been collected from a crystal belonging to the monoclinic space group P2{sub 1}. Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functionsmore » of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P2{sub 1} with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit.« less

Caspofungin exposure alters the core septin AspB interactome of Aspergillus fumigatus.

PubMed

Vargas-Muñiz, José M; Renshaw, Hilary; Waitt, Greg; Soderblom, Erik J; Moseley, M Arthur; Palmer, Jonathan M; Juvvadi, Praveen R; Keller, Nancy P; Steinbach, William J

2017-04-01

Aspergillus fumigatus, the main etiological agent of invasive aspergillosis, is a leading cause of death in immunocompromised patients. Septins, a conserved family of GTP-binding proteins, serve as scaffolding proteins to recruit enzymes and key regulators to different cellular compartments. Deletion of the A. fumigatus septin aspB increases susceptibility to the echinocandin antifungal caspofungin. However, how AspB mediates this response to caspofungin is unknown. Here, we characterized the AspB interactome under basal conditions and after exposure to a clinically relevant concentration of caspofungin. While A. fumigatus AspB interacted with 334 proteins, including kinases, cell cycle regulators, and cell wall synthesis-related proteins under basal growth conditions, caspofungin exposure altered AspB interactions. A total of 69 of the basal interactants did not interact with AspB after exposure to caspofungin, and 54 new interactants were identified following caspofungin exposure. We generated A. fumigatus deletion strains for 3 proteins (ArpB, Cyp4, and PpoA) that only interacted with AspB following exposure to caspofungin that were previously annotated as induced after exposure to antifungal agents, yet only PpoA was implicated in the response to caspofungin. Taken together, we defined how the septin AspB interactome is altered in the presence of a clinically relevant antifungal. Copyright © 2017 Elsevier Inc. All rights reserved.

The dipeptide Pro-Asp promotes IGF-1 secretion and expression in hepatocytes by enhancing JAK2/STAT5 signaling pathway.

PubMed

Wang, Songbo; Wang, Guoqing; Zhang, Mengyuan; Zhuang, Lu; Wan, Xiaojuan; Xu, Jingren; Wang, Lina; Zhu, Xiaotong; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Shu, Gang; Jiang, Qingyan

2016-11-15

It has been implicated that IGF-1 secretion can be regulated by dietary protein. However, whether the dipeptides, one of digested products of dietary protein, have influence on IGF-1 secretion remain largely unknown. Our study aimed to investigate the effects of the dipeptide Pro-Asp on IGF-1 secretion and expression in hepatocytes and to explore the possible underlying mechanisms. Our findings demonstrated that Pro-Asp promoted the secretion and gene expression of IGF-1 in HepG2 cells and primary porcine hepatocytes. Meanwhile, Pro-Asp activated the ERK and Akt signaling pathways, downstream of IGF-1. In addition, Pro-Asp enhanced GH-mediated JAK2/STAT5 signaling pathway, while inhibition of JAK2/STAT5 blocked the promotive effect of Pro-Asp on IGF-1 secretion and expression. Moreover, acute injection of Pro-Asp stimulated IGF-1 expression and activated JAK2/STAT5 signaling pathway in mice liver. Together, these results suggested that the dipeptide Pro-Asp promoted IGF-1 secretion and expression in hepatocytes by enhancing GH-mediated JAK2/STAT5 signaling pathway. Copyright © 2016. Published by Elsevier Ireland Ltd.

Crystallization and preliminary X-ray analysis of Na-ASP-1, a multi-domain pathogenesis-related-1 protein from the human hookworm parasite Necator americanus

PubMed Central

Asojo, Oluwatoyin A.; Loukas, Alex; Inan, Mehmet; Barent, Rick; Huang, Jicai; Plantz, Brad; Swanson, Amber; Gouthro, Mark; Meagher, Michael M.; Hotez, Peter J.

2005-01-01

Human hookworm infection is a major cause of anemia and malnutrition in the developing world. In an effort to control hookworm infection, the Human Hookworm Vaccine Initiative has identified candidate vaccine antigens from the infective larval stage (L3) of the parasite, including a family of pathogenesis-related-1 (PR-1) proteins known as the ancylostoma-secreted proteins (ASPs). The functions of the ASPs are unknown. In addition, it is unclear why some ASPs have one while others have multiple PR-1 domains. There are no known structures of a multi-domain ASP and in an effort to remedy this situation, recombinant Na-ASP-1 has been expressed, purified and crystallized. Na-ASP-1 is a 406-amino-acid multi-domain ASP from the prevalent human hookworm parasite Necator americanus. Useful X-ray data to 2.2 Å have been collected from a crystal that belongs to the monoclinic space group P21 with unit-cell parameters a = 67.7, b = 74.27, c = 84.60 Å, β = 112.12°. An initial molecular-replacement solution has been obtained with one monomer in the asymmetric unit. PMID:16511050

Structural Basis for the Kexin-like Serine Protease from Aeromonas sobria as Sepsis-causing Factor*

PubMed Central

Kobayashi, Hidetomo; Utsunomiya, Hiroko; Yamanaka, Hiroyasu; Sei, Yoshihisa; Katunuma, Nobuhiko; Okamoto, Keinosuke; Tsuge, Hideaki

2009-01-01

The anaerobic bacterium Aeromonas sobria is known to cause potentially lethal septic shock. We recently proposed that A. sobria serine protease (ASP) is a sepsis-related factor that induces vascular leakage, reductions in blood pressure via kinin release, and clotting via activation of prothrombin. ASP preferentially cleaves peptide bonds that follow dibasic amino acid residues, as do Kex2 (Saccharomyces cerevisiae serine protease) and furin, which are representative kexin family proteases. Here, we revealed the crystal structure of ASP at 1.65 Å resolution using the multiple isomorphous replacement method with anomalous scattering. Although the overall structure of ASP resembles that of Kex2, it has a unique extra occluding region close to its active site. Moreover, we found that a nicked ASP variant is cleaved within the occluding region. Nicked ASP shows a greater ability to cleave small peptide substrates than the native enzyme. On the other hand, the cleavage pattern for prekallikrein differs from that of ASP, suggesting the occluding region is important for substrate recognition. The extra occluding region of ASP is unique and could serve as a useful target to facilitate development of novel antisepsis drugs. PMID:19654332

School Violence: Prevalence, Precursors, and Prevention.

ERIC Educational Resources Information Center

Juvonen, Jaanna

2002-01-01

Reviews types of school violence students confront, including a frequent precursor thereto: bullying. Discusses positive and negative aspects of current approach to school violence prevention such as surveillance, zero-tolerance policies, anti-bullying programs. Describes components of model school violence-prevention program. (Contains 38…

Interface design and reinforced features of arrowroot (Maranta arundinacea) starch/polyester-based membranes: Preparation, antioxidant activity, and cytocompatibility.

PubMed

Wu, Chin-San; Liao, Hsin-Tzu

2017-01-01

The structural, mechanical, antioxidant, and cytocompatibility properties of membranes prepared from the polyhydroxyalkanoate (PHA) and arrowroot (Maranta arundinacea) starch powder (ASP) blend (PHA/ASP) were studied. The acrylic acid-grafted PHA (PHA-g-AA) and the coupling agent treated ASP (TASP) were used to enhance the desired characteristics of these membranes. The PHA-g-AA/TASP membranes had better mechanical properties than the PHA/ASP membrane. This effect was attributed to greater compatibility between the grafted PHA and TASP. The water resistance of the PHA-g-AA/TASP membranes was greater than that of the PHA/ASP membranes, and a cytocompatibility evaluation with human foreskin fibroblasts (FBs) indicated that both materials were nontoxic. Moreover, both ASP and TASP enhanced the polyphenol content and antioxidant properties of the membranes. PHA-g-AA/TASP and PHA/ASP membranes had better antioxidant activity than the control group. Copyright © 2016 Elsevier B.V. All rights reserved.

Biomass characterization of laboratory-scale thermophilic-mesophilic wastewater treatment processes.

PubMed

Suvilampi, J; Lehtomäki, A; Rintala, J

2006-01-01

Two thermophilic-mesophilic wastewater treatment processes, one as the combination of the thermophilic activated sludge process (ASP), followed by the mesophilic ASP and the other as thermophilic suspended carrier biofilm process (SCBP), followed by the mesophilic ASP, were used to study sludge characteristics and floc formation. Thermophilic bacteria in both ASP and SCBP were able to form flocs, which were <50 microm in size and had a weak structure and irregular shape. Flocs in both the mesophilic ASPs were larger in size (50-500 microm) and had more compact structures. Filamentous bacteria played an important role in both the thermophilic and mesophilic processes by forming bridges between small flocs. Both thermophilic processes showed a high density of dispersed particles, such as free bacteria. When hydraulic retention time (HRT) was decreased the biofilm was retained in the thermophilic SCBP better than the flocs in the thermophilic ASP. The mesophilic ASPs efficiently removed dispersed particles originating from the thermophilic processes.

The Edelman Galileoscope Education Program: A Collaboration Among Professional Societies

NASA Astrophysics Data System (ADS)

Pompea, Stephen M.; Marvel, K. B.; Fienberg, R. T.; Arion, D. N.; Herrold, A.; Kruse, B.; Sparks, R. T.; Dugan, C.

2011-01-01

The Edelman Galileoscope Education Program is an ongoing national effort to provide K-12 teachers with Galileoscope refractor kits and the proper training to use them effectively for teaching scientific concepts and observational skills. As such it represents a strategic effort to excite children about astronomy and provides them with a powerful tool to increase science literacy. The program was made possible by a generous gift from Jean and Ric Edelman to the American Astronomical Society (AAS). The AAS teamed with the National Optical Astronomy Observatory (NOAO); Galileoscope, LLC; the National Earth Science Teachers Association (NESTA); and the Astronomical Society of the Pacific (ASP) to distribute telescopes, mainly during teacher workshops. Through the professional development efforts of NESTA, ASP, and NOAO's Teaching With Telescopes program some 1,400 teachers received Galileoscopes and hands-on training on how to teach optics and astronomy with them. All participating teachers received Galileoscopes free of charge. Another 1,500 or so teachers not connected with these organizations also received telescopes free of charge through an Internet ordering system, paying only for shipping. Under this combination of programs more than 15,000 Galileoscopes have been given to active teachers, reaching an estimated 300,000 students. The professional development program uses a combination of face-to-face workshops, a train-the-trainer model, and Internet-based self-paced instruction. We describe the Edelman Galileoscope Education Program design, training materials, and distribution networks, as well as the geographic distribution of the teachers who received Galileoscopes. This program represents an efficient and effective model for quickly distributing valuable science teaching materials to urban, suburban, and rural teachers _ including homeschoolers _ across the United States.

Competing Death Programs in Poliovirus-Infected Cells: Commitment Switch in the Middle of the Infectious Cycle

PubMed Central

Agol, Vadim I.; Belov, George A.; Bienz, Kurt; Egger, Denise; Kolesnikova, Marina S.; Romanova, Lyudmila I.; Sladkova, Larissa V.; Tolskaya, Elena A.

2000-01-01

Productive poliovirus infection of HeLa cells leads to the canonical cytopathic effect (CPE), whereas certain types of abortive infection result in apoptosis. To define the time course of commitment to the different types of poliovirus-induced death, inhibitors of viral replication (guanidine HCl) or translation (cycloheximide) were added at different times postinfection (p.i.). Early in the infection (during the first ∼2 h p.i.), predominantly proapoptotic viral function was expressed, rendering the cells committed to apoptosis, which developed several hours after viral expression was arrested. In the middle of infection, concomitantly with the onset of fast generation of viral progeny, the implementation of the viral apoptotic program was abruptly interrupted. In particular, activation of an Asp-Glu-Val-Asp (DEVD)-specific caspase(s) occurring in the apoptosis-committed cells was prevented by the ongoing productive infection. Simultaneously, the cells retaining normal or nearly normal morphology became committed to CPE, which eventually developed regardless of whether or not further viral expression was allowed to proceed. The implementation of the poliovirus-induced apoptotic program was suppressed in HeLa cells overexpressing the Bcl-2 protein, indicating that the fate of poliovirus-infected cells depends on the balance of host and viral pro- and antiapoptotic factors. PMID:10823859

The Global Epidemiology of Syphilis in the Past Century - A Systematic Review Based on Antenatal Syphilis Prevalence.

PubMed

Kenyon, Chris Richard; Osbak, Kara; Tsoumanis, Achilleas

2016-05-01

How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990-1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3-5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990-1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa.

Methanolic extract of white asparagus shoots activates TRAIL apoptotic death pathway in human cancer cells and inhibits colon carcinogenesis in a preclinical model

PubMed Central

BOUSSEROUEL, SOUAD; LE GRANDOIS, JULIE; GOSSÉ, FRANCINE; WERNER, DALAL; BARTH, STEPHAN W.; MARCHIONI, ERIC; MARESCAUX, JACQUES; RAUL, FRANCIS

2013-01-01

Shoots of white asparagus are a popular vegetable dish, known to be rich in many bioactive phytochemicals reported to possess antioxidant, and anti-inflammatory and antitumor activities. We evaluated the anticancer mechanisms of a methanolic extract of Asparagus officinalis L. shoots (Asp) on human colon carcinoma cells (SW480) and their derived metastatic cells (SW620), and Asp chemopreventive properties were also assessed in a model of colon carcinogenesis. SW480 and SW620 cell proliferation was inhibited by 80% after exposure to Asp (80 μg/ml). We demonstrated that Asp induced cell death through the activation of TRAIL DR4/DR5 death receptors leading to the activation of caspase-8 and caspase-3 and to cell apoptosis. By specific blocking agents of DR4/DR5 receptors we were able to prevent Asp-triggered cell death confirming the key role of DR4/DR5 receptors. We found also that Asp (80 μg/ml) was able to potentiate the effects of the cytokine TRAIL on cell death even in the TRAIL-resistant metastatic SW620 cells. Colon carcinogenesis was initiated in Wistar rats by intraperitoneal injections of azoxymethane (AOM), once a week for two weeks. One week after (post-initiation) rats received daily Asp (0.01%, 14 mg/kg body weight) in drinking water. After 7 weeks of Asp-treatment the colon of rats exhibited a 50% reduction of the number of preneoplastic lesions (aberrant crypt foci). In addition Asp induced inhibition of several pro-inflammatory mediators, in association with an increased expression of host-defense mediators. In the colonic mucosa of Asp-treated rats we also confirmed the pro-apoptotic effects observed in vitro including the activation of the TRAIL death-receptor signaling pathway. Taken together, our data highlight the chemopreventive effects of Asp on colon carcinogenesis and its ability to promote normal cellular homeostasis. PMID:23754197

Efficacy and safety of once-daily insulin degludec/insulin aspart compared with once-daily insulin glargine in participants with Type 2 diabetes: a randomized, treat-to-target study.

PubMed

Kumar, S; Jang, H C; Demirağ, N G; Skjøth, T V; Endahl, L; Bode, B

2017-02-01

To investigate, in a 26-week, open-label, randomized, treat-to-target trial, the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) once daily vs insulin glargine (IGlar) once daily in adults with Type 2 diabetes, inadequately controlled on basal insulin. Participants were randomized (1:1) to IDegAsp once daily or IGlar once daily in combination with existing oral antidiabetic drugs. IDegAsp once daily was administered with the main evening meal or the largest meal of the day (agreed at baseline); dosing time was maintained throughout the trial. Participants titrated their insulin dose weekly to a mean pre-breakfast self-measured plasma glucose target [3.9-4.9 mmol/l (70-89 mg/dl)]. IDegAsp once daily was non-inferior to IGlar once daily in reducing HbA 1c after 26 weeks [mean estimated treatment difference IDegAsp once daily - IGlar once daily: -0.03% (95% CI -0.20, 0.14)]. The evening meal glucose increment was significantly lower with IDegAsp once daily vs IGlar once daily [estimated treatment difference IDegAsp once daily - IGlar once daily: -1.32 mmol/l (95% CI -1.93, -0.72); P < 0.05]. The overall confirmed hypoglycaemia rate was higher with IDegAsp once daily (estimated rate ratio 1.43; 95% CI 1.07, 1.92; P < 0.05). The rate of nocturnal hypoglycaemia did not significantly differ between the IDegAsp and IGlar groups [estimated rate ratio 0.80 (95% CI 0.49, 1.30); not significant]. In participants with Type 2 diabetes inadequately controlled on basal insulin, IDegAsp once daily improved glycaemic control and was non-inferior to IGlar once daily. IDegAsp led to higher rates of overall hypoglycaemia than IGlar, with no significant difference in rates of nocturnal hypoglycaemia. © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Angelica sinensis polysaccharides promotes apoptosis in human breast cancer cells via CREB-regulated caspase-3 activation

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

Zhou, Wei-Jie; Wang, Sheng; Hu, Zhuang, E-mail: zhuanghu475000@sina.com

Angelica sinensis polysaccharide (ASP) is purified from the fresh roots of Angelica sinensis (AS). This traditional Chinese medicine has been used for thousands of years for treating gynecological diseases and used in functional foods for the prevention and treatment of various diseases, such as inflammation and cancer. The antitumor activity of ASP is related to its biological activities, because it suppresses a variety of pro-proliferative or anti-apoptotic factors that are dramatically expressed in cancer cells of given types. In this study, we show that angelica sinensis polysaccharide induced apoptosis in breast cancer cells of T47D over-expressing the Cyclic AMP responsemore » element binding protein (CREB), inducing apoptosis-related signaling pathway activity. The result also found that ASP caused cell death was linked to caspase activity, accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. We found that ASP significantly affected the poly-ADP-ribose polymerase (PARP), Bcl-2 Associated X Protein (Bax), Bcl-2, Bcl-xL and apoptotic protease activating facter-1 (Apaf1) protein expression in a dose- and time-dependent manner. DAPI staining and Flow cytometry were used to analyze apoptosis. The nude mice xenograft model was used to evaluate the antitumor effect of ASP in vivo. ASP has profound antitumor effect on T47D cells, probably by inducing apoptosis through CREB signaling pathway. Thus, these results suggest that ASP would be a promising therapeutic agent for breast cancer. - Highlights: • CREB and Caspase-3 signaling pathways are involved in the ASP induced breast cancer cells apoptosis. • ROCK1/Mlc signaling pathway plays a critical role in this ASP-mediated apoptosis. • Angelica sinensis polysaccharide (ASP) affected the PARP, Bax, Bcl-2, Bcl-xL and Apaf1 protein expression. • The activation of CREB and ROCK1 promotes caspase-3 activation and apoptosis induced by ASP.« less

Development of Novel Radiogallium-Labeled Bone Imaging Agents Using Oligo-Aspartic Acid Peptides as Carriers

PubMed Central

Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Kiwada, Tatsuto; Shiba, Kazuhiro; Odani, Akira

2013-01-01

68Ga (T 1/2 = 68 min, a generator-produced nuclide) has great potential as a radionuclide for clinical positron emission tomography (PET). Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting 68Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Asp)n (n = 2, 5, 8, 11, or 14) with easy-to-handle 67Ga, with the previously described 67Ga-DOTA complex conjugated bisphosphonate, 67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Asp)n by a Fmoc-based solid-phase method, complexes were formed with 67Ga, resulting in 67Ga-DOTA-(Asp)n with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of 67Ga-DOTA-(Asp)n increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, 67Ga-DOTA-(Asp)8, 67Ga-DOTA-(Asp)11, and 67Ga-DOTA-(Asp)14 showed high accumulation in bone (10.5±1.5, 15.1±2.6, and 12.8±1.7% ID/g, respectively) but were barely observed in other tissues at 60 min after injection. Although bone accumulation of 67Ga-DOTA-(Asp)n was lower than that of 67Ga-DOTA-Bn-SCN-HBP, blood clearance of 67Ga-DOTA-(Asp)n was more rapid. Accordingly, the bone/blood ratios of 67Ga-DOTA-(Asp)11 and 67Ga-DOTA-(Asp)14 were comparable with those of 67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of 68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases. PMID:24391942

Topology of AspT, the aspartate:alanine antiporter of Tetragenococcus halophilus, determined by site-directed fluorescence labeling.

PubMed

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C; Abe, Keietsu

2007-10-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of L-aspartate (Asp) with release of L-alanine (Ala) and CO(2). The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an L-aspartate-beta-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity.

Topology of AspT, the Aspartate:Alanine Antiporter of Tetragenococcus halophilus, Determined by Site-Directed Fluorescence Labeling▿ †

PubMed Central

Nanatani, Kei; Fujiki, Takashi; Kanou, Kazuhiko; Takeda-Shitaka, Mayuko; Umeyama, Hideaki; Ye, Liwen; Wang, Xicheng; Nakajima, Tasuku; Uchida, Takafumi; Maloney, Peter C.; Abe, Keietsu

2007-01-01

The gram-positive lactic acid bacterium Tetragenococcus halophilus catalyzes the decarboxylation of l-aspartate (Asp) with release of l-alanine (Ala) and CO2. The decarboxylation reaction consists of two steps: electrogenic exchange of Asp for Ala catalyzed by an aspartate:alanine antiporter (AspT) and intracellular decarboxylation of the transported Asp catalyzed by an l-aspartate-β-decarboxylase (AspD). AspT belongs to the newly classified aspartate:alanine exchanger family (transporter classification no. 2.A.81) of transporters. In this study, we were interested in the relationship between the structure and function of AspT and thus analyzed the topology by means of the substituted-cysteine accessibility method using the impermeant, fluorescent, thiol-specific probe Oregon Green 488 maleimide (OGM) and the impermeant, nonfluorescent, thiol-specific probe [2-(trimethylammonium)ethyl]methanethiosulfonate bromide. We generated 23 single-cysteine variants from a six-histidine-tagged cysteineless AspT template. A cysteine position was assigned an external location if the corresponding single-cysteine variant reacted with OGM added to intact cells, and a position was assigned an internal location if OGM labeling required cell lysis. The topology analyses revealed that AspT has a unique topology; the protein has 10 transmembrane helices (TMs), a large hydrophilic cytoplasmic loop (about 180 amino acids) between TM5 and TM6, N and C termini that face the periplasm, and a positively charged residue (arginine 76) within TM3. Moreover, the three-dimensional structure constructed by means of the full automatic modeling system indicates that the large hydrophilic cytoplasmic loop of AspT possesses a TrkA_C domain and a TrkA_C-like domain and that the three-dimensional structures of these domains are similar to each other even though their amino acid sequences show low similarity. PMID:17660287

ASP6537, a novel highly selective cyclooxygenase-1 inhibitor, exerts potent antithrombotic effect without "aspirin dilemma".

PubMed

Sakata, Chinatsu; Kawasaki, Tomihisa; Kato, Yasuko; Abe, Masaki; Suzuki, Ken-ichi; Ohmiya, Makoto; Funatsu, Toshiyuki; Morita, Yoshiaki; Okada, Masamichi

2013-07-01

Aspirin inhibits both the cyclooxygenase (COX)-1-dependent production of thromboxane A2 (TXA2) in platelets and COX-2-dependent production of anti-aggregatory prostaglandin I2 (PGI2) in vessel walls, resulting in "aspirin dilemma." Our objective is to investigate whether ASP6537 can overcome aspirin dilemma and exert a potent antithrombotic effect without a concurrent ulcerogenic effect. We evaluated the inhibitory effects of ASP6537 on recombinant human COX-1 (rhCOX-1) and rhCOX-2 activities using a COX-1/2 selectivity test. To determine whether ASP6537 induces aspirin dilemma, we examined the effects of ASP6537 on in vitro TXA2 and PGI2 metabolite production from platelets and isolated aorta of guinea pigs, and on plasma concentrations of TXA2 and PGI2 metabolites in aged rats. Finally, we evaluated the antithrombotic effects and ulcerogenic activity of ASP6537 using an electrically induced carotid arterial thrombosis model and a gastric ulcer model in guinea pigs. The IC50 ratios of rhCOX-2 to rhCOX-1 for ASP6537 and aspirin were >142,000 and 1.63 fold, respectively. ASP6537 inhibited TXA2 production more selectively than aspirin in in vitro and in vivo TXA2/PGI2 production studies. ASP6537 exerted a significant antithrombotic effect at ≥3 mg/kg, while aspirin tended to inhibit thrombosis at 300 mg/kg but it was not statistically significant. Further, ASP6537 did not induce ulcer formation at 100 mg/kg, whereas aspirin exhibited an ulcerogenic effect at doses of ≥100 mg/kg. ASP6537 functions as a highly selective COX-1 inhibitor with a superior ability to aspirin for normalizing TXA2/PGI2 balance, and exerts antithrombotic effect without ulcerogenic effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

D-aspartic acid supplementation combined with 28 days of heavy resistance training has no effect on body composition, muscle strength, and serum hormones associated with the hypothalamo-pituitary-gonadal axis in resistance-trained men.

PubMed

Willoughby, Darryn S; Leutholtz, Brian

2013-10-01

It was hypothesized that D-aspartic acid (D-ASP) supplementation would not increase endogenous testosterone levels or improve muscular performance associated with resistance training. Therefore, body composition, muscle strength, and serum hormone levels associated with the hypothalamo-pituitary-gonadal axis were studied after 28 days of resistance training and D-ASP supplementation. Resistance-trained men resistance trained 4 times/wk for 28 days while orally ingesting either 3 g of placebo or 3 g of D-ASP. Data were analyzed with 2 × 2 analysis of variance (P < .05). Before and after resistance training and supplementation, body composition and muscle strength, serum gonadal hormones, and serum D-ASP and d-aspartate oxidase (DDO) were determined. Body composition and muscle strength were significantly increased in both groups in response to resistance training (P < .05) but not different from one another (P > .05). Total and free testosterone, luteinizing hormone, gonadotropin-releasing hormone, and estradiol were unchanged with resistance training and D-ASP supplementation (P > .05). For serum D-ASP and DDO, D-ASP resulted in a slight increase compared with baseline levels (P > .05). For the D-ASP group, the levels of serum DDO were significantly increased compared with placebo (P < .05). The gonadal hormones were unaffected by 28 days of D-ASP supplementation and not associated with the observed increases in muscle strength and mass. Therefore, at the dose provided, D-ASP supplementation is ineffective in up-regulating the activity of the hypothalamo-pituitary-gonadal axis and has no anabolic or ergogenic effects in skeletal muscle. © 2013 Elsevier Inc. All rights reserved.

Developing a financial framework for academic service partnerships: models of the United States and Europe.

PubMed

De Geest, Sabina; Sullivan Marx, Eileen M; Rich, Victoria; Spichiger, Elisabeth; Schwendimann, Rene; Spirig, Rebecca; Van Malderen, Greet

2010-09-01

Academic service partnerships (ASPs) are structured linkages between academe and service which have demonstrated higher levels of innovation. In the absence of descriptions in the literature on financial frameworks to support ASPs, the purpose of this paper is to present the supporting financial frameworks of a Swiss and a U.S. ASP. This paper used a case study approach. Two frameworks are presented. The U.S. model presented consists of a variety of ASPs, all linked to the School of Nursing of the University of Pennsylvania. The structural integration and governance system is elucidated. Each ASP has its own source of revenue or grant support with the goal to be fiscally in the black. Joint appointments are used as an instrument to realize these ASPs. The Swiss ASP entails a detailed description of the financial framework of one ASP between the Institute of Nursing Science at the University of Basel and the Inselspital Bern University Hospital. Balance in the partnership, in terms of both benefit and cost between both partners, was a main principle that guided the development of the financial framework and the translation of the ASP in budgetary terms. The model builds on a number of assumptions and provides the partnership management within a simple framework for monitoring and evaluation of the progress of the partnership. In operationalizing an ASP, careful budgetary planning should be an integral part of the preparation and evaluation of the collaboration. The proposed Swiss and U.S. financial frameworks allow doing so. Outcomes of care can be improved with strong nursing service and academic partnerships. Sustaining such partnerships requires attention to financial and contractual arrangements.

The Next Generation of NASA Night Sky Network: A Searchable Nationwide Database of Astronomy Events

NASA Astrophysics Data System (ADS)

Ames, Z.; Berendsen, M.; White, V.

2010-08-01

With support from NASA, the Astronomical Society of the Pacific (ASP) first developed the Night Sky Network (NSN) in 2004. The NSN was created in response to research conducted by the Institute for Learning Innovation (ILI) to determine what type of support amateur astronomers could use to increase the efficiency and extent of their educational outreach programs. Since its creation, the NSN has grown to include an online searchable database of toolkit resources, Presentation Skills Videos covering topics such as working with kids and how to answer difficult questions, and a searchable nationwide calendar of astronomy events that supports club organization. The features of the NSN have allowed the ASP to create a template that amateur science organizations might use to create a similar support network for their members and the public.

Point-of-Prescription Interventions to Improve Antimicrobial Stewardship

PubMed Central

Hamilton, Keith W.; Gerber, Jeffrey S.; Moehring, Rebekah; Anderson, Deverick J.; Calderwood, Michael S.; Han, Jennifer H.; Mehta, Jimish M.; Pollack, Lori A.; Zaoutis, Theoklis; Srinivasan, Arjun; Camins, Bernard C.; Schwartz, David N.; Lautenbach, Ebbing

2015-01-01

Antimicrobial stewardship is pivotal to improving patient outcomes, reducing adverse events, decreasing healthcare costs, and preventing further emergence of antimicrobial resistance. In an era in which antimicrobial resistance is increasing, judicious antimicrobial use is the responsibility of every healthcare provider. Antimicrobial stewardship programs (ASPs) have made headway in improving antimicrobial prescribing using such “top-down” methods as formulary restriction and prospective audit with feedback; however, engagement of prescribers has not been fully explored. Strategies that include frontline prescribers and other unit-based healthcare providers have the potential to expand stewardship, both to augment existing centralized ASPs and to provide alternative approaches to perform stewardship at healthcare facilities with limited resources. This review discusses interventions focusing on antimicrobial prescribing at the point of prescription as well as a pilot project to engage unit-based healthcare providers in antimicrobial stewardship. PMID:25595748

Research activities to improve the utilization of antibiotics in Africa.

PubMed

Massele, Amos; Tiroyakgosi, Celda; Matome, Matshediso; Desta, Abayneh; Muller, Arno; Paramadhas, Bene D Anand; Malone, Brighid; Kurusa, Gobuiwang; Didimalang, Thatayaone; Moyo, Mosana; Godman, Brian

2017-02-01

There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

[Effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides on hormonal activity and thyroid morphology in hypophysectomized mature and old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-01-01

The aim of the paper was to investigate effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides which were designed and synthesized on the basis of amino acid study of the hypophyseal anterior and posterior lobe peptides on the thyroid morphology and hormonal activity in mature chicken and old birds. Hypophysectomy was established to produce atrophic changes in the thyroid gland and development of secondary hypothyrosis. Administration of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly tetrapeptides significantly prevented these impairments by increasing the levels of the thyroid-stimulating hormone (TSH) as well as T3 and T4. Restoration of the thyroid functions and morphology was registered to be greater in one-year-old chicken as compared to five-year-old ones.

Efficacy and safety of native versus pegylated Escherichia coli asparaginase for treatment of adults with high-risk, Philadelphia chromosome-negative acute lymphoblastic leukemia.

PubMed

Ribera, Josep-Maria; Morgades, Mireia; Montesinos, Pau; Martino, Rodrigo; Barba, Pere; Soria, Beatriz; Bermúdez, Arancha; Moreno, María-José; González-Campos, José; Vives, Susana; Gil, Cristina; Abella, Eugenia; Guàrdia, Ramon; Martínez-Carballeira, Daniel; Martínez-Sánchez, Pilar; Amigo, María-Luz; Mercadal, Santiago; Serrano, Alfons; López-Martínez, Aurelio; Vall-Llovera, Ferran; Sánchez-Sánchez, María-José; Peñarrubia, María-Jesús; Calbacho, María; Méndez, Jose-Angel; Bergua, Juan; Cladera, Antonia; Tormo, Mar; García-Belmonte, Daniel; Feliu, Evarist; Ciudad, Juana; Orfao, Alberto

2017-11-22

Native or pegylated (PEG) asparaginase (ASP) are commonly used in treatment of acute lymphoblastic leukemia (ALL), but have been scarcely compared in the same trial in adult patients. Native vs. PEG-ASP administered according to availability in each center were prospectively evaluated in adults with high-risk ALL. Ninety-one patients received native ASP and 35 PEG-ASP in induction. No significant differences were observed in complete remission, minimal residual disease levels after induction and after consolidation, disease-free survival, and overall survival. No significant differences in grades 3-4 toxicity were observed in the induction period, although a trend for higher hepatic toxicity was observed in patients receiving PEG-ASP. In this trial the type of ASP did not influence patient response and outcome.

Anaphylactic reaction to polyethylene-glycol conjugated-asparaginase: premedication and desensitization may not be sufficient.

PubMed

Sahiner, Umit M; Yavuz, S Tolga; Gökce, Muge; Buyuktiryaki, Betul; Altan, Ilhan; Aytac, Selin; Tuncer, Murat; Tuncer, Ayfer; Sackesen, Cansin

2013-08-01

In hypersensitive reactions to native L-asparaginase, either premedication and desensitization or substitution with polyethylene glycol conjugated asparaginase (PEG-ASP) is preferred. Anaphylaxis with PEG-ASP is rare. An 8-year-old girl and a 2.5-year-old boy, both diagnosed as having acute lymphoblastic leukemia, presented with native L-asparaginase hypersensitivity and substitution with PEG-ASP was preferred. They received a premedication (methylprednisolone, hydroxyzine and ranitidine) followed by desensitization with PEG-ASP infusion. Both patients developed anaphylaxis with peg-asparaginase. These are the first reported cases of anaphylactic reaction to PEG-ASP, despite the application of both premedication and desensitization. Anaphylaxis with PEG-ASP is very rare and premedication and desensitization protocols may not prevent these hypersensitive reactions. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

Phosphate-Catalyzed Succinimide Formation from Asp Residues: A Computational Study of the Mechanism.

PubMed

Kirikoshi, Ryota; Manabe, Noriyoshi; Takahashi, Ohgi

2018-02-24

Aspartic acid (Asp) residues in proteins and peptides are prone to the non-enzymatic reactions that give biologically uncommon l-β-Asp, d-Asp, and d-β-Asp residues via the cyclic succinimide intermediate (aminosuccinyl residue, Suc). These abnormal Asp residues are known to have relevance to aging and pathologies. Despite being non-enzymatic, the Suc formation is thought to require a catalyst under physiological conditions. In this study, we computationally investigated the mechanism of the Suc formation from Asp residues that were catalyzed by the dihydrogen phosphate ion, H₂PO₄ - . We used Ac-l-Asp-NHMe (Ac = acetyl, NHMe = methylamino) as a model compound. The H₂PO₄ - ion (as a catalyst) and two explicit water molecules (as solvent molecules stabilizing the negative charge) were included in the calculations. All of the calculations were performed by density functional theory with the B3LYP functional. We revealed a phosphate-catalyzed two-step mechanism (cyclization-dehydration) of the Suc formation, where the first step is predicted to be rate-determining. In both steps, the reaction involved a proton relay mediated by the H₂PO₄ - ion. The calculated activation barrier for this mechanism (100.3 kJ mol -1 ) is in reasonable agreement with an experimental activation energy (107 kJ mol -1 ) for the Suc formation from an Asp-containing peptide in a phosphate buffer, supporting the catalytic mechanism of the H₂PO₄ - ion that is revealed in this study.

Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii

PubMed Central

Chen, Yu; Bensing, Barbara A.; Seepersaud, Ravin; Mi, Wei; Liao, Maofu; Jeffrey, Philip D.; Shajahan, Asif; Sonon, Roberto N.; Azadi, Parastoo; Sullam, Paul M.; Rapoport, Tom A.

2018-01-01

Many pathogenic bacteria, including Streptococcus gordonii, possess a pathway for the cellular export of a single serine-rich-repeat protein that mediates the adhesion of bacteria to host cells and the extracellular matrix. This adhesin protein is O-glycosylated by several cytosolic glycosyltransferases and requires three accessory Sec proteins (Asp1–3) for export, but how the adhesin protein is processed for export is not well understood. Here, we report that the S. gordonii adhesin GspB is sequentially O-glycosylated by three enzymes (GtfA/B, Nss, and Gly) that attach N-acetylglucosamine and glucose to Ser/Thr residues. We also found that modified GspB is transferred from the last glycosyltransferase to the Asp1/2/3 complex. Crystal structures revealed that both Asp1 and Asp3 are related to carbohydrate-binding proteins, suggesting that they interact with carbohydrates and bind glycosylated adhesin, a notion that was supported by further analyses. We further observed that Asp1 also has an affinity for phospholipids, which is attenuated by Asp2. In summary, our findings support a model in which the GspB adhesin is sequentially glycosylated by GtfA/B, Nss, and Gly and then transferred to the Asp1/2/3 complex in which Asp1 mediates the interaction of the Asp1/2/3 complex with the lipid bilayer for targeting of matured GspB to the export machinery. PMID:29462788

Unraveling the sequence of cytosolic reactions in the export of GspB adhesin from Streptococcus gordonii.

PubMed

Chen, Yu; Bensing, Barbara A; Seepersaud, Ravin; Mi, Wei; Liao, Maofu; Jeffrey, Philip D; Shajahan, Asif; Sonon, Roberto N; Azadi, Parastoo; Sullam, Paul M; Rapoport, Tom A

2018-04-06

Many pathogenic bacteria, including Streptococcus gordonii , possess a pathway for the cellular export of a single serine-rich-repeat protein that mediates the adhesion of bacteria to host cells and the extracellular matrix. This adhesin protein is O -glycosylated by several cytosolic glycosyltransferases and requires three accessory Sec proteins (Asp1-3) for export, but how the adhesin protein is processed for export is not well understood. Here, we report that the S. gordonii adhesin GspB is sequentially O -glycosylated by three enzymes (GtfA/B, Nss, and Gly) that attach N -acetylglucosamine and glucose to Ser/Thr residues. We also found that modified GspB is transferred from the last glycosyltransferase to the Asp1/2/3 complex. Crystal structures revealed that both Asp1 and Asp3 are related to carbohydrate-binding proteins, suggesting that they interact with carbohydrates and bind glycosylated adhesin, a notion that was supported by further analyses. We further observed that Asp1 also has an affinity for phospholipids, which is attenuated by Asp2. In summary, our findings support a model in which the GspB adhesin is sequentially glycosylated by GtfA/B, Nss, and Gly and then transferred to the Asp1/2/3 complex in which Asp1 mediates the interaction of the Asp1/2/3 complex with the lipid bilayer for targeting of matured GspB to the export machinery.

Drug release patterns and cytotoxicity of PEG-poly(aspartate) block copolymer micelles in cancer cells.

PubMed

Eckman, Allison M; Tsakalozou, Eleftheria; Kang, Nayon Y; Ponta, Andrei; Bae, Younsoo

2012-07-01

To test physicochemical and biological properties of PEG-poly(aspartate) [PEG-p(Asp)] block copolymer micelles entrapping doxorubicin hydrochloride (DOX) through ionic interaction. PEG-p(Asp) was synthesized from 5 kDa PEG and 20 Asp units. Carboxyl groups of p(Asp) were present as benzyl ester [PEG-p(Asp/Bz)], sodium salt [PEG-p(Asp/Na)] or free acid [PEG-p(Asp/H)]. Block copolymers and DOX were mixed at various ratios to prepare polymer micelles, which were subsequently characterized to determine particle size, drug loading and release patterns, and cytotoxicity against prostate (PC3 and DU145) and lung (A549) cancer cell lines. PEG-p(Asp/Bz), Na- and H-micelles entrapped 1.1, 56.8 and 40.6 wt.% of DOX, respectively. Na- and H-micelles (<100 nm) showed time-dependent DOX release at pH 7.4, which was accelerated at pH 5.0. Na-micelles were most stable at pH 7.4, retaining 31.8% of initial DOX for 48 h. Cytotoxicity of Na-micelles was 23.2% (A549), 28.5% (PC3) and 45.9% (DU145) more effective than free DOX. Ionic interaction appeared to entrap DOX efficiently in polymer micelles from PEG-p(Asp) block copolymers. Polymer micelles possessing counter ions (Na) of DOX in the core were the most stable, releasing drugs for prolonged time in a pH-dependent manner, and suppressing cancer cells effectively.

Effect of tetrapeptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on the structure and function of the thyroid gland in neonatally hypophysectomized chickens.

PubMed

Kuznik, B I; Pateyuk, A V; Rusaeva, N S

2008-01-01

Tetrapeptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly were synthesized on the basis of amino acid composition of pituitary cytomedins. Administration of these tetrapeptides to hypophysectomized chickens for 40 days was followed by an increase in the concentrations of thyrotropic hormone and thyroid hormones and recovery of thyroid gland structure.

Two Salt Bridges Differentially Contribute to the Maintenance of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channel Function*

PubMed Central

Cui, Guiying; Freeman, Cody S.; Knotts, Taylor; Prince, Chengyu Z.; Kuang, Christopher; McCarty, Nael A.

2013-01-01

Previous studies have identified two salt bridges in human CFTR chloride ion channels, Arg352-Asp993 and Arg347-Asp924, that are required for normal channel function. In the present study, we determined how the two salt bridges cooperate to maintain the open pore architecture of CFTR. Our data suggest that Arg347 not only interacts with Asp924 but also interacts with Asp993. The tripartite interaction Arg347-Asp924-Asp993 mainly contributes to maintaining a stable s2 open subconductance state. The Arg352-Asp993 salt bridge, in contrast, is involved in stabilizing both the s2 and full (f) open conductance states, with the main contribution being to the f state. The s1 subconductance state does not require either salt bridge. In confirmation of the role of Arg352 and Asp993, channels bearing cysteines at these sites could be latched into a full open state using the bifunctional cross-linker 1,2-ethanediyl bismethanethiosulfonate, but only when applied in the open state. Channels remained latched open even after washout of ATP. The results suggest that these interacting residues contribute differently to stabilizing the open pore in different phases of the gating cycle. PMID:23709221

78 FR 31558 - Medicare Program; Second Semi-Annual Meeting of the Advisory Panel on Hospital Outpatient Payment...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... will need to type ``CMS Public Events'' in the search bar to access the webcast. FOR FURTHER... register online, during the above specified timeframe at: https://www.cms.gov/apps/events/default.asp . On..., Auditorium, 7500 Security Boulevard, Woodlawn, Maryland 21244-1850. Alternately, the public may view this...

Rapid Reaction Peacekeeping Under a Blue Flag: A Viable Response to Today’s Global Environment

DTIC Science & Technology

2002-05-14

Plutarch , On the Fortunes of Alexander. As cited in Martha Nussbaum. Partriotism and Cosmopolitanism, available from www.phil.uga.edu/faculty/wolf/nussbaum1...Challenges for the 21st Century. United Nations Foundation. http://www.unfoundation.org/programs/humanitarian/challenges_pshr.asp. 3/25/02 Plutarch , On the

Bacterial communities and enzymatic activities in the vegetation-activated sludge process (V-ASP) and related advantages by comparison with conventional constructed wetland.

PubMed

Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Zhao, Ke; Du, Changhang; Shao, Yunxian

2016-11-01

A new-developed vegetation-activated sludge process (V-ASP) was implemented for decentralized domestic wastewater treatment, and studied in lab-scale and full-scale. The main purpose of this work was the investigation of biomass activities and microbial communities in V-ASP by comparison with conventional constructed wetland (CW), to unveil the causations of its consistently higher pollutants removal efficiencies. Compared with CWs, V-ASP has greater vegetation nitrogen and phosphorus uptake rates, higher biomass and enzymatic activities, and more bacteria community diversity. The microbial community structure was comprehensively analyzed by using high-throughput sequencing. It was observed that Proteobacteria was dominated in both CWs and V-ASPs, while their subdivisions distribution was rather different. V-ASPs contained a higher nitrite-oxidizing bacteria (Nitrospira) abundances that resulted in a consistently better nitrogen removal efficiency. Hence, a long-term experiment of full-scale V-ASP displayed stably excellent capability in resistance of influent loading shocks and seasonal temperature effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Takata, Takumi; Shimo-Oka, Tadashi; Kojima, Masami

Although proteins are generally composed of L-{alpha}-amino acids, D-{beta}-aspartic acid (Asp)-containing proteins have been reported in various elderly tissues. Our previous study detected several D-{beta}-Asp-containing proteins in a rabbit lens derived from epithelial cell line by Western blot analysis of a 2D-gel using a polyclonal antibody that is highly specific for D-{beta}-Asp-containing proteins. The identity of each spot was subsequently determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the Ms-Fit online database searching algorithm. In this study, we discovered novel D-{beta}-Asp-containing proteins from rabbit lens. The results indicate that {beta}-crystallin A3, {beta}-crystallin A4, {beta}-crystallin B1, {beta}-crystallin B2, {beta}-crystallin B3,more » {gamma}-crystallin C, {gamma}-crystallin D, and {lambda}-crystallin in rabbit lens contain D-{beta}-Asp residues. Furthermore, the occurrence of D-{beta}-Asp residues increases with infrared ray (IR) irradiation. Additionally, some D-{beta}-Asp-containing proteins only appear after IR irradiation. One such protein is the {alpha}-enolase, which shows homology to {tau}-crystallin.« less

Elucidating the Role of Many-Body Forces in Liquid Water. I. Simulations of Water Clusters on the VRT (ASP-W) Potential Surfaces

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

Goldman, N; Saykally, R J

We test the new VRT(ASP-W)II and VRT(ASP-W)III potentials by employing Diffusion Quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials are fits of the highly detailed ASP-W ab initio potential to (D{sub 2}O){sub 2} microwave and far-IR data, and along with the SAPT5s potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compare to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)II and the spectroscopically ''tuned'' SAPT5st (with N-body induction included) accurately reproduce themore » vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispension are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.« less

Duck-billed platypus venom peptides induce Ca2+ influx in neuroblastoma cells.

PubMed

Kita, Masaki; Black, David StC; Ohno, Osamu; Yamada, Kaoru; Kigoshi, Hideo; Uemura, Daisuke

2009-12-23

The duck-billed platypus (Ornithorhynchus anatinus) is one of the few venomous Australian mammals. We previously found that its crude venom potently induces Ca(2+) influx in human neuroblastoma IMR-32 cells. Guided by this bioassay, we identified 11 novel peptides, including the heptapeptide H-His-Asp-His-Pro-Asn-Pro-Arg-OH (1). Compounds 1-4 and 5-11 coincided with the 6-9 N-terminal residues of Ornithorhynchus venom C-type natriuretic peptide (OvCNP) and the 132-150 part of OvCNP precursor peptide, respectively. Heptapeptide 1, which is one of the primary components of the venom fluid (approximately 200 ng/microL), induced a significant increase in [Ca(2+)](i) in IMR-32 cells at 75 microM. To the best of our knowledge, this is the first example of the isolation of the N-terminal linear fragments of CNPs in any mammal.

Night Sky Network: A partnership with NASA, the ASP and Astronomical League

NASA Astrophysics Data System (ADS)

Chippindale, S.; Berendsen, M.

2003-12-01

In 2002, the Astronomical Society of the Pacific (ASP) surveyed amateur astronomers to determine their views and experiences with public outreach. The ultimate goal was to discover methods to support amateur astronomers in their outreach efforts. The survey discovered that they are looking for ready-made, themed materials, training in astronomy content and presentation skills, mentoring, and networking to enhance their astronomy events and support their ability to do educational outreach. Acting on these results and with funding from NASA, the ASP is forming a nationwide coalition of amateur astronomy clubs whose members bring the science, technology and inspiration of NASA's missions to the general public. The program consists of three primary components: outreach materials, training, and community building. Member-based astronomy clubs will receive kits of materials on various astronomy topics to supplement and enhance their events as well as a "professional development" component that includes training on how to use the materials and tips to strengthen their individual presentation skills. The Night Sky Network web site includes public pages and a user area where success stories and challenges can be exchanged, new information downloaded, and a support area for amateur astronomers doing outreach. We are currently testing our first kit, "PlanetQuest: The Search for Another Earth", in over two dozen clubs across the country. The second kit, "Big Bang to Black Holes" is under development for NASA's Structure and Evolution of the Universe Forum through the SAO and will be beta tested over the spring and summer of 2004. Sponsored and supported by NASA-Navigator Program, NASA-SAO Education Forum, the Astronomical Society of the Pacific, and the Astronomical League.

Effects of Asp-179 mutations in TEMpUC19 beta-lactamase on susceptibility to beta-lactams.

PubMed Central

Vakulenko, S B; Tóth, M; Taibi, P; Mobashery, S; Lerner, S A

1995-01-01

To examine the effect of disruption of the salt bridge (between Arg-164 and Asp-179 [numbering of Ambler et al. (Biochem J. 267:269-272, 1991)]) that anchors the conserved omega-loop in class A beta-lactamases, we obtained mutant enzymes with each of the 19 other amino acid residues replacing Asp-179 in the TEM beta-lactamase encoded by pUC19 and studied the level of resistance to various beta-lactams conferred by each enzyme. All mutations of Asp-179 compromised the level of resistance to ampicillin, but most of them enhanced resistance to ceftazidime. In contrast, mutations of Asp-179 generally impaired the low levels of resistance to cefepime and aztreonam. One might expect to find clinical isolates with mutant TEM beta-lactamases with replacements of Asp-179 that express an expanded spectrum of resistance to beta-lactams including ceftazidime. PMID:7486939

Sustained reduction in antibiotic consumption in a South African public sector hospital; Four year outcomes from the Groote Schuur Hospital antibiotic stewardship program.

PubMed

Boyles, T H; Naicker, V; Rawoot, N; Raubenheimer, P J; Eick, B; Mendelson, M

2017-01-30

Overuse of antibiotics has driven global bacterial resistance to the extent that we have entered a post-antibiotic era, where infections that were once easily treatable are now becoming untreatable. Efforts to control consumption have focused on antibiotic stewardship programmes (ASPs), aimed at optimising use. To report antibiotic consumption and cost over 4 years from a public hospital ASP in South Africa (SA). A comprehensive ASP comprising online education, a dedicated antibiotic prescription chart and weekly dedicated ward rounds was introduced at Groote Schuur Hospital, Cape Town, in 2012. Electronic records were used to collect data on volume and cost of antibiotics and related laboratory tests, and to determine inpatient mortality and 30-day readmission rates. These data were compared with a control period before the intervention. Total antibiotic consumption fell from 1 046 defined daily doses/1 000 patient days in 2011 (control period) to 868 by 2013 and remained at similar levels for the next 2 years. This was driven by reductions in intravenous antibiotic use, particularly ceftriaxone. Inflation-adjusted cost savings on antibiotics were ZAR3.2 million over 4 years. Laboratory tests increased over the same period with a total increased cost of ZAR0.4 million. There was no significant change in mortality or 30-day readmission rates. The effects of a comprehensive ASP on medical inpatients at a public sector hospital in SA were durable over 4 years, leading to a reduction in total antibiotic consumption without adverse effect. When increased laboratory costs were offset there was a net cost saving of ZAR2.8 million.

Evaluation of Antimicrobial Stewardship-Related Alerts Using a Clinical Decision Support System.

PubMed

Ghamrawi, Riane J; Kantorovich, Alexander; Bauer, Seth R; Pallotta, Andrea M; Sekeres, Jennifer K; Gordon, Steven M; Neuner, Elizabeth A

2017-11-01

Background: Information technology, including clinical decision support systems (CDSS), have an increasingly important and growing role in identifying opportunities for antimicrobial stewardship-related interventions. Objective: The aim of this study was to describe and compare types and outcomes of CDSS-built antimicrobial stewardship alerts. Methods: Fifteen alerts were evaluated in the initial antimicrobial stewardship program (ASP) review. Preimplementation, alerts were reviewed retrospectively. Postimplementation, alerts were reviewed in real-time. Data collection included total number of actionable alerts, recommendation acceptance rates, and time spent on each alert. Time to de-escalation to narrower spectrum agents was collected. Results: In total, 749 alerts were evaluated. Overall, 306 (41%) alerts were actionable (173 preimplementation, 133 postimplementation). Rates of actionable alerts were similar for custom-built and prebuilt alert types (39% [53 of 135] vs 41% [253 of 614], P = .68]. In the postimplementation group, an intervention was attempted in 97% of actionable alerts and 70% of interventions were accepted. The median time spent per alert was 7 minutes (interquartile range [IQR], 5-13 minutes; 15 [12-17] minutes for actionable alerts vs 6 [5-7] minutes for nonactionable alerts, P < .001). In cases where the antimicrobial was eventually de-escalated, the median time to de-escalation was 28.8 hours (95% confidence interval [CI], 10.0-69.1 hours) preimplementation vs 4.7 hours (95% CI, 2.4-22.1 hours) postimplementation, P < .001. Conclusions: CDSS have played an important role in ASPs to help identify opportunities to optimize antimicrobial use through prebuilt and custom-built alerts. As ASP roles continue to expand, focusing time on customizing institution specific alerts will be of vital importance to help redistribute time needed to manage other ASP tasks and opportunities.

Platelet inhibition during ticagrelor monotherapy versus ticagrelor plus aspirin in patients with coronary artery disease (TEMPLATE study): study protocol for a randomised controlled trial.

PubMed

Baos, Sarah; Underwood, Wendy; Culliford, Lucy; Reeves, Barnaby C; Rogers, Chris A; Bowles, Ruth; Johnson, Tom; Baumbach, Andreas; Mumford, Andrew

2017-11-09

Dual antiplatelet therapy (DAPT) with aspirin (ASP) and a P2Y 12 blocker is currently standard care after percutaneous coronary intervention (PCI) with stent insertion, and aims to inhibit platelet function in order to prevent stent thrombosis. The P2Y 12 blocker ticagrelor (TIC) has greater antiplatelet effect than the previously used members of this class, such as clopidogrel. In healthy volunteers, TIC is sufficient to cause strong platelet inhibition, with little additional effect from ASP. Omission of ASP may improve the safety of antiplatelet regimes by reducing bleeding. However, the effect of single antiplatelet treatment with TIC, compared to DAPT with TIC + ASP, has not been studied in detail in patients with coronary artery disease. To compare TIC with TIC + ASP, we have initiated a single centre, open-label randomised controlled trial (TEMPLATE study) in adults receiving DAPT following PCI with a sample size of 110 patients. Patients are invited to join the study when, as part of standard care, they are due to switch from DAPT (ASP + any P2Y 12 blocker) to single antiplatelet treatment with ASP alone after 6-12 months. Patients are randomised to receive either TIC or TIC + ASP for 4 weeks. All patients then revert to standard care with ASP alone. Blood samples and clinical data are collected at three study visits: at baseline during treatment with ASP + any P2Y 12 blocker (visit 1); approximately 4 weeks after visit 1 during treatment with either TIC or TIC + ASP (visit 2); and approximately 8 weeks after visit 1 when treatment has reverted to ASP alone (visit 3). The primary outcome is the extent of platelet inhibition, measured by light transmission aggregation, flow cytometry, flow chamber and plasma biomarker tests. The primary analysis will compare the extent of platelet inhibition between the TIC and TIC + ASP groups at visit 2, adjusted for baseline platelet reactivity. Secondary analyses will compare the extent of platelet inhibition at visit 2 with that at visit 3. This is the first study to compare in detail the extent of platelet inhibition in patients who are receiving TIC compared with TIC + ASP. The study findings will complement larger-scale trials of the clinical efficacy and safety of TIC compared to TIC + ASP. ISRCTN registry, identifier ISRCTN84335288 . Registered on 23 June 2014.

Neutropenia associated with vincristine and L-asparaginase induction chemotherapy for canine lymphoma.

PubMed

Northrup, Nicole C; Rassnick, Kenneth M; Snyder, Laura A; Stone, Michael S; Kristal, Orna; Cotter, Susan M; Moore, Antony S

2002-01-01

Vincristine (VCR) and L-asparaginase (L-ASP) are commonly used to treat canine lymphoma. As single agents, these drugs are not myelosuppressive. However, in combination, VCR and L-ASP cause severe neutropenia in some dogs. It has been recommended that L-ASP be administered 12-24 hours after VCR to minimize toxicity. The purpose of this retrospective study was to determine the prevalence of neutropenia after VCR/L-ASP induction therapy for canine lymphoma and to evaluate risk factors for myelosuppression, especially the interval between VCR and L-ASP administration. Medical records of 147 dogs were reviewed. L-ASP was given 0 (n = 50), 6 (n = 23), 18 (n = 20), or 24 (n = 54) hours after VCR. Forty percent of the dogs were neutropenic 7 days after VCR/L-ASP, and 18% had neutrophil counts of <1,000 cells/microL. The median neutrophil count was 3,712 cells/microL (range 0-30,968 cells/microL). No correlation was found between administration interval and day 7 neutrophil count (P = .84) or development of gastrointestinal signs, including vomiting (P = .80), diarrhea (P = .52), and decreased appetite (P = .30). No significant predictors of neutropenia were identified. Higher clinical stage and substage b were associated with decreased appetite after treatment (P = .04 and .01, respectively). Sixteen percent of the dogs were hospitalized. This study demonstrates that VCR/L-ASP induction for canine lymphoma may result in neutropenia but that separation of VCR and L-ASP administration may not be necessary to avoid toxicity.

Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study.

PubMed

Rozen, Laurence; Noubouossie, Denis; Dedeken, Laurence; Huybrechts, Sophie; Lê, Phu Quoc; Ferster, Alina; Demulder, Anne

2017-02-01

Asparaginase (Asp) and corticosteroid (CS) treatment in patients with acute lymphoblastic leukaemia (ALL) is associated with an increased risk of thrombotic events. Characterization of global haemostatic phenotypes of patients with ALL during Asp therapy. Thrombin generation (TG) was monitored in platelet-poor plasma of 56 children treated for a B lineage ALL (36 with native, 20 with PEG Asp) using 1 pM tissue factor and 4 μM phospholipids, with and without thrombomodulin. Protein C activity (PC), free protein S (PS), antithrombin (AT) and fibrinogen levels were also measured. Elevated endogenous thrombin potential (ETP) and peak of TG were noted at diagnosis, throughout the Induction phase and Late Intensification but was significantly less for PEG than for native Asp (P < 0.001), while age, sex, type of corticosteroid during Induction and molecular response had no significant effect. The reduction of ETP after addition of thrombomodulin was significantly lower in ALL children compared with that in controls, suggesting impairment in PS/PC pathway. Three patients experienced thrombosis: two treated with native and one with PEG Asp. The two patients with native Asp had, at the time of thrombosis, a prothrombotic profile. Treatment with Asp, in combination with CS, enhances TG in children with ALL, more significantly with native than PEG Asp, which is present early at diagnosis, persists during Induction and reappears during Late Intensification. This is consistent with the high incidence of thrombotic events described during these phases of therapy. The less pronounced effect of PEG Asp remains to be elucidated. © 2016 Wiley Periodicals, Inc.

Low acylation stimulating protein levels are associated with cardiometabolic disorders–secondary to autoimmune activation?

PubMed Central

Onat, Altan; Altay, Servet; Yüksel, Murat; Karadeniz, Yusuf; Can, Günay; Yüksel, Hüsniye; Ademoğlu, Evin

2017-01-01

Objective: We investigated the possible association of serum acylation stimulating protein (ASP) with cardiometabolic disorders and the evidence of autoimmune activation. Methods: Population-based randomly selected 1024 participants were cross-sectionally and prospectively analyzed. ASP concentrations were measured with a validated ELISA kit. Correlations were sought separately in subjects with no cardiometabolic disorders (n=427) designated as “healthy.” Results: ASP was positively correlated with total testosterone and inversely correlated with platelet activating factor (PAF), PAF-acetylhydrolase (AH), in each gender, and positively correlated in “healthy” men with lipoprotein [Lp](a) and apolipoprotein B. Correlations of ASP with PAF values ≥22 nmol/L were abolished, contrasted to a strongly inverse one in subjects with PAF <22 nmol/L. In linear regression analyses in the whole sample, ASP was inversely associated independently with PAF and PAF-AH and, in men, positively with Lp(a) and sex hormone-binding globulin. Prevalent and (at 2.0 years’ follow-up) incident metabolic syndrome (MetS, n=393), diabetes (n=154), and coronary heart disease (CHD, n=171) were analyzed by sex-, age-, and Lp(a)-adjusted logistic regression, using tertiles of ASP and PAF. The lower two (<42 nmol/L) ASP tertiles were a risk factor in combined sexes for MetS and diabetes. In women, incident CHD was predicted by either reduced or elevated ASP tertiles. Conclusion: Findings can be explained by the notion of operation of immune responses against both ASP and oxidized PAF-like lipids of Lp(a) to yield for “reduced” values and increased likelihood of cardiometabolic disorders. PMID:27599666

Roles of Copper and a Conserved Aspartic Acid in the Autocatalytic Hydroxylation of a Specific Tryptophan Residue during Cysteine Tryptophylquinone Biogenesis.

PubMed

Williamson, Heather R; Sehanobish, Esha; Shiller, Alan M; Sanchez-Amat, Antonio; Davidson, Victor L

2017-02-21

The first posttranslational modification step in the biosynthesis of the tryptophan-derived quinone cofactors is the autocatalytic hydroxylation of a specific Trp residue at position C-7 on the indole side chain. Subsequent modifications are catalyzed by modifying enzymes, but the mechanism by which this first step occurs is unknown. LodA possesses a cysteine tryptophylquinone (CTQ) cofactor. Metal analysis as well as spectroscopic and kinetic studies of the mature and precursor forms of a D512A LodA variant provides evidence that copper is required for the initial hydroxylation of the precursor protein and that if alternative metals are bound, the modification does not occur and the precursor is unstable. It is shown that the mature native LodA also contains loosely bound copper, which affects the visible absorbance spectrum and quenches the fluorescence spectrum that is attributed to the mature CTQ cofactor. When copper is removed, the fluorescence appears, and when it is added back to the protein, the fluorescence is quenched, indicating that copper reversibly binds in the proximity of CTQ. Removal of copper does not diminish the enzymatic activity of LodA. This distinguishes LodA from enzymes with protein-derived tyrosylquinone cofactors in which copper is present near the cofactor and is absolutely required for activity. Mechanisms are proposed for the role of copper in the hydroxylation of the unactivated Trp side chain. These results demonstrate that the reason that the highly conserved Asp512 is critical for LodA, and possibly all tryptophylquinone enzymes, is not because it is required for catalysis but because it is necessary for CTQ biosynthesis, more specifically to facilitate the initial copper-dependent hydroxylation of a specific Trp residue.

The Global Epidemiology of Syphilis in the Past Century – A Systematic Review Based on Antenatal Syphilis Prevalence

PubMed Central

Kenyon, Chris Richard; Osbak, Kara; Tsoumanis, Achilleas

2016-01-01

Background How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. Methods 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990–1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. Results In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3–5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990–1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Conclusions Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa. PMID:27167068

Array Simulations Platform (ASP) predicts NASA Data Link Module (NDLM) performance

NASA Technical Reports Server (NTRS)

Snook, Allen David

1993-01-01

Through a variety of imbedded theoretical and actual antenna patterns, the array simulation platform (ASP) enhanced analysis of the array antenna pattern effects for the KTx (Ku-Band Transmit) service of the NDLM (NASA Data Link Module). The ASP utilizes internally stored models of the NDLM antennas and can develop the overall pattern of antenna arrays through common array calculation techniques. ASP expertly assisted in the diagnosing of element phase shifter errors during KTx testing and was able to accurately predict the overall array pattern from combinations of the four internally held element patterns. This paper provides an overview of the use of the ASP software in the solving of array mis-phasing problems.

Effect of short peptides on expression of signaling molecules in organotypic pineal cell culture.

PubMed

Khavinson, V Kh; Linkova, N S; Chalisova, N I; Dudkov, A V; Koncevaya, E A

2011-11-01

We demonstrated the influence of short peptides on the expression of signaling molecules in organotypic culture of the pineal gland from 3-month-old rats. Peptides Ala-Glu-Asp-Gly and Lys-Glu-Asp stimulate the expression of proliferative protein Ki-67 in pineal gland culture. These peptides as well as Glu-Asp-Arg and Lys-Glu do not affect the expression of apoptosis marker AIF. The synthesis of transcription factor CGRP by pinealocytes was stimulated only by Ala-Glu-Asp-Gly. Thus, peptide Ala-Glu-Asp-Gly tissue-specifically stimulates proliferative and secretory activities of pinealocytes, which can be used for recovery of pineal gland functions at the molecular level.

Athlete support personnel and anti-doping: Knowledge, attitudes, and ethical stance.

PubMed

Mazanov, J; Backhouse, S; Connor, J; Hemphill, D; Quirk, F

2014-10-01

Athlete support personnel (ASP) failing to meet responsibilities under the World Anti-Doping Code risk sanction. It is unclear whether the poor knowledge of responsibilities seen in sports physicians and coaches applies to other ASP (e.g., administrators, chiropractors, family, nutritionists, physiotherapists, psychologists, and trainers). A purposive sample of Australian ASP (n = 292) responded to a survey on knowledge of anti-doping rules (35 true/false questions), ethical beliefs and practice, and attitudes toward performance enhancement. Some ASP declined to participate, claiming doping was irrelevant to their practice. Physicians were most knowledgeable (30.8/35), with family and trainers the least (26.0/35). ASP reported that improvements were needed to support anti-doping education (e.g., basis for anti-doping) and practice (e.g., rules). ASP also had a slightly negative attitude toward performance enhancement. Linear regression showed that being a sports physician, providing support at the elite level, and 15 years of experience influenced knowledge. The results confirm gaps in knowledge, suggesting that stronger engagement with ASP anti-doping education and practice is needed. Applying the principles of andragogy could help foster active engagement through emphasis on active inquiry, rather than passive reception of content. Future work on the context within which ASP experience anti-doping is needed, exploring acquisition and translation of knowledge into practice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Incremental Value of Live/Real Time Three-Dimensional over Two-Dimensional Transesophageal Echocardiography in the Assessment of Atrial Septal Pouch.

PubMed

Elsayed, Mahmoud; Hsiung, Ming C; Meggo-Quiroz, L David; Elguindy, Mostafa; Uygur, Begum; Tandon, Rohit; Guvenc, Tolga; Keser, Nurgul; Vural, Mustafa G; Bulur, Serkan; Chahwala, Jugal R; Abtahi, Firoozeh; Nanda, Navin C

2015-12-01

An atrial septal pouch (ASP) results from partial fusion of the septum primum and the septum secundum, and depending on the site of fusion, the pouch can be left-sided (LASP) or right-sided (RASP). LASPs have been described in association with thrombi found in patients admitted with acute strokes, raising awareness of its potential cardioembolic role, especially in those with no other clearly identifiable embolic source. We retrospectively studied 39 patients in whom the presence of an ASP had been identified by three-dimensional transesophageal echocardiography (3DTEE) and who had a two-dimensional transesophageal echocardiogram (2DTEE) performed during the same clinical encounter. The incremental value provided by 3DTEE over 2DTEE included the detection of six ASPs not found by 2DTEE; the detection of two ASPs in the same subject (in four patients) not identified by 2DTEE; larger ASP measurements of length and height in over 80% of the cases; and measurement of the ASP width (elevational axis) for the calculation of the area of the ASP opening, because of its unique capability to view the pouch en face. In addition, the volume of ASP and of the echogenic masses contained in the ASP (four of 39 patients) could be calculated by 3DTEE, which is a superior parameter of size characterization when compared to individual dimensions. One of these patients who presented with ischemic stroke diagnosed by magnetic resonance imaging had a large (>2 cm) mass in a LASP, with echolucencies similar to those seen in thrombi and associated with clot lysis and resolution. This mass completely disappeared on anticoagulant therapy lending credence that it was most likely a thrombus. There was no history of stroke or any other type of embolic event in the other three patients with masses in ASP. In conclusion, this retrospective study highlights the incremental value of 3DTEE over 2DTEE in the comprehensive assessment and characterization of ASPs, which can aid in the clarification of their role in cryptogenic stroke patients. © 2015, Wiley Periodicals, Inc.

Active Play in After-school Programmes: development of an intervention and description of a matched-pair cluster-randomised trial assessing physical activity play in after-school programmes.

PubMed

Riiser, Kirsti; Helseth, Sølvi; Ellingsen, Hanna; Fallang, Bjørg; Løndal, Knut

2017-08-04

Interventions delivered in after-school programmes (ASPs) have the potential to become a means of ensuring adequate physical activity among schoolchildren. This requires a motivational climate, allowing for self-determined play. If trained, ASP staff may represent a valuable resource for supporting such play. Increasing knowledge and supportive skills among ASP staff may also potentially increase their motivation for work. The purpose of this article is to describe the development of the 'Active Play in ASP' intervention, which aims to promote physical activity among first graders attending ASP, and to present a protocol for a matched-pair cluster-randomised trial to evaluate the intervention. Informed by experiences from practice, evidence-based knowledge and theory, the intervention was developed in a stepwise process including focus group meetings and a small-scale pilot test. The intervention contains a course programme for ASP staff to increase their skills in how to support physical activity through play. In a cluster randomised controlled trial, the ASPs will be matched and randomly allocated to receive the 7-month intervention or to a control group. Outcomes will be assessed at baseline, after 7 and 19 months. First graders attending the ASPs included are eligible. The primary outcome will be accelerometer-determined minutes in moderate to vigorous physical activity in the ASP. The study uses a mixed methods approach including observations and interviews to provide rich descriptions of the concept of children's physical activity in ASP. Moreover, the trial will assess whether the ASP staff benefits from participation in the intervention in terms of increased work motivation. Lastly, process evaluations of programme fidelity, satisfaction and suggestions on improvement will be performed. The study is approved by the Data Protection Official for Research (reference no 46008). Results will be presented in conferences and peer-reviewed journals. Clinical Trials (NCT02954614), pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Insulin Degludec/Insulin Aspart Administered Once Daily at Any Meal, With Insulin Aspart at Other Meals Versus a Standard Basal-Bolus Regimen in Patients With Type 1 Diabetes

PubMed Central

Hirsch, Irl B.; Bode, Bruce; Courreges, Jean-Pierre; Dykiel, Patrik; Franek, Edward; Hermansen, Kjeld; King, Allen; Mersebach, Henriette; Davies, Melanie

2012-01-01

OBJECTIVE To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp. RESEARCH DESIGN AND METHODS Adults (n = 548) with type 1 diabetes (A1C 7.0–10.0%; BMI ≤35.0 kg/m2) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed. RESULTS Non-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp − IDet: –0.05% [95% CI –0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events. CONCLUSIONS IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy. PMID:22933438

Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

PubMed

Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

2006-05-01

To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

Effects of aspirin on immobile behavior and endocrine and immune changes in the forced swimming test: comparison to fluoxetine and imipramine.

PubMed

Guan, Xi-ting; Shao, Feng; Xie, Xi; Chen, Lin; Wang, Weiwen

2014-09-01

Aspirin (ASP) is the most commonly used non-steroidal anti-inflammatory drug in the world. Recent clinical and preclinical evidence suggests that ASP may also exert psychoactive effects. It remains unclear whether ASP has antidepressant-like activity, and any molecular mechanisms underlying such activity have yet to be elucidated. Using the forced swimming test (FST), a well-established animal model of depression widely used to screen potential antidepressants in rodents, we investigated the effects of subacute treatment with ASP (0, 6, 12, 25, and 50mg/kg, i.p.) on immobility in the FST, and on FST-induced changes in endocrine and immune parameters in rats, in comparison to the clinical antidepressants imipramine (IMI) and fluoxetine (FLU). Serum levels of corticosterone, pro-inflammatory cytokine interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. ASP dose-dependently decreased immobility in the FST, without altering the locomotor activity in the open-field test. The inhibitory effects of higher doses (25 and 50mg/kg) of ASP on immobility were similar to that of FLU and IMI at a dose of 10mg/kg. In addition, the levels of corticosterone, IL-6, and TNF-α in peripheral blood were significantly increased after the FST exposure. IMI, but not FLU and ASP at any dose tested, significantly attenuated corticosterone responses in the FST. Both FLU and IMI treatment reduced the increase of IL-6 and TNF-α levels following the FST exposure. ASP dose-dependently decreased FST-induced increase of cytokine levels, as manifested by significantly stronger effects on IL-6 and TNF-α levels at higher doses (25 and 50mg/kg) than the lowest dose of ASP (6 mg/kg). In all, these results indicate that ASP treatment dose-dependently decreased the immobility time and the release of pro-inflammatory cytokines in the FST, suggesting that the anti-inflammatory effects of ASP might be involved in the antidepressant-like effect. Copyright © 2014 Elsevier Inc. All rights reserved.

Unraveling the effect of genes and environment in the transmission of parental antisocial behavior to children’s conduct disturbance, depression, and hyperactivity

PubMed Central

Silberg, Judy L.; Maes, Hermine; Eaves, Lindon J.

2011-01-01

Background A critical issue in devising effective interventions for the treatment of children’s behavioral and emotional problems rests upon identifying genuine family environmental factors that place children at risk. In most twin and family studies, environmental factors are confounded with both direct genetic risk from parents and the indirect effect of genes influencing parents’ ability to provide an optimal rearing environment. The present study was undertaken to determine whether parental psychopathology, specifically parental antisocial behavior (ASP), is a genuine environmental risk factor for juvenile conduct disturbance, depression, and hyperactivity, or whether the association between parental ASP and children’s behavioral and emotional problems can be explained as a secondary consequence of the intergenerational transmission of genetic factors Methods An extended Children of Twins design (E-COT) comprised of data collected on 2,674 adult female and male twins, their spouses, and 2,454 of their children was used to test whether genetic and/or family environmental factors best accounted for the association between parental antisocial behavior children’s behavioral problems. An age matched sample of 2,826 juvenile twin pairs from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was also included to examine developmental differences in gene expression by partitioning child specific transmissible effects from those effects that persist into adulthood. The fit of alternative models was evaluated using the statistical program Mx Results We found distinct patterns of transmission between parental antisocial behavior and juvenile conduct, depression, and hyperactivity. Genetic and family environmental factors accounted for the resemblance between parents’ ASP and children’s conduct disturbance. Family environmental factors alone explained the association between child depression and parental ASP, and the impact of parental ASP on hyperactivity was entirely genetic. Conclusions These findings underscore differences in the contribution of genetic and environmental factors on the patterns of association between parental antisocial behavior and juvenile psychopathology, having important clinical implications for the prevention and amelioration of child behavioral and emotional problems. PMID:22141405

Unraveling the effect of genes and environment in the transmission of parental antisocial behavior to children's conduct disturbance, depression and hyperactivity.

PubMed

Silberg, Judy L; Maes, Hermine; Eaves, Lindon J

2012-06-01

  A critical issue in devising effective interventions for the treatment of children's behavioral and emotional problems identifying genuine family environmental factors that place children at risk. In most twin and family studies, environmental factors are confounded with both direct genetic risk from parents and the indirect effect of genes influencing parents' ability to provide an optimal rearing environment. The present study was undertaken to determine whether parental psychopathology, specifically parental antisocial behavior (ASP), is a genuine environmental risk factor for juvenile conduct disturbance, depression and hyperactivity, or whether the association between parental ASP and children's behavioral and emotional problems can be explained as a secondary consequence of the intergenerational transmission of genetic factors.   An extended children of twins design comprised of data collected on 2,674 adult female and male twins, their spouses, and 2,454 of their children was used to test whether genetic and/or family environmental factors best accounted for the association between parental antisocial behavior and children's behavioral problems. An age-matched sample of 2,826 juvenile twin pairs from the Virginia Twin Study of Adolescent Behavioral Development was also included to examine developmental differences in gene expression by partitioning child-specific transmissible effects from those effects that persist into adulthood. The fit of alternative models was evaluated using the statistical program Mx.   We found distinct patterns of transmission between parental antisocial behavior and juvenile conduct, depression and hyperactivity. Genetic and family environmental factors accounted for the resemblance between parents' ASP and children's conduct disturbance. Family environmental factors alone explained the association between child depression and parental ASP, and the impact of parental ASP on hyperactivity was entirely genetic.   These findings underscore differences in the contribution of genetic and environmental factors on the patterns of association between parental antisocial behavior and juvenile psychopathology, having important clinical implications for the prevention and amelioration of child behavioral and emotional problems. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.

Molecular cloning, expression, and functional analysis of the copper amine oxidase gene in the endophytic fungus Shiraia sp. Slf14 from Huperzia serrata.

PubMed

Yang, Huilin; Peng, Silu; Zhang, Zhibin; Yan, Riming; Wang, Ya; Zhan, Jixun; Zhu, Du

2016-12-01

Huperzine A (HupA) is a drug used for the treatment of Alzheimer's disease. However, the biosynthesis of this medicinally important compound is not well understood. The HupA biosynthetic pathway is thought to be initiated by the decarboxylation of lysine to form cadaverine, which is then converted to 5-aminopentanal by copper amine oxidase (CAO). In this study, we cloned and expressed an SsCAO gene from a HupA-producing endophytic fungus, Shiraia sp. Slf14. Analysis of the deduced protein amino acid sequence showed that it contained the Asp catalytic base, conserved motif Asn-Tyr-Asp/Glu, and three copper-binding histidines. The cDNA of SsCAO was amplified and expressed in Escherichia coli BL21(DE3), from which a 76 kDa protein was obtained. The activity of this enzyme was tested, which provided more information about the SsCAO gene in the endophytic fungus. Gas Chromatograph-Mass Spectrometry (GC-MS) revealed that this SsCAO could accept cadaverine as a substrate to produce 5-aminopentanal, the precursor of HupA. Phylogenetic tree analysis indicated that the SsCAO from Shiraia sp. Slf14 was closely related to Stemphylium lycopersici CAO. This is the first report on the cloning and expression of a CAO gene from HupA-producing endophytic fungi. Functional characterization of this enzyme provides new insights into the biosynthesis of the HupA an anti-Alzheimer's drug. Copyright © 2016 Elsevier Inc. All rights reserved.

Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc00980a Click here for additional data file.

PubMed Central

Aguayo-Ortiz, Rodrigo; Chávez-García, Cecilia; Straub, John E.

2017-01-01

γ-Secretase is an intramembrane-cleaving aspartyl protease that plays an essential role in the processing of a variety of integral membrane proteins. Its role in the ultimate cleavage step in the processing of amyloid precursor protein to form amyloid-β (Aβ) peptide makes it an important therapeutic target in Alzheimer's disease research. Significant recent advances have been made in structural studies of this critical membrane protein complex. However, details of the mechanism of activation of the enzyme complex remain unclear. Using a multiscale computational modeling approach, combining multiple coarse-grained microsecond dynamic trajectories with all-atom models, the structure and two conformational states of the γ-secretase complex were evaluated. The transition between enzymatic state 1 and state 2 is shown to critically depend on the protonation states of the key catalytic residues Asp257 and Asp385 in the active site domain. The active site formation, related to our γ-secretase state 2, is observed to involve a concerted movement of four transmembrane helices from the catalytic subunit, resulting in the required localization of the catalytic residues. Global analysis of the structural ensemble of the enzyme complex was used to identify collective fluctuations important to the mechanism of substrate recognition and demonstrate that the corresponding fluctuations observed were uncorrelated with structural changes associated with enzyme activation. Overall, this computational study provides essential insight into the role of structure and dynamics in the activation and function of γ-secretase. PMID:28970936

Solution Structure of the Squash Aspartic Acid Proteinase Inhibitor (SQAPI) and Mutational Analysis of Pepsin Inhibition

PubMed Central

Headey, Stephen J.; MacAskill, Ursula K.; Wright, Michele A.; Claridge, Jolyon K.; Edwards, Patrick J. B.; Farley, Peter C.; Christeller, John T.; Laing, William A.; Pascal, Steven M.

2010-01-01

The squash aspartic acid proteinase inhibitor (SQAPI), a proteinaceous proteinase inhibitor from squash, is an effective inhibitor of a range of aspartic proteinases. Proteinaceous aspartic proteinase inhibitors are rare in nature. The only other example in plants probably evolved from a precursor serine proteinase inhibitor. Earlier work based on sequence homology modeling suggested SQAPI evolved from an ancestral cystatin. In this work, we determined the solution structure of SQAPI using NMR and show that SQAPI shares the same fold as a plant cystatin. The structure is characterized by a four-strand anti-parallel β-sheet gripping an α-helix in an analogous manner to fingers of a hand gripping a tennis racquet. Truncation and site-specific mutagenesis revealed that the unstructured N terminus and the loop connecting β-strands 1 and 2 are important for pepsin inhibition, but the loop connecting strands 3 and 4 is not. Using ambiguous restraints based on the mutagenesis results, SQAPI was then docked computationally to pepsin. The resulting model places the N-terminal strand of SQAPI in the S′ side of the substrate binding cleft, whereas the first SQAPI loop binds on the S side of the cleft. The backbone of SQAPI does not interact with the pepsin catalytic Asp32–Asp215 diad, thus avoiding cleavage. The data show that SQAPI does share homologous structural elements with cystatin and appears to retain a similar protease inhibitory mechanism despite its different target. This strongly supports our hypothesis that SQAPI evolved from an ancestral cystatin. PMID:20538608

Probing electrostatic interactions and ligand binding in aspartyl-tRNA synthetase through site-directed mutagenesis and computer simulations.

PubMed

Thompson, Damien; Lazennec, Christine; Plateau, Pierre; Simonson, Thomas

2008-05-15

Faithful genetic code translation requires that each aminoacyl-tRNA synthetase recognise its cognate amino acid ligand specifically. Aspartyl-tRNA synthetase (AspRS) distinguishes between its negatively-charged Asp substrate and two competitors, neutral Asn and di-negative succinate, using a complex network of electrostatic interactions. Here, we used molecular dynamics simulations and site-directed mutagenesis experiments to probe these interactions further. We attempt to decrease the Asp/Asn binding free energy difference via single, double and triple mutations that reduce the net positive charge in the active site of Escherichia coli AspRS. Earlier, Glutamine 199 was changed to a negatively-charged glutamate, giving a computed reduction in Asp affinity in good agreement with experiment. Here, Lysine 198 was changed to a neutral leucine; then, Lys198 and Gln199 were mutated simultaneously. Both mutants are predicted to have reduced Asp binding and improved Asn binding, but the changes are insufficient to overcome the initial, high specificity of the native enzyme, which retains a preference for Asp. Probing the aminoacyl-adenylation reaction through pyrophosphate exchange experiments, we found no detectable activity for the mutant enzymes, indicating weaker Asp binding and/or poorer transition state stabilization. The simulations show that the mutations' effect is partly offset by proton uptake by a nearby histidine. Therefore, we performed additional simulations where the nearby Histidines 448 and 449 were mutated to neutral or negative residues: (Lys198Leu, His448Gln, His449Gln), and (Lys198Leu, His448Glu, His449Gln). This led to unexpected conformational changes and loss of active site preorganization, suggesting that the AspRS active site has a limited structural tolerance for electrostatic modifications. The data give insights into the complex electrostatic network in the AspRS active site and illustrate the difficulty in engineering charged-to-neutral changes of the preferred ligand. 2007 Wiley-Liss, Inc.

Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model.

PubMed

Namvar, S; Warn, P; Farnell, E; Bromley, M; Fraczek, M; Bowyer, P; Herrick, S

2015-05-01

In susceptible individuals, exposure to Aspergillus fumigatus can lead to the development of atopic lung diseases such as allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitization (SAFS). Protease allergens including Asp f 5 and Asp f 13 from Aspergillus fumigatus are thought to be important for initiation and progression of allergic asthma. To assess the importance of secreted protease allergens Asp f 5 (matrix metalloprotease) and Asp f 13 (serine protease) in Aspergillus fumigatus-induced inflammation, airway hyperactivity, atopy and airway wall remodelling in a murine model following chronic exposure to secreted allergens. BALB/c mice were repeatedly intranasally dosed over the course of 5 weeks with culture filtrate from wild-type (WT), Asp f 5 null (∆5) or Asp f 13 null (∆13) strains of Aspergillus fumigatus. Airway hyper-reactivity was measured by non-invasive whole-body plethysmography, Th2 response and airway inflammation by ELISA and cell counts, whilst airway remodelling was assessed by histological analysis. Parent WT and ∆5 culture filtrates showed high protease activity, whilst protease activity in ∆13 culture filtrate was low. Chronic intranasal exposure to the three different filtrates led to comparable airway hyper-reactivity and Th2 response. However, protease allergen deleted strains, in particular ∆13 culture filtrate, induced significantly less airway inflammation and remodelling compared to WT culture filtrate. Aspergillus fumigatus-secreted allergen proteases, Asp f 5 and Asp f 13, are important for recruitment of inflammatory cells and remodelling of the airways in this murine model. However, deletion of a single allergen protease fails to alleviate airway hyper-reactivity and allergic immune response. Targeting protease activity of Aspergillus fumigatus in conditions such as SAFS or ABPA may have beneficial effects in preventing key aspects of airway pathology. © 2014 John Wiley & Sons Ltd.

Impact of antimicrobial stewardship programme on hospitalized patients at the intensive care unit: a prospective audit and feedback study.

PubMed

Khdour, Maher R; Hallak, Hussein O; Aldeyab, Mamoon A; Nasif, Mowaffaq A; Khalili, Aliaa M; Dallashi, Ahamad A; Khofash, Mohammad B; Scott, Michael G

2018-04-01

Inappropriate use of antibiotics is one of the most important factors contributing to the emergence of drug resistant pathogens. The purpose of this study was to measure the clinical impact of antimicrobial stewardship programme (ASP) interventions on hospitalized patients at the Intensive care unit at Palestinian Medical Complex. A prospective audit with intervention and feedback by ASP team within 48-72 h of antibiotic administration began in September 2015. Four months of pre-ASP data were compared with 4 months of post-ASP data. Data collected included clinical and demographic data; use of antimicrobials measured by defined daily doses, duration of therapy, length of stay, readmission and all-cause mortality. Overall, 176 interventions were made the ASP team with an average acceptance rate of 78.4%. The most accepted interventions were dose optimization (87.0%) followed by de-escalation based on culture results with an acceptance rate of 84.4%. ASP interventions significantly reduces antimicrobial use by 24.3% (87.3 defined daily doses/100 beds vs. 66.1 defined daily doses/100 beds P < 0.001). The median (interquartile range) of length of stay was significantly reduced post ASP [11 (3-21) vs. 7 (4-19) days; P < 0.01]. Also, the median (interquartile range) of duration of therapy was significantly reduced post-ASP [8 (5-12) days vs. 5 (3-9); P = 0.01]. There was no significant difference in overall 30-day mortality or readmission between the pre-ASP and post-ASP groups (26.9% vs. 23.9%; P = 0.1) and (26.1% vs. 24.6%; P = 0.54) respectively. Our prospective audit and feedback programme was associated with positive impact on antimicrobial use, duration of therapy and length of stay. © 2017 The British Pharmacological Society.

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

Identification of angiotensin I in several vertebrate species: its structural and functional evolution.

PubMed

Takei, Yoshio; Joss, Jean M P; Kloas, Werner; Rankin, J Cliff

2004-02-01

In order to delineate further the molecular evolution of the renin-angiotensin system in vertebrates, angiotensin I (ANG I) has been isolated after incubation of plasma and kidney extracts of emu (Dromiceus novaehollandiae), axolotl (Ambystoma mexicanum), and sea lamprey (Petromyzon marinus). The identified sequences were [Asp1, Val5, Asn9] ANG I in emu, [Asp1, Val5, His9] ANG I in axolotl, and [Asn1, Val5, Thr9] ANG I in sea lamprey. These results confirmed the previous findings that tetrapods have Asp and fishes including cyclostomes have Asn at the N-terminus, and that the amino acid residue at position 9 of ANG I was highly variable but, those at other positions were well conserved among different species. Since Asp and Asn are convertible during incubation, angiotensinogen sequences were searched in the genome and/or EST database to determine the N-terminal amino acid residue from the gene. The screening detected 12 tetrapod (10 mammalian, one avian, and one amphibian) and seven teleostean angiotensinogen sequences. Among them, all tetrapods have [Asp1] ANG except for Xenopus, and all teleosts have [Asn1] ANG, thereby confirming the above rule. Comparison of the vasopressor activity in the eel revealed that [Asn1] ANG I and II were more potent than [Asp1] peptides, which was opposite to the previous results in mammals and birds, in which [Asp1] ANG I and II were more potent. Collectively, the present results support the general rule that tetrapods have [Asp1] ANG and fishes including cyclostomes have [Asn1] ANG. However, an aquatic anuran (Xenopus) has [Asn1] ANG in its gene despite another aquatic urodele (axolotl) has [Asp1] ANG. From the functional viewpoint, homologous [Asn1] ANG was more potent in fish as is homologous [Asp1] ANG in tetrapods, suggesting that ANG II molecule has undergone co-evolution with its receptor during vertebrate phylogeny.

Elucidating the role of many-body forces in liquid water. I. Simulations of water clusters on the VRT(ASP-W) potential surfaces.

PubMed

Goldman, Nir; Saykally, R J

2004-03-08

We test two new potentials for water, fit to vibration-rotation tunneling (VRT) data by employing diffusion quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials, VRT(ASP-W)II and VRT(ASP-W)III, are fits of the highly detailed ASP-W (anisotropic site potential with Woermer dispersion) ab initio potential to (D(2)O)(2) microwave and far-infrared data, and along with the SAPT5s (five-site symmetry adapted perturbation theory) potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compared to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)III and the spectroscopically "tuned" SAPT5st (with N-body induction included) accurately reproduce the vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispersion are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.

Elucidating the role of many-body forces in liquid water. I. Simulations of water clusters on the VRT(ASP-W) potential surfaces

NASA Astrophysics Data System (ADS)

Goldman, Nir; Saykally, R. J.

2004-03-01

We test two new potentials for water, fit to vibration-rotation tunneling (VRT) data by employing diffusion quantum Monte Carlo simulations to calculate the vibrational ground-state properties of water clusters. These potentials, VRT(ASP-W)II and VRT(ASP-W)III, are fits of the highly detailed ASP-W (anisotropic site potential with Woermer dispersion) ab initio potential to (D2O)2 microwave and far-infrared data, and along with the SAPT5s (five-site symmetry adapted perturbation theory) potentials, are the most accurate water dimer potential surfaces in the literature. The results from VRT(ASP-W)II and III are compared to those from the original ASP-W potential, the SAPT5s family of potentials, and several bulk water potentials. Only VRT(ASP-W)III and the spectroscopically "tuned" SAPT5st (with N-body induction included) accurately reproduce the vibrational ground-state structures of water clusters up to the hexamer. Finally, the importance of many-body induction and three-body dispersion are examined, and it is shown that the latter can have significant effects on water cluster properties despite its small magnitude.

Ground state destabilization from a positioned general base in the ketosteroid isomerase active site.

PubMed

Ruben, Eliza A; Schwans, Jason P; Sonnett, Matthew; Natarajan, Aditya; Gonzalez, Ana; Tsai, Yingssu; Herschlag, Daniel

2013-02-12

We compared the binding affinities of ground state analogues for bacterial ketosteroid isomerase (KSI) with a wild-type anionic Asp general base and with uncharged Asn and Ala in the general base position to provide a measure of potential ground state destabilization that could arise from the close juxtaposition of the anionic Asp and hydrophobic steroid in the reaction's Michaelis complex. The analogue binding affinity increased ~1 order of magnitude for the Asp38Asn mutation and ~2 orders of magnitude for the Asp38Ala mutation, relative to the affinity with Asp38, for KSI from two sources. The increased level of binding suggests that the abutment of a charged general base and a hydrophobic steroid is modestly destabilizing, relative to a standard state in water, and that this destabilization is relieved in the transition state and intermediate in which the charge on the general base has been neutralized because of proton abstraction. Stronger binding also arose from mutation of Pro39, the residue adjacent to the Asp general base, consistent with an ability of the Asp general base to now reorient to avoid the destabilizing interaction. Consistent with this model, the Pro mutants reduced or eliminated the increased level of binding upon replacement of Asp38 with Asn or Ala. These results, supported by additional structural observations, suggest that ground state destabilization from the negatively charged Asp38 general base provides a modest contribution to KSI catalysis. They also provide a clear illustration of the well-recognized concept that enzymes evolve for catalytic function and not, in general, to maximize ground state binding. This ground state destabilization mechanism may be common to the many enzymes with anionic side chains that deprotonate carbon acids.

Structure-guided modification of Rhizomucor miehei lipase for production of structured lipids.

PubMed

Zhang, Jun-Hui; Jiang, Yu-Yan; Lin, Ying; Sun, Yu-Fei; Zheng, Sui-Ping; Han, Shuang-Yan

2013-01-01

To improve the performance of yeast surface-displayed Rhizomucor miehei lipase (RML) in the production of human milk fat substitute (HMFS), we mutated amino acids in the lipase substrate-binding pocket based on protein hydrophobicity, to improve esterification activity. Five mutants: Asn87Ile, Asn87Ile/Asp91Val, His108Leu/Lys109Ile, Asp256Ile/His257Leu, and His108Leu/Lys109Ile/Asp256Ile/His257Leu were obtained and their hydrolytic and esterification activities were assayed. Using Discovery Studio 3.1 to build models and calculate the binding energy between lipase and substrates, compared to wild-type, the mutant Asp256Ile/His257Leu was found to have significantly lower energy when oleic acid (3.97 KJ/mol decrease) and tripalmitin (7.55 KJ/mol decrease) were substrates. This result was in accordance with the esterification activity of Asp256Ile/His257Leu (2.37-fold of wild-type). The four mutants were also evaluated for the production of HMFS in organic solvent and in a solvent-free system. Asp256Ile/His257Leu had an oleic acid incorporation of 28.27% for catalyzing tripalmitin and oleic acid, and 53.18% for the reaction of palm oil with oleic acid. The efficiency of Asp256Ile/His257Leu was 1.82-fold and 1.65-fold that of the wild-type enzyme for the two reactions. The oleic acid incorporation of Asp256Ile/His257Leu was similar to commercial Lipozyme RM IM for palm oil acidolysis with oleic acid. Yeast surface-displayed RML mutant Asp256Ile/His257Leu is a potential, economically feasible catalyst for the production of structured lipids.

Probing the Catalytic Mechanism of Vibrio harveyi GH20 β-N-Acetylglucosaminidase by Chemical Rescue

PubMed Central

Meekrathok, Piyanat; Suginta, Wipa

2016-01-01

Background Vibrio harveyi GH20 β-N-acetylglucosaminidase (VhGlcNAcase) is a chitinolytic enzyme responsible for the successive degradation of chitin fragments to GlcNAc monomers, activating the onset of the chitin catabolic cascade in marine Vibrios. Methods Two invariant acidic pairs (Asp303-Asp304 and Asp437-Glu438) of VhGlcNAcase were mutated using a site-directed mutagenesis strategy. The effects of these mutations were examined and the catalytic roles of these active-site residues were elucidated using a chemical rescue approach. Enhancement of the enzymic activity of the VhGlcNAcase mutants was evaluated by a colorimetric assay using pNP-GlcNAc as substrate. Results Substitution of Asp303, Asp304, Asp437 or Glu438 with Ala/Asn/Gln produced a dramatic loss of the GlcNAcase activity. However, the activity of the inactive D437A mutant was recovered in the presence of sodium formate. Our kinetic data suggest that formate ion plays a nucleophilic role by mimicking the β-COO-side chain of Asp437, thereby stabilizing the reaction intermediate during both the glycosylation and the deglycosylation steps. Conclusions Chemical rescue of the inactive D437A mutant of VhGlcNAcase by an added nucleophile helped to identify Asp437 as the catalytic nucleophile/base, and hence its acidic partner Glu438 as the catalytic proton donor/acceptor. General Significance Identification of the catalytic nucleophile of VhGlcNAcases supports the proposal of a substrate-assisted mechanism of GH20 GlcNAcases, requiring the catalytic pair Asp437-Glu438 for catalysis. The results suggest the mechanistic basis of the participation of β-N-acetylglucosaminidase in the chitin catabolic pathway of marine Vibrios. PMID:26870945

D-Aspartic acid and nitric oxide as regulators of androgen production in boar testis.

PubMed

Lamanna, Claudia; Assisi, Loredana; Vittoria, Alfredo; Botte, Virgilio; Di Fiore, Maria Maddalena

2007-01-15

D-Aspartic acid (D-Asp) and nitric oxide (NO) are two biologically active molecules playing important functions as neurotransmitters and neuromodulators of nerve impulse and as regulators of hormone production by endocrine organs. We studied the occurrence of D-Asp and NO as well as their effects on testosterone synthesis in the testis of boar. This model was chosen for our investigations because it contains more Leydig cells than other mammals. Indirect immunofluorescence applied to cryostat sections was used to evaluate the co-localization of D-Asp and of the enzyme nitric oxide synthase (NOS) in the same Leydig cells. D-Asp and NOS often co-existed in the same Leydig cells and were found, separately, in many other testicular cytotypes. D-Asp level was dosed by an enzymatic method performed on boar testis extracts and was 40+/-3.6 nmol/g of fresh tissue. NO measurement was carried out using a biochemical method by NOS activity determination and expressed as quantity of nitrites produced: it was 155.25+/-21.9 nmol/mg of tissue. The effects of the two molecules on steroid hormone production were evaluated by incubating testis homogenates, respectively with or without D-Asp and/or the NO-donor L-arginine (L-Arg). After incubation, the testosterone presence was measured by immunoenzymatic assay (EIA). These in vitro experiments showed that the addition of D-Asp to incubated testicular homogenates significantly increased testosterone concentration, whereas the addition of L-Arg decreased the hormone production. Moreover, the inclusion of L-Arg to an incubation medium of testicular homogenates with added D-Asp, completely inhibited the stimulating effects of this enantiomer. Our results suggest an autocrine action of both D-Asp and NO on the steroidogenetic activity of the Leydig cell.

Aspartic acid functions as carbonyl trapper to inhibit the formation of advanced glycation end products by chemical chaperone activity.

PubMed

Prasanna, Govindarajan; Saraswathi, N T

2016-05-01

Advanced glycation end products (AGEs) were implicated in pathology of numerous diseases. In this study, we present the bioactivity of aspartic acid (Asp) to inhibit the AGEs. Hemoglobin and bovine serum albumin (BSA) were glycated with glucose, fructose, and ribose in the presence and absence of Asp (100-200 μM). HbA1c inhibition was investigated using human blood and characterized by micro-column ion exchange chromatography. The effect of methyl glyoxal (MG) on hemoglobin and BSA was evaluated by fluorescence spectroscopy and gel electrophoresis. The effect of MG on red blood cells morphology was characterized by scanning electron micrographs. Molecular docking was performed on BSA with Asp. Asp is capable of inhibiting the formation of fluorescent AGEs by reacting with the reducing sugars. The presence of Asp as supplement in whole blood reduced the HbA1c% from 8.8 to 6.1. The presence of MG showed an increase in fluorescence and the presence of Asp inhibited the glycation thereby the fluorescence was quenched. MG also affected the electrophoretic mobility of hemoglobin and BSA by forming high molecular weight aggregates. Normal RBCs showed typical biconcave shape. MG modified RBCs showed twisted and elongated shape whereas the presence of ASP tends to protect RBC from twisting. Asp interacted with arginine residues of bovine serum albumin particularly ARG 194, ARG 198, and ARG 217 thereby stabilized the protein complex. We conclude that Asp has dual functions as a chemical chaperone to stabilize protein and as a dicarbonyl trapper, and thereby it can prevent the complications caused by glycation.

Neural network versus activity-specific prediction equations for energy expenditure estimation in children.

PubMed

Ruch, Nicole; Joss, Franziska; Jimmy, Gerda; Melzer, Katarina; Hänggi, Johanna; Mäder, Urs

2013-11-01

The aim of this study was to compare the energy expenditure (EE) estimations of activity-specific prediction equations (ASPE) and of an artificial neural network (ANNEE) based on accelerometry with measured EE. Forty-three children (age: 9.8 ± 2.4 yr) performed eight different activities. They were equipped with one tri-axial accelerometer that collected data in 1-s epochs and a portable gas analyzer. The ASPE and the ANNEE were trained to estimate the EE by including accelerometry, age, gender, and weight of the participants. To provide the activity-specific information, a decision tree was trained to recognize the type of activity through accelerometer data. The ASPE were applied to the activity-type-specific data recognized by the tree (Tree-ASPE). The Tree-ASPE precisely estimated the EE of all activities except cycling [bias: -1.13 ± 1.33 metabolic equivalent (MET)] and walking (bias: 0.29 ± 0.64 MET; P < 0.05). The ANNEE overestimated the EE of stationary activities (bias: 0.31 ± 0.47 MET) and walking (bias: 0.61 ± 0.72 MET) and underestimated the EE of cycling (bias: -0.90 ± 1.18 MET; P < 0.05). Biases of EE in stationary activities (ANNEE: 0.31 ± 0.47 MET, Tree-ASPE: 0.08 ± 0.21 MET) and walking (ANNEE 0.61 ± 0.72 MET, Tree-ASPE: 0.29 ± 0.64 MET) were significantly smaller in the Tree-ASPE than in the ANNEE (P < 0.05). The Tree-ASPE was more precise in estimating the EE than the ANNEE. The use of activity-type-specific information for subsequent EE prediction equations might be a promising approach for future studies.

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed Central

Wicks, J

2000-01-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs. PMID:10788332

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed

Wicks, J

2000-06-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.

E-Learning in Supplemental Educational Systems in Taiwan: Present Status and Future Challenges

ERIC Educational Resources Information Center

Zhang, Ke; Hung, Jui-Long

2009-01-01

As Taiwan's full-scale e-learning initiatives moved to the seventh year in 2009, the current status and challenges of e-learning development there are yet to be fully understood. Further extending Zhang and Hung's (2006) investigation on e-learning in all universities and colleges in Taiwan, this study investigated the after-school programs (ASPs)…

75 FR 58414 - Medicare Program; Meeting of the Medicare Evidence Development and Coverage Advisory Committee...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... focus on issues specific to the list of topics that we have proposed to the Committee. The list of research topics to be discussed at the meeting will be available on the following Web site prior to the... topic, including panel materials, is available at http://www.cms.hhs.gov/center/coverage.asp . We...

R76 in transmembrane domain 3 of the aspartate:alanine transporter AspT is involved in substrate transport.

PubMed

Suzuki, Satomi; Nanatani, Kei; Abe, Keietsu

2016-01-01

The L-aspartate:L-alanine antiporter of Tetragenococcus halophilus (AspT) possesses an arginine residue (R76) within the GxxxG motif in the central part of transmembrane domain 3 (TM3)-a residue that has been estimated to transport function. In this study, we carried out amino acid substitutions of R76 and used proteoliposome reconstitution for analyzing the transport function of each substitution. Both l-aspartate and l-alanine transport assays showed that R76K has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than the AspT-WT. These results suggest that R76 is involved in AspT substrate transport.

Building Community: A 2005 Conference for Education and Public Outreach Professionals

NASA Astrophysics Data System (ADS)

Slater, T. F.; Bennett, M.; Garmany, K.

2004-12-01

In support of the Astronomical Society of the Pacific's (ASP) mission to increase the understanding and appreciation of astronomy, the ASP will host an international meeting in September 14-16, 2005 in Tucson focused on building and supporting a vibrant and connected community of individuals and groups engaged in educational and public outreach (EPO) in the disciplines of astronomy, astrobiology, space, and earth science. This conference is specially designed for individuals who are bringing the excitement of astronomy to non-astronomers. This community of science communicators includes: NASA and NSF-funded EPO program managers, developers, evaluators, PIOs, and others who support outreach efforts by government agencies and commercial industries; Scientists working with or assigned to EPO programs or efforts; Individuals working in formal science education: K-14 schools/colleges and minority-serving institutions as faculty or curriculum developers; Informal educators working in widely diverse settings including science centers, planetariums, museums, parks, and youth programs; Amateur astronomers involved in or interested in engaging children and adults in the excitement of astronomy; Public outreach specialists working in observatories, visitor centers, public information offices, and in multimedia broadcasting and journalism. The conference goals are to improve the quality and increase the effective dissemination of EPO materials, products, and programs through a multi-tiered professional development conference utilizing: Visionary plenary talks; Highly interactive panel discussions; Small group workshops and clinics focused on a wide range of EPO topics including evaluation and dissemination, with separate sessions for varying experience levels; Poster and project exhibition segments; Opportunities to increase program leveraging through structured and unstructured networking sessions; and Individual program action planning sessions. There will both separate and combined sessions for individuals working in formal, informal, public outreach, and scientific communications settings; and specific professional development sessions.

Substitution of Asp-309 by Asn in the Arg-Asp-Pro (RDP) motif of Acetobacter diazotrophicus levansucrase affects sucrose hydrolysis, but not enzyme specificity.

PubMed Central

Batista, F R; Hernández, L; Fernández, J R; Arrieta, J; Menéndez, C; Gómez, R; Támbara, Y; Pons, T

1999-01-01

beta-Fructofuranosidases share a conserved aspartic acid-containing motif (Arg-Asp-Pro; RDP) which is absent from alpha-glucopyranosidases. The role of Asp-309 located in the RDP motif of levansucrase (EC 2.4.1.10) from Acetobacter diazotrophicus SRT4 was studied by site-directed mutagenesis. Substitution of Asp-309 by Asn did not affect enzyme secretion. The kcat of the mutant levansucrase was reduced 75-fold, but its Km was similar to that of the wild-type enzyme, indicating that Asp-309 plays a major role in catalysis. The two levansucrases showed optimal activity at pH 5.0 and yielded similar product profiles. Thus the mutation D309N affected the efficiency of sucrose hydrolysis, but not the enzyme specificity. Since the RDP motif is present in a conserved position in fructosyltransferases, invertases, levanases, inulinases and sucrose-6-phosphate hydrolases, it is likely to have a common functional role in beta-fructofuranosidases. PMID:9895294

Multinational Consensus: Insulin Initiation with Insulin Degludec/Aspart (IDegAsp).

PubMed

Kalra, Sanjay; Atkin, Stephen; Cervera, Antonio; Das, Ashok Kumar; Demir, Ozgur; Demir, Tevfik; Fariduddin, Md; Vo, Khoa Tuan; Ku, Bon Jeong; Kumar, Ajay; Latif, Zafar A; Malek, Rachid; Matawaran, Bien J; Mehta, Roopa; Tran, Nam Quang; Panelo, Araceli; Ruder, Sundeep; Saldana, Joel Rodriquez; Shaikh, Khalid A; Shakya, Amit; Shrestha, Dina; Unnikrishnan, A G

2018-05-23

Insulin degludec/aspart (IDegAsp) is the first soluble insulin co-formulation, combining a long-acting insulin degludec (IDeg) and rapid-acting insulin aspart (IAsp). In type 2 diabetes patients with oral antidiabetes agent (OAD) inadequacy, insulin initiation with IDegAsp once daily provides superior long-term glycemic control compared to insulin glargine, with similar fasting plasma glucose (FPG) and insulin doses, and numerically lower rates of overall and nocturnal hypoglycemia. Furthermore, in patients with uncontrolled type 2 diabetes previously treated with insulins, IDegAsp twice daily effectively improves glycated hemoglobin and FPG, with fewer hypoglycemic episodes versus premix insulins and basal bolus therapy. In patients with type 1 diabetes mellitus, IDegAsp once daily with two doses of IAsp is a convenient, yet effective, regimen as compared to the conventional 4-5 injection-based basal bolus therapy. IDegAsp is an appropriate and reasonable option for initiation of insulin therapy in both type 1 and type 2 diabetes.

Face-selective crystal growth behavior of L-aspartic acid in the presence of L-asparagine

NASA Astrophysics Data System (ADS)

Sato, Hiroyasu; Doki, Norihito; Yoshida, Saki; Yokota, Masaaki; Shimizu, Kenji

2016-02-01

The kinetic mechanism of L-asparagine (L-Asn) action on L-aspartic acid (L-Asp) crystal growth, namely the face-selective effect of L-Asn on the L-Asp crystal growth rate in each direction, was examined. In the a-axis direction, the effect of L-Asn on the L-Asp crystal growth rate was small. Enhancement and inhibition of L-Asp crystal growth, and interestingly the dissolution of the L-Asp crystal face, were observed in the b-axis direction, depending on the amount of L-Asn added. In the c-axis direction, the L-Asp crystal growth rate decreased with the increase in the amount of L-Asn added, and the experimental results were well fitted with a Langmuir adsorption isotherm. The study showed that there were crystal growth conditions where enhancement and inhibition, as well as inhibition and dissolution, coexisted in the presence of an additive with a structure similar to the growing crystal.

Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

PubMed

Coppedè, Fabio; Lo Gerfo, Annalisa; Carlesi, Cecilia; Piazza, Selina; Mancuso, Michelangelo; Pasquali, Livia; Murri, Luigi; Migliore, Lucia; Siciliano, Gabriele

2010-02-01

Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression. We screened 134 sALS Italian patients and 129 matched controls for the presence of the APEX1 Asp148Glu polymorphism. No difference in APEX1 Asp148Glu allele and genotype frequencies was found between the groups, nor was the polymorphism associated with age and site of onset or disease progression. Present results do not support a role for the APEX1 Asp148Glu polymorphism in sALS pathogenesis in the Italian population.

Computational Study on Substrate Specificity of a Novel Cysteine Protease 1 Precursor from Zea mays

PubMed Central

Liu, Huimin; Chen, Liangcheng; Li, Quan; Zheng, Mingzhu; Liu, Jingsheng

2014-01-01

Cysteine protease 1 precursor from Zea mays (zmCP1) is classified as a member of the C1A family of peptidases (papain-like cysteine protease) in MEROPS (the Peptidase Database). The 3D structure and substrate specificity of the zmCP1 is still unknown. This study is the first one to build the 3D structure of zmCP1 by computer-assisted homology modeling. In order to determine the substrate specificity of zmCP1, docking study is used for rapid and convenient analysis of large populations of ligand–enzyme complexes. Docking results show that zmCP1 has preference for P1 position and P2 position for Arg and a large hydrophobic residue (such as Phe). Gly147, Gly191, Cys189, and Asp190 are predicted to function as active residues at the S1 subsite, and the S2 subsite contains Leu283, Leu193, Ala259, Met194, and Ala286. SIFt results indicate that Gly144, Arg268, Trp308, and Ser311 play important roles in substrate binding. Then Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) method was used to explain the substrate specificity for P1 position of zmCp1. This study provides insights into the molecular basis of zmCP1 activity and substrate specificity. PMID:24921705

Engineering acidic Streptomyces rubiginosus D-xylose isomerase by rational enzyme design.

PubMed

Waltman, Mary Jo; Yang, Zamin Koo; Langan, Paul; Graham, David E; Kovalevsky, Andrey

2014-02-01

To maximize bioethanol production from lignocellulosic biomass, all sugars must be utilized. Yeast fermentation can be improved by introducing the d-xylose isomerase enzyme to convert the pentose sugar d-xylose, which cannot be fermented by Saccharomyces cerevisiae, into the fermentable ketose d-xylulose. The low activity of d-xylose isomerase, especially at the low pH required for optimal fermentation, limits its use. A rational enzyme engineering approach was undertaken, and seven amino acid positions were replaced to improve the activity of Streptomyces rubiginosus d-xylose isomerase towards its physiological substrate at pH values below 6. The active-site design was guided by mechanistic insights and the knowledge of amino acid protonation states at low pH obtained from previous joint X-ray/neutron crystallographic experiments. Tagging the enzyme with 6 or 12 histidine residues at the N-terminus resulted in a significant increase in the active-site affinity towards substrate at pH 5.8. Substituting an asparagine at position 215, which hydrogen bonded to the metal-bound Glu181 and Asp245, with an aspartate gave a variant with almost an order of magnitude lower KM than measured for the native enzyme, with a 4-fold increase in activity. Other studied variants showed similar (Asp57Asn, Glu186Gln/Asn215Asp), lower (Asp57His, Asn247Asp, Lys289His, Lys289Glu) or no (Gln256Asp, Asp287Asn, ΔAsp287) activity in acidic conditions relative to the native enzyme.

Ameliorative effect of Pimpinella anisum oil on immunohistochemical and ultrastuctural changes of cerebellum of albino rats induced by aspartame.

PubMed

Abdul-Hamid, Manal; Gallaly, Sanaa Rida

2014-05-01

The study aims to investigate the protective effect of Pimpinella anisum oil on aspartame (ASP) which resulted in cerebellar changes. The rats were divided into four equal groups: Group 1: (control group): served as control animals. Group 2: control P. anisum oil received .5 mL/kg/d/b wt. once daily. Group 3 (ASP group): received daily 250 mg/kg/b wt. of ASP dissolved in distilled water and given orally to the animals by intra-gastric tube for 2 months. Group 4: received .5 mL/kg/b wt. of prophylactic P. anisum oil once daily, followed by ASP after 2 h for 2 months. The histopathological approach revealed marked changes in the Purkinje cells, myleinated nerve fibers and granular cells of ASP-treated animals. Some of these cells appeared with deeply stained cytoplasm. Ultrastructural examination showed Purkinje cells with dilated rough endoplasmic reticulum and condensed mitochondria. Granular cells appeared with less c nuclei and surrounded by dissolution of most Mossy rosettes structures. Most myelinated nerve fibers showed thickening of myelinated sheath and others showed splitting of their myelin sheath. The histopathological, immunohistochemical and ultrastructural alterations were much less observed in concomitant use of P. anisum oil with ASP. Cerebellar cortex is considered target areas of ASP neurotoxicity, while P. anisum oil, when used in combination with ASP displays a protective action against neurotoxicity.

ACE-like hydrolysis of gastrin analogs and CCK-8 by fundic mucosal cells of different species with release of the amidated C-terminal dipeptide.

PubMed

Dubreuil, P; Fulcrand, P; Rodriguez, M; Laur, J; Bali, J P; Martinez, J

1990-06-19

Various gastrin analogues and CCK-8 (Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2) are hydrolyzed in vitro by angiotensin-converting enzyme (ACE), the main and initial cleavage occurring at the Met-Asp (or Leu-Asp) bond, releasing the C-terminal dipeptide amide Asp-Phe-NH2. Tetragastrin analogues (e.g., Boc-Trp-Leu-Asp-Phe-NH2) are degraded by a vesicular membrane fraction from rat gastric mucosa, yielding the C-terminal dipeptide Asp-Phe-NH2. We report here on the degradation of gastrin analogues and CCK-8 by a gastric mucosal cell preparation containing specific gastrin receptors. We have shown that gastrin analogues were specifically degraded by gastric mucosal cells from different species (e.g., rabbit and dog) at 37 degrees C (pH 7.4), releasing the C-terminal dipeptide Asp-Phe-NH2, similarly to ACE. This cleavage was found to be temperature and pH sensitive, and was inhibited by metalloproteinase inhibitors and by captopril, strongly suggesting that this enzymatic system closely resembles ACE. We have also demonstrated that a close correlation seems to exist between the apparent affinity of the gastrin analogues for gastrin receptors on gastric mucosal cells, and their ability of being hydrolyzed by this cell preparation. Moreover, all gastrin analogues which have been demonstrated to act as gastrin antagonists remained unaffected in the incubation conditions.

Adult student satisfaction in an accelerated RN-to-BSN program: a follow-up study.

PubMed

Boylston, Mary T; Jackson, Christina

2008-01-01

This mixed-method study revealed accelerated RN-to-BSN (bachelor of science in nursing) students' levels of satisfaction with a wide range of college services in a small university. Building on seminal research on the topic [Boylston, M. T., Peters, M. A., & Lacey, M. (2004). Adult student satisfaction in traditional and accelerated RN-to-BSN programs. Journal of Professional Nursing, 20, 23-32.], the Noel-Levitz Adult Student Priorities Survey (ASPS) and qualitative interview data revealed primary factors involved in nontraditional (adult) accelerated RN-to-BSN student satisfaction. The ASPS assesses both satisfaction with and importance of the following factors: academic advising effectiveness, academic services, admissions and financial aid effectiveness, campus climate, instructional effectiveness, registration effectiveness, safety and security, and service excellence. Of these factors, participants considered instructional effectiveness and academic advising effectiveness as most important and concomitantly gave high satisfaction ratings to each. In contrast, convenience of the bookstore, counseling services, vending machines, and computer laboratories were given low importance ratings. The participants cited convenience as a strong marketing factor. Loss of financial aid or family crisis was given as a reason for withdrawal and, for most students, would be the only reason for not completing the BSN program. Outcomes of this investigation may guide faculty, staff, and administrators in proactively creating an educational environment in which a nontraditional student can succeed.

Process Evaluation of Making HEPA Policy Practice: A Group Randomized Trial.

PubMed

Weaver, Robert G; Moore, Justin B; Huberty, Jennifer; Freedman, Darcy; Turner-McGrievy, Brie; Beighle, Aaron; Ward, Diane; Pate, Russell; Saunders, Ruth; Brazendale, Keith; Chandler, Jessica; Ajja, Rahma; Kyryliuk, Becky; Beets, Michael W

2016-09-01

This study examines the link between implementation of Strategies to Enhance Practice (STEPs) and outcomes. Twenty after-school programs (ASPs) participated in an intervention to increase children's accumulation of 30 minutes/day of moderate to vigorous physical activity (MVPA) and quality of snacks served during program time. Outcomes were measured via accelerometer (MVPA) and direct observation (snacks). STEPs implementation data were collected via document review and direct observation. Based on implementation data, ASPs were divided into high/low implementers. Differences between high/low implementers' change in percentage of boys accumulating 30 minutes/day of MVPA were observed. There was no difference between high/low implementers for girls. Days fruits and/or vegetables and water were served increased in the high/low implementation groups, while desserts and sugar-sweetened beverages decreased. Effect sizes (ES) for the difference in changes between the high and low group ranged from low (ES = 0.16) to high (ES = 0.97). Higher levels of implementation led to increased MVPA for boys, whereas girls MVPA benefited from the intervention regardless of high/low implementation. ESs of the difference between high/low implementers indicate that increased implementation of STEPs increases days healthier snacks are served. Programs in the high-implementation group implemented a variety of STEPs strategies, suggesting local adoption/adaptation is key to implementation. © 2016 Society for Public Health Education.

Improved ASP I/O performance. [For 370/195

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

Engert, D.E.

1975-11-01

An improvement to the I/0 routines of ASP is described, which can save 25% of the EXCPs issued by ASP. Unused buffers in the buffer pool are used to retain parts of the single track table, and only two modules are changed. 4 figures (auth)

Canadian Ranger Rifle: Human Factors Requirements Validation

DTIC Science & Technology

2010-08-01

index-eng.asp retrieved 9 February 2010 2 http://www.armee.forces.gc.ca/land-terre/cr-rc/history- histoire -eng.asp retrieved 9 February 2010 3 http... histoire -eng.asp Department of National Defence. (2010). Canadian Ranger Patrol (CRPG). Retrieved June 3, 2010, from http://www.army.forces.gc.ca

Cardioprotection activity and mechanism of Astragalus polysaccharide in vivo and in vitro.

PubMed

Liu, Debin; Chen, Lei; Zhao, Jianye; Cui, Kang

2018-05-01

Astragalus polysaccharides (ASP) is extracted from Astragalus, and is the main active ingredient of Astragalus membranaceus. The purpose of this study was to investigate the protective effect of ASP on rat cardiomyocytes damage induced by myocardial ischemia and reperfusion injury (MVRI) and isoprenaline(ISO) in vivo and in vitro. The model of cardiomyocytes damage was induced using MVRI in a rat in vivo and also using ISO in cell. After ASP intervention, the protective effect of ASP on cardiomyocytes was evaluated by animal experimental and cell experimental. The results show that ASP can relieve the increase of cell volume in myocardium, reduce the apoptosis of cell in myocardial tissue caused by MVRI in vivo. At the cellular level, ASP can reverse the decrease of cell activity induced by ISO, inhibit the apoptosis, and decrease the levels of intracellular reactive oxygen species. Mechanistically at the molecular level, these effects are elicited via down-regulation of the protein levels of caspase-3 and bax and up-regulation of the protein levels of bcl-2 in both in vivo and in vitro. These results demonstrate that ASP has a protective efficacy in MVRI/ISO-treated cardiomyocytes by inhibiting the apoptosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Comparative study of (Asp)7-CHOL-modified liposome prepared using pre-insertion and post-insertion methods for bone targeting in vivo.

PubMed

Zhang, Lijing; Cao, Hua; Zhang, Jiaxin; Yang, Chengli; Hu, Tingting; Li, Huili; Yang, Wu; He, Gu; Song, Xiangrong; Tong, Aiping; Guo, Gang; Li, Rui; Jiang, Yu; Liu, Jiyan; Cai, Lulu; Zheng, Yu

2017-02-01

Specific delivery of drugs to bone tissue is very challenging due to the architecture and structure of bone tissue. A seven-repeat sequence of aspartate, a representative bone-targeting oligopeptide, is preferentially used for targeted therapy for bone diseases. In this study, Asp7-cholesterol((Asp)7-CHOL) was synthesized and (Asp)7-CHOL-modified liposome loaded with doxorubicin (DOX) was successfully prepared using both pre-insertion (pre-L) and post-insertion (post-L) methods. The formulation was optimized according to particle size, zeta potential and the drug-loading efficiency of the liposome. In addition, the bone affinity of the (Asp)7-CHOL-modified liposome was evaluated using a hydroxyapatite (HA) absorption method. The results suggested that (Asp)7-CHOL-modified liposome show excellent HA absorption; pre-L showed slightly higher HA binding than post-L. However, post-L had a higher DOX entrapment efficiency than pre-L. In vivo imaging further demonstrated that pre-L showed a higher bone-targeting efficiency than post-L, which was consistent with in vitro results. In all, (Asp)7-CHOL-modified liposome showed excellent bone-targeting activity, suggesting their potential for use as a drug delivery system for bone disease-targeted therapies.

Selectivity Mechanism of the Voltage-gated Proton Channel, HV1

NASA Astrophysics Data System (ADS)

Dudev, Todor; Musset, Boris; Morgan, Deri; Cherny, Vladimir V.; Smith, Susan M. E.; Mazmanian, Karine; Decoursey, Thomas E.; Lim, Carmay

2015-05-01

Voltage-gated proton channels, HV1, trigger bioluminescence in dinoflagellates, enable calcification in coccolithophores, and play multifarious roles in human health. Because the proton concentration is minuscule, exquisite selectivity for protons over other ions is critical to HV1 function. The selectivity of the open HV1 channel requires an aspartate near an arginine in the selectivity filter (SF), a narrow region that dictates proton selectivity, but the mechanism of proton selectivity is unknown. Here we use a reduced quantum model to elucidate how the Asp-Arg SF selects protons but excludes other ions. Attached to a ring scaffold, the Asp and Arg side chains formed bidentate hydrogen bonds that occlude the pore. Introducing H3O+ protonated the SF, breaking the Asp-Arg linkage and opening the conduction pathway, whereas Na+ or Cl- was trapped by the SF residue of opposite charge, leaving the linkage intact, thus preventing permeation. An Asp-Lys SF behaved like the Asp-Arg one and was experimentally verified to be proton-selective, as predicted. Hence, interacting acidic and basic residues form favorable AspH0-H2O0-Arg+ interactions with hydronium but unfavorable Asp--X-/X+-Arg+ interactions with anions/cations. This proposed mechanism may apply to other proton-selective molecules engaged in bioenergetics, homeostasis, and signaling.

Genetic immunization based on the ubiquitin-fusion degradation pathway against Trypanosoma cruzi

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

Chou, Bin; Department of Parasitology, Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582; Hiromatsu, Kenji, E-mail: khiromatsu@fukuoka-u.ac.jp

2010-02-12

Cytotoxic CD8{sup +} T cells are particularly important to the development of protective immunity against the intracellular protozoan parasite, Trypanosoma cruzi, the etiological agent of Chagas disease. We have developed a new effective strategy of genetic immunization by activating CD8{sup +} T cells through the ubiquitin-fusion degradation (UFD) pathway. We constructed expression plasmids encoding the amastigote surface protein-2 (ASP-2) of T. cruzi. To induce the UFD pathway, a chimeric gene encoding ubiquitin fused to ASP-2 (pUB-ASP-2) was constructed. Mice immunized with pUB-ASP-2 presented lower parasitemia and longer survival period, compared with mice immunized with pASP-2 alone. Depletion of CD8{sup +}more » T cells abolished protection against T. cruzi in mice immunized with pUB-ASP-2 while depletion of CD4{sup +} T cells did not influence the effective immunity. Mice deficient in LMP2 or LMP7, subunits of immunoproteasomes, were not able to develop protective immunity induced. These results suggest that ubiquitin-fused antigens expressed in antigen-presenting cells were effectively degraded via the UFD pathway, and subsequently activated CD8{sup +} T cells. Consequently, immunization with pUB-ASP-2 was able to induce potent protective immunity against infection of T. cruzi.« less

Proteolytic cleavage of polymeric tau protein by caspase-3: implications for Alzheimer disease.

PubMed

Jarero-Basulto, Jose J; Luna-Muñoz, Jose; Mena, Raul; Kristofikova, Zdena; Ripova, Daniela; Perry, George; Binder, Lester I; Garcia-Sierra, Francisco

2013-12-01

Truncated tau protein at Asp(421) is associated with neurofibrillary pathology in Alzheimer disease (AD); however, little is known about its presence in the form of nonfibrillary aggregates. Here, we report immunohistochemical staining of the Tau-C3 antibody, which recognizes Asp(421)-truncated tau, in a group of AD cases with different extents of cognitive impairment. In the hippocampus, we found distinct nonfibrillary aggregates of Asp(421)-truncated tau. Unlike Asp(421)-composed neurofibrillary tangles, however, these nonfibrillary pathologies did not increase significantly with respect to the Braak staging and, therefore, make no significant contribution to cognitive impairment. On the other hand, despite in vitro evidence that caspase-3 cleaves monomeric tau at Asp(421), to date, this truncation has not been demonstrated to be executed by this protease in polymeric tau entities. We determined that Asp(421) truncation can be produced by caspase-3 in oligomeric and multimeric complexes of recombinant full-length tau in isolated native tau filaments in vitro and in situ in neurofibrillary tangles analyzed in fresh brain slices from AD cases. Our data suggest that generation of this pathologic Asp(421) truncation of tau in long-lasting fibrillary structures may produce further permanent toxicity for neurons in the brains of patients with AD.

Chronic administration of Angelica sinensis polysaccharide effectively improves fatty liver and glucose homeostasis in high-fat diet-fed mice.

PubMed

Wang, Kaiping; Cao, Peng; Wang, Hanxiang; Tang, Zhuohong; Wang, Na; Wang, Jinglin; Zhang, Yu

2016-05-18

This study aimed to investigate the therapeutic effects of Angelica sinensis polysaccharide (ASP), an active component derived from a water extract of Angelica sinensis, in high-fat diet (HFD)-fed BALB/c mice. The potential mechanisms underlying the activity of this compound were also considered. Specifically, serum and hepatic biochemical parameters were evaluated, and key proteins involved in the lipid/glucose metabolism were analyzed. Long-term feeding with a HFD induced severe fatty liver and hyperglycemia. Histological examination clearly showed that ASP reduced lipid accumulation in the liver and attenuated hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and liver lipid disorders and fatty liver via the upregulation of PPARγ expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress, demonstrating that ASP might attenuate nonalcoholic fatty liver disease via a "two-hit" mechanism. In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs.

Methodology for the systematic reviews on an adjacent segment pathology.

PubMed

Norvell, Daniel C; Dettori, Joseph R; Skelly, Andrea C; Riew, K Daniel; Chapman, Jens R; Anderson, Paul A

2012-10-15

A systematic review. To provide a detailed description of the methods undertaken in the systematic search and analytical summary of adjacent segment pathology (ASP) issues and to describe the process used to develop consensus statements and clinical recommendations regarding factors associated with the prevention and treatment of ASP. We present methods used in conducting the systematic, evidence-based reviews and development of expert panel consensus statements and clinical recommendations on the classification, natural history, risk factors, and treatment of radiographical and clinical ASP. Our intent is that clinicians will combine the information from these reviews with an understanding of their own capacities and experience to better manage patients at risk of ASP and consider future research for the prevention and treatment of ASP. A systematic search and critical review of the English-language literature was undertaken for articles published on the classification, risk, risk factors, and treatment of radiographical and clinical ASP. Articles were screened for relevance using a priori criteria, and relevant articles were critically reviewed. Whether an article was included for review depended on whether the study question was descriptive, one of therapy, or one of prognosis. The strength of evidence for the overall body of literature in each topic area was determined by 2 independent reviewers considering risk of bias, consistency, directness, and precision of results using a modification of the Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria. Disagreements were resolved by consensus. Findings from articles meeting inclusion criteria were summarized. From these summaries, consensus statements or clinical recommendations were formulated among subject experts through a modified Delphi process using the GRADE approach. A total of 3382 articles were identified and screened on 14 topics relating to the classification, risks, risk factors, and treatment of radiographical and clinical ASP. Of these, 127 met our predetermined inclusion criteria and were used to answer specific clinical questions within each topic. Lack of precision in the terminology related to adjacent segment disease and critical evaluation of definitions used across included articles led to a consensus to use ASP and suggest it as a standard. No validated comprehensive classification system for ASP currently exists. The expert panel developed a consensus definition of radiographical and clinical ASP (RASP and CASP). Some of the highlights from the analyses included the annual, 5- and 10-year risks of developing cervical and lumbar ASP after surgery, several important risk factors associated with the development of cervical and lumbar ASP, and the possibility that some motion sparing procedures may be associated with a lower risk of ASP compared with fusion despite kinematic studies demonstrating similar adjacent segment mobility following these procedures. Other highlights included a high risk of proximal junctional kyphosis (PJK) following long fusions for deformity correction, postsurgical malalignment as a potential risk factor for RASP and the paucity of studies on treatment of cervical and lumbar ASP. Systematic reviews were undertaken to understand the classification, risks, risk factors, and treatment of RASP and CASP and to provide consensus statements and clinical recommendations. This article reports the methods used in the reviews.

Briefing to University of Porto on NASA Airborne Science Program and Ames UAVs

NASA Technical Reports Server (NTRS)

Fladeland, Matthew

2015-01-01

NASA Ames is exploring a partnership with the University of Portugal to jointly develop and test new autonomous vehicle technologies. As part of the discussions I will be briefing the University of Portugal faculty on the NASA Airborne Science Program (ASP) and associated activities at NASA Ames Research Center. The presentation will communicate the requirements that drive the program, the assets available to NASA researchers, and discuss research projects that have used unmanned aircraft systems including MIZOPEX, Surprise Valley, and Florida Keys Coral Reef assessment. Other topics will include the SIERRA and Dragon Eye UAV projects operated at Ames.

A Cyclic Nucleotide-Gated Channel Mutation Associated with Canine Daylight Blindness Provides Insight into a Role for the S2 Segment Tri-Asp motif in Channel Biogenesis

PubMed Central

Tanaka, Naoto; Delemotte, Lucie; Klein, Michael L.; Komáromy, András M.; Tanaka, Jacqueline C.

2014-01-01

Cone cyclic nucleotide-gated channels are tetramers formed by CNGA3 and CNGB3 subunits; CNGA3 subunits function as homotetrameric channels but CNGB3 exhibits channel function only when co-expressed with CNGA3. An aspartatic acid (Asp) to asparagine (Asn) missense mutation at position 262 in the canine CNGB3 (D262N) subunit results in loss of cone function (daylight blindness), suggesting an important role for this aspartic acid residue in channel biogenesis and/or function. Asp 262 is located in a conserved region of the second transmembrane segment containing three Asp residues designated the Tri-Asp motif. This motif is conserved in all CNG channels. Here we examine mutations in canine CNGA3 homomeric channels using a combination of experimental and computational approaches. Mutations of these conserved Asp residues result in the absence of nucleotide-activated currents in heterologous expression. A fluorescent tag on CNGA3 shows mislocalization of mutant channels. Co-expressing CNGB3 Tri-Asp mutants with wild type CNGA3 results in some functional channels, however, their electrophysiological characterization matches the properties of homomeric CNGA3 channels. This failure to record heteromeric currents suggests that Asp/Asn mutations affect heteromeric subunit assembly. A homology model of S1–S6 of the CNGA3 channel was generated and relaxed in a membrane using molecular dynamics simulations. The model predicts that the Tri-Asp motif is involved in non-specific salt bridge pairings with positive residues of S3/S4. We propose that the D262N mutation in dogs with CNGB3-day blindness results in the loss of these inter-helical interactions altering the electrostatic equilibrium within in the S1–S4 bundle. Because residues analogous to Tri-Asp in the voltage-gated Shaker potassium channel family were implicated in monomer folding, we hypothesize that destabilizing these electrostatic interactions impairs the monomer folding state in D262N mutant CNG channels during biogenesis. PMID:24586388

Clinical experiences with an ASP model backup archive for PACS images

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Cao, Fei; Documet, Luis; Huang, H. K.; Muldoon, Jean

2003-05-01

Last year we presented a Fault-Tolerant Backup Archive using an Application Service Provider (ASP) model for disaster recovery. The purpose of this paper is to update and provide clinical experiences related towards implementing the ASP model archive solution for short-term backup of clinical PACS image data as well as possible applications other than disaster recovery. The ASP backup archive provides instantaneous, automatic backup of acquired PACS image data and instantaneous recovery of stored PACS image data all at a low operational cost and with little human intervention. This solution can be used for a variety of scheduled and unscheduled downtimes that occur on the main PACS archive. A backup archive server with hierarchical storage was implemented offsite from the main PACS archive location. Clinical data from a hospital PACS is sent to this ASP storage server in parallel to the exams being archived in the main server. Initially, connectivity between the main archive and the ASP storage server is established via a T-1 connection. In the future, other more cost-effective means of connectivity will be researched such as the Internet 2. We have integrated the ASP model backup archive with a clinical PACS at Saint John's Health Center and has been operational for over 6 months. Pitfalls encountered during integration with a live clinical PACS and the impact to clinical workflow will be discussed. In addition, estimations of the cost of establishing such a solution as well as the cost charged to the users will be included. Clinical downtime scenarios, such as a scheduled mandatory downtime and an unscheduled downtime due to a disaster event to the main archive, were simulated and the PACS exams were sent successfully from the offsite ASP storage server back to the hospital PACS in less than 1 day. The ASP backup archive was able to recover PACS image data for comparison studies with no complex operational procedures. Furthermore, no image data loss was encountered during the recovery. During any clinical downtime scenario, the ASP backup archive server can repopulate a clinical PACS quickly with the majority of studies available for comparison during the interim until the main PACS archive is fully recovered.

Impact of Iron-Enriched Aspergillus oryzae on Iron Bioavailability, Safety, and Gut Microbiota in Rats.

PubMed

Reddy, Manju B; Armah, Seth M

2018-06-20

Iron deficiency is a leading global nutritional problem. Ferrous sulfate (FeSO 4 ) is the most common iron source used for supplementation. Because of many side effects associated with its consumption, it is important to identify new forms of iron. The objectives of this study were to assess the bioavailability of iron-enriched Aspergillus oryzae, Aspiron (ASP), evaluate the toxicity of high-dose iron supplementation with ASP, and determine the ASP impact on gut microbiota in rats. In this study, we investigated iron bioavailability using the hemoglobin repletion test. Aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen levels were determined to evaluate the effect on liver and kidney functions. Protein carbonyls were measured to assess oxidative damage to proteins. Fecal samples at the end of the 14 day repletion period were used for 16S rRNA sequencing for gut microbiota analysis. The slope ratio method using a common intercept linear regression model was used to compare the bioavailability of ASP to FeSO 4 . Iron repletion increased hemoglobin concentrations with both ASP and FeSO 4 treatments compared to the control group, except in the lowest ASP group. The slope ratio indicated that relative iron bioavailability of ASP was 60% of that of FeSO 4 when hemoglobin change was compared to iron in the diet. Similar results were obtained when absolute iron intake was compared on the basis of food consumption. In comparison to the control, protein carbonyl concentrations were significantly ( p < 0.05) higher in the FeSO 4 group but not with the ASP group. Supplementation with both sources of iron reduced the Enterobacteriaceae population in the gut microbiota of the rats. A higher relative abundance of bacteria from the phylum Verrucomicrobia was also observed with the highest dose of ASP. Iron-enriched A. oryzae with 60% relative bioavailability of FeSO 4 did not show any signs of adverse effects after 14 days of iron supplementation. Future human studies are needed to understand the ASP detailed effect on gut microbiota.

Metabolism of aspartame by human and pig intestinal microvillar peptidases.

PubMed Central

Hooper, N M; Hesp, R J; Tieku, S

1994-01-01

The artificial sweetener aspartame (N-L-alpha-aspartyl-L-phenyl-alanine-1-methyl ester; Nutrasweet), its decomposition product alpha Asp-Phe and the related peptide alpha Asp-PheNH2 were rapidly hydrolysed by microvillar membranes prepared from human duodenum, jejunum and ileum, and from pig duodenum and kidney. The metabolism of aspartame by the human and pig intestinal microvillar membrane preparations was inhibited significantly (> 78%) by amastatin or 1,10-phenanthroline, and partially (> 38%) by actinonin or bestatin, and was activated 2.9-4.5-fold by CaCl2. The inhibition by amastatin and 1,10-phenanthroline, and the activation by CaCl2 are characteristic of the cell-surface ectoenzyme aminopeptidase A (EC 3.4.11.7) and a purified preparation of this enzyme hydrolysed aspartame with a Km of 0.25 mM and a Vmax of 126 mumol/min per mg. A purified preparation of aminopeptidase W (EC 3.4.11.16) also hydrolysed aspartame but with a Km of 4.96 mM and a Vmax of 110 mumol/min per mg. However, rentiapril, an inhibitor of aminopeptidase W, caused only slight inhibition (maximally 19%) of the hydrolysis of aspartame by the microvillar membrane preparations. Similar patterns of inhibition and kinetic parameters were observed for alpha Asp-Phe and alpha Asp-PheNH2. Two other decomposition products of aspartame, beta Asp-PheMe and cyclo-Asp-Phe, were essentially resistant to hydrolysis by both the human and pig intestinal microvillar membrane preparations and the purified preparations of aminopeptidases A and W. Although the relatively selective inhibitor of aminopeptidase N (EC 3.4.11.2), actinonin, partially inhibited the metabolism of aspartame, alpha Asp-Phe and alpha Asp-PheNH2 by the human and pig intestinal microvillar membrane preparations, these peptides were not hydrolysed by a purified preparation of aminopeptidase N. Membrane dipeptidase (EC 3.4.13.19) only hydrolysed the unblocked dipeptide, alpha Asp-Phe, but the selective inhibitor of this enzyme, cilastatin, did not block the metabolism of alpha Asp-Phe by the microvillar membrane preparations. PMID:8141778

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

PubMed Central

Gul, Sarah S.; Hamilton, A. Rebecca L.; Munoz, Alexander R.; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K.; Economopoulos, Konstantinos P.; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R.; Hodin, Richard A.

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks. PMID:27997218

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

PubMed

Gul, Sarah S; Hamilton, A Rebecca L; Munoz, Alexander R; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K; Economopoulos, Konstantinos P; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R; Hodin, Richard A

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period.

PubMed

Saleh, J; Summers, L K; Cianflone, K; Fielding, B A; Sniderman, A D; Frayn, K N

1998-04-01

The objective of this study was to determine whether Acylation Stimulating Protein (ASP) is generated in vivo by human adipose tissue during the postprandial period. After a fat meal, samples from 12 subjects were obtained (up to 6 h) from an arterialized hand vein and an anterior abdominal wall vein that drains adipose tissue. Veno-arterial (V-A) gradients across the subcutaneous adipose tissue bed were calculated. The data demonstrate that ASP is produced in vivo (positive V-A gradient) With maximal production at 3-5 h postprandially. The plasma triacylglycerol (TAG) clearance was evidenced by a negative V-A gradient. It increased substantially after 3 h and remained prominent until the final time point. There was, therefore, a close temporal coordination between ASP generation and TAG clearance. In contrast, plasma insulin and non-esterified fatty acid (NEFA) had an early (1-2 h) postprandial change. Fatty acid incorporation into adipose tissue (FIAT) was calculated from V-A glycerol and non-esterified fatty acid (NEFA) differences postprandially. FIAT was negative during the first hour, implying net fat mobilization. FIAT then became increasingly positive, implying net fat deposition, and overall followed the same time course as ASP and TAG clearance. There was a direct positive correlation between total ASP production and total FIAT (r = 0.566, P < 0.05). These data demonstrate that ASP is generated in vivo by human adipocytes and that this process is accentuated postprandially, supporting the concept that ASP plays an important role in clearance of TAG from plasma and fatty acid storage in adipose tissue.

Role of C-Terminal Cysteine Residues of Aspergillus fumigatus Allergen Asp f 4 in Immunoglobulin E Binding

PubMed Central

Ramachandran, Harikrishnan; Banerjee, Banani; Greenberger, Paul A.; Kelly, Kevin J.; Fink, Jordan N.; Kurup, Viswanath P.

2004-01-01

Among the several allergens cloned and expressed from Aspergillus fumigatus, Asp f 4 is a major one associated with allergic bronchopulmonary aspergillosis (ABPA). The structure-function relationship of allergens is important in understanding the immunopathogenesis, diagnosis, and treatment of allergic diseases. These include the epitopes, conformational or linear, deletion of the N or C terminus or both N and C termini, and glycosylation or nonglycosylation, all of which affect immune responses. Similarly, the role of cysteine residues present in allergens may yield useful information regarding the conformational structure of allergens and the immunoglobulin E (IgE) epitope interaction. Such information may help in developing new strategies towards immunotherapy. In order to define the role of cysteine in the interaction of the antibody with Asp f 4, we have constructed mutants by selectively deleting cysteine residues from the C-terminal region of the Asp f 4. Immunological evaluation of these engineered recombinant constructs was conducted by using sera from patients with ABPA, Aspergillus skin test-positive asthmatics, and healthy controls. The results demonstrate strong IgE binding with Asp f 4 and two truncated mutants, Asp f 41-234 (amino acids [aa] 1 to 234) and Asp f 41-241 (aa 1 to 241), while another mutant, Asp f 41-196 (aa 1 to 196), showed reactivity with fewer patients. The result suggests that deletion of cysteines and the alteration of IgE epitopes at the C-terminal end resulted in conformational changes, which may have a potential role in the immunomodulation of the disease. PMID:15013973

Implementation of an ASP model offsite backup archive for clinical images utilizing Internet 2

NASA Astrophysics Data System (ADS)

Liu, Brent J.; Chao, Sander S.; Documet, Jorge; Lee, Jasper; Lee, Michael; Topic, Ian; Williams, Lanita

2005-04-01

With the development of PACS technology and an increasing demand by medical facilities to become filmless, there is a need for a fast and efficient method of providing data backup for disaster recovery and downtime scenarios. At the Image Processing Informatics Lab (IPI), an ASP Backup Archive was developed using a fault-tolerant server with a T1 connection to serve the PACS at the St. John's Health Center (SJHC) Santa Monica, California. The ASP archive server has been in clinical operation for more than 18 months, and its performance was presented at this SPIE Conference last year. This paper extends the ASP Backup Archive to serve the PACS at the USC Healthcare Consultation Center II (HCC2) utilizing an Internet2 connection. HCC2 is a new outpatient facility that recently opened in April 2004. The Internet2 connectivity between USC's HCC2 and IPI has been established for over one year. There are two novelties of the current ASP model: 1) Use of Internet2 for daily clinical operation, and 2) Modifying the existing backup archive to handle two sites in the ASP model. This paper presents the evaluation of the ASP Backup Archive based on the following two criteria: 1) Reliability and performance of the Internet2 connection between HCC2 and IPI using DICOM image transfer in a clinical environment, and 2) Ability of the ASP Fault-Tolerant backup archive to support two separate clinical PACS sites simultaneously. The performances of using T1 and Internet2 at the two different sites are also compared.

Microarray analysis sheds light on the dedifferentiating role of agouti signal protein in murine melanocytes via the Mc1r

PubMed Central

Le Pape, Elodie; Passeron, Thierry; Giubellino, Alessio; Valencia, Julio C.; Wolber, Rainer; Hearing, Vincent J.

2009-01-01

The melanocortin-1 receptor (MC1R) is a key regulator of pigmentation in mammals and is tightly linked to an increased risk of skin cancers, including melanoma, in humans. Physiologically activated by α-melanocyte stimulating hormone (αMSH), MC1R function can be antagonized by a secreted factor, agouti signal protein (ASP), which is responsible for the lighter phenotypes in mammals (including humans), and is also associated with increased risk of skin cancer. It is therefore of great interest to characterize the molecular effects elicited by those MC1R ligands. In this study, we determined the gene expression profiles of murine melan-a melanocytes treated with ASP or αMSH over a 4-day time course using genome-wide oligonucleotide microarrays. As expected, there were significant reductions in expression of numerous melanogenic proteins elicited by ASP, which correlates with its inhibition of pigmentation. ASP also unexpectedly modulated the expression of genes involved in various other cellular pathways, including glutathione synthesis and redox metabolism. Many genes up-regulated by ASP are involved in morphogenesis (especially in nervous system development), cell adhesion, and extracellular matrix-receptor interactions. Concomitantly, ASP enhanced the migratory potential and the invasiveness of melanocytic cells in vitro. These results demonstrate the role of ASP in the dedifferentiation of melanocytes, identify pigment-related genes targeted by ASP and by αMSH, and provide insights into the pleiotropic molecular effects of MC1R signaling that may function during development and may affect skin cancer risk. PMID:19174519

Egypt: Background and U.S. Relations

DTIC Science & Technology

2007-12-12

additional contributions from Germany , Japan, and Switzerland. For more information on the MFO, see [http://www.mfo.org/Default.asp?bhcp=1]. On the...and deregulation between 2006 and 2007 ranked first worldwide. In recent years, the state has reinvigorated its privatization program by divesting...shares in the state-dominated banking and insurance sectors. Additionally, the government removed import service fees and surcharges and reduced the

Egypt: Background and U.S. Relations

DTIC Science & Technology

2009-05-12

contributions from Germany , Japan, and Switzerland. For more information on the MFO, see http://www.mfo.org/Default.asp?bhcp=1. Egypt: Background and...2008 Report, Egypt’s pace of business reforms and deregulation between 2006 and 2007 ranked first worldwide. In recent years, the state has...reinvigorated its privatization program by divesting shares in the state-dominated banking and insurance sectors. Additionally, the government removed import

Turbulence Characterization and Control

DTIC Science & Technology

1976-06-01

INSTRUMENTATION 2. 1 Real-Time Data Processing System 2. 2 Routine Meteorological Sensors 2. 3 Microthermal Sensors 2.4 Seeing Monitor 2. 5...Meteorological Tower l8 2-4 Fat Wire Microthermal Probe, Partially Disassembled to 19 Show Integral Electronics 2-5 ASP/SM Combination Shown Mounted...section. 1. 2 PROGRAM STATUS As of the date of this report, the status of the experimental systems are as follows: • Microthermal and

Effects of a Classwide Teacher-Implemented Program to Promote Preschooler Compliance

ERIC Educational Resources Information Center

Beaulieu, Lauren; Hanley, Gregory P.

2014-01-01

We used a multiple baseline design across skills to evaluate the effects of a program to teach a classroom of children to respond to their name and a group call (i.e., precursors) as well as to peer mediate these precursors to promote compliance with a variety of multistep instructions. Teachers taught these skills via classwide behavior skills…

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2013 CFR

2013-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2014 CFR

2014-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

26 CFR 51.4T - Information provided by the agencies (temporary).

Code of Federal Regulations, 2012 CFR

2012-04-01

... sales price (ASP) for each Healthcare Common Procedure Coding System (HCPCS) code for the sales year...IdentifiableDataFiles/03_PartBNationalSummaryDataFile.asp to obtain the number of allowed billing units per... respective NDCs) manufactured by a single entity, CMS will multiply the annual weighted ASP by the total...

75 FR 57271 - Creating an Offshore Wind Industry in the United States: A National Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-20

... Webinar is available at: http://www.windpoweringamerica.gov/filter_detail.asp?itemid=2817 . Information on the September 21 seminar is available at: http://www.windpoweringamerica.gov/filter_detail.asp?itemid.../filter_detail.asp?itemid=2820 . Disclaimer DOE will not reimburse costs associated with participation in...

Impact of magnetic isolation on pointing system performance in the presence of structural flexibility

NASA Technical Reports Server (NTRS)

Seller, J.

1985-01-01

The inertial pointing stability of a gimbal pointing system (AGS) was compared with a magnetic pointing/gimbal followup system (ASPS), under certain conditions of system structural flexibility and disturbance inputs from the gimbal support structure. Separate 3 degree-of-freedom (3DOF) linear models based on NASTRAN modal flexibility data for the gimbal and support structures were generated for the ASPS configurations. Using the models inertial pointing control loops providing 6dB of gain margin and 45 deg of phase margin were defined for each configuration. The pointing loop bandwidth obtained for the ASPS is more than twice the level achieved for the AGS configuration. The AGS limit is attributed to the gimbal and support structure flexibility. As a result of the higher ASPS pointing loop bandwidth and the disturbance rejection provided by the magnetic isolation ASPS pointing performane is significantly better than that of the AGS system. The low frequency peak of the ASPS transfer function from base disturbance to payload angular motion is almost 60dB lower than AGS low frequency peak.

Prooxidative effects of aspartame on antioxidant defense status in erythrocytes of rats.

PubMed

Prokic, Marko D; Paunovic, Milica G; Matic, Milos M; Djordjevic, Natasa Z; Ognjanovic, Branka I; Stajn, Andras S; Saicic, Zorica S

2014-12-01

Since aspartame (L-aspartyl-L-phenylalanine methyl ester, ASP) is one of the most widely used artificial sweeteners, the aim of the present study was to investigate its effects on serum glucose and lipid levels as well as its effects on oxidative/antioxidative status in erythrocytes of rats. The experiment included two groups of animals: the control group was administered with water only, while the experimental group was orally administered with ASP (40 mg/kg b.w.) daily, for a period of six weeks. When compared with the control group, the group administrated with ASP indicated higher values of serum glucose, cholesterol and triglycerides. Significantly increased concentrations of superoxide anion (O2 .-), hydrogen peroxide (H2O2), peroxynitrite (?N??-) and lipid peroxides (LPO) were recorded in the erythrocytes of ASP treated group in comparison to the control group. In the course of chronic ASP administration, the following was observed: the concentration of reduced glutathione (GSH) and the activity of catalase (CAT) increased. Thus, these findings suggest that long-term consumption of ASP leads to hyperglycemia and hyperlipidemia, as well as to oxidative stress in erythrocytes.

Gender differences in D-aspartic acid content in skull bone.

PubMed

Torikoshi-Hatano, Aiko; Namera, Akira; Shiraishi, Hiroaki; Arima, Yousuke; Toubou, Hirokazu; Ezaki, Jiro; Morikawa, Masami; Nagao, Masataka

2012-12-01

In forensic medicine, the personal identification of cadavers is one of the most important tasks. One method of estimating age at death relies on the high correlation between racemization rates in teeth and actual age, and this method has been applied successfully in forensic odontology for several years. In this study, we attempt to facilitate the analysis of racemized amino acids and examine the determination of age at death on the basis of the extent of aspartic acid (Asp) racemization in skull bones. The specimens were obtained from 61 human skull bones (19 females and 42 males) that underwent judicial autopsy from October 2010 to May 2012. The amount of D-Asp and L-Asp, total protein, osteocalcin, and collagen I in the skull bones was measured. Logistic regression analysis was performed for age, sex, and each measured protein. The amount of D-Asp in the female skull bones was significantly different from that in the male skull bones (p = 0.021), whereas the amount of L-Asp was similar. Thus, our study indicates that the amount of D-Asp in skull bones is different between the sexes.

Molecular Mechanisms Elicited by d-Aspartate in Leydig Cells and Spermatogonia

PubMed Central

Di Fiore, Maria Maddalena; Santillo, Alessandra; Falvo, Sara; Longobardi, Salvatore; Chieffi Baccari, Gabriella

2016-01-01

A bulk of evidence suggests that d-aspartate (d-Asp) regulates steroidogenesis and spermatogenesis in vertebrate testes. This review article focuses on intracellular signaling mechanisms elicited by d-Asp possibly via binding to the N-methyl-d-aspartate receptor (NMDAR) in both Leydig cells, and spermatogonia. In Leydig cells, the amino acid upregulates androgen production by eliciting the adenylate cyclase-cAMP and/or mitogen-activated protein kinase (MAPK) pathways. d-Asp treatment enhances gene and protein expression of enzymes involved in the steroidogenic cascade. d-Asp also directly affects spermatogonial mitotic activity. In spermatogonial GC-1 cells, d-Asp induces phosphorylation of MAPK and AKT serine-threonine kinase proteins, and stimulates expression of proliferating cell nuclear antigen (PCNA) and aurora kinase B (AURKB). Further stimulation of spermatogonial GC-1 cell proliferation might come from estradiol/estrogen receptor β (ESR2) interaction. d-Asp modulates androgen and estrogen levels as well as the expression of their receptors in the rat epididymis by acting on mRNA levels of Srd5a1 and Cyp19a1 enzymes, hence suggesting involvement in spermatozoa maturation. PMID:27428949

Quantitative separation of murine leukemia virus proteins by reversed-phase high-pressure liquid chromatography reveals newly described gag and env cleavage products.

PubMed Central

Henderson, L E; Sowder, R; Copeland, T D; Smythers, G; Oroszlan, S

1984-01-01

The structural proteins of murine type C retroviruses are proteolytic cleavage products of two different precursor polyproteins coded by the viral gag and env genes. To further investigate the nature and number of proteolytic cleavages involved in virus maturation, we quantitatively isolated the structural proteins of the Rauscher and Moloney strains of type C murine leukemia virus (R-MuLV and M-MuLV, respectively) by reversed-phase high-pressure liquid chromatography. Proteins and polypeptides isolated from R-MuLV included p10, p12, p15, p30, p15(E), gp69, and gp71 and three previously undescribed virus components designated here as p10', p2(E), and p2(E). Homologous proteins and polypeptides were isolated from M-MuLV. Complete or partial amino acid sequences of all the proteins listed above were either determined in this study or were available in previous reports from this laboratory. These data were compared with those from the translation of the M-MuLV proviral DNA sequence (Shinnick et al., Nature [London] 293:543-548, 1981) to determine the exact nature of proteolytic cleavages for all the structural proteins described above and to determine the origin of p10' and p2(E)s. The results showed that, during proteolytic processing of gp80env from M-MuLV (M-gp 80env), a single Arg residue was excised between gp70 and p15(E) and a single peptide bond was cleaved between p15(E) and p2(E). The structure of M-gPr80env is gp70-(Arg)-p15(E)-p2(E). The data suggest that proteolytic cleavage sites in R-gp85env are identical to corresponding cleavage sites in M-gp80env. The p2(E)s are shown to be different genetic variants of p2(E) present in the uncloned-virus preparations. The data for R- and M-p10's shows that they are cleavage products of the gag precursor with the structure p10-Thr-Leu-Asp-Asp-OH. The complete structure of Pr65gag is p15-p12-p30-p10'. Stoichiometries of the gag and env cleavage products in mature R- and M-MuLV were determined. In each virus, gag cleavage products (p15, p12, p30, and p10 plus p10') were found in equimolar amounts and p15(E)s were equimolar with p2(E)s. The stoichiometry of gag to env cleavage products was 4:1. These data are consistent with the proposal that proteolytic processing of precursor polyproteins occurs after virus assembly and that the C-terminal portion of Pr15(E) [i.e., p15(E)-p2(E)] is located on the inner side of the lipid bilayer of the virus. Images PMID:6333515

Precursors and adjuncts of a lunar base

NASA Technical Reports Server (NTRS)

Burke, J. D.

1988-01-01

The automated, teleoperated, robotic and human-tended subsystems which will precede and accompany a lunar base program are discussed. The information about lunar conditions that can be provided by such precursors and adjuncts is addressed. The use of precursors and adjuncts for communications and navigation, for safety and survival, for lunar archives, and for entertainment and leisure is examined.

A fluorescently labeled undecapeptide derived from a protein in royal jelly of the honeybee-royalisin-for specific detection of oxidized low-density lipoprotein.

PubMed

Sato, Akira; Unuma, Hiroto; Yamazaki, Yoji; Ebina, Keiichi

2018-06-01

The probes for detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to facilitate the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that a heptapeptide (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled through the ε-amino group of N-terminal Lys to fluorescein isothiocyanate (FITC), (FITC)KP6, can be useful as a fluorescent probe for specific detection of ox-LDL. In the present study, to develop a novel fluorescent peptide for specific detection of ox-LDL, we investigated the interaction (with ox-LDL) of an undecapeptide corresponding to positions 41 to 51 of a potent antimicrobial protein (royalisin, which consists of 51 residues; from royal jelly of honeybees), conjugated at the N-terminus to FITC in the presence of 6-amino-n-caproic acid (AC) linker, (FITC-AC)-royalisin P11, which contains both sequences, Phe-Lys-Asp and Asp-Lys-Tyr, similar to Tyr-Lys-Asp in (FITC)KP6. The (FITC-AC)-royalisin P11 bound with high specificity to ox-LDL in a dose-dependent manner, through the binding to major lipid components in ox-LDL (lysophosphatidylcholine and oxidized phosphatidylcholine). In contrast, a (FITC-AC)-shuffled royalisin P11 peptide, in which sequences Phe-Lys-Asp and Asp-Lys-Tyr were modified to Lys-Phe-Asp and Asp-Tyr-Lys, respectively, hardly bound to LDL and ox-LDL. These findings strongly suggest that (FITC-AC)-royalisin P11 may be an effective fluorescent probe for specific detection of ox-LDL and that royalisin from the royal jelly of honeybees may play a role in the treatment of atherosclerosis through the specific binding of the region at positions 41 to 51 to ox-LDL. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

The glutaminase activity of l-asparaginase is not required for anticancer activity against ASNS-negative cells

PubMed Central

Chan, Wai Kin; Lorenzi, Philip L.; Anishkin, Andriy; Purwaha, Preeti; Rogers, David M.; Sukharev, Sergei; Rempe, Susan B.; Weinstein, John N.

2014-01-01

l-Asparaginase (l-ASP) is a key component of therapy for acute lymphoblastic leukemia. Its mechanism of action, however, is still poorly understood, in part because of its dual asparaginase and glutaminase activities. Here, we show that l-ASP’s glutaminase activity is not always required for the enzyme’s anticancer effect. We first used molecular dynamics simulations of the clinically standard Escherichia coli l-ASP to predict what mutated forms could be engineered to retain activity against asparagine but not glutamine. Dynamic mapping of enzyme substrate contacts identified Q59 as a promising mutagenesis target for that purpose. Saturation mutagenesis followed by enzymatic screening identified Q59L as a variant that retains asparaginase activity but shows undetectable glutaminase activity. Unlike wild-type l-ASP, Q59L is inactive against cancer cells that express measurable asparagine synthetase (ASNS). Q59L is potently active, however, against ASNS-negative cells. Those observations indicate that the glutaminase activity of l-ASP is necessary for anticancer activity against ASNS-positive cell types but not ASNS-negative cell types. Because the clinical toxicity of l-ASP is thought to stem from its glutaminase activity, these findings suggest the hypothesis that glutaminase-negative variants of l-ASP would provide larger therapeutic indices than wild-type l-ASP for ASNS-negative cancers. PMID:24659632

Comparison of laboratory-scale thermophilic biofilm and activated sludge processes integrated with a mesophilic activated sludge process.

PubMed

Suvilampi, J; Lehtomäki, A; Rintala, J

2003-07-01

A combined thermophilic-mesophilic wastewater treatment was studied using a laboratory-scale thermophilic activated sludge process (ASP) followed by mesophilic ASP or a thermophilic suspended carrier biofilm process (SCBP) followed by mesophilic ASP, both systems treating diluted molasses (dilution factor 1:500 corresponding GF/A-filtered COD (COD(filt)) of 1900+/-190 mgl(-1)). With hydraulic retention times (HRTs) of 12-18 h the thermophilic ASP and thermophilic SCBP removed 60+/-13% and 62+/-7% of COD(filt), respectively, with HRT of 8 h the removals were 48+/-1% and 69+/-4%. The sludge volume index (SVI) was notably lower in the thermophilic SCBP (measured from suspended sludge) than in the thermophilic ASP. Under the lowest HRT the mesophilic ASP gave better performance (as SVI, COD(filt), and COD(tot) removals) after the thermophilic SCBP than after the thermophilic ASP. Measured sludge yields were low (less than 0.1 kg suspended solids (SS) kg COD(filt removed)(-1)) in all processes. Both thermophilic treatments removed 80-85% of soluble COD (COD(sol)) whereas suspended COD (COD(susp)) and colloidal COD (COD(col)) were increased. Both mesophilic post-treatments removed all COD(col) and most of the COD(susp) from the thermophilic effluents. In conclusion, combined thermophilic-mesophilic treatment appeared to be easily operable and produced high effluent quality.

Variants in Several Genomic Regions Associated with Asperger Disorder

PubMed Central

Salyakina, D.; Ma, D.Q.; Jaworski, J.M.; Konidari, I.; Whitehead, P.L.; Henson, R.; Martinez, D.; Robinson, J.L.; Sacharow, S.; Wright, H.H.; Abramson, R.K.; Gilbert, J.R.; Cuccaro, M.L.; Pericak-Vance, M.A.

2010-01-01

Asperger disorder (ASP) is one of the autism spectrum disorders (ASD) and is differentiated from autism largely on the absence of clinically significant cognitive and language delays. Analysis of a homogenous subset of families with ASP may help to address the corresponding effect of genetic heterogeneity on identifying ASD genetic risk factors. To examine the hypothesis that common variation is important in ASD, we performed a genome-wide association study (GWAS) in 124 ASP families in a discovery data set and 110 ASP families in a validation data set. We prioritized the top 100 association results from both cohorts by employing a ranking strategy. Novel regions on 5q21.1 (P = 9.7 × 10−7) and 15q22.1–q22.2 (P = 7.3 × 10−6) were our most significant findings in the combined data set. Three chromosomal regions showing association, 3p14.2 (P = 3.6 × 10−6), 3q25–26 (P = 6.0 × 10−5) and 3p23 (P = 3.3 × 10−4) overlapped linkage regions reported in Finnish ASP families, and eight association regions overlapped ASD linkage areas. Our findings suggest that ASP shares both ASD-related genetic risk factors, as well as has genetic risk factors unique to the ASP phenotype. PMID:21182207

77 FR 16113 - ASP Ventures Corp., Order of Suspension of Trading

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... SECURITIES AND EXCHANGE COMMISSION [File No. 500-1] ASP Ventures Corp., Order of Suspension of Trading March 15, 2012. It appears to the Securities and Exchange Commission that there is a lack of current and accurate information concerning the securities of ASP Ventures Corp. because it has not filed any periodic reports since the period ended...

Brief Report: Insight into Illness and Social Attributional Style in Asperger's Syndrome

ERIC Educational Resources Information Center

Didehbani, Nyaz; Shad, Mujeeb U.; Kandalaft, Michelle R.; Allen, Tandra T.; Tamminga, Carol A.; Krawczyk, Daniel C.; Chapman, Sandra B.

2012-01-01

A number of psychiatric illnesses have been recognized to have some level of insight deficits, including developmental disorders, such as Asperger's Syndrome (ASP). However insight into illness has not been empirically investigated in ASP and little research has examined how individuals with ASP view their deficits. This is the first study to…

An Evaluation of μ-Opioid Receptor (OPRM1) as a Predictor of Naltrexone Response in the Treatment of Alcohol Dependence

PubMed Central

Anton, Raymond F.; Oroszi, Gabor; O'Malley, Stephanie; Couper, David; Swift, Robert; Pettinati, Helen; Goldman, David

2008-01-01

Context: Naltrexone hydrochloride treatment for alcohol dependence works for some individuals but not for everyone. Asn40Asp, a functional polymorphism of the μ-opioid receptor gene (OPRM1), might predict naltrexone response. Objective: To evaluate whether individuals with alcoholism who are heterozygous (Asp40/Asn40) or homozygous (Asp40/Asp40) for the OPRM1 Asp40 allele respond better to naltrexone. Design: Pharmacogenetic analysis conducted between January 1, 2001, and January 31, 2004. Setting: Eleven academic sites in the COMBINE Study. Participants: Recently abstinent volunteers who met all 3 of the following conditions: (1) DSM-IV criteria for primary alcohol dependence; (2) participation in the COMBINE Study; and (3) availability of DNA. Interventions: Alcoholic subjects were treated for 16 weeks with 100 mg of naltrexone hydrochloride (234 Asn40 homozygotes and 67 with at least 1 copy of the Asp40 allele) or placebo (235 Asn40 homozygotes and 68 with at least 1 copy of the Asp40 allele). All participants received medical management (MM) alone or with combined behavioral intervention (CBI). Main Outcome Measures: Time trends in percentage of days abstinent, percentage of heavy drinking days, and rates of good clinical outcome. Results: Alcoholic subjects with an Asp40 allele receiving MM alone (no CBI) had an increased percentage of days abstinent (P=.07) and a decreased percentage of heavy drinking days (P=.04) if treated with naltrexone vs placebo, while those with the Asn40/Asn40 genotype showed no medication differences. If treated with MM alone and naltrexone, 87.1% of Asp40 carriers had a good clinical outcome, compared with only 54.8% of individuals with the Asn40/Asn40 genotype (odds ratio, 5.75; confidence interval, 1.88-17.54), while, if treated with placebo, 48.6% of Asp40 carriers and 54.0% of individuals with the Asn40/Asn40 genotype had a good clinical outcome (interaction between medication and genotype, P=.005). No gene×medication interactions were observed in those treated with both MM and CBI. Conclusions: These results confirm and extend the observation that the functionally significant OPRM1 Asp40 allele predicts naltrexone treatment response in alcoholic individuals. This relationship might be obscured, however, by other efficacious treatments. OPRM1 geno-typing in alcoholic individuals might be useful to assist in selecting treatment options. PMID:18250251

The Bacillus subtilis and Bacillus halodurans Aspartyl-tRNA Synthetases Retain Recognition of tRNA(Asn).

PubMed

Nair, Nilendra; Raff, Hannah; Islam, Mohammed Tarek; Feen, Melanie; Garofalo, Denise M; Sheppard, Kelly

2016-02-13

Synthesis of asparaginyl-tRNA (Asn-tRNA(Asn)) in bacteria can be formed either by directly ligating Asn to tRNA(Asn) using an asparaginyl-tRNA synthetase (AsnRS) or by synthesizing Asn on the tRNA. In the latter two-step indirect pathway, a non-discriminating aspartyl-tRNA synthetase (ND-AspRS) attaches Asp to tRNA(Asn) and the amidotransferase GatCAB transamidates the Asp to Asn on the tRNA. GatCAB can be similarly used for Gln-tRNA(Gln) formation. Most bacteria are predicted to use only one route for Asn-tRNA(Asn) formation. Given that Bacillus halodurans and Bacillus subtilis encode AsnRS for Asn-tRNA(Asn) formation and Asn synthetases to synthesize Asn and GatCAB for Gln-tRNA(Gln) synthesis, their AspRS enzymes were thought to be specific for tRNA(Asp). However, we demonstrate that the AspRSs are non-discriminating and can be used with GatCAB to synthesize Asn. The results explain why B. subtilis with its Asn synthetase genes knocked out is still an Asn prototroph. Our phylogenetic analysis suggests that this may be common among Firmicutes and 30% of all bacteria. In addition, the phylogeny revealed that discrimination toward tRNA(Asp) by AspRS has evolved independently multiple times. The retention of the indirect pathway in B. subtilis and B. halodurans likely reflects the ancient link between Asn biosynthesis and its use in translation that enabled Asn to be added to the genetic code. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Neuroprotective and Ameliorating Impacts of Omega-3 Against Aspartame-induced Neuronal and Astrocytic Degeneration.

PubMed

Ali, Eyad M T; Sonpol, Hany M A

2017-07-01

Aspartame (ASP) is one of the commonest artificial sweetener used all over the world and considered as an extremely risky compound and raises a lot of controversy. Therefore, this study was designed to investigate cellular damage of the anterior horn cells in the spinal cord of albino male rats and the possibility of hindering these changes by using omega-3 (OM3).Thirty seven adult male albino rats were divided into three groups: Control, ASP-treated and ASP + OM3-treated groups. Spinal cord sections were prepared and stained with Hx&E, caspase-3 and GFAP immunostaining. All data were morphometrically and statistically analyzed. In ASP-treated group, the cell body of some degenerated neurons was swollen and its cytoplasm was vacuolated. Their nuclei were eccentric and pyknotic. Moreover, other neurons were of a heterogeneous pattern in the form of cell body shrinkage, loss of Nissl substance, intensely stained eosinophilic cytoplasm and a small darkly stained nucleus that may eventually fragment. However, the cells were apparently normal in ASP+ OM3-treated group. Strong +ve caspase-3 stained neurons were detected in ASP-treated group. Furthermore, the immunoreaction was faint on treating the rats with both ASP and OM3. Few number of +ve GFAP- stained astrocytes were observed in ASP-treated rats. On the other hand, the immunoreactivity for GFAP was found to be intense in the ASP + OM3-treated group. Additionally, there was a significant decrease in the surface area percentage of the +ve GFAP-stained astrocytes of the ASP-treated group compared to the control and the ASP + OM3-treated groups. Anat Rec, 300:1290-1298, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

ASP-G: an ASP-based method for finding attractors in genetic regulatory networks

PubMed Central

Mushthofa, Mushthofa; Torres, Gustavo; Van de Peer, Yves; Marchal, Kathleen; De Cock, Martine

2014-01-01

Motivation: Boolean network models are suitable to simulate GRNs in the absence of detailed kinetic information. However, reducing the biological reality implies making assumptions on how genes interact (interaction rules) and how their state is updated during the simulation (update scheme). The exact choice of the assumptions largely determines the outcome of the simulations. In most cases, however, the biologically correct assumptions are unknown. An ideal simulation thus implies testing different rules and schemes to determine those that best capture an observed biological phenomenon. This is not trivial because most current methods to simulate Boolean network models of GRNs and to compute their attractors impose specific assumptions that cannot be easily altered, as they are built into the system. Results: To allow for a more flexible simulation framework, we developed ASP-G. We show the correctness of ASP-G in simulating Boolean network models and obtaining attractors under different assumptions by successfully recapitulating the detection of attractors of previously published studies. We also provide an example of how performing simulation of network models under different settings help determine the assumptions under which a certain conclusion holds. The main added value of ASP-G is in its modularity and declarativity, making it more flexible and less error-prone than traditional approaches. The declarative nature of ASP-G comes at the expense of being slower than the more dedicated systems but still achieves a good efficiency with respect to computational time. Availability and implementation: The source code of ASP-G is available at http://bioinformatics.intec.ugent.be/kmarchal/Supplementary_Information_Musthofa_2014/asp-g.zip. Contact: Kathleen.Marchal@UGent.be or Martine.DeCock@UGent.be Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25028722

Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway.

PubMed

Wu, Jun; Yu, Junxian; Wang, Jing; Zhang, Chenguang; Shang, Kun; Yao, Xiaojun; Cao, Bangwei

2018-04-01

Apatinib has been proved effective in the treatment of advanced gastric cancer. Traditional Chinese medicine is often considered as adjuvants which could increase the effects and counteract the side effects of chemotherapy. The present study aims to explore the antitumor effects of Astragalus polysaccharide (AsPs) in combination with Apatinib in gastric cancer AGS cells. Our results demonstrated that the expression of VEGFR-2 was observed in human gastric cancer line AGS. Both Apatinib and AsPs could significantly inhibit the proliferation of AGS cells in a dose-dependent manner and Apatinib in combination with AsPs showed enhanced inhibitory effects on cell proliferation, migration and invasion compared with Apatinib monotherapy. Moreover, there was a remarkable increase in apoptosis following Apatinib treatment which could be enhanced by the addition of AsPs. Western blotting showed that the combination of Apatinib and AsPs could inhibit the expression of phosphorylated AKT (p-AKT) and MMP-9 expression. In addition, both Apatinib alone and Apatinib in combination with AsPs induced celluar autophagy which could be attenuated by the autophagy inhibitor 3-MA. The suppression of autophagy leaded to further apoptosis induction and cell proliferation suppression. In conclusion, the current study showed AsPs enhanced antitumor effects of Apatinib on AGS cells by the mechanism which includes inhibition of AKT signaling pathway. Apatinib-induced autophagy could be attenuated by 3-MA, which subsequently increased the apoptosis rate. On the basis of our study, the combination of Apatinib and AsPs could be considered as a potential candidate in the gastric cancer treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Solving Assembly Sequence Planning using Angle Modulated Simulated Kalman Filter

NASA Astrophysics Data System (ADS)

Mustapa, Ainizar; Yusof, Zulkifli Md.; Adam, Asrul; Muhammad, Badaruddin; Ibrahim, Zuwairie

2018-03-01

This paper presents an implementation of Simulated Kalman Filter (SKF) algorithm for optimizing an Assembly Sequence Planning (ASP) problem. The SKF search strategy contains three simple steps; predict-measure-estimate. The main objective of the ASP is to determine the sequence of component installation to shorten assembly time or save assembly costs. Initially, permutation sequence is generated to represent each agent. Each agent is then subjected to a precedence matrix constraint to produce feasible assembly sequence. Next, the Angle Modulated SKF (AMSKF) is proposed for solving ASP problem. The main idea of the angle modulated approach in solving combinatorial optimization problem is to use a function, g(x), to create a continuous signal. The performance of the proposed AMSKF is compared against previous works in solving ASP by applying BGSA, BPSO, and MSPSO. Using a case study of ASP, the results show that AMSKF outperformed all the algorithms in obtaining the best solution.

Molecular dynamics simulation study reveals potential substrate entry path into γ-secretase/presenilin-1.

PubMed

Kong, Ren; Chang, Shan; Xia, Weiming; Wong, Stephen T C

2015-08-01

Presenilin 1 (PS1) is the catalytic unit of γ-secretase which cleaves more than one hundred substrates. Among them, amyloid precursor protein (APP) and Notch are notable for their pivotal role in the pathogenesis of Alzheimer's disease (AD) and certain types of cancer. The hydrolysis process occurring inside the hydrophobic lipid bilayer remains unclear. With the aim to understand the mechanism of intramembrane proteolysis by γ-secretase, we constructed a homology model of human PS1 and performed molecular dynamics simulation in explicit membrane phospholipids with different components. During the simulation, TM9 was found to exhibit a high level of flexibility that involved in "gate-open" movement of TM2 and TM6, and thus partially exposed the catalytic residues. The highly conserved PALP motif acts as an anchor to mediate the conformation changes of TM6 induced by TM9. Moreover, direct interactions were observed between 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and the active site of γ-secretase, indicating that the lipid molecules have the potential to modulate γ-secretase by contacting with the catalytic residues, i.e., ASP 257 and ASP 385 of PS1. The intermediate states indicate a potential substrate penetration pathway through the interface of TM2 and TM6, which may be induced by changes of TM9. To our knowledge, this is the first molecular simulation study that reveals dynamic behavior of the human PS1 structure in the lipid bilayer and provides insight into the substrate entry path for subsequent intramembrane hydrolysis, which is critical information required for new strategy development of γ-secretase modulators to alleviate devastating AD. Copyright © 2015 Elsevier Inc. All rights reserved.

Structural Basis for Recognition of L-lysine, L-ornithine, and L-2,4-diamino Butyric Acid by Lysine Cyclodeaminase.

PubMed

Min, Kyungjin; Yoon, Hye-Jin; Matsuura, Atsushi; Kim, Yong Hwan; Lee, Hyung Ho

2018-04-30

L-pipecolic acid is a non-protein amino acid commonly found in plants, animals, and microorganisms. It is a well-known precursor to numerous microbial secondary metabolites and pharmaceuticals, including anticancer agents, immunosuppressants, and several antibiotics. Lysine cyclodeaminase (LCD) catalyzes β-deamination of L-lysine into L-pipecolic acid using β-nicotinamide adenine dinucleotide as a cofactor. Expression of a human homolog of LCD, μ-crystallin, is elevated in prostate cancer patients. To understand the structural features and catalytic mechanisms of LCD, we determined the crystal structures of Streptomyces pristinaespiralis LCD (SpLCD) in (i) a binary complex with NAD + , (ii) a ternary complex with NAD + and L-pipecolic acid, (iii) a ternary complex with NAD + and L-proline, and (iv) a ternary complex with NAD + and L-2,4-diamino butyric acid. The overall structure of SpLCD was similar to that of ornithine cyclodeaminase from Pseudomonas putida . In addition, SpLCD recognized L-lysine, L-ornithine, and L-2,4-diamino butyric acid despite differences in the active site, including differences in hydrogen bonding by Asp236, which corresponds with Asp228 from Pseudomonas putida ornithine cyclodeaminase. The substrate binding pocket of SpLCD allowed substrates smaller than lysine to bind, thus enabling binding to ornithine and L-2,4-diamino butyric acid. Our structural and biochemical data facilitate a detailed understanding of substrate and product recognition, thus providing evidence for a reaction mechanism for SpLCD. The proposed mechanism is unusual in that NAD + is initially converted into NADH and then reverted back into NAD + at a late stage of the reaction.

Correlation of Specific Mutations in Line Probe Assay (LPA) and Drug Susceptibility Test (DST) with respect to Fluoroquinolone Resistance in Drug Resistant Mycobacterium tuberculosis

PubMed Central

Agrawal, Umang; Savaj, Pratik; Davda, Kanishka; Rodrigues, Camilla; Soman, Rajeev

2017-01-01

Abstract Background This study was done to investigate the utility of specific fluoroquinolone mutations in LPA in predicting the susceptibility in DST at WHO recommended Critical Concentrations of 0.5 and 2 µg/dL of moxifloxacin within a short time frame as provided by LPA. Methods In a retrospective study performed at a tertiary care hospital of Mumbai, India from October 2015 to February 2017, consecutive samples demonstrating fluoroquinolone resistance by LPA were selected. The LPA kit used was Hain Lifescience Genotype MTBDRsl (Version 1). It detects the following mutations in gyrA gene: MUT1: Ala90Val, MUT2: Ser91Pro, MUT3A: Asp94Ala, MUT3B: Asp94Asn/Tyr, MUT3C: Asp94Gly, MUT3D: Asp94His. The causal mutation was noted. For 89 of these samples, DST had been requested and results with Critical Concentration of 0.5µg/dL and 2µg/dL for moxifloxacin were available Results The 89 samples studied were as follows: Sputum (n = 60), paravertebral soft tissue (n = 2), bronchoalveolar fluid (n = 2), cerebrospinal fluid (n = 1), endotracheal tube secretion (n = 1), pleural fluid (n = 1) and site not recorded (22). 3 of these samples had double mutations. Results are as follows. Mutation in gyrA gene Number of samples (n) Susceptible at 0.5 µg/dL [n (%)] Susceptible at 2 µg/dL [n (%)] MUT1 (Ala90Val) 18 6(33.33) 16(88.89) MUT2 (Ser91Pro) 2 0(0) 1(50) MUT3A (Asp94Asn) 13 3(23.07) 11(84.61) MUT3B (Asp94Asn/Tyr) 6 1(16.67) 4(66.67) MUT3C (Asp94Gly) 51 4(8) 43(84.31) MUT3D (Asp94His) 2 0(0) 2(100) Conclusion This study showed a higher proportion of M. tuberculosis susceptibility at 2 µg/dL rather than at 0.5 µg/dL, to moxifloxacin for gyrA mutations Ala90Val (MUT1), Asp94Ala (MUT3A), Asp94Gly (MUT3C), Asp94His (MUT3D) but not for Ser91Pro (MUT2) and Asp94Asn/Tyr (MUT3B). However, the number of samples with Ser91Pro (MUT2) and Asp94Asn/Tyr (MUT3B) mutations was too small for meaningful conclusion. This susceptibility at a higher critical concentration of moxifloxacin may have clinical implications for use of high dose moxifloxacin. Since this information is available within a short time frame as provided by LPA, a more effective regimen could be devised 4 to 8 weeks earlier than after results of DST. This may result in faster sputum conversion and prevent amplification of resistance. Disclosures All authors: No reported disclosures.

Evaluating Model Parameterizations of Submicron Aerosol Scattering and Absorption with in situ Data from ARCTAS 2008

NASA Technical Reports Server (NTRS)

Alvarado, Matthew J.; Lonsdale, Chantelle R.; Macintyre, Helen L.; Bian, Huisheng; Chin, Mian; Ridley, David A.; Heald, Colette L.; Thornhill, Kenneth L.; Anderson, Bruce E.; Cubison, Michael J.;

Evaluating model parameterizations of submicron aerosol scattering and absorption with in situ data from ARCTAS 2008

NASA Astrophysics Data System (ADS)

Alvarado, Matthew J.; Lonsdale, Chantelle R.; Macintyre, Helen L.; Bian, Huisheng; Chin, Mian; Ridley, David A.; Heald, Colette L.; Thornhill, Kenneth L.; Anderson, Bruce E.; Cubison, Michael J.; Jimenez, Jose L.; Kondo, Yutaka; Sahu, Lokesh K.; Dibb, Jack E.; Wang, Chien

2016-07-01

Accurate modeling of the scattering and absorption of ultraviolet and visible radiation by aerosols is essential for accurate simulations of atmospheric chemistry and climate. Closure studies using in situ measurements of aerosol scattering and absorption can be used to evaluate and improve models of aerosol optical properties without interference from model errors in aerosol emissions, transport, chemistry, or deposition rates. Here we evaluate the ability of four externally mixed, fixed size distribution parameterizations used in global models to simulate submicron aerosol scattering and absorption at three wavelengths using in situ data gathered during the 2008 Arctic Research of the Composition of the Troposphere from Aircraft and Satellites (ARCTAS) campaign. The four models are the NASA Global Modeling Initiative (GMI) Combo model, GEOS-Chem v9-02, the baseline configuration of a version of GEOS-Chem with online radiative transfer calculations (called GC-RT), and the Optical Properties of Aerosol and Clouds (OPAC v3.1) package. We also use the ARCTAS data to perform the first evaluation of the ability of the Aerosol Simulation Program (ASP v2.1) to simulate submicron aerosol scattering and absorption when in situ data on the aerosol size distribution are used, and examine the impact of different mixing rules for black carbon (BC) on the results. We find that the GMI model tends to overestimate submicron scattering and absorption at shorter wavelengths by 10-23 %, and that GMI has smaller absolute mean biases for submicron absorption than OPAC v3.1, GEOS-Chem v9-02, or GC-RT. However, the changes to the density and refractive index of BC in GC-RT improve the simulation of submicron aerosol absorption at all wavelengths relative to GEOS-Chem v9-02. Adding a variable size distribution, as in ASP v2.1, improves model performance for scattering but not for absorption, likely due to the assumption in ASP v2.1 that BC is present at a constant mass fraction throughout the aerosol size distribution. Using a core-shell mixing rule in ASP overestimates aerosol absorption, especially for the fresh biomass burning aerosol measured in ARCTAS-B, suggesting the need for modeling the time-varying mixing states of aerosols in future versions of ASP.

Patients with Advanced, Rare Sarcoma Respond to Cediranib | Center for Cancer Research

Cancer.gov

Alveolar soft part sarcomas (ASPS) are highly vascular tumors that usually affect adolescents and young adults. Comprising less than one percent of soft tissue sarcomas, ASPS can be cured with surgery. However, its tendency to metastasize and its lack of response to standard soft tissue sarcoma chemotherapy regimens makes ASPS a particularly lethal cancer with a five-year

78 FR 60271 - Hollow Dam Power Company; Ampersand Hollow Dam Hydro, LLC; Notice of Application for Transfer of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

...Library link of Commission's Web site at http://www.ferc.gov/docs-filing/elibrary.asp . Enter the docket...) and the instructions on the Commission's Web site under http://www.ferc.gov/docs-filing/efiling.asp... system at http://www.ferc.gov/docs-filing/ecomment.asp . You must include your name and contact...

An Arabidopsis ATP-dependent, DEAD-box RNA helicase loses activity upon iosAsp formation but is restored by Protein Isoaspartyl Methltransferase

USDA-ARS?s Scientific Manuscript database

Arabidopsis thaliana PLANT RNA HELICASE75 (AtPRH75) demonstrated an ATP-dependent, RNA duplex unwinding capacity and an ATP-independent, RNA duplex reforming ability. It is known to accumulate isoAsp, but the consequences of isoAsp formation in AtPRH75 are unknown. Duplex unwinding was abolished by ...

Site-directed mutagenesis of the conserved Asp-443 and Asp-498 carboxy-terminal residues of HIV-1 reverse transcriptase.

PubMed Central

Mizrahi, V; Usdin, M T; Harington, A; Dudding, L R

1990-01-01

Substitution of the conserved Asp-443 residue of HIV-1 reverse transcriptase by asparagine specifically suppressed the ribonuclease H activity of the enzyme without affecting the reverse transcriptase activity, suggesting involvement of this ionizable residue at the ribonuclease H active site. An analogous asparagine substitution of the Asp-498 residue yielded an unstable enzyme that was difficult to enzymatically characterize. However, the instability caused by the Asn-498 mutation was relieved by the introduction of a second distal Asn-443 substitution, yielding an enzyme with wild type reverse transcriptase activity, but lacking ribonuclease H activity. Images PMID:1699202

Design of the annular suspension and pointing system /ASPS/ through decoupling and pole placement. [for Space Shuttle

NASA Technical Reports Server (NTRS)

Kuo, B. C.; Lin, W. C. W.

1980-01-01

A decoupling and pole-placement technique has been developed for the Annular Suspension and Pointing System (ASPS) of the Space Shuttle which uses bandwidths as performance criteria. The dynamics of the continuous-data ASPS allows the three degrees of freedom to be totally decoupled by state feedback through constant gains, so that the bandwidth of each degree of freedom can be independently specified without interaction. Although it is found that the digital ASPS cannot be completely decoupled, the bandwidth requirements are satisfied by pole placement and a trial-and-error method based on approximate decoupling.

Effects of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on hormonal activity and structure of the thyroid gland in hypophysectomized young chickens and old hens.

PubMed

Kuznik, B I; Pateyuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-02-01

Hypophysectomy in 5-days chickens and old hens was followed by hormonal disturbances and structural changes in the thyroid gland. Administration of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis the amino acid composition of extracts from the anterior and posterior lobes of the pituitary gland, respectively, to hypophysectomized birds for 40 days significantly reduced the degree of these changes. The normalizing effect of synthetic peptides on the concentration of thyrotrophic hormone and thyroid hormones in old hens was less pronounced than in chickens.

Structural specificity of Rn nuclease I as probed on yeast tRNA(Phe) and tRNA(Asp).

PubMed Central

Przykorska, A; el Adlouni, C; Keith, G; Szarkowski, J W; Dirheimer, G

1992-01-01

A single-strand-specific nuclease from rye germ (Rn nuclease I) was characterized as a tool for secondary and tertiary structure investigation of RNAs. To test the procedure, yeast tRNA(Phe) and tRNA(Asp) for which the tertiary structures are known, as well as the 3'-half of tRNA(Asp) were used as substrates. In tRNA(Phe) the nuclease introduced main primary cuts at positions U33 and A35 of the anticodon loop and G18 and G19 of the D loop. No primary cuts were observed within the double stranded stems. In tRNA(Asp) the main cuts occurred at positions U33, G34, U35, C36 of the anticodon loop and G18 and C20:1 positions in the D loop. No cuts were observed in the T loop in intact tRNA(Asp) but strong primary cleavages occurred at positions psi 55, C56, A57 within that loop in the absence of the tertiary interactions between T and D loops (use of 3'-half tRNA(Asp)). These results show that Rn nuclease I is specific for exposed single-stranded regions. Images PMID:1542562

Lock-and-key dimerization in dense Brownian systems of hard annular sector particles

NASA Astrophysics Data System (ADS)

Hodson, Wade D.; Mason, Thomas G.

2016-08-01

We develop a translational-rotational cage model that describes the behavior of dense two-dimensional (2D) Brownian systems of hard annular sector particles (ASPs), resembling C shapes. At high particle densities, pairs of ASPs can form mutually interdigitating lock-and-key dimers. This cage model considers either one or two mobile central ASPs which can translate and rotate within a static cage of surrounding ASPs that mimics the system's average local structure and density. By comparing with recent measurements made on dispersions of microscale lithographic ASPs [P. Y. Wang and T. G. Mason, J. Am. Chem. Soc. 137, 15308 (2015), 10.1021/jacs.5b10549], we show that mobile two-particle predictions of the probability of dimerization Pdimer, equilibrium constant K , and 2D osmotic pressure Π2 D as a function of the particle area fraction ϕA correspond closely to these experiments. By contrast, predictions based on only a single mobile particle do not agree well with either the two-particle predictions or the experimental data. Thus, we show that collective entropy can play an essential role in the behavior of dense Brownian systems composed of nontrivial hard shapes, such as ASPs.

β-Cyclodextrin inclusion complex: preparation, characterization, and its aspirin release in vitro

NASA Astrophysics Data System (ADS)

Zhou, Hui-Yun; Jiang, Ling-Juan; Zhang, Yan-Ping; Li, Jun-Bo

2012-09-01

In this work, the optimal clathration condition was investigated for the preparation of aspirin-β-cyclodextrin (Asp-β-CD) inclusion complex using design of experiment (DOE) methodology. A 3-level, 3-factor Box-Behnken design with a total of 17 experimental runs was used. The Asp-β-CD inclusion complex was prepared by saturated solution method. The influence on the embedding rate was investigated, including molar ratio of β-CD to Asp, clathration temperature and clathration time, and the optimum values of such three test variables were found to be 0.82, 49°C and 2.0 h, respectively. The embedding rate could be up to 61.19%. The formation of the bonding between -COOH group of Asp and O-H group of β-CD might play an important role in the process of clathration according to FT-IR spectra. Release kinetics of Asp from inclusion complex was studied for the evaluation of drug release mechanism and diffusion coefficients. The results showed that the drug release from matrix occurred through Fickian diffusion mechanism. The cumulative release of Asp reached only 40% over 24 h, so the inclusion complex could potentially be applied as a long-acting delivery system.

The Effect of Arthrospira platensis Capsules on CD4 T-Cells and Antioxidative Capacity in a Randomized Pilot Study of Adult Women Infected with Human Immunodeficiency Virus Not under HAART in Yaoundé, Cameroon

PubMed Central

Winter, Frank Stéphane; Emakam, Francois; Kfutwah, Anfumbom; Hermann, Johannes; Azabji-Kenfack, Marcel; Krawinkel, Michael B.

2014-01-01

Dietary supplements are often used to improve the nutritional status of people living with HIV/AIDS (PLHIV). Arthrospira platensis (Asp), also known as Spirulina, is a cyanobacterium rich in proteins and micronutrients. Cell and animal trials described immune-modulating, antiretroviral and antioxidant activities. This pilot study describes the effects of the supplementation of 5 g/day of Asp on a pre-highly-active antiretroviral therapy (pre-HAART), HIV-infected, adult female population. It was conducted as a three-month randomized controlled trial (RCT) that compared a cup supplementation of five grams/day of Asp with a placebo of equal protein content and energy. The study included 73 HIV-infected women. The immediate outcome variables were CD4 T-cells, viral load and immune activation by CD8 T-cells expressing CD38. The antioxidant status was assessed by way of the total antioxidant capacity of the serum (TAOS). The renal function was documented by way of creatinine, urea and the calculated glomerular filtration rate. Statistical analyses were carried out with non-parametric tests, and the effect size of each interaction was calculated. No differences in the immunological and virological markers between the Asp and the placebo group could be observed. In the placebo group, 21 of 30 patients (70%) developed concomitant events, while in the Asp group, only 12 of 28 patients (43%) did. Both groups registered a significant weight increase; 0.5 kg (p < 0.05) in the Asp group and 0.65 kg (p < 0.05) in the placebo group. The antioxidant capacity increase of 56 (1–98) µM for Asp was significantly different from the decrease observed in the placebo group (p < 0.001). A slight increase in the creatinine level of 0.1 g/dL (p < 0.001) was observed in the Asp group, and no effect was observed in the urea levels. The improvement of the antioxidant capacity under Asp, shown for the first time on PLHIV, could become a focus for future research on the nutritional and health effects of Spirulina. The observed slight, but significant increase of serum creatinine needs further evaluation, especially with varying doses of Asp. PMID:25057105

Dark Skies are a Universal Resource: IYA Programs on Dark Skies Awareness

NASA Astrophysics Data System (ADS)

Walker, Constance E.; Bueter, C.; Pompea, S. M.; Berglund, K.; Mann, T.; Gay, P.; Crelin, B.; Collins, D.; Sparks, R.

2008-05-01

The loss of a dark night sky as a natural resource is a growing concern. It impacts not only astronomical research, but also health, ecology, safety, economics and energy conservation. Because of its relevance, "Dark Skies” is a theme of the US Node for the International Year of Astronomy (IYA). Its goal is to raise public awareness of the impact of artificial lighting on local environments by getting people involved in a variety of dark skies-related programs. To reach this goal, the ASP session will immerse participants in hands-on, minds-on activities, events and resources on dark skies awareness. These include a planetarium show on DVD, podcasting, social networking, a digital photography contest, The Great Switch Out, Earth Hour, National Dark Skies Week, a traveling exhibit, a 6-minute video tutorial, Dark Skies Teaching Sites, Astronomy Nights in the (National) Parks, Sidewalk Astronomy Nights, and unaided-eye and digital-meter star counting programs like GLOBE at Night. The ASP "Dark Skies” session is offered to provide IYA dark skies-related programs to a variety of attendees. Participants include professional or amateur astronomers, education and public outreach professionals, science center/museum/planetarium staff and educators who want to lead activities involving dark skies awareness in conjunction with IYA. During the session, each participant will be given a package of educational materials on the various dark skies programs. We will provide the "know-how” and the means for session attendees to become community leaders in promoting these dark skies programs as public events at their home institutions during IYA. Participants will be able to jump-start their education programs through the use of well-developed instructional materials and kits sent later if they commit to leading IYA dark skies activities. For more information about the IYA Dark Skies theme, visit http://astronomy2009.us/darkskies/.

[Design and implementation of medical instrument standard information retrieval system based on APS.NET].

PubMed

Yu, Kaijun

2010-07-01

This paper Analys the design goals of Medical Instrumentation standard information retrieval system. Based on the B /S structure,we established a medical instrumentation standard retrieval system with ASP.NET C # programming language, IIS f Web server, SQL Server 2000 database, in the. NET environment. The paper also Introduces the system structure, retrieval system modules, system development environment and detailed design of the system.

An Analysis of Federal Airport and Air Carrier Employee Access Control, Screening. and Training Regulations

DTIC Science & Technology

1998-03-01

traveling public, air carriers, and persons employed by or conducting business at public airports. 14. SUBJECT TERMS Airport Security , Federal...26 4. Sterile Area 28 5. Exclusive Area 28 E. SECURITY ALERT LEVELS 29 F. AIRPORT SECURITY TOOLS 30 1. Electronic Detection System 31 a... Security Coordinator ASP Airport Security Program BIS Biometrie Identification System CCTV Closed Circuit Television CJIS Criminal Justice Information

Screening for Inhibitors of Essential Leishmania Glucose Transporters

DTIC Science & Technology

2013-07-01

stationed in that region (see reports in DoD – GEISWeb: www.geis.fhp.osd.mil/GEIS/IDTopics/ Leishmaniasis /LeishNavyPolicy.asp, entitled ‘ Leishmaniasis ...Troops Being Treated For Leishmaniasis ’). Drugs for treatment of leishmaniasis are generally expensive, toxic, and suffer from increasing occurrence of...this research program. Indeed current pharmacological treatments for leishmaniasis suffer from use of a limited number of compounds that were often

Defining Protein Electrostatic Recognition Processes

DTIC Science & Technology

1989-11-30

of the electrostatic potentiai on the molecular surface of negatively charged Asp-101 in the fifth residue of JH1. the hapten and the V regions of...making and aligning expanded molecular dot surfaces for each molecule and checking these surfaces for interpenetration. The program TURNIP used these...the molecular surfaces are separated by 6 and 12A. All orientations have the exposed heme edge of cytochrome c facing the acidic patch of plastocyanin

Identification of Novel BACE1 Inhibitors by Combination of Pharmacophore Modeling, Structure-Based Design and In Vitro Assay.

PubMed

Ju, Yuan; Li, Zicheng; Deng, Yong; Tong, Aiping; Zhou, Liangxue; Luo, Youfu

2016-01-01

The protease β-secretase plays a critical role in the synthesis of pathogenic amyloid-β in Alzheimer's disease. In this study, pharmacophore constructed from receptor-ligand complex was used to screen Chemdiv and Zinc database and the resulting hits were subjected to docking experiments using LiandFit and CDOCKER programs. Molecules with high consensus scores and good interaction patterns in docking programs were retained. Drug-likeness assay including Lipinski's rule of five and ADMET properties filters were further used to identify BACE1 inhibitor. Finally, 13 compounds with novel scaffolds were selected and, considering of the nature of relative high LogP value of many marketed AD drugs, three of them with top 3 predicted LogP value were evaluated for their IC50 values in vitro by BACE1 enzymatic activity study. We believe that compound 13 with an IC50 value of 136 µM can be a lead compound with great potential in BACE1 inhibition and increasing activity by subsequently structure modification or optimization. At the same time, we found that the interaction between the residues Asp228, Asp32 of BACE1 and ligands is significant through analyzing the binding mode of 13 candidate compounds.

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

Qasim, Mohammad A., E-mail: qasimm@ipfw.edu; Song, Jikui; Markley, John L.

Research highlights: {yields} Large pK shifts in ionizable groups when buried in the protein interior. {yields} Substrate dependent shifts in pH optimum for serine proteases. {yields} Lys side chain is a stronger acid in serine protease S{sub 1} pocket than Asp side chain. -- Abstract: Enzymatic hydrolysis of the synthetic substrate succinyl-Ala-Ala-Pro-Xxx-pNA (where Xxx = Leu, Asp or Lys) catalyzed by bovine chymotrypsin (CHYM) or Streptomyces griseus protease B (SGPB) has been studied at different pH values in the pH range 3-11. The pH optima for substrates having Leu, Asp, and Lys have been found to be 7.5-8.0, 5.5-6.0, andmore » {approx}10, respectively. At the normally reported pH optimum (pH 7-8) of CHYM and SGPB, the substrate with Leu at the reactive site is more than 25,000-fold more reactive than that with Asp. However, when fully protonated, Asp is nearly as good a substrate as Leu. The pK values of the side chains of Asp and Lys in the hydrophobic S{sub 1} pocket of CHYM and SGPB have been calculated from pH-dependent hydrolysis data and have been found to be about 9 for Asp and 7.4 and 9.7 for Lys for CHYM and SGPB, respectively. The results presented in this communication suggest a possible application of CHYM like enzymes in cleaving peptide bonds contributed by acidic amino acids between pH 5 and 6.« less

Tetrapod-type [Asp1] angiotensin is present in a holostean fish, Amia calva.

PubMed

Takei, Y; Itahara, Y; Butler, D G; Watanabe, T X; Oudit, G Y

1998-05-01

The renin-angiotensin system has been identified in various vertebrates, from elasmobranchs to mammals. Tetrapod (amphibians to mammals) angiotensin (ANG) has Asp at the N-terminus, but Asp is replaced by Asn in elasmobranch and teleost fish. ANG I has been isolated from incubates of plasma and kidney extracts of the bowfin Amia calva, a holostean fish, using the eel vasopressor activity as an assay system; its sequence was found to be H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Asn-Leu-OH after sequence analysis, mass spectrometry, and comparison with the synthetic peptide. This sequence is identical to bullfrog ANG I. [Asn1] ANG I was not detected. Thus the bowfin is the first fish species which contains only [Asp1] ANG I. The bowfin ANG I and II were no more vasopressor than eel peptides in the bowfin, indicating that bowfin ANG II receptors do not distinguish between [Asp1] and [Asn1] peptides. In the rat, bowfin ANG I and rat [Ile5, His9] ANG I have equipressor activities when examined in different animals, but the vasopressor activity of bowfin ANG I decreased following rat ANG I in the same animals, although the activity of rat ANG I was unaffected after bowfin ANG I. The present study directly demonstrates the presence of the renin-angiotensin system in a holostean fish and showed that its ANG II receptors have not yet fully coevolved with the homologous [Asp1] peptide.

Characterization of angiotensin receptors on bovine adrenal fasciculata cells.

PubMed Central

Vallotton, M B; Capponi, A M; Grillet, C; Knupfer, A L; Hepp, R; Khosla, M C; Bumpus, F M

1981-01-01

We have further characterized angiotensin receptors on bovine adrenal fasciculata cells whose presence was previously demonstrated by the intrinsic agonistic activity of angiotensin II (AII), dex-Asp1-AII, angiotensin I (AI), and des-ASp1-AI on steroidogenesis. The specific binding of AII and des-Asp1-AII labeled with 125I to dispersed bovine fasciculata cells was studied. For both peptides, a single class of binding sites accounted for the data with a mean (+/- SEM) Ka value of 0.23 +/- 0.123 X 10(8) liters/mol for AII and 0.68 X 10(8) liters/mol for des-Asp1-AII. The concentration at which unlabeled AII and des-Asp1-AII displaced 50% of the tracers (Kd) was similar to that at which they induced half-maximal stimulation of steroidogenesis (Kact). For AI and des-Asp1-AI, Kd greater than Kact. Analogs of AII or des-Asp1-AII with antagonistic properties upon steroidogenesis competed also with binding of the tracers. Corticotropin (ACTH) did not inhibit binding. Although ACTH stimulated the formation of cyclic AMP, none of the angiotensins with intrinsic activity did so. Calcium, but not potassium, appeared to potentiate the steroidogenic activity of AII. These data suggest that there is a single class of receptors for angiotensins and analogs in zona fasciculata. These receptors show characteristics that differentiate them from ACTH receptors in zona fasciculata or angiotensin receptors in zona glomerulosa cells. PMID:6264451

The Maturation of Oocyte Follicular Epithelium of Podarcis s. sicula Is Promoted by d-Aspartic Acid

PubMed Central

Raucci, Franca; Di Fiore, Maria Maddalena

2010-01-01

We investigated whether the maturation of oocyte follicular epithelium of lizard is affected by d-aspartic acid (d-Asp). Our results demonstrated that d-Asp is endogenously present in the oocytes, and its distribution varies during the reproductive cycle and following intraperitoneal administration. At previtellogenesis, it is observed in the cytoplasm and nucleus of pyriform cells, in intermediate cells, in some small cells of the granulosa, in the ooplasm, and in some thecal elements. At vitellogenesis, d-Asp is localized in the proximity of the zona pellucida, in the theca, and in the ooplasm. Injected d-Asp is mainly captured by pyriform cells and ooplasm of previtellogenic oocytes, but a moderate accumulation is evident in the cytoplasm of some small granulosa cells and in the theca. d-Asp also increases the ovarian and plasmatic levels of 17β-estradiol and decreases those of testosterone. As a direct and/or indirect consequence of d-Asp, previtellogenic oocytes grow up and mature, resulting in a higher accumulation of carbohydrates in the granulosa, zona pellucida, and ooplasm, but also a reduction in the thickness of the granulosa layer and an increase of the theca stratum. Taken together, our results show that d-Asp may be related to the synchrony of reproduction, either enhancing the growth and maturation of follicular epithelium or influencing its endocrine functions. (J Histochem Cytochem 58:157–171, 2010) PMID:19826072

Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity

PubMed Central

Kutszegi, Nóra; Semsei, Ágnes F.; Gézsi, András; Sági, Judit C.; Nagy, Viktória; Csordás, Katalin; Jakab, Zsuzsanna; Lautner-Csorba, Orsolya; Gábor, Krisztina Míta; Kovács, Gábor T.; Erdélyi, Dániel J.; Szalai, Csaba

2015-01-01

L-asparaginase (ASP) is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL). However, hypersensitivity reactions (HSRs) to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin—Frankfurt—Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs) in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01–0.26); p = 4.70E-04), while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176) were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09–0.53); p = 8.48E-04 and OR = 3.02 (1.36–6.73); p = 6.76E-03, respectively). Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect. PMID:26457809

Genetic polymorphisms of xeroderma pigmentosum group D gene Asp312Asn and Lys751Gln and susceptibility to prostate cancer: a systematic review and meta-analysis.

PubMed

Ma, Qingtong; Qi, Can; Tie, Chong; Guo, Zhanjun

2013-11-10

Many studies have reported the role of xeroderma pigmentosum group D (XPD) with prostate cancer risk, but the results remained controversial. To derive a more precise estimation of the relationship, a meta-analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association between XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. A total of 8 studies including 2620 cases and 3225 controls described Asp312Asn genotypes, among which 10 articles involving 3230 cases and 3582 controls described Lys751Gln genotypes and were also involved in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, a significant association between prostate cancer risk and XPD Asp312Asn polymorphism was found. For Asp312Asn polymorphism, in the stratified analysis by ethnicity and source of controls, prostate cancer risk was observed in co-dominant, dominant and recessive models, while no evidence of any associations of XPD Lys751Gln polymorphism with prostate cancer was found in the overall or subgroup analyses. Our meta-analysis supports that the XPD Asp312Asn polymorphism contributed to the risk of prostate cancer from currently available evidence. However, a study with a larger sample size is needed to further evaluate gene-environment interaction on XPD Asp312Asn and Lys751Gln polymorphisms and prostate cancer risk. © 2013.

Identification and expression of an allergen Asp f 13 from Aspergillus fumigatus and epitope mapping using human IgE antibodies and rabbit polyclonal antibodies.

PubMed Central

Chow, L P; Liu, S L; Yu, C J; Liao, H K; Tsai, J J; Tang, T K

2000-01-01

The Aspergillus genus of fungi is known to be one of the most prevalent aeroallergens. On two-dimensional immunoblotting using patients' sera containing IgE specific for Asp f 13, an allergen with a molecular mass of 33 kDa and a pI of 6.2 was identified. This allergen was also present in A. fumigatus culture filtrates. Furthermore, the sequence of the Asp f 13 cDNA was identical to that for alkaline protease isolated from A. fumigatus and showed 42-49% identity of amino acids with two proteases from P. cyclopium and T. album and with the Pen c 1 allergen from P. citrinum. Asp f 13 coding sequences were expressed in Escherichia coli as a [His](6)-tagged fusion protein which was purified by Ni(2+)-chelate affinity chromatography. Recombinant Asp f 13 was recognized by rabbit polyclonal antibodies against Asp f 13 and by IgE antibodies from subject allergic to A. fumigatus. To identify and characterize the linear epitopes of this allergen, a combination of chemical and enzymatic cleavage and immunoblotting techniques, with subsequent N-terminal sequencing and mass spectrometry, were performed. At least 13 different linear epitopes reacting with the rabbit anti-Asp f 13 antiserum were identified, located throughout the entire molecule. In contrast, IgE from A. fumigatus-sensitive patients bound to three immunodominant epitopes at the C-terminal of the protein. PMID:10677362

Adherence in the CAPRISA 004 Tenofovir Gel Microbicide Trial

PubMed Central

Mansoor, Leila E

2014-01-01

High adherence is key to microbicide effectiveness. Here we provide a description of adherence interventions and the adherence rates achieved in the CAPRISA 004 Tenofovir Gel Trial. Adherence support for the before-and-after dosing strategy (BAT 24) was provided at enrolment and at each monthly study visit. This initially comprised individual counselling and was replaced midway by a structured theory-based adherence support program (ASP) based on motivational interviewing. The 889 women were followed for an average of 18 months and attended a total of 17031 monthly visits. On average women reported 5 sex acts and returned 5.9 empty applicators per month. The adherence rate based on applicator count in relation to all reported sex acts was 72.2% compared to the 82.0% self-reported adherence during the last sex act. Adherence support activities, which achieve levels of adherence similar to or better than those achieved by the CAPRISA 004 ASP, will be critical to the success of future microbicide trials. PMID:24643315

Supramolecular Assembly of Single-Source Metal-Chalcogenide Nanocrystal Precursors.

PubMed

Smith, Stephanie C; Bryks, Whitney; Tao, Andrea R

2018-05-28

In this Feature Article, we discuss our recent work in the synthesis of novel supramolecular precursors for semiconductor nanocrystals. Metal chalcogenolates that adopt liquid crystalline phases are employed as single-source precursors that template the growth of shaped solid-state nanocrystals. Supramolecular assembly is programmed by both precursor chemical composition and molecular parameters such alkyl chain length, steric bulk, and the intercalation of halide ions. Here, we explore the various design principles that enable the rational synthesis of these single-source precursors, their liquid crystalline phases, and the various semiconductor nanocrystal products that can be generated by thermolysis, ranging from highly anisotropic two-dimensional nanosheets and nanodisks to spheres.

Activity of [des-Aspartyl1]-Angiotensin II in Primary Aldosteronism

PubMed Central

Carey, Robert M.; Ayers, Carlos R.; Vaughan, E. Darracott; Peach, Michael J.; Herf, Steven M.

1979-01-01

This study describes the effects of [des-Aspartyl1]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6±1 to 14±3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33±8 to 65±13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III. Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history. PMID:438332

Electron Transport in a Dioxygenase-Ferredoxin Complex: Long Range Charge Coupling between the Rieske and Non-Heme Iron Center

PubMed Central

Jono, Ryota; Shimizu, Kentaro

2016-01-01

Dioxygenase (dOx) utilizes stereospecific oxidation on aromatic molecules; consequently, dOx has potential applications in bioremediation and stereospecific oxidation synthesis. The reactive components of dOx comprise a Rieske structure Cys2[2Fe-2S]His2 and a non-heme reactive oxygen center (ROC). Between the Rieske structure and the ROC, a universally conserved Asp residue appears to bridge the two structures forming a Rieske-Asp-ROC triad, where the Asp is known to be essential for electron transfer processes. The Rieske and ROC share hydrogen bonds with Asp through their His ligands; suggesting an ideal network for electron transfer via the carboxyl side chain of Asp. Associated with the dOx is an itinerant charge carrying protein Ferredoxin (Fdx). Depending on the specific cognate, Fdx may also possess either the Rieske structure or a related structure known as 4-Cys-[2Fe-2S] (4-Cys). In this study, we extensively explore, at different levels of theory, the behavior of the individual components (Rieske and ROC) and their interaction together via the Asp using a variety of density function methods, basis sets, and a method known as Generalized Ionic Fragment Approach (GIFA) that permits setting up spin configurations manually. We also report results on the 4-Cys structure for comparison. The individual optimized structures are compared with observed spectroscopic data from the Rieske, 4-Cys and ROC structures (where information is available). The separate pieces are then combined together into a large Rieske-Asp-ROC (donor/bridge/acceptor) complex to estimate the overall coupling between individual components, based on changes to the partial charges. The results suggest that the partial charges are significantly altered when Asp bridges the Rieske and the ROC; hence, long range coupling through hydrogen bonding effects via the intercalated Asp bridge can drastically affect the partial charge distributions compared to the individual isolated structures. The results are consistent with a proton coupled electron transfer mechanism. PMID:27656882

Intrinsic and extrinsic rewards in a nonformal environmental education program.

PubMed

Price, Emily A; Vining, Joanne; Saunders, Carol D

2009-09-01

Humans are surrounded by threats to the environment, many of their own making. The severity of environmental problems will not decrease unless action is taken to develop and encourage greater environmentally responsible behavior (ERB) in the general populace. Environmental education (EE) is one method for strengthening precursors to ERB such as knowledge and attitudes, but research on the connection is currently unclear. In this paper we present the results of a study investigating the role played by rewards in encouraging ERB precursors for adults and children involved in a zoo-based Nature Swap program. We used semistructured interviews to question 91 participants, including 38 children, 38 adult guardians, and 15 staff members regarding the importance of rewards in the program. We content analyzed the interviews to identify and describe major themes and then coded them. We found that adult guardians and Play Partners perceived intrinsic and extrinsic rewards as aiding in maintaining motivation and interest in the nonformal Nature Swap program. In addition, both children and adult companion participants in the program mentioned strengthened precursors to ERB. Overall we found that adult companions perceived that children who participated in the program spent more quality time outdoors and had a heightened awareness of their surroundings as a result of program-based rewards. Implications for other EE and conservation education programs are discussed.

Verocytotoxin-induced apoptosis of human microvascular endothelial cells.

PubMed

Pijpers, A H; van Setten, P A; van den Heuvel, L P; Assmann, K J; Dijkman, H B; Pennings, A H; Monnens, L A; van Hinsbergh, V W

2001-04-01

The pathogenesis of the epidemic form of hemolytic uremic syndrome is characterized by endothelial cell damage. In this study, the role of apoptosis in verocytotoxin (VT)-mediated endothelial cell death in human glomerular microvascular endothelial cells (GMVEC), human umbilical vein endothelial cells, and foreskin microvascular endothelial cells (FMVEC) was investigated. VT induced apoptosis in GMVEC and human umbilical vein endothelial cells when the cells were prestimulated with the inflammatory mediator tumor necrosis factor-alpha (TNF-alpha). FMVEC displayed strong binding of VT and high susceptibility to VT under basal conditions, which made them suitable for the study of VT-induced apoptosis without TNF-alpha interference. On the basis of functional (flow cytometry and immunofluorescence microscopy using FITC-conjugated annexin V and propidium iodide), morphologic (transmission electron microscopy), and molecular (agarose gel electrophoresis of cellular DNA fragments) criteria, it was documented that VT induced programmed cell death in microvascular endothelial cells in a dose- and time-dependent manner. Furthermore, whereas partial inhibition of protein synthesis by VT was associated with a considerable number of apoptotic cells, comparable inhibition of protein synthesis by cycloheximide was not. This suggests that additional pathways, independent of protein synthesis inhibition, may be involved in VT-mediated apoptosis in microvascular endothelial cells. Specific inhibition of caspases by Ac-Asp-Glu-Val-Asp-CHO, but not by Ac-Tyr-Val-Ala-Asp-CHO, was accompanied by inhibition of VT-induced apoptosis in FMVEC and TNF-alpha-treated GMVEC. These data indicate that VT can induce apoptosis in human microvascular endothelial cells.

Proceedings, phenomenology and applications of high temperature superconductors

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

Bedell, K.S.

1991-01-01

Phenomenology and Applications of High Temperature Superconductors, The Los Alamos Symposium: 1991, was sponsored by the Los Alamos National Laboratory, Center for Materials Science, the Advanced Studies Program on High Temperature Superconductivity Theory (ASP) and the Exploratory Research and Development Center. This is the second symposium in the series. High Temperature Superconductivity, The Los Alamos Symposium: 1989, also published by Addison Wesley, focused on the cutting-edge theoretical and experimental issues in high temperature superconductors. This symposium, with its focus on the phenomenology and applications of high temperature superconductors, gives a complementary review of the aspects of the field closely relatedmore » to the impact of high temperature superconductors on technology. The objective of ASP is to advance the field on a broad front with no specific point of view by bringing a team of leading academic theorists into a joint effort with the theoretical and experimental scientists of a major DOE national laboratory. The ASP consisted of fellows led by Robert Schrieffer (UCSB and now FSU) joined by David Pines (University of illinois), Elihu Abrahams (Rutgers), Sebastian Doniach (Stanford), and Maurice Rice (ETH, Zurich) and theoretical and experimental staff of Los Alamos National Laboratory. This synergism of academic, laboratory, theoretical and experimental research produced a level of interaction and excitement that would not be possible otherwise. This publication and the previous one in the series are just examples of how this approach to advancing science can achieve significant contributions.« less

Proceedings, phenomenology and applications of high temperature superconductors

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

Bedell, K.S.

1991-12-31

Phenomenology and Applications of High Temperature Superconductors, The Los Alamos Symposium: 1991, was sponsored by the Los Alamos National Laboratory, Center for Materials Science, the Advanced Studies Program on High Temperature Superconductivity Theory (ASP) and the Exploratory Research and Development Center. This is the second symposium in the series. High Temperature Superconductivity, The Los Alamos Symposium: 1989, also published by Addison Wesley, focused on the cutting-edge theoretical and experimental issues in high temperature superconductors. This symposium, with its focus on the phenomenology and applications of high temperature superconductors, gives a complementary review of the aspects of the field closely relatedmore » to the impact of high temperature superconductors on technology. The objective of ASP is to advance the field on a broad front with no specific point of view by bringing a team of leading academic theorists into a joint effort with the theoretical and experimental scientists of a major DOE national laboratory. The ASP consisted of fellows led by Robert Schrieffer (UCSB and now FSU) joined by David Pines (University of illinois), Elihu Abrahams (Rutgers), Sebastian Doniach (Stanford), and Maurice Rice (ETH, Zurich) and theoretical and experimental staff of Los Alamos National Laboratory. This synergism of academic, laboratory, theoretical and experimental research produced a level of interaction and excitement that would not be possible otherwise. This publication and the previous one in the series are just examples of how this approach to advancing science can achieve significant contributions.« less

The value of participatory development to support antimicrobial stewardship with a clinical decision support system.

PubMed

Beerlage-de Jong, Nienke; Wentzel, Jobke; Hendrix, Ron; van Gemert-Pijnen, Lisette

2017-04-01

Current clinical decision support systems (CDSSs) for antimicrobial stewardship programs (ASPs) are guideline- or expert-driven. They are focused on (clinical) content, not on supporting real-time workflow. Thus, CDSSs fail to optimally support prudent antimicrobial prescribing in daily practice. Our aim was to demonstrate why and how participatory development (involving end-users and other stakeholders) can contribute to the success of CDSSs in ASPs. A mixed-methods approach was applied, combining scenario-based prototype evaluations (to support verbalization of work processes and out-of-the-box thinking) among 6 medical resident physicians with an online questionnaire (to cross-reference findings of the prototype evaluations) among 54 Dutch physicians. The prototype evaluations resulted in insight into the end-users and their way of working, as well as their needs and expectations. The online questionnaire that was distributed among a larger group of medical specialists, including lung and infection experts, complemented the findings of the prototype evaluations. It revealed a say/do problem concerning the unrecognized need of support for selecting diagnostic tests. Low-fidelity prototypes of a technology allow researchers to get to know the end-users, their way of working, and their work context. Involving experts allows technology developers to continuously check the fit between technology and clinical practice. The combination enables the participatory development of technology to successfully support ASPs. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

[Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2010-01-01

Neonatal hypophysectomy in chicken produces enlarged follicles of the thyroid gland, accumulation of colloids, impressed follicular epithelium, increased nucleus-cytoplasm ratio in thyrocytes, atrophied inter-follicular epithelium, depressed immunity, development of hypercoagulation and depressed fibrinolysis. When hypophysectomy is performed in one-year-old birds the impairments developing in thyroid morphology, immunity and hemostasis are less pronounced. Peptides of the anterior (Lys-Glu-Asp-Gly) and posterior (Ala-Glu-Asp-Gly) thyroid lobes injected to hypophysectomized birds prevent atrophic changes of the thyroid gland, normalize immune and hemostatic parameters.

Pure detection of the acoustic spin pumping in Pt/YIG/PZT structures

NASA Astrophysics Data System (ADS)

Uchida, Ken-ichi; Qiu, Zhiyong; Kikkawa, Takashi; Saitoh, Eiji

2014-11-01

The acoustic spin pumping (ASP) stands for the generation of a spin voltage from sound waves in a ferromagnet/paramagnet junction. In this letter, we propose and demonstrate a method for pure detection of the ASP, which enables the separation of sound-wave-driven spin currents from the spin Seebeck effect due to the heating of a sample caused by a sound-wave injection. Our demonstration using a Pt/YIG/PZT sample shows that the ASP signal in this structure measured by a conventional method is considerably offset by the heating signal and that the pure ASP signal is one order of magnitude greater than that reported in the previous study.

A meta-analysis of differences in IQ profiles between individuals with Asperger's disorder and high-functioning autism.

PubMed

Chiang, Hsu-Min; Tsai, Luke Y; Cheung, Ying Kuen; Brown, Alice; Li, Huacheng

2014-07-01

A meta-analysis was performed to examine differences in IQ profiles between individuals with Asperger's disorder (AspD) and high-functioning autism (HFA). Fifty-two studies were included for this study. The results showed that (a) individuals with AspD had significantly higher full-scale IQ, verbal IQ (VIQ), and performance IQ (PIQ) than did individuals with HFA; (b) individuals with AspD had significantly higher VIQ than PIQ; and (c) VIQ was similar to PIQ in individuals with HFA. These findings seem to suggest that AspD and HFA are two different subtypes of Autism. The implications of the present findings to DSM-5 Autism Spectrum Disorder are discussed.

High-stability Shuttle pointing system

NASA Technical Reports Server (NTRS)

Van Riper, R.

1981-01-01

It was recognized that precision pointing provided by the Orbiter's attitude control system would not be good enough for Shuttle payload scientific experiments or certain Defense department payloads. The Annular Suspension Pointing System (ASPS) is being developed to satisfy these more exacting pointing requirements. The ASPS is a modular pointing system which consists of two principal parts, including an ASPS Gimbal System (AGS) which provides three conventional ball-bearing gimbals and an ASPS Vernier System (AVS) which magnetically isolates the payload. AGS performance requirements are discussed and an AGS system description is given. The overall AGS system consists of the mechanical hardware, sensors, electronics, and software. Attention is also given to system simulation and performance prediction, and support facilities.

Proteome Analysis of the Penicillin Producer Penicillium chrysogenum

PubMed Central

Jami, Mohammad-Saeid; Barreiro, Carlos; García-Estrada, Carlos; Martín, Juan-Francisco

2010-01-01

Proteomics is a powerful tool to understand the molecular mechanisms causing the production of high penicillin titers by industrial strains of the filamentous fungus Penicillium chrysogenum as the result of strain improvement programs. Penicillin biosynthesis is an excellent model system for many other bioactive microbial metabolites. The recent publication of the P. chrysogenum genome has established the basis to understand the molecular processes underlying penicillin overproduction. We report here the proteome reference map of P. chrysogenum Wisconsin 54-1255 (the genome project reference strain) together with an in-depth study of the changes produced in three different strains of this filamentous fungus during industrial strain improvement. Two-dimensional gel electrophoresis, peptide mass fingerprinting, and tandem mass spectrometry were used for protein identification. Around 1000 spots were visualized by “blue silver” colloidal Coomassie staining in a non-linear pI range from 3 to 10 with high resolution, which allowed the identification of 950 proteins (549 different proteins and isoforms). Comparison among the cytosolic proteomes of the wild-type NRRL 1951, Wisconsin 54-1255 (an improved, moderate penicillin producer), and AS-P-78 (a penicillin high producer) strains indicated that global metabolic reorganizations occurred during the strain improvement program. The main changes observed in the high producer strains were increases of cysteine biosynthesis (a penicillin precursor), enzymes of the pentose phosphate pathway, and stress response proteins together with a reduction in virulence and in the biosynthesis of other secondary metabolites different from penicillin (pigments and isoflavonoids). In the wild-type strain, we identified enzymes to utilize cellulose, sorbitol, and other carbon sources that have been lost in the high penicillin producer strains. Changes in the levels of a few specific proteins correlated well with the improved penicillin biosynthesis in the high producer strains. These results provide useful information to improve the production of many other bioactive secondary metabolites. PMID:20154335

Serum protein adsorption and platelet adhesion on aspartic-acid-immobilized polysulfone membranes.

PubMed

Higuchi, Akon; Hashiba, Hirokazu; Hayashi, Rika; Yoon, Boo Ok; Sakurai, Masaru; Hara, Mariko

2004-01-01

Polysulfone (PSf) membranes that covalently conjugated with aspartic acid (ASP-PSf) were prepared and analyzed for hemocompatability. Compared to PSf or other types of surface-modified PSf membranes, the ASP-PSf membranes had a reduced ability to adsorb protein from either a plasma solution or a mixed solution of albumin, globulin and fibrinogen. This appears to be due to the creation of a hydrophilic surface by the aspartic acid zwitterion immobilized on the ASP-PSf membranes. Furthermore, the analyses of membrane protein adsorption showed that a mixed protein solution recapitulates the cooperative adsorption of proteins that occurs in plasma. We also found that the number of adhering platelets was the lowest on the ASP-PSf membranes and, in general, that platelet adhesion decreased in parallel with fibrinogen adsorption. In summary, aspartic acid immobilized on the ASP-PSf membranes, which have zwitterions with a net zero charge, effectively contributes to the hydrophilic and hemocompatible sites on the surface of the hydrophobic PSf membranes.

Fidelity of Automatic Speech Processing for Adult and Child Talker Classifications.

PubMed

VanDam, Mark; Silbert, Noah H

2016-01-01

Automatic speech processing (ASP) has recently been applied to very large datasets of naturalistically collected, daylong recordings of child speech via an audio recorder worn by young children. The system developed by the LENA Research Foundation analyzes children's speech for research and clinical purposes, with special focus on of identifying and tagging family speech dynamics and the at-home acoustic environment from the auditory perspective of the child. A primary issue for researchers, clinicians, and families using the Language ENvironment Analysis (LENA) system is to what degree the segment labels are valid. This classification study evaluates the performance of the computer ASP output against 23 trained human judges who made about 53,000 judgements of classification of segments tagged by the LENA ASP. Results indicate performance consistent with modern ASP such as those using HMM methods, with acoustic characteristics of fundamental frequency and segment duration most important for both human and machine classifications. Results are likely to be important for interpreting and improving ASP output.

Fidelity of Automatic Speech Processing for Adult and Child Talker Classifications

PubMed Central

2016-01-01

Automatic speech processing (ASP) has recently been applied to very large datasets of naturalistically collected, daylong recordings of child speech via an audio recorder worn by young children. The system developed by the LENA Research Foundation analyzes children's speech for research and clinical purposes, with special focus on of identifying and tagging family speech dynamics and the at-home acoustic environment from the auditory perspective of the child. A primary issue for researchers, clinicians, and families using the Language ENvironment Analysis (LENA) system is to what degree the segment labels are valid. This classification study evaluates the performance of the computer ASP output against 23 trained human judges who made about 53,000 judgements of classification of segments tagged by the LENA ASP. Results indicate performance consistent with modern ASP such as those using HMM methods, with acoustic characteristics of fundamental frequency and segment duration most important for both human and machine classifications. Results are likely to be important for interpreting and improving ASP output. PMID:27529813

Update on the Use of l-Asparaginase in Infants and Adolescent Patients with Acute Lymphoblastic Leukemia

PubMed Central

Andrade, Augusto F; Borges, Kleiton S; Silveira, Vanessa S

2014-01-01

Great improvements have been made in acute lymphoblastic leukemia (ALL) treatment in the past decades, especially due to the use of l-asparaginase (l-ASP). Despite the significant success rate, several side effects mainly caused by toxicity, asparaginase silent inactivation, and cellular resistance, encourage an open debate regarding the optimal dosage and formulation of l-ASP. Alternative sources of asparaginases have been constantly investigated in order to overcome hypersensitivity clinical toxicity. Additionally, genomic modulation as gene expression profiling, genetic polymorphisms, and epigenetic changes is also being investigated concerning their role in cellular resistance to l-ASP. Understanding the mechanisms that mediate the resistance to l-ASP treatment may bring new insights into ALL pathobiology and contribute to the development of more effective treatment strategies. In summary, this review presents an overview on l-ASP data and focuses on cellular mechanisms underlying resistance and alternative therapies for the use of asparaginase in childhood ALL treatment. PMID:25210485

Products of cholecystokinin (CCK)-octapeptide proteolysis interact with central CCK receptors.

PubMed

Steardo, L; Knight, M; Tamminga, C A; Chase, T N

1985-03-15

Peptidases present in central nervous system (CNS) synaptic membranes, hydrolyze the neuroactive peptide cholecystokinin-octapeptide (CCK-8; Asp-Tyr-SO3H-Met-Gly-Trp-Met-Asp-Phe-NH2). In order to determine the pathway of degradation, synthetic CCK-8 was incubated at 37 degrees C with purified synaptic membranes; at various intervals reaction samples were removed from the reaction mixture and analysed by high-performance liquid chromatography to identify and quantify the peptide fragments. The results indicate an initial endopeptidase cleavage at the Met-Gly bond producing CCK-5 (Gly-Trp-Met-Asp-Phe-NH2). The carboxyl-terminal pentapeptide is further proteolysed to CCK-4 (Trp-Met-Asp-Phe-NH2) by a puromycin-sensitive aminopeptidase and to CCK-3 (Met-Asp-Phe-NH2) and Gly-Trp by an endopeptidase action. CCK-3 and CCK-2 appear to be relatively stable end-products. Moreover, these proteolytic fragments are shown to bind to the CCK receptor in brain with varying potencies.

Acidic Polysaccharide from Angelica sinensis Reverses Anemia of Chronic Disease Involving the Suppression of Inflammatory Hepcidin and NF-κB Activation.

PubMed

Wang, Kaiping; Wu, Jun; Cheng, Fang; Huang, Xiao; Zeng, Fang; Zhang, Yu

2017-01-01

Anemia of chronic disease (ACD) is the second most prevalent anemia and frequently occurs in patients with acute or chronic immune activation. In the current study, we evaluated the therapeutic efficacy of Angelica sinensis polysaccharide (ASP) against ACD in rats and the potential mechanisms involved. The results showed that ASP inhibited inflammatory hepcidin in both HepG2 cells and ACD rats by blocking the IL-6/STAT3 and BMP/SMAD pathways. In ACD rats, the administration of ASP increased ferroportin expression, mobilized iron from the liver and spleen, increased serum iron levels, caused an elevation of serum EPO, and effectively relieved the anemia. Furthermore, ASP inhibited NF- κ B p65 activation via the I κ B kinases- (IKKs-) I κ B α pathway, thereby reducing the secretion of interleukin-6 (IL-6) and TNF- α , which is known to inhibit erythropoiesis. Our findings indicate that ASP is a potential treatment option for patients suffering from ACD.

Study of Water-Oil Emulsion Breaking by Stabilized Solution Consisting of Anionic Surface Acting Agent - Soda Ash - Polymer (ASP)

NASA Astrophysics Data System (ADS)

Kulichkov, S. V.; Avtomonov, E. G.; Andreeva, L. V.; Solomennik, S. F.; Nikitina, A. V.

2018-01-01

The paper provides a laboratory research of breaking natural water-oil emulsions: - by non-stabilized ASP; by stabilized ASP; by mixture of stabilized and non-stabilized ASP in different proportions and production of refinery water of the required quality with the use of IronGuard 2495 as flocculant. Oil-in-water emulsion is stable. Classic methods are not suitable for residual water treatment: sediment gravity flow; filtration; centrifuge test. Microemulsion formed after ASP application has low boundary tension and high pH. It contributes to transfer of oil phase into a water one, forming oil-in-water emulsion. Alkaline condition has adverse effect on demulsifying ability of agents, flocculation and boundary tension. For breaking of water-oil emulsion at EBU before the interchanger water or water-oil emulsion from the wells that were not APS-treated in ratio of 1:9 shall be delivered. Residual water after EBU must be prepared in water tanks by dilution in great volume.

Immunohistochemical localization of D-aspartate oxidase in porcine peripheral tissues.

PubMed

Yamamoto, Atsushi; Tanaka, Hiroyuki; Ishida, Tetsuo; Horiike, Kihachiro

2011-07-01

D-Aspartate (D-Asp) is an endogenous substance in mammals. Degradation of D-Asp is carried out only by D-aspartate oxidase (DDO). We measured DDO activity in porcine tissues, and produced an anti-porcine DDO antibody to examine the cellular localization of DDO. All the tissues examined showed DDO activities, whereas the substrate D-Asp was not detected in kidney cortex, liver, heart, and gastric mucosa. In the kidney, intensive immunohistochemical staining for DDO was found in the epithelial cells of the proximal tubules. In the liver, the epithelial cells of interlobular bile ducts, liver sinusoid-lining cells with cytoplasmic processes, and the smooth muscle cells of arterioles were strongly stained for DDO. In the heart, cardiomyocytes and the smooth muscle cells of arterioles showed DDO-immunoreactivity. In the gastric mucosa, only the chief cells were DDO-positive. These newly identified DDO-positive cells seem to actively degrade D-Asp to prevent an excess of D-Asp from exerting harmful effects on the respective functions of porcine tissues.

Efficient peptide ligation between allyl-protected Asp and Cys followed by palladium-mediated deprotection.

PubMed

Kamo, Naoki; Hayashi, Gosuke; Okamoto, Akimitsu

2018-04-24

An efficient method for peptide ligation between C-terminal Asp(OAllyl) and N-terminal Cys has been developed. Peptide ligation and removal of the allyl group at the Asp carboxylate side chain proceeded in one pot by adding a small amount of Pd/TPPTS complex. Based on this efficient synthetic method, PEP-19 (61 amino acids), which is highly expressed in Purkinje cells, was synthesized.

Crystallization and preliminary X-ray diffraction analysis of the periplasmic domain of the Escherichia coli aspartate receptor Tar and its complex with aspartate

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

Mise, Takeshi; Matsunami, Hideyuki; Samatey, Fadel A.

The periplasmic domain of the E. coli aspartate receptor Tar was cloned, expressed, purified and crystallized with and without bound ligand. The crystals obtained diffracted to resolutions of 1.58 and 1.95 Å, respectively. The cell-surface receptor Tar mediates bacterial chemotaxis toward an attractant, aspartate (Asp), and away from a repellent, Ni{sup 2+}. To understand the molecular mechanisms underlying the induction of Tar activity by its ligands, the Escherichia coli Tar periplasmic domain with and without bound aspartate (Asp-Tar and apo-Tar, respectively) were each crystallized in two different forms. Using ammonium sulfate as a precipitant, crystals of apo-Tar1 and Asp-Tar1 weremore » grown and diffracted to resolutions of 2.10 and 2.40 Å, respectively. Alternatively, using sodium chloride as a precipitant, crystals of apo-Tar2 and Asp-Tar2 were grown and diffracted to resolutions of 1.95 and 1.58 Å, respectively. Crystals of apo-Tar1 and Asp-Tar1 adopted space group P4{sub 1}2{sub 1}2, while those of apo-Tar2 and Asp-Tar2 adopted space groups P2{sub 1}2{sub 1}2{sub 1} and C2, respectively.« less

Application service provider (ASP) financial models for off-site PACS archiving

NASA Astrophysics Data System (ADS)

Ratib, Osman M.; Liu, Brent J.; McCoy, J. Michael; Enzmann, Dieter R.

2003-05-01

For the replacement of its legacy Picture Archiving and Communication Systems (approx. annual workload of 300,000 procedures), UCLA Medical Center has evaluated and adopted an off-site data-warehousing solution based on an ASP financial with a one-time single payment per study archived. Different financial models for long-term data archive services were compared to the traditional capital/operational costs of on-site digital archives. Total cost of ownership (TCO), including direct and indirect expenses and savings, were compared for each model. Financial parameters were considered: logistic/operational advantages and disadvantages of ASP models versus traditional archiving systems. Our initial analysis demonstrated that the traditional linear ASP business model for data storage was unsuitable for large institutions. The overall cost markedly exceeds the TCO of an in-house archive infrastructure (when support and maintenance costs are included.) We demonstrated, however, that non-linear ASP pricing models can be cost-effective alternatives for large-scale data storage, particularly if they are based on a scalable off-site data-warehousing service and the prices are adapted to the specific size of a given institution. The added value of ASP is that it does not require iterative data migrations from legacy media to new storage media at regular intervals.

Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

PubMed

Cochard, A; Guilhermet, R; Bonneau, M

1998-01-01

The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

Modification of Pectin and Hemicellulose Polysaccharides in Relation to Aril Breakdown of Harvested Longan Fruit

PubMed Central

Wang, Duoduo; Zhang, Haiyan; Wu, Fuwang; Li, Taotao; Liang, Yuxiang; Duan, Xuewu

2013-01-01

To investigate the modification of cell wall polysaccharides in relation to aril breakdown in harvested longan fruit, three pectin fractions (WSP, water soluble pectin; CSP, CDTA-soluble pectin; ASP, alkali soluble pectin) and one hemicellulose fraction (4 M KOH-SHC, 4 M KOH-soluble hemicellulose) were extracted, and their contents, monosaccharide compositions and molecular weights were evaluated. As aril breakdown intensified, CSP content increased while ASP and 4 M KOH-SHC contents decreased, suggesting the solubilization and conversion of cell wall components. Furthermore, the molar percentage of arabinose (Ara), as the main component of the side-chains, decreased largely in CSP and ASP while that of rhamnose (Rha), as branch point for the attachment of neutral sugar side chains, increased during aril breakdown. Analysis of (Ara + Gal)/Rha ratio showed that the depolymerization of CSP and ASP happened predominantly in side-chains formed of Ara residues. For 4 M KOH-SHC, more backbones were depolymerized during aril breakdown. Moreover, it was found that the molecular weights of CSP, ASP and 4 M KOH-SHC polysaccharides tended to decrease as aril breakdown intensified. These results suggest that both enhanced depolymerization and structural modifications of polysaccharides in the CSP, ASP and 4 M KOH-SHC fractions might be responsible for aril breakdown of harvested longan fruit. PMID:24287911

Effects of mutations of thermolysin, as N116 to asp and asp150 to glu, on salt-induced activation and stabilization.

PubMed

Menach, Evans; Yasukawa, Kiyoshi; Inouye, Kuniyo

2013-01-01

Neutral salts activate and stabilize thermolysin. We previously found that two single mutations, Asn116→Asp and Asp150→Glu, increase the activity of thermolysin. In the present study, we examined their effects on NaCl-induced activation and stabilization. In the hydrolysis of N-[3-(2-furyl)acryloyl]-glycyl-L-leucine amide, the relative activities (the ratios of the specificity constant, kcat/Km, at x M NaCl to that at 0 M NaCl) at 0.5-4.0 M NaCl of D150E and N116D/D150E were lower than those of wild-type thermolysin (WT) and N116D, respectively. In thermal inactivation at 70 °C, the relative stabilities (the ratios of the first-order rate constant, kobs, at 0 M NaCl to that at x M NaCl) at 0.5-4.0 M NaCl of D150E and N116D/D150E were lower than those of WT and N116D, respectively. These results indicate that unlike Asn116→Asp, Asp150→Glu reduced NaCl-induced activation and stabilization, suggesting that the binding of ions with certain residues of thermolysin is involved in the activation and stabilization.

Effects of early pregnancy diagnosis by per rectal palpation of the amniotic sac on pregnancy loss in dairy cattle.

PubMed

Romano, Juan E; Fahning, Melvyn L

2013-11-15

To determine effects of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during early gestation on pregnancy loss in lactating cows. Controlled, randomized block design. 368 pregnant dairy cows. Pregnancy was detected via transrectal ultrasonography (TRUS) at day 29 (day of estrus = day 0), and cows were allocated into a control group (n = 167 cows) and ASP group (180). Control cows were not subjected to pregnancy diagnosis via palpation per rectum. Per rectal ASP was performed between days 34 and 43 by only 1 experienced veterinarian. All cows were reevaluated with TRUS on days 45, 60, and 90. 21 cows were removed because of illness. Pregnancy loss between days 29 and 90 occurred in 44 of 347 (12.7%) cows. Pregnancy loss for the control and ASP groups from days 29 to 90 occurred in 22 of 167 (13.2%) and 22 of 180 (12.2%) cows, respectively. Late embryonic pregnancy loss (days 29 to 45) for the control and ASP groups occurred in 18 (10.8%) and 15 (8.3%) cows, respectively. Early fetal pregnancy loss (days 46 to 60) for the control and ASP groups occurred in 2 of 149 (1.3%) and 6 of 165 (3.6%) cows, respectively, and late fetal pregnancy loss (days 61 to 90) for the same groups occurred in 2 of 147 (1.4%) and 1 of 159 (0.6%) cows, respectively. Pregnancy diagnosis via per rectal ASP during early gestation did not increase pregnancy loss in dairy cattle.

Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease

PubMed Central

Matthews, Qiana L.; Farrow, Anitra L.; Rachakonda, Girish; Gu, Linlin; Nde, Pius; Krendelchtchikov, Alexandre; Pratap, Siddharth; Sakhare, Shruti S.; Sabbaj, Steffanie; Lima, Maria F.; Villalta, Fernando

2016-01-01

Background Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the T. cruzi amastigote surface protein 2. Methods Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated, characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and intracellular staining. Immunized mice were challenged with T. cruzi to evaluate the vaccine efficacy. Results Our findings indicate that Ad5-pIX-ASP-M was viable. Specific CD8+ T-cell mediated responses prior to the challenge show an increase in IFNγ and TNFα production. A single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi infection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher immunoprotection and increased survival rate of mice. Conclusions Overall, these results suggest that the combination of gp83 and ASP-M specific epitopes onto the capsid-incorporated adenoviruses would provide superior protection against Chagas disease as compared with Ad5-gp83 alone. PMID:27709126