Sample records for ai tertiary structures

  1. Effects of a high-pressure treatment on the wheat alpha-amylase inhibitor and its relationship to elimination of allergenicity

    NASA Astrophysics Data System (ADS)

    Yamamoto, S.; Takanohashi, K.; Hara, T.; Odani, S.; Suzuki, A.; Nishiumi, T.

    2010-03-01

    In this study, the effects of high-pressure treatment on structure and allergeincity of alpha amylase inhibitor (a-AI) were investigated. The pressure-induced structural changes of α-AI were estimated by fluorescence spectra and by fourth derivative UV-spectroscopy for probed tyrosine residues and by circular dichroism (CD) spectroscopy. The changes in the tertiary structure detected by fluorescence spectra and by fourth derivative UV-spectroscopy under high pressure were indicated at over 300 MPa. Measurements of CD spectroscopy suggested that the effects of a high-pressure treatment on changes in the secondary structure of α-AI were little. From our results, pressure-induced changes of the α-AI structure were not apparent. On the other hands, the IgE-specific binding activities of pressurized α-AI to sera from allergic patients against wheat, which is estimated by observations of dot-blotting, were decreased by high-pressure treatment. It is known that the pressure-induced elimination of allergenicity is related to the tertiary structural changes of allergen molecules. This study are suspected that the epitopes of α-AI do not contain tyrosine residues, and thus the decrease of IgE-specific binding activities is probably caused by the tertiary structural changes of these parts of α-AI.

  2. Apolipoprotein AI tertiary structures determine stability and phospholipid-binding activity of discoidal high-density lipoprotein particles of different sizes

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

    Chen, Bin; Ren, Xuefeng; Neville, Tracey

    2009-05-18

    Human high-density lipoprotein (HDL) plays a key role in the reverse cholesterol transport pathway that delivers excess cholesterol back to the liver for clearance. In vivo, HDL particles vary in size, shape and biological function. The discoidal HDL is a 140-240 kDa, disk-shaped intermediate of mature HDL. During mature spherical HDL formation, discoidal HDLs play a key role in loading cholesterol ester onto the HDL particles by activating the enzyme, lecithin:cholesterol acyltransferase (LCAT). One of the major problems for high-resolution structural studies of discoidal HDL is the difficulty in obtaining pure and, foremost, homogenous sample. We demonstrate here that themore » commonly used cholate dialysis method for discoidal HDL preparation usually contains 5-10% lipid-poor apoAI that significantly interferes with the high-resolution structural analysis of discoidal HDL using biophysical methods. Using an ultracentrifugation method, we quickly removed lipid-poor apoAI. We also purified discoidal reconstituted HDL (rHDL) into two pure discoidal HDL species of different sizes that are amendable for high-resolution structural studies. A small rHDL has a diameter of 7.6 nm, and a large rHDL has a diameter of 9.8 nm. We show that these two different sizes of discoidal HDL particles display different stability and phospholipid-binding activity. Interestingly, these property/functional differences are independent from the apoAI -helical secondary structure, but are determined by the tertiary structural difference of apoAI on different discoidal rHDL particles, as evidenced by two-dimensional NMR and negative stain electron microscopy data. Our result further provides the first high-resolution NMR data, demonstrating a promise of structural determination of discoidal HDL at atomic resolution using a combination of NMR and other biophysical techniques.« less

  3. Agent Supported Serious Game Environment

    ERIC Educational Resources Information Center

    Terzidou, Theodouli; Tsiatsos, Thrasyvoulos; Miliou, Christina; Sourvinou, Athanasia

    2016-01-01

    This study proposes and applies a novel concept for an AI enhanced serious game collaborative environment as a supplementary learning tool in tertiary education. It is based on previous research that investigated pedagogical agents for a serious game in the OpenSim environment. The proposed AI features to support the serious game are the…

  4. Teetering near the edge; women's experiences of anal incontinence following obstetric anal sphincter injury: an interpretive phenomenological research study.

    PubMed

    Tucker, Julie; Clifton, Vicki; Wilson, Anne

    2014-08-01

    Obstetric anal sphincter injury (OASIS) following vaginal delivery increases the risk of anal incontinence (AI). Subsequent vaginal delivery and ageing increase the risk of worsening symptoms. Very little literature describes any in-depth understanding of what it is like to live with AI following a history of known OASIS. To describe and interpret women's experience of AI following OASIS and its impact on quality of life. An interpretive phenomenological study was conducted in a level 2 tertiary hospital in South Australia. Women with a history of OASIS and AI were purposefully recruited. The St Marks Vaizey score was utilised to identify symptom severity. Semi-structured open-ended interviews were conducted, and data were analysed utilising Van Manen thematic analysis. Participants (n = 10) aged 26-56 years. All women were symptomatic of AI following OASIS, and 80% had received a primary OASIS at their first vaginal delivery. The St Marks Vaizey score mean was 9.1 (range within 4-22). Three essential themes grieving for loss, silence, striving for normality with eight subthemes identified a significant sense of loss and psychological impact of AI for this group of women. Health professionals require a greater understanding of the negative impact of OASIS and AI on women's quality of life. This may improve the management, education and clinical care of this condition which may result as a consequence of OASIS. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  5. Integrated Health Care Barcelona Esquerra (Ais-Be): A Global View of Organisational Development, Re-Engineering of Processes and Improvement of the Information Systems. The Role of the Tertiary University Hospital in the Transformation

    PubMed Central

    Escarrabill, Joan; Gómez, Mónica; Ruiz, Rafael; Enfedaque, Belén; Altimiras, Xavier

    2016-01-01

    The Integrated Health Area “Barcelona Esquerra” (Área Integral de Salud de Barcelona Esquerra – AIS-BE), which covers a population of 524,000 residents in Barcelona city, is running a project to improve healthcare quality and efficiency based on co-ordination between the different suppliers in its area through the participation of their professionals. Endowed with an Organisational Model that seeks decision-taking that starts out from clinical knowledge and from Information Systems tools that facilitate this co-ordination (an interoperability platform and a website) it presents important results in its structured programmes that have been implemented such as the Reorganisation of Emergency Care, Screening for Colorectal Cancer, the Onset of type 2 Diabetes Mellitus, Teledermatology and the Development of Cross-sectional Healthcare Policies for Care in Chronicity. PMID:27616964

  6. Integrated Health Care Barcelona Esquerra (Ais-Be): A Global View of Organisational Development, Re-Engineering of Processes and Improvement of the Information Systems. The Role of the Tertiary University Hospital in the Transformation.

    PubMed

    Font, David; Escarrabill, Joan; Gómez, Mónica; Ruiz, Rafael; Enfedaque, Belén; Altimiras, Xavier

    2016-05-23

    The Integrated Health Area "Barcelona Esquerra" (Área Integral de Salud de Barcelona Esquerra - AIS-BE), which covers a population of 524,000 residents in Barcelona city, is running a project to improve healthcare quality and efficiency based on co-ordination between the different suppliers in its area through the participation of their professionals. Endowed with an Organisational Model that seeks decision-taking that starts out from clinical knowledge and from Information Systems tools that facilitate this co-ordination (an interoperability platform and a website) it presents important results in its structured programmes that have been implemented such as the Reorganisation of Emergency Care, Screening for Colorectal Cancer, the Onset of type 2 Diabetes Mellitus, Teledermatology and the Development of Cross-sectional Healthcare Policies for Care in Chronicity.

  7. Cervical spine injuries, mechanisms, stability and AIS scores from vertical loading applied to military environments.

    PubMed

    Yoganandan, Narayan; Pintar, Frank A; Humm, John R; Maiman, Dennis J; Voo, Liming; Merkle, Andrew

    2016-07-01

    The purpose of this study was to determine injuries to osteo-ligamentous structures of cervical column, mechanisms, forces, severities and AIS scores from vertical accelerative loading. Seven human cadaver head-neck complexes (56.9 ± 9.5 years) were aligned based on seated the posture of military soldiers. Army combat helmets were used. Specimens were attached to a vertical accelerator to apply caudo-cephalad g-forces. They were accelerated with increasing insults. Intermittent palpation and radiography were done. A roof structure mimicking military vehicle interior was introduced after a series of tests and experiments were conducted following similar protocols. Upon injury detection, CT and dissection were done. Temporal force responses were extracted, peak forces and times of occurrence were obtained, injury severities were graded, and spine stability was determined. Injuries occurred in tests only when the roof structure was included. Responses were tri-phasic: initial thrust, secondary tensile, tertiary roof contact phases. Peak forces: 1364-4382 N, initial thrust, 165-169 N, secondary tensile, 868-3368 N tertiary helmet-head roof contact phases. Times of attainments: 5.3-9.6, 31.7-42.6, 55.0-70.8 ms. Injuries included fractures and joint disruptions. Multiple injuries occurred in all but one specimen. A majority of injury severities were AIS = 2. Spines were considered unstable in a majority of cases. Spine response was tri-phasic. Injuries occurred in roof contact tests with the helmeted head-neck specimen. Multiplicity and unstable nature of AIS = 2 level injuries, albeit at lower severities, might predispose the spine to long-term accelerated degenerative changes. Clinical protocols should include a careful evaluation of sub-catastrophic injuries in military patients.

  8. Working Together: Planting the Seed. "Kia Pihi Ai Te Mahi Ngatahi." Proceedings of the 2012 Annual International Conference of the Association of Tertiary Learning Advisors of Aotearoa/New Zealand (ATLAANZ) (Hamilton, New Zealand, Nov 21-23, 2013). Volume 8

    ERIC Educational Resources Information Center

    Gera, Christina, Ed.

    2013-01-01

    The 7 articles in this 8th volume comprise the referred proceedings of the 2012 ATLAANZ (Association of Tertiary Learning Advisors Aotearoa/New Zealand) conference. The first three chapters present tools that can assist students with their academic development: In chapter 1, ("The DELNA Language Advisory Session: How do Students…

  9. The “Beta-Clasp” model of apolipoprotein A-I - a lipid-free solution structure determined by electron paramagnetic resonance spectroscopy

    PubMed Central

    Lagerstedt, Jens O.; Budamagunta, Madhu S.; Liu, Grace S.; DeValle, Nicole C.; Voss, John C.; Oda, Michael N.

    2012-01-01

    Apolipoprotein A-I (apoA-I) is the major protein component of high density lipoproteins (HDL) and plays a central role in cholesterol metabolism. The lipid-free / lipid-poor form of apoA-I is the preferred substrate for the ATP-binding cassette transporter A1 (ABCA1). The interaction of apoA-I with ABCA1 leads to the formation of cholesterol laden high density lipoprotein (HDL) particles, a key step in reverse cholesterol transport and the maintenance of cholesterol homeostasis. Knowledge of the structure of lipid-free apoA-I is essential to understanding its critical interaction with ABCA1 and the molecular mechanisms underlying HDL biogenesis. We therefore examined the structure of lipid-free apoA-I by electron paramagnetic resonance spectroscopy (EPR). Through site directed spin label EPR, we mapped the secondary structure of apoA-I and identified sites of spin coupling as residues 26, 44, 64, 167, 217 and 226. We capitalize on the fact that lipid-free apoA-I self-associates in an anti-parallel manner in solution. We employed these sites of spin coupling to define the central plane in the dimeric apoA-I complex. Applying both the constraints of dipolar coupling with the EPR-derived pattern of solvent accessibility, we assembled the secondary structure into a tertiary context, providing a solution structure for lipid-free apoA-I. PMID:22245143

  10. Evaluation of AIS-2 (1986) data over hydrothermally altered granitoid rocks of the Singatse Range (Yerington) Nevada and comparison with 1985 AIS-1 data

    NASA Technical Reports Server (NTRS)

    Lyon, R. J. P.

    1987-01-01

    The Airborne Imaging Spectrometer-2 (AIS-2) flights along 2 subparallel lines (bearing 013) were designed to traverse 3 major rock assemblages - the Triassic sedimentary sequence; the granitoid rocks of the Yerington batholith and the Tertiary ignimbritic ash flow and ash fall tuffs. The first 2 sites are hydrothermally altered to a quartz-sericite-tourmaline mineralogy. The first AIS-2 data set showed numerous line dropouts and a considerable number of randomly distributed dark pixels. A second decommutation reduced the dropout essentially to near zero and the dark pixels by about 75 percent. Vertical striping was removed by histogram matching, column by column. A log residual spectrum was calculated which showed the departure of a 2 x 2 pixel area from the spatially and spectrally averaged scene. A 1:1 correlation was found with the log residual AIS-2 data and a large open pit area of gypsum. An area with known sericite agreed with the overflight data, and an area known to be free of any significant amount of O-H bearing materials showed no evidence of any in the AIS-2 log residuals.

  11. Abundance and distribution of ultramafic microbreccia in Moses Rock Dike: Quantitative application of AIS data

    NASA Technical Reports Server (NTRS)

    Mustard, John F.; Pieters, Carle M.

    1987-01-01

    Moses Rock dike is a Tertiary diatreme containing serpentinized ultramafic microbreccia (SUM). Field evidence indicates the SUM was emplaced first followed by breccias derived from the Permian strata exposed in the walls of the diatreme and finally by complex breccias containing basement and mantle derived rocks. SUM is found primarily dispersed throughout the matrix of the diatreme. Moses Rock dike was examined with Airborne Imaging Spectrometer (AIS) to map the distribution and excess of SUM in the matrix and to better understand the nature of the eruption which formed this explosive volcanic feature. AIS data was calibrated by dividing the suite of AIS data by data from an internal standard area and then multiplying this relative reflectance data by the absolute bidirectional reflectance of a selected sample from the standard area which was measured in the lab. From the calibrated AIS data the minerals serpentine, gypsum, and illite as well as desert varnish and the lithologies SUM and other sandstones were identified. SUM distribution and abundance in the matrix of the diatreme were examined in detail and two distinct styles of SUM dispersion were observed. The two styles are discussed in detail.

  12. A Complete NMR Spectral Assignment of the Lipid-free Mouse Apolipoprotein A-I (ApoAI) C-terminal Truncation Mutant, ApoAI(1-216)

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

    Yang, Yunhuang; Hoyt, David W.; Wang, Jianjun

    2007-07-28

    Apolipoprotein A-I (apoAI) is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. Upon lipid-binding, apoAI undergoes conformational changes from lipid-free to several different HDL-associated states (1). These different conformational states regulate HDL formation, maturation and transportation. Recent crystal structure of lipid-free human apoAI represents a major progress of structural study of lipid-free apoAI (2). However, no structural is available for lipid-free mouse apoAI (240-residues). Since mouse HDL is homogenous with only HDL2-like size, whereas human HDL is heterogeneous, containing HDL2/HDL3 as its main species, a structuralmore » comparison between human and mouse apoAI may allow us to identify structure basis of HDL size distribution difference between human and mouse. We carried out an NMR structure determination of lipid-free mouse apoAI (1-216) and completely assigned backbone atoms (except backbone amide proton and nitrogen atoms for residues D1, N48, W107, K108, K132, E135, F147, R148, M169 and K203). Secondary structure prediction using backbone NMR parameters indicates that lipid-free mouse apoAI consists of a four helical segments in the N-terminal domain, residues 1-180. In addition, two short helices are also observed between residues 190-195 and 210-215. The helix locations are significantly different from those in the crystal structure of human apoAI, suggesting that mouse apoAI may have a different conformational adaptation upon lipid-binding. BMRB deposit with accession number: 15091.« less

  13. Inpatient allergy/immunology consultations in a tertiary care setting.

    PubMed

    Otto, Hans F; England, Ronald W; Quinn, James M

    2010-01-01

    Few studies have examined inpatient referral patterns for fellowship training programs and none for allergy/immunology (AI) since 2003. The primary end point was the reason for consultation, and secondary end points included the AI diagnosis made and outcomes. We retrospectively reviewed all inpatient AI consultations from July 1, 2001 through June 30, 2007. These 6 years of data were combined with 14 years of data examining the reason for consult from a previous study. The data were analyzed for trends and changes over the entire 20-year period. A total of 254 AI inpatient consults were reviewed over the 6 years studied. Thirty-six percent (92/254) of inpatient consults were for evaluation of adverse drug reactions (ADRs), 22% (55/254) miscellaneous reasons, 17% (43/254) urticaria/angioedema, 13% (32/254) for possible immunodeficiency, 9% (23/254) for anaphylaxis, and 3% (8/254) for asthma. AI inpatient consults show a significant decline over the recent 6-year period (p = 0.0023) despite stable total hospital admissions since 1998. Over the last 20 years, an 85% decrease (p < 0.00001) in inpatient asthma consults and increases (p < 0.05) in immunodeficiency, rash, and urticaria/angioedema evaluations have been observed. Not following AI recommendations resulted in a 16.6 odds ratio (95% CI, 5.55-49.93) that a patient's clinical status would be worse or unchanged. Inpatient AI consults have declined with associated reduction in asthma inpatient consults. Although ADRs and anaphylaxis consults have been stable, evaluations for immunodeficiency, rash, and urticaria/angioedema have increased. Following inpatient AI recommendations is associated with improved patient outcomes.

  14. A complete backbone spectral assignment of human apolipoprotein AI on a 38 kDa preβHDL (Lp1-AI) particle

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

    Ren, Xuefeng; Yang, Yunhuang; Neville, T.

    2007-06-12

    Apolipoprotein A-I (apoAI, 243-residues) is the major protein component of the high-density lipoprotein (HDL) that has been a hot subject of interests because of its anti-atherogenic properties. This important property of apoAI is related to its roles in reverse cholesterol transport pathway. Upon lipid-binding, apoAI undergoes conformational changes from lipid-free to several different HDL-associated states (1). These different conformational states regulate HDL formation, maturation and transportation. Two initial conformational states of apoAI are lipid-free apoAI and apoAI/preβHDL that recruit phospholipids and cholesterol to form HDL particles. In particular, lipid-free apoAI specifically binds to phospholipids to form lipid-poor apoAI, including apoAI/preβ-HDLmore » (~37 kDa). As a unique class of lipid poor HDL, both in vitro and in vivo evidence demonstrates that apoAI/preβ-HDLs are the most effective acceptors specifically for free cholesterol in human plasma and serves as the precursor of HDL particles (2). Here we report a complete backbone spectral assignment of human apoAI/preβHDL. Secondary structure prediction using backbone NMR parameters indicates that apoAI/preβHDL displays a two-domain structure: the N-terminal four helix-bundle domain (residues 1-186) and the C-terminal flexible domain (residues 187-243). A structure of apoAI/preβ-HDL is the first lipid-associated structure of apoAI and is critical for us to understand how apoAI recruits cholesterol to initialize HDL formation. BMRB deposit with accession number: 15093.« less

  15. Interactions between lipid-free apolipoprotein-AI and a lipopeptide incorporating the RGDS cell adhesion motif

    NASA Astrophysics Data System (ADS)

    Castelletto, V.; Hamley, I. W.; Reza, M.; Ruokolainen, J.

    2014-11-01

    The interaction of a designed bioactive lipopeptide C16-GGGRGDS, comprising a hexadecyl lipid chain attached to a functional heptapeptide, with the lipid-free apoliprotein, Apo-AI, is examined. This apolipoprotein is a major component of high density lipoprotein and it is involved in lipid metabolism and may serve as a biomarker for cardiovascular disease and Alzheimers' disease. We find via isothermal titration calorimetry that binding between the lipopeptide and Apo-AI occurs up to a saturation condition, just above equimolar for a 10.7 μM concentration of Apo-AI. A similar value is obtained from circular dichroism spectroscopy, which probes the reduction in α-helical secondary structure of Apo-AI upon addition of C16-GGGRGDS. Electron microscopy images show a persistence of fibrillar structures due to self-assembly of C16-GGGRGDS in mixtures with Apo-AI above the saturation binding condition. A small fraction of spheroidal or possibly ``nanodisc'' structures was observed. Small-angle X-ray scattering (SAXS) data for Apo-AI can be fitted using a published crystal structure of the Apo-AI dimer. The SAXS data for the lipopeptide/Apo-AI mixtures above the saturation binding conditions can be fitted to the contribution from fibrillar structures coexisting with flat discs corresponding to Apo-AI/lipopeptide aggregates.

  16. Anal sphincter trauma and anal incontinence in urogynecological patients.

    PubMed

    Guzmán Rojas, R A; Kamisan Atan, I; Shek, K L; Dietz, H P

    2015-09-01

    To determine the prevalence of evidence of residual obstetric anal sphincter injury, to evaluate its association with anal incontinence (AI) and to establish minimal diagnostic criteria for significant (residual) external anal sphincter (EAS) trauma. This was a retrospective analysis of ultrasound volume datasets of 501 patients attending a tertiary urogynecological unit. All patients underwent a standardized interview including determination of St Mark's score for those presenting with AI. Tomographic ultrasound imaging (TUI) was used to evaluate the EAS and the internal anal sphincter (IAS). Among a total of 501 women, significant EAS and IAS defects were found in 88 and 59, respectively, and AI was reported by 69 (14%). Optimal prediction of AI was achieved using a model that included four abnormal slices of the EAS on TUI. IAS defects were found to be less likely to be associated with AI. In a multivariable model controlling for age and IAS trauma, the presence of at least four abnormal slices gave an 18-fold (95% CI, 9-36; P < 0.0001) increase in the likelihood of AI, compared with those with fewer than four abnormal slices. Using receiver-operating characteristics curve statistics, this model yielded an area under the curve of 0.86 (95% CI, 0.80-0.92). Both AI and significant EAS trauma are common in patients attending urogynecological units, and are strongly associated with each other. Abnormalities of the IAS seem to be less important in predicting AI. Our data support the practice of using, as a minimal criterion, defects present in four of the six slices on TUI for the diagnosis of significant EAS trauma. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  17. Crystal structures, vibrational spectra and DFT calculations of five halogeno-derivatives of 7-azaindole (3Br7AI, 4Br7AI, 4Cl7AI, 3Br4Cl7AI and 5Br3Cl7AI): a comparative study

    NASA Astrophysics Data System (ADS)

    Morzyk-Ociepa, Barbara; Dysz, Karolina; Turowska-Tyrk, Ilona; Michalska, Danuta

    2018-01-01

    Structures and vibrational spectra of 3-bromo-7-azaindole (3Br7AI), 4-bromo-7-azaindole (4Br7AI), 4-chloro-7-azaindole (4Cl7AI), 5-bromo-3-chloro-7-azaindole (5Br3Cl7AI) and 3-bromo-4-chloro-7-azaindole (3Br4Cl7AI) have been investigated. For the first time a single crystal analysis is reported for the three compounds: 3Br7AI (P21/n space group; a = 12.6586(3), b = 3.98664(12), c = 14.1189(4)Å, β = 100.901(2)o, Z = 4); 4Br7AI (P21/n space group; a = 5.38136 (13), b = 9.2262 (2), c = 13.9806 (4)Å, β = 90.052 (2)o, Z = 4); and 5Br3Cl7AI (C2/c space group; a = 22.9444(10), b = 3.91953(12), c = 17.8500(6)Å, β = 102.621(4)o, Z = 8). In the crystal structure, a pair of molecules forms a centrosymmetric dimer connected by dual nearly linear Nsbnd H⋯N hydrogen bonds between the pyrrole and pyridine rings. In addition, the structures of 4Br7AI and 5Br3Cl7AI are stabilized by C2sbnd H2⋯Br hydrogen bonds. The IR and Raman spectra of all compounds and their N-deuterated derivatives were recorded in the solid state. The theoretical molecular structures and vibrational spectra of the centrosymmetric dimers of five investigated compounds were calculated using the B3LYP method with the 6-311G++(d,p) basis set. The optimized structural parameters and the calculated vibrational spectra reproduce well the experiment. Detailed vibrational assignments for all these compounds have been made on the basis of the calculated potential energy distributions (PEDs). The characteristic marker bands for the chloro- and bromo-derivativeds of 7-azaindoles are reported.

  18. L-Arabinose isomerase and its use for biotechnological production of rare sugars.

    PubMed

    Xu, Zheng; Li, Sha; Feng, Xiaohai; Liang, Jinfeng; Xu, Hong

    2014-11-01

    L-Arabinose isomerase (AI), a key enzyme in the microbial pentose phosphate pathway, has been regarded as an important biological catalyst in rare sugar production. This enzyme could isomerize L-arabinose into L-ribulose, as well as D-galactose into D-tagatose. Both the two monosaccharides show excellent commercial values in food and pharmaceutical industries. With the identification of novel AI family members, some of them have exhibited remarkable potential in industrial applications. The biological production processes for D-tagatose and L-ribose (or L-ribulose) using AI have been developed and improved in recent years. Meanwhile, protein engineering techniques involving rational design has effectively enhanced the catalytic properties of various AIs. Moreover, the crystal structure of AI has been disclosed, which sheds light on the understanding of AI structure and catalytic mechanism at molecular levels. This article reports recent developments in (i) novel AI screening, (ii) AI-mediated rare sugar production processes, (iii) molecular modification of AI, and (iv) structural biology study of AI. Based on previous reports, an analysis of the future development has also been initiated.

  19. Guidelines for the diagnosis and treatment of adrenal insufficiency in the adult.

    PubMed

    de Miguel Novoa, Paz; Vela, Elena Torres; García, Nuria Palacios; Rodríguez, Manuela Moreira; Guerras, Icíar Solache; Martínez de Salinas Santamaría, María de Los Ángeles; Masó, Anna Aulinas

    2014-09-01

    Adrenal insufficiency (AI) is a disease characterized by a deficient production or action of glucocorticoids, with or without deficiency in mineral corticoids and/or adrenal androgens. It can result from disease intrinsic to the adrenal cortex (primary AI), from pituitary diseases that hamper the release of corticotropin (secondary AI) or from hypothalamic disorders that impair the secretion of the corticotropin-releasing hormone (tertiary AI). It is a disease with a low prevalence but its impact on the affected individual is very high as it can be life-threathening if not treated or lead to health problems if inadequately treated. However, currently there are no specific guidelines for the management of this disease. Therefore, at the proposal of the Spanish Society of Endocrinology and Nutrition (SEEN) board, a task-force under the Neuroendocrinology Knowledge Area of the SEEN was established, with the mandate of updating the diagnosis and treatment of AI. In fulfilment of this mandate the task-force has elaborated the present guide that, based on a comprehensive review of literature, is intended to provide an answer to questions related to the management of this disease. It is, therefore, an essentially practical document, mainly aimed at guiding the health professionals involved in the care of IA patients. Copyright © 2014 Sociedad Española de Endocrinología y Nutrición. Published by Elsevier Espana. All rights reserved.

  20. Understanding the role of the immune system in adolescent idiopathic scoliosis: Immunometabolic CONnections to Scoliosis (ICONS) study protocol

    PubMed Central

    Samaan, M Constantine; Missiuna, Paul; Peterson, Devin; Thabane, Lehana

    2016-01-01

    Introduction Adolescent idiopathic scoliosis (AIS) affects up to 3% of children around the world. There is limited knowledge of AIS aetiopathogenesis, and this evidence is needed to develop new management strategies. Paraspinal muscle in AIS demonstrates evidence of differential fibrosis based on curve sidedness. Fibrosis is the hallmark of macrophage-driven inflammation and tissue remodelling, yet the mechanisms of fibrosis in paraspinal muscle in AIS are poorly understood. Objectives The primary objective of this study is to determine the influence of curve sidedness on paraspinal muscle inflammation. Secondary objectives include defining the mechanisms of macrophage homing to muscle, and determining muscle–macrophage crosstalk in muscle fibrosis in AIS. Methods and analysis This is a cross-sectional study conducted in a tertiary paediatric centre in Hamilton, Ontario, Canada. We will recruit boys and girls, 10–17 years of age, who are having surgery to correct AIS. We will exclude children who have an active infection or are on immunosuppressive therapies within 2 weeks of surgery, smokers and pregnant girls. Paraspinal muscle biopsies will be obtained at the start of surgery. Also, blood and urine samples will be collected from participants, who will fill questionnaires about their lifestyle. Anthropometric measures will also be collected including height, weight, waist and hip circumferences. Ethics and dissemination This study has received ethics authorisation by the institutional review board. This work will be published in peer-reviewed journals and will be presented in oral and poster formats at scientific meetings. Discussion This study will explore the mechanisms of paraspinal muscle inflammation, remodelling and fibrosis in AIS. This will help identify pathways and molecules as potential therapeutic targets to treat and prevent AIS. It may also yield markers that predict scoliosis progression and response to treatment in these children. PMID:27401365

  1. Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons.

    PubMed

    Guo, Yu; Su, Zi-Jun; Chen, Yi-Kun; Chai, Zhen

    2017-07-01

    Plasticity of the axon initial segment (AIS) has aroused great interest in recent years because it regulates action potential initiation and neuronal excitability. AIS plasticity manifests as modulation of ion channels or variation in AIS structure. However, the mechanisms underlying structural plasticity of the AIS are not well understood. Here, we combined immunofluorescence, patch-clamp recordings, and pharmacological methods in cultured hippocampal neurons to investigate the factors participating in AIS structural plasticity during development. With lowered neuronal density, the distance between the AIS and the soma increased, while neuronal excitability decreased, as shown by the increased action potential threshold and current threshold for firing an action potential. This variation in the location of the AIS was associated with cellular secretory substances, including brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3). Indeed, blocking BDNF and NT3 with TrkB-Fc eliminated the effect of conditioned medium collected from high-density cultures on AIS relocation. Elevating the extracellular concentration of BDNF or NT3 promoted movement of the AIS proximally to the soma and increased neuronal excitability. Furthermore, knockdown of neurotrophin receptors TrkB and TrkC caused distal movement of the AIS. Our results demonstrate that BDNF and NT3 regulate AIS location and neuronal excitability. These regulatory functions of neurotrophic factors provide insight into the molecular mechanisms underlying AIS biology. © 2017 International Society for Neurochemistry.

  2. The Crystal Structure of the Escherichia coli Autoinducer-2 Processing Protein LsrF

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

    Diaz, Z.; Xavier, K; Miller, S

    2009-01-01

    Many bacteria produce and respond to the quorum sensing signal autoinducer-2 (AI-2). Escherichia coli and Salmonella typhimurium are among the species with the lsr operon, an operon containing AI-2 transport and processing genes that are up regulated in response to AI-2. One of the Lsr proteins, LsrF, has been implicated in processing the phosphorylated form of AI-2. Here, we present the structure of LsrF, unliganded and in complex with two phospho-AI-2 analogues, ribose-5-phosphate and ribulose-5-phosphate. The crystal structure shows that LsrF is a decamer of (??)8-barrels that exhibit a previously unseen N-terminal domain swap and have high structural homology withmore » aldolases that process phosphorylated sugars. Ligand binding sites and key catalytic residues are structurally conserved, strongly implicating LsrF as a class I aldolase.« less

  3. Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: Subtle Features Not to Be Missed.

    PubMed

    Schwock, Joerg; Ko, Hyang Mi; Dubé, Valérie; Rouzbahman, Marjan; Cesari, Matthew; Ghorab, Zeina; Geddie, William R

    2016-01-01

    Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon premalignant lesion of the uterine cervix. A detailed examination of preinvasive SMILE cases including a comparison of the cytologic features with usual-type adenocarcinoma in situ (AIS) and human papillomavirus (HPV) genotyping was performed. Excisions and preceding Papanicolaou (Pap) tests were retrieved from the files of 2 tertiary care centers. Histologic review estimated the lesional SMILE proportion. Pap tests were reviewed and assessed for architectural, cellular and background features. Cobas® HPV test was performed. 13 cases were identified. Mean/median patient age was 35/33 years (range 23-51 years). Concurrent high-grade squamous intraepithelial lesion was found in 10/13 (77%) and AIS in 8/13 (62%) cases. In 6 cases, SMILE was dominant (≥50%) and represented in 5/6 corresponding Pap tests. Cytology interpretations differed more often in the SMILE-dominant group (p < 0.05). SMILE and AIS had overlapping features. Feathering and prominent nucleoli were absent in SMILE. HPV DNA was detected in all 12 cases tested. HPV 18 was most common (7/12). Excisions with positive/suspicious margins were reported in 5/6 SMILE-dominant versus 3/7 nondominant cases. SMILE is best considered as an AIS variant for cytologic, etiologic and management purposes. Cytologic features overlap with AIS, but are more subtle and easily missed. HPV testing may play a role in facilitating SMILE detection. © 2016 S. Karger AG, Basel.

  4. Contributions of the N- and C-terminal helical segments to the lipid-free structure and lipid interaction of apolipoprotein A-I.

    PubMed

    Tanaka, Masafumi; Dhanasekaran, Padmaja; Nguyen, David; Ohta, Shinya; Lund-Katz, Sissel; Phillips, Michael C; Saito, Hiroyuki

    2006-08-29

    The tertiary structure of lipid-free apolipoprotein (apo) A-I in the monomeric state comprises two domains: a N-terminal alpha-helix bundle and a less organized C-terminal domain. This study examined how the N- and C-terminal segments of apoA-I (residues 1-43 and 223-243), which contain the most hydrophobic regions in the molecule and are located in opposite structural domains, contribute to the lipid-free conformation and lipid interaction. Measurements of circular dichroism in conjunction with tryptophan and 8-anilino-1-naphthalenesulfonic acid fluorescence data demonstrated that single (L230P) or triple (L230P/L233P/Y236P) proline insertions into the C-terminal alpha helix disrupted the organization of the C-terminal domain without affecting the stability of the N-terminal helix bundle. In contrast, proline insertion into the N terminus (Y18P) disrupted the bundle structure in the N-terminal domain, indicating that the alpha-helical segment in this region is part of the helix bundle. Calorimetric and gel-filtration measurements showed that disruption of the C-terminal alpha helix significantly reduced the enthalpy and free energy of binding of apoA-I to lipids, whereas disruption of the N-terminal alpha helix had only a small effect on lipid binding. Significantly, the presence of the Y18P mutation offset the negative effects of disruption/removal of the C-terminal helical domain on lipid binding, suggesting that the alpha helix around Y18 concealed a potential lipid-binding region in the N-terminal domain, which was exposed by the disruption of the helix-bundle structure. When these results are taken together, they indicate that the alpha-helical segment in the N terminus of apoA-I modulates the lipid-free structure and lipid interaction in concert with the C-terminal domain.

  5. Artificial intelligence in healthcare: past, present and future.

    PubMed

    Jiang, Fei; Jiang, Yong; Zhi, Hui; Dong, Yi; Li, Hao; Ma, Sufeng; Wang, Yilong; Dong, Qiang; Shen, Haipeng; Wang, Yongjun

    2017-12-01

    Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI.

  6. Artificial intelligence in healthcare: past, present and future

    PubMed Central

    Jiang, Fei; Jiang, Yong; Zhi, Hui; Dong, Yi; Li, Hao; Ma, Sufeng; Wang, Yilong; Dong, Qiang; Shen, Haipeng; Wang, Yongjun

    2017-01-01

    Artificial intelligence (AI) aims to mimic human cognitive functions. It is bringing a paradigm shift to healthcare, powered by increasing availability of healthcare data and rapid progress of analytics techniques. We survey the current status of AI applications in healthcare and discuss its future. AI can be applied to various types of healthcare data (structured and unstructured). Popular AI techniques include machine learning methods for structured data, such as the classical support vector machine and neural network, and the modern deep learning, as well as natural language processing for unstructured data. Major disease areas that use AI tools include cancer, neurology and cardiology. We then review in more details the AI applications in stroke, in the three major areas of early detection and diagnosis, treatment, as well as outcome prediction and prognosis evaluation. We conclude with discussion about pioneer AI systems, such as IBM Watson, and hurdles for real-life deployment of AI. PMID:29507784

  7. Crystal structure of RlmAI: Implications for understanding the 23S rRNA G745/G748-methylation at the macrolide antibiotic-binding site

    PubMed Central

    Das, Kalyan; Acton, Thomas; Chiang, Yiwen; Shih, Lydia; Arnold, Eddy; Montelione, Gaetano T.

    2004-01-01

    The RlmA class of enzymes (RlmAI and RlmAII) catalyzes N1-methylation of a guanine base (G745 in Gram-negative and G748 in Gram-positive bacteria) of hairpin 35 of 23S rRNA. We have determined the crystal structure of Escherichia coli RlmAI at 2.8-Å resolution, providing 3D structure information for the RlmA class of RNA methyltransferases. The dimeric protein structure exhibits features that provide new insights into its molecular function. Each RlmAI molecule has a Zn-binding domain, responsible for specific recognition and binding of its rRNA substrate, and a methyltransferase domain. The asymmetric RlmAI dimer observed in the crystal structure has a well defined W-shaped RNA-binding cleft. Two S-adenosyl-l-methionine substrate molecules are located at the two valleys of the W-shaped RNA-binding cleft. The unique shape of the RNA-binding cleft, different from that of known RNA-binding proteins, is highly specific and structurally complements the 3D structure of hairpin 35 of bacterial 23S rRNA. Apart from the hairpin 35, parts of hairpins 33 and 34 also interact with the RlmAI dimer. PMID:14999102

  8. Correlation between high-resolution remote-sensing imagery and detailed field mapping in Cordilleran Miogeocline

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

    Feldman, S.C.; Taranik, J.V.

    1986-05-01

    Selected areas were mapped at a scale of 1:6000 in the southern hot Creek Range (south-central Nevada), which is underlain by Paleozoic autochthonous limestone, shale, and sandstone, Paleozoic allochthonous chert and siltstone, and Tertiary rhyolitic to dactitic ash flow tuff. The mapping was compared with computer-processed Airborne Imaging Spectrometer (AIS) data and Landsat Thematic Mapper (TM) imagery. The AIS imagery of the Hot Creek Range was acquired in 1984 by a NASA C-130 aircraft; it has a spatial resolution of 12 m, and swath width of 380 m. The sensor was developed by the Jet Propulsion Laboratory and is themore » first in a series of NASA imaging spectrometers. The AIS collects 128 spectral bands, having a bandwidth of approximately 9 nm, in the short-wave infrared between 1.2 and 2.4 ..mu..m. This part of the spectrum contains important narrow spectral absorption features for the carbonate ion, hydroxyl ion, and water of hydration. Using computer-processed AIS imagery, therefore, the authors can separate calcite from dolomite, and kaolinite from illite and montmorillonite as well as differentiate geologic units containing these minerals. On the AIS imagery, the Upper Mississippian Tripon Pass Limestone shows a distinctive calcite absorption feature at 2.34 ..mu..m; this feature is not as pronounced in Cambrian and Ordovician limestones. The dolomitized Nevada Formation exhibits the dolomite absorption feature at 2.32 ..mu..m. Clay mineral absorption features near 2.2 ..mu..m can be distinguished in altered volcanics. Mineralogic identification was confirmed with field and laboratory spectroradiometer measurements, thin-section examination, and x-ray analysis. AIS results and field mapping were also compared to computer-processed Landsat TM imagery, the highest spectral and spatial resolution worldwide data set currently available.« less

  9. Improving cancer care for American Indians with cervical cancer in the Indian Health Service (IHS) system - Navigation may not be enough.

    PubMed

    Dockery, Lauren E; Motwani, Anita; Ding, Kai; Doescher, Mark; Dvorak, Justin D; Moore, Kathleen N; Holman, Laura L

    2018-04-01

    Patient navigation programs have been shown to positively impact cancer outcomes for minority populations. Little is known regarding the effects of these programs on American Indian (AI) populations. The purpose of this study is to characterize the impact of a patient navigation program on AI cervical cancer patients at a tertiary care center. A retrospective review of all AI cervical cancer patients receiving navigation services and a cohort of AI patients treated prior to navigation services was performed. Additional comparisons were made between those with and without Indian Health Service (IHS) funding. Summary statistics were used to describe demographic, clinical characteristics, treatment, and survivorship across groups. Of 55 patients identified, 34 received navigation and 21 did not. In navigated patients, median age was 46years (27-80years) compared with 42years (17-68years) in pre-navigation patients (p=0.53). There was no difference between stage at diagnosis (p=0.73). No difference was noted in treatment received between groups (p=0.48). Distance traveled for treatment between groups did not differ (p=0.46). Median time to initiation of treatment was not different between groups, 30.5days vs. 27.5days (p=0.18). Among patients with IHS funding, navigation services did not alter time to initiation of treatment (p=0.57), and there was no difference in completion of prescribed therapy between groups (92% navigated vs 100% pre-navigation). Navigation services for AI cervical cancer patients did not alter initiation or completion of treatment. Navigation programs may provide less tangible benefits to AI cervical cancer patients and further study is warranted. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity

    PubMed Central

    Svitkina, Tatyana M.

    2016-01-01

    The axon initial segment (AIS) is a specialized structure in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in neurons is ideal for its two major functions: it serves as the site of action potential firing and helps to maintain neuron polarity. It has become increasingly clear that the AIS cytoskeleton is fundamental to AIS functions. In this review, we discuss current understanding of the AIS cytoskeleton with particular interest in its unique architecture and role in maintenance of neuron polarity. The AIS cytoskeleton is divided into two parts, submembrane and cytoplasmic, based on localization, function, and molecular composition. Recent studies using electron and subdiffraction fluorescence microscopy indicate that submembrane cytoskeletal components (ankyrin G, βIV-spectrin, and actin filaments) form a sophisticated network in the AIS that is conceptually similar to the polygonal/triangular network of erythrocytes, with some important differences. Components of the AIS cytoplasmic cytoskeleton (microtubules, actin filaments, and neurofilaments) reside deeper within the AIS shaft and display structural features distinct from other neuronal domains. We discuss how the AIS submembrane and cytoplasmic cytoskeletons contribute to different aspects of AIS polarity function and highlight recent advances in understanding their AIS cytoskeletal assembly and stability. PMID:27493806

  11. Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms

    PubMed Central

    Goyal, Nitin; Tsivgoulis, Georgios; Zand, Ramin; Sharma, Vijay K.; Barlinn, Kristian; Male, Shailesh; Katsanos, Aristeidis H.; Bodechtel, Ulf; Iftikhar, Sulaiman; Arthur, Adam; Elijovich, Lucas; Alexandrov, Anne W.

    2015-01-01

    Objective: We sought to determine the safety of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a multicenter study and a comprehensive meta-analysis of available case series. Methods: We analyzed prospectively collected data from consecutive AIS patients treated with IVT during a 4-year period at 4 tertiary-care stroke centers. All patients routinely underwent CT or magnetic resonance angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIH Stroke Scale score of ≥4 points. A systematic meta-analysis of case series reporting safety of IVT in AIS with concomitant UIA was conducted according to PRISMA recommendations. Results: Among 1,398 AIS patients treated with IVT, we identified 42 cases (3.0%) harboring a total of 48 UIAs. The rates of symptomatic and asymptomatic ICH were 2.4% (95% confidence interval [CI] by adjusted Wald method: 0%–12.6%) and 7.1% (95% CI: 1.8%–19.7%), respectively. A total of 5 case series met our inclusion criteria for meta-analysis, and the pooled rate of sICH among 120 IVT-treated AIS patients harboring UIA was 6.7% (95% CI: 3.1%–13.7%). In the overall analysis of 5 case-series studies, the risk ratio of sICH did not differ between AIS patients with and without UIA (risk ratio = 1.60; 95% CI: 0.54–4.77; p = 0.40) with no evidence of heterogeneity across included studies (I2 = 22% and p = 0.27 for Cochran Q test). Conclusions: Our prospectively collected multicenter data, coupled with the findings of the meta-analysis, indicate the potential safety of IVT in AIS patients with UIA. PMID:26408492

  12. Systemic thrombolysis in acute ischemic stroke patients with unruptured intracranial aneurysms.

    PubMed

    Goyal, Nitin; Tsivgoulis, Georgios; Zand, Ramin; Sharma, Vijay K; Barlinn, Kristian; Male, Shailesh; Katsanos, Aristeidis H; Bodechtel, Ulf; Iftikhar, Sulaiman; Arthur, Adam; Elijovich, Lucas; Alexandrov, Anne W; Alexandrov, Andrei V

    2015-10-27

    We sought to determine the safety of IV thrombolysis (IVT) in acute ischemic stroke (AIS) patients harboring unruptured intracranial aneurysm (UIA) in a multicenter study and a comprehensive meta-analysis of available case series. We analyzed prospectively collected data from consecutive AIS patients treated with IVT during a 4-year period at 4 tertiary-care stroke centers. All patients routinely underwent CT or magnetic resonance angiography during hospitalization. The presence of UIA was documented on the basis of neuroradiology reports. Symptomatic intracranial hemorrhage (sICH) was defined as imaging evidence of ICH combined with an increase in NIH Stroke Scale score of ≥4 points. A systematic meta-analysis of case series reporting safety of IVT in AIS with concomitant UIA was conducted according to PRISMA recommendations. Among 1,398 AIS patients treated with IVT, we identified 42 cases (3.0%) harboring a total of 48 UIAs. The rates of symptomatic and asymptomatic ICH were 2.4% (95% confidence interval [CI] by adjusted Wald method: 0%-12.6%) and 7.1% (95% CI: 1.8%-19.7%), respectively. A total of 5 case series met our inclusion criteria for meta-analysis, and the pooled rate of sICH among 120 IVT-treated AIS patients harboring UIA was 6.7% (95% CI: 3.1%-13.7%). In the overall analysis of 5 case-series studies, the risk ratio of sICH did not differ between AIS patients with and without UIA (risk ratio = 1.60; 95% CI: 0.54-4.77; p = 0.40) with no evidence of heterogeneity across included studies (I(2) = 22% and p = 0.27 for Cochran Q test). Our prospectively collected multicenter data, coupled with the findings of the meta-analysis, indicate the potential safety of IVT in AIS patients with UIA. © 2015 American Academy of Neurology.

  13. The exponential function transforms the Abbreviated Injury Scale, which both improves accuracy and simplifies scoring.

    PubMed

    Wang, M D; Fan, W H; Qiu, W S; Zhang, Z L; Mo, Y N; Qiu, F

    2014-06-01

    We present here the exponential function which transforms the Abbreviated Injury Scale (AIS). It is called the Exponential Injury Severity Score (EISS), and significantly outperforms the venerable but dated New Injury Severity Score (NISS) and Injury Severity Score (ISS) as a predictor of mortality. The EISS is defined as a change of AIS values by raising each AIS severity score (1-6) by 3 taking a power of AIS minus 2 and then summing the three most severe injuries (i.e., highest AIS), regardless of body regions. EISS values were calculated for every patient in two large independent data sets: 3,911 and 4,129 patients treated during a 6-year period at the Class A tertiary hospitals in China. The power of the EISS to predict mortality was then compared with previously calculated NISS values for the same patients in each of the two data sets. We found that the EISS is more predictive of survival [Zhejiang: area under the receiver operating characteristic curve (AUC): NISS = 0.932, EISS = 0.949, P = 0.0115; Liaoning: AUC: NISS = 0.924, EISS = 0.942, P = 0.0139]. Moreover, the EISS provides a better fit throughout its entire range of prediction (Hosmer-Lemeshow statistic for Zhejiang: NISS = 21.86, P = 0.0027, EISS = 13.52, P = 0.0604; Liaoning: NISS = 23.27, P = 0.0015, EISS = 15.55, P = 0.0164). The EISS may be used as the standard summary measure of human trauma.

  14. Structure of the thermophilic l-Arabinose isomerase from Geobacillus kaustophilus reveals metal-mediated intersubunit interactions for activity and thermostability.

    PubMed

    Choi, Jin Myung; Lee, Yong-Jik; Cao, Thinh-Phat; Shin, Sun-Mi; Park, Min-Kyu; Lee, Han-Seung; di Luccio, Eric; Kim, Seong-Bo; Lee, Sang-Jae; Lee, Sang Jun; Lee, Sung Haeng; Lee, Dong-Woo

    2016-04-15

    Thermophilic l-arabinose isomerase (AI), which catalyzes the interconversion of l-arabinose and l-ribulose, can be used to produce d-tagatose, a sugar substitute, from d-galactose. Unlike mesophilic AIs, thermophilic AIs are highly dependent on divalent metal ions for their catalytic activity and thermostability at elevated temperatures. However, the molecular basis underlying the substrate preferences and metal requirements of multimeric AIs remains unclear. Here we report the first crystal structure of the apo and holo forms of thermophilic Geobacillus kaustophilus AI (GKAI) in hexamer form. The structures, including those of GKAI in complex with l-arabitol, and biochemical analyses revealed not only how the substrate-binding site of GKAI is formed through displacement of residues at the intersubunit interface when it is bound to Mn(2+), but also revealed the water-mediated H-bonding networks that contribute to the structural integrity of GKAI during catalysis. These observations suggest metal-mediated isomerization reactions brought about by intersubunit interactions at elevated temperatures are responsible for the distinct active site features that promote the substrate specificity and thermostability of thermophilic AIs. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Structure and inhibition analysis of the mouse SAD-B C-terminal fragment.

    PubMed

    Ma, Hui; Wu, Jing-Xiang; Wang, Jue; Wang, Zhi-Xin; Wu, Jia-Wei

    2016-10-01

    The SAD (synapses of amphids defective) kinases, including SAD-A and SAD-B, play important roles in the regulation of neuronal development, cell cycle, and energy metabolism. Our recent study of mouse SAD-A identified a unique autoinhibitory sequence (AIS), which binds at the junction of the kinase domain (KD) and the ubiquitin-associated (UBA) domain and exerts autoregulation in cooperation with UBA. Here, we report the crystal structure of the mouse SAD-B C-terminal fragment including the AIS and the kinase-associated domain 1 (KA1) at 2.8 Å resolution. The KA1 domain is structurally conserved, while the isolated AIS sequence is highly flexible and solvent-accessible. Our biochemical studies indicated that the SAD-B AIS exerts the same autoinhibitory role as that in SAD-A. We believe that the flexible isolated AIS sequence is readily available for interaction with KD-UBA and thus inhibits SAD-B activity.

  16. A First Look at Airborne Imaging Spectrometer (AIS) Data in an Area of Altered Volcanic Rocks and Carbonate Formations, Hot Creek Range, South Central Nevada

    NASA Technical Reports Server (NTRS)

    Feldman, S. C.; Taranik, J. V.; Mouat, D. A.

    1985-01-01

    Three flight lines of Airborne Imaging Spectrometer (AIS) data were collected in 128 bands between 1.2 and 2.4 microns in the Hot Creek Range, Nevada on July 25, 1984. The flight lines are underlain by hydrothermally altered and unaltered Paleozoic carbonates and Tertiary rhyolitic to latitic volcanics in the Tybo mining district. The original project objectives were to discriminate carbonate rocks from other rock types, to distinguish limestone from dolomite, and to discriminate carbonate units from each other using AIS imagery. Because of high cloud cover over the prime carbonate flight line and because of the acquisition of another flight line in altered and unaltered volcanics, the study has been extended to the discrimination of alteration products. In an area of altered and unaltered rhyolites and latites in Red Rock Canyon, altered and unaltered rock could be discriminated from each other using spectral features in the 1.16 to 2.34 micron range. The altered spectral signatures resembled montmorillonite and kaolinite. Field samples were gathered and the presence of montmorillonite was confirmed by X-ray analysis.

  17. Automated diabetic retinopathy detection in smartphone-based fundus photography using artificial intelligence.

    PubMed

    Rajalakshmi, Ramachandran; Subashini, Radhakrishnan; Anjana, Ranjit Mohan; Mohan, Viswanathan

    2018-06-01

    To assess the role of artificial intelligence (AI)-based automated software for detection of diabetic retinopathy (DR) and sight-threatening DR (STDR) by fundus photography taken using a smartphone-based device and validate it against ophthalmologist's grading. Three hundred and one patients with type 2 diabetes underwent retinal photography with Remidio 'Fundus on phone' (FOP), a smartphone-based device, at a tertiary care diabetes centre in India. Grading of DR was performed by the ophthalmologists using International Clinical DR (ICDR) classification scale. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The retinal photographs were graded using a validated AI DR screening software (EyeArt TM ) designed to identify DR, referable DR (moderate non-proliferative DR or worse and/or DME) or STDR. The sensitivity and specificity of automated grading were assessed and validated against the ophthalmologists' grading. Retinal images of 296 patients were graded. DR was detected by the ophthalmologists in 191 (64.5%) and by the AI software in 203 (68.6%) patients while STDR was detected in 112 (37.8%) and 146 (49.3%) patients, respectively. The AI software showed 95.8% (95% CI 92.9-98.7) sensitivity and 80.2% (95% CI 72.6-87.8) specificity for detecting any DR and 99.1% (95% CI 95.1-99.9) sensitivity and 80.4% (95% CI 73.9-85.9) specificity in detecting STDR with a kappa agreement of k = 0.78 (p < 0.001) and k = 0.75 (p < 0.001), respectively. Automated AI analysis of FOP smartphone retinal imaging has very high sensitivity for detecting DR and STDR and thus can be an initial tool for mass retinal screening in people with diabetes.

  18. The natural logarithm transforms the abbreviated injury scale and improves accuracy scoring.

    PubMed

    Wang, Xu; Gu, Xiaoming; Zhang, Zhiliang; Qiu, Fang; Zhang, Keming

    2012-11-01

    The Injury Severity Score (ISS) and the New Injury Severity Score (NISS) are widely used for anatomic severity assessments, but they do not display a linear relation to mortality. The mortality rates are significantly different between pairs of the Abbreviated Injury Scale (AIS) triplets that generate the same ISS/NISS total. The Logarithm Injury Severity Score (LISS) is defined as a change in AIS values by raising each AIS severity score (1-6) by taking the natural logarithm to a power of 5.53 multiplied by 1.7987 and then adding the three most severe injuries (i.e. highest AIS), regardless of body region. LISS values were calculated for every patient in three large independent data sets: 3,784, 4,436, and 4,018 patients treated over a six-year period at Class A tertiary comprehensive hospitals in China. The power of LISS to predict morality was then compared with previously calculated NISS values for the same patients in each of the three data sets. We found that LISS is more predictive of survival as well (Hangzhou: receiver operating characteristic (ROC): NISS=0.931, LISS=0.949, p=0.006; Similarly, Zhejiang and Shenyang: ROC NISS vs. LISS, p<0.05). Moreover, LISS provides a better fit throughout its entire range of predicting (Hosmer-Lemeshow statistic for Hangzhou NISS=15.76, p=0.027; LISS=13.79, p=0.055; Similarly, for Zhejiang and Shenyang). LISS should be used as the standard summary measure of human trauma.

  19. Pelvic Floor Disorders 6 Months after Attempted Operative Vaginal Delivery According to the Fetal Head Station: A Prospective Cohort Study

    PubMed Central

    Ducarme, Guillaume; Hamel, Jean-François; Brun, Stéphanie; Madar, Hugo; Merlot, Benjamin; Sentilhes, Loïc

    2016-01-01

    Objective To evaluate the effect of the fetal head station at attempted operative vaginal delivery (aOVD), and specifically midpelvic or low aOVD, on urinary incontinence (UI), anal incontinence (AI), and perineal pain at 6 months. Design Prospective cohort study. Setting 1941 women with singleton term fetuses in vertex presentation with midpelvic or low aOVD between 2008 and 2013 in a tertiary care university hospital. Methods Symptoms of urinary incontinence (UI) using the Bristol Female Lower Urinary Tract Symptoms questionnaire, and symptoms of anal incontinence (AI) severity using Fecal Incontinence Severity Index (FISI) were assessed 6 months after aOVD. We measured the association between midpelvic or low aOVD and symptoms of UI, AI, and perineal pain at 6 months using multiple regression and adjusting for demographics, and risk factors of UI and AI, with adjusted odds ratios (aORs) and 95% confidence intervals (95% CI). Results The study included 907 women (46.7%) who responded to the questionnaire; 18.4% (167/907) had midpelvic aOVD, and 81.6% (740/907) low; and none of women with symptoms of UI (26.6%, and 22.4%, respectively; p = 0.31), AI (15.9%, and 21.8%; p = 0.09), the FISI score, and perineal pain (17.2%, and 12.7%; p = 0.14) differed significantly between groups. The same was true for stress, urge, and mixed-type UI, severe UI and difficulty voiding. Compared with low pelvic aOVD, the aORs for symptoms of UI in midpelvic aOVD were 0.70 (0.46–1.05) and AI 1.42 (0.85–2.39). Third- and fourth-degree tears were a major risk factor of symptoms of UI (aOR 3.08, 95% CI 1.35–7.00) and AI (aOR 3.47, 95% CI 1.43–8.39). Conclusion Neither symptoms of urinary nor anal incontinence differed at 6 months among women who had midpelvic and low pelvic aOVD. These findings are reassuring and need further studies at long-term to confirm these short-term data. PMID:27992558

  20. Nanoscopic compartmentalization of membrane protein motion at the axon initial segment.

    PubMed

    Albrecht, David; Winterflood, Christian M; Sadeghi, Mohsen; Tschager, Thomas; Noé, Frank; Ewers, Helge

    2016-10-10

    The axon initial segment (AIS) is enriched in specific adaptor, cytoskeletal, and transmembrane molecules. During AIS establishment, a membrane diffusion barrier is formed between the axonal and somatodendritic domains. Recently, an axonal periodic pattern of actin, spectrin, and ankyrin forming 190-nm-spaced, ring-like structures has been discovered. However, whether this structure is related to the diffusion barrier function is unclear. Here, we performed single-particle tracking time-course experiments on hippocampal neurons during AIS development. We analyzed the mobility of lipid-anchored molecules by high-speed single-particle tracking and correlated positions of membrane molecules with the nanoscopic organization of the AIS cytoskeleton. We observe a strong reduction in mobility early in AIS development. Membrane protein motion in the AIS plasma membrane is confined to a repetitive pattern of ∼190-nm-spaced segments along the AIS axis as early as day in vitro 4, and this pattern alternates with actin rings. Mathematical modeling shows that diffusion barriers between the segments significantly reduce lateral diffusion along the axon. © 2016 Albrecht et al.

  1. Urban American Indian Adolescent Girls: Framing Sexual Risk Behavior

    PubMed Central

    Martyn, Kristy K.; Momper, Sandra L.; Loveland-Cherry, Carol J.; Low, Lisa Kane

    2014-01-01

    Purpose American Indian (AI) adolescent girls have higher rates of sexual activity, births and STIs compared to the national average. The purpose of this study was to explore factors that influence urban adolescent AI girls' sexual risk behavior (SRB). Design A qualitative study was conducted using grounded theory methodology to reveal factors and processes that influence SRB. Methods Talking circles, individual interviews, and event history calendars were used with 20 urban AI 15-19 year old girls to explore influences on their sexual behavior. Findings The generated theory, Framing Sexual Risk Behavior, describes both social and structural factors and processes that influenced the girls' sexual behaviors. The theory extends Bronfenbrenner's ecological model by identifying microsystem, mesosystem, and macrosystem influences on sexual behavior, including: Microsystem: Being “Normal,” Native, and Having Goals; Mesosystem: Networks of Family and Friends, Environmental Influences, and Sex Education; and Macrosystem: Tribal Traditions/History and Federal Policy. Discussion Urban AI girls reported similar social and structural influences on SRB as urban adolescents from other racial and ethnic groups. However, differences were noted in the family structure, cultural heritage, and unique history of AIs. Implications for Practice This theory can be used in culturally responsive practice with urban AI girls. PMID:24803532

  2. Lessons from a large trauma center: impact of blunt chest trauma in polytrauma patients-still a relevant problem?

    PubMed

    Chrysou, Konstantina; Halat, Gabriel; Hoksch, Beatrix; Schmid, Ralph A; Kocher, Gregor J

    2017-04-20

    Thoracic trauma is the third most common cause of death after abdominal injury and head trauma in polytrauma patients. The purpose of this study was to investigate epidemiological data, treatment and outcome of polytrauma patients with blunt chest trauma in order to help improve management, prevent complications and decrease polytrauma patients' mortality. In this retrospective study we included all polytrauma patients with blunt chest trauma admitted to our tertiary care center emergency department for a 2-year period, from June 2012 until May 2014. Data collection included details of treatment and outcome. Patients with chest trauma and Injury Severity Score (ISS) ≥18 and Abbreviated Injury Scale (AIS) >2 in more than one body region were included. A total of 110 polytrauma patients with blunt chest injury were evaluated. 82 of them were males and median age was 48.5 years. Car accidents, falls from a height and motorbike accidents were the most common causes (>75%) for blunt chest trauma. Rib fractures, pneumothorax and pulmonary contusion were the most common chest injuries. Most patients (64.5%) sustained a serious chest injury (AIS thorax 3), 19.1% a severe chest injury (AIS thorax 4) and 15.5% a moderate chest injury (AIS thorax 2). 90% of patients with blunt chest trauma were treated conservatively. Chest tube insertion was indicated in 54.5% of patients. The need for chest tube was significantly higher among the AIS thorax 4 group in comparison to the AIS groups 3 and 2 (p < 0.001). Also, admission to the ICU was directly related to the severity of the AIS thorax (p < 0.001). The severity of chest trauma did not correlate with ICU length of stay, intubation days, complications or mortality. Although 84.5% of patients suffered from serious or even severe chest injury, neither in the conservative nor in the surgically treated group a significant impact of injury severity on ICU stay, intubation days, complications or mortality was observed. AIS thorax was only related to the rate of chest tube insertions and ICU admission. Management with early chest tube insertion when necessary, pain control and chest physiotherapy resulted in good outcome in the majority of patients.

  3. Modeling of the phase evolution in Mg1-xAlxB2 (0

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

    Andersson, Anders David; Casillas, Luis; Lezama Pacheco, Juan

    Despite the chemical and structural simplicity of MgB{sub 2}, at 39 K this compound has the highest known {Tc} of any binary compound. Electron doping by substituting Al for Mg leads to decreasing Tc and the observed concentration dependent rate of decrease has been proposed to arise from the non-ideal character of MgB{sub 2}-AIB{sub 2} solid solutions, which derives from the existence of an ordered Mg{sub 0.5}Al{sub 0.5}B{sub 2} compound. Heterogeneous nano-scale structure patterns in solid solutions have emerged as an important concept for complex materials, ranging from actinide alloys and oxides to high-temperature cuprate superconductors and mallganite-based materials exhibitingmore » colossal magnetoresistivity. In this work we investigate the formation of structural heterogeneities in Mg{sub 1-x}AI{sub x}B{sub 2}, which take the form of nano-scale AI-AI and AI-Mg domains of different geometry and size, using molecular statics/dynamics simulations and in particular we study the corresponding signatures in diffraction experiments. In order to undertake this task we first derive appropriate Mg-AI-B semi-empirical potentials within the Modified Embedded Atom Method formalism. These potentials are also applied to explore the equilibrium Mg{sub 1-x}AI{sub x}B{sub 2} phase diagram for 0 < x < 0.5. Additionally, density functional theory calculations were utilized to study the influence of heterogeneities on the electronic structure and charge distribution in Mg{sub 1-x}AI{sub x}B{sub 2}.« less

  4. Atomistic study on the FCC/BCC interface structure with {112}KS orientation

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

    Kang, Keonwook; Beyerlein, Irene; Han, Weizhong

    2011-09-23

    In this study, atomistic simulation is used to explore the atomic interface structure, the intrinsic defect network, and mechanism of twin formation from the {112}KS Cu-Nb interface. The interface structure of different material systems AI-Fe and AI-Nb are also compared with Cu-Nb interface.

  5. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    EPA Science Inventory

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  6. Robust inference of population structure for ancestry prediction and correction of stratification in the presence of relatedness.

    PubMed

    Conomos, Matthew P; Miller, Michael B; Thornton, Timothy A

    2015-05-01

    Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model-based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC-AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC-AiR utilizes genome-screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC-AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC-AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC-AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC-AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness. © 2015 WILEY PERIODICALS, INC.

  7. On the Nature of Intelligence

    NASA Astrophysics Data System (ADS)

    Churchland, Paul M.

    Alan Turing is the consensus patron saint of the classical research program in Artificial Intelligence (AI), and his behavioral test for the possession of conscious intelligence has become his principal legacy in the mind of the academic public. Both takes are mistakes. That test is a dialectical throwaway line even for Turing himself, a tertiary gesture aimed at softening the intellectual resistance to a research program which, in his hands, possessed real substance, both mathematical and theoretical. The wrangling over his celebrated test has deflected attention away from those more substantial achievements, and away from the enduring obligation to construct a substantive theory of what conscious intelligence really is, as opposed to an epistemological account of how to tell when you are confronting an instance of it. This essay explores Turing's substantive research program on the nature of intelligence, and argues that the classical AI program is not its best expression, nor even the expression intended by Turing. It then attempts to put the famous Test into its proper, and much reduced, perspective.

  8. Effects of amyloid-β plaque proximity on the axon initial segment of pyramidal cells.

    PubMed

    León-Espinosa, Gonzalo; DeFelipe, Javier; Muñoz, Alberto

    2012-01-01

    The output of cortical pyramidal cells reflects the balance between excitatory inputs of cortical and subcortical origin, and inhibitory inputs from distinct populations of cortical GABAergic interneurons, each of which selectively innervate different domains of neuronal pyramidal cells (i.e., dendrites, soma and axon initial segment [AIS]). In Alzheimer's disease (AD), the presence of amyloid-β (Aβ) plaques alters the synaptic input to pyramidal cells in a number of ways. However, the effects of Aβ plaques on the AIS have still not been investigated to date. This neuronal domain is involved in input integration, as well as action potential initiation and propagation, and it exhibits Ca2+- and activity-dependent structural plasticity. The AIS is innervated by GABAergic axon terminals from chandelier cells, which are thought to exert a strong influence on pyramidal cell output. In the AβPP/PS1 transgenic mouse model of AD, we have investigated the effects of Aβ plaques on the morphological and neurochemical features of the AIS, including the cisternal organelle, using immunocytochemistry and confocal microscopy, as well as studying the innervation of the AIS by chandelier cell axon terminals. There is a strong reduction in GABAergic terminals that appose AIS membrane surfaces that are in contact with Aβ plaques, indicating altered inhibitory synapsis at the AIS. Thus, despite a lack of gross structural alterations in the AIS, this decrease in GABAergic innervation may deregulate AIS activity and contribute to the hyperactivity of neurons in contact with Aβ plaques.

  9. LsrF, a coenzyme A-dependent thiolase, catalyzes the terminal step in processing the quorum sensing signal autoinducer-2

    PubMed Central

    Marques, João C.; Oh, Il Kyu; Ly, Daniel C.; Lamosa, Pedro; Ventura, M. Rita; Miller, Stephen T.; Xavier, Karina B.

    2014-01-01

    The quorum sensing signal autoinducer-2 (AI-2) regulates important bacterial behaviors, including biofilm formation and the production of virulence factors. Some bacteria, such as Escherichia coli, can quench the AI-2 signal produced by a variety of species present in the environment, and thus can influence AI-2–dependent bacterial behaviors. This process involves uptake of AI-2 via the Lsr transporter, followed by phosphorylation and consequent intracellular sequestration. Here we determine the metabolic fate of intracellular AI-2 by characterizing LsrF, the terminal protein in the Lsr AI-2 processing pathway. We identify the substrates of LsrF as 3-hydroxy-2,4-pentadione-5-phosphate (P-HPD, an isomer of AI-2-phosphate) and coenzyme A, determine the crystal structure of an LsrF catalytic mutant bound to P-HPD, and identify the reaction products. We show that LsrF catalyzes the transfer of an acetyl group from P-HPD to coenzyme A yielding dihydroxyacetone phosphate and acetyl-CoA, two key central metabolites. We further propose that LsrF, despite strong structural homology to aldolases, acts as a thiolase, an activity previously undescribed for this family of enzymes. With this work, we have fully characterized the biological pathway for AI-2 processing in E. coli, a pathway that can be used to quench AI-2 and control quorum-sensing–regulated bacterial behaviors. PMID:25225400

  10. Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions.

    PubMed

    Wiech, K; Jbabdi, S; Lin, C S; Andersson, J; Tracey, I

    2014-10-01

    Functional neuroimaging studies suggest that the anterior, mid, and posterior division of the insula subserve different functions in the perception of pain. The anterior insula (AI) has predominantly been associated with cognitive-affective aspects of pain, while the mid and posterior divisions have been implicated in sensory-discriminative processing. We examined whether this functional segregation is paralleled by differences in (1) structural and (2) resting state connectivity and (3) in correlations with pain-relevant psychological traits. Analyses were restricted to the 3 insular subdivisions and other pain-related brain regions. Both type of analyses revealed largely overlapping results. The AI division was predominantly connected to the ventrolateral prefrontal cortex (structural and resting state connectivity) and orbitofrontal cortex (structural connectivity). In contrast, the posterior insula showed strong connections to the primary somatosensory cortex (SI; structural connectivity) and secondary somatosensory cortex (SII; structural and resting state connectivity). The mid insula displayed a hybrid connectivity pattern with strong connections with the ventrolateral prefrontal cortex, SII (structural and resting state connectivity) and SI (structural connectivity). Moreover, resting state connectivity revealed strong connectivity of all 3 subdivisions with the thalamus. On the behavioural level, AI structural connectivity was related to the individual degree of pain vigilance and awareness that showed a positive correlation with AI-amygdala connectivity and a negative correlation with AI-rostral anterior cingulate cortex connectivity. In sum, our findings show a differential structural and resting state connectivity for the anterior, mid, and posterior insula with other pain-relevant brain regions, which might at least partly explain their different functional profiles in pain processing. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library.

    PubMed

    Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L; Merrick, B Alex; Teng, Christina T; Tice, Raymond R

    2015-10-01

    Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Cell-Based High-Throughput Screening for Aromatase Inhibitors in the Tox21 10K Library

    PubMed Central

    Chen, Shiuan; Hsieh, Jui-Hua; Huang, Ruili; Sakamuru, Srilatha; Hsin, Li-Yu; Xia, Menghang; Shockley, Keith R.; Auerbach, Scott; Kanaya, Noriko; Lu, Hannah; Svoboda, Daniel; Witt, Kristine L.; Merrick, B. Alex; Teng, Christina T.; Tice, Raymond R.

    2015-01-01

    Multiple mechanisms exist for endocrine disruption; one nonreceptor-mediated mechanism is via effects on aromatase, an enzyme critical for maintaining the normal in vivo balance of androgens and estrogens. We adapted the AroER tri-screen 96-well assay to 1536-well format to identify potential aromatase inhibitors (AIs) in the U.S. Tox21 10K compound library. In this assay, screening with compound alone identifies estrogen receptor alpha (ERα) agonists, screening in the presence of testosterone (T) identifies AIs and/or ERα antagonists, and screening in the presence of 17β-estradiol (E2) identifies ERα antagonists. Screening the Tox-21 library in the presence of T resulted in finding 302 potential AIs. These compounds, along with 31 known AI actives and inactives, were rescreened using all 3 assay formats. Of the 333 compounds tested, 113 (34%; 63 actives, 50 marginal actives) were considered to be potential AIs independent of cytotoxicity and ER antagonism activity. Structure-activity analysis suggested the presence of both conventional (eg, 1, 2, 4, - triazole class) and novel AI structures. Due to their novel structures, 14 of the 63 potential AI actives, including both drugs and fungicides, were selected for confirmation in the biochemical tritiated water-release aromatase assay. Ten compounds were active in the assay; the remaining 4 were only active in high-throughput screen assay, but with low efficacy. To further characterize these 10 novel AIs, we investigated their binding characteristics. The AroER tri-screen, in high-throughput format, accurately and efficiently identified chemicals in a large and diverse chemical library that selectively interact with aromatase. PMID:26141389

  13. Playing to Your Strengths: Appreciative Inquiry in the Visioning Process

    ERIC Educational Resources Information Center

    Fifolt, Matthew; Stowe, Angela M.

    2011-01-01

    "Appreciative Inquiry" (AI) is a structured approach to visioning focused on reflection, introspection, and collaboration. Rooted in organizational behavior theory, AI was introduced in the early 1980s as a life-centric approach to human systems (Watkins and Mohr 2001). Since then, AI has been used widely within the business community;…

  14. Oxidative Stress Induces Disruption of the Axon Initial Segment

    PubMed Central

    Clark, Kareem C.; Sword, Brooke A.; Dupree, Jeffrey L.

    2017-01-01

    The axon initial segment (AIS), the domain responsible for action potential initiation and maintenance of neuronal polarity, is targeted for disruption in a variety of central nervous system pathological insults. Previous work in our laboratory implicates oxidative stress as a potential mediator of structural AIS alterations in two separate mouse models of central nervous system inflammation, as these effects were attenuated following reactive oxygen species scavenging and NADPH oxidase-2 ablation. While these studies suggest a role for oxidative stress in modulation of the AIS, the direct effects of reactive oxygen and nitrogen species (ROS/RNS) on the stability of this domain remain unclear. Here, we demonstrate that oxidative stress, as induced through treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator, drives a reversible loss of AIS protein clustering in primary cortical neurons in vitro. Pharmacological inhibition of both voltage-dependent and intracellular calcium (Ca2+) channels suggests that this mechanism of AIS disruption involves Ca2+ entry specifically through L-type voltage-dependent Ca2+ channels and its release from IP3-gated intracellular stores. Furthermore, ROS/RNS-induced AIS disruption is dependent upon activation of calpain, a Ca2+-activated protease previously shown to drive AIS modulation. Overall, we demonstrate for the first time that oxidative stress, as induced through exogenously applied ROS/RNS, is capable of driving structural alterations in the AIS complex. PMID:29228786

  15. A model of lipid-free Apolipoprotein A-I revealed by iterative molecular dynamics simulation

    DOE PAGES

    Zhang, Xing; Lei, Dongsheng; Zhang, Lei; ...

    2015-03-20

    Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, has been proven inversely correlated to cardiovascular risk in past decades. The lipid-free state of apo A-I is the initial stage which binds to lipids forming high-density lipoprotein. Molecular models of lipid-free apo A-I have been reported by methods like X-ray crystallography and chemical cross-linking/mass spectrometry (CCL/MS). Through structural analysis we found that those current models had limited consistency with other experimental results, such as those from hydrogen exchange with mass spectrometry. Through molecular dynamics simulations, we also found those models could not reach a stable equilibrium state. Therefore,more » by integrating various experimental results, we proposed a new structural model for lipidfree apo A-I, which contains a bundled four-helix N-terminal domain (1–192) that forms a variable hydrophobic groove and a mobile short hairpin C-terminal domain (193–243). This model exhibits an equilibrium state through molecular dynamics simulation and is consistent with most of the experimental results known from CCL/MS on lysine pairs, fluorescence resonance energy transfer and hydrogen exchange. This solution-state lipid-free apo A-I model may elucidate the possible conformational transitions of apo A-I binding with lipids in high-density lipoprotein formation.« less

  16. Protective effect of tadalafil on the functional and structural changes of the rat ventral prostate caused by chronic pelvic ischemia.

    PubMed

    Zarifpour, Mona; Nomiya, Masanori; Sawada, Norifumi; Andersson, Karl-Erik

    2015-02-15

    The etiology of Benign Prostatic Hyperplasia (BPH), a common among aged men, is not fully understood, however, in addition to androgens and aging, chronic ischemia has been proposed to contribute. Using an established rat model, we investigated whether chronic ischemia alters the structural and functional properties of the ventral rat prostate, and whether phosphodiesterase type 5 (PDE5) inhibitor (tadalafil) may have a protective action. Adult male Sprague-Dawley rats were divided into control, arterial endothelial injury (AI), and AI with tadalafil treatment (AI-tadalafil) groups. AI and AI-tadalafil groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-tadalafil rats were treated with tadalafil (2 mg/kg/day) orally for 8 weeks after AI. The control group received a regular diet. After 8 weeks, animals were sacrificed, and pharmacological and morphological studies on prostate tissues were performed. Iliac arteries from AI rats displayed neo-intimal formation and luminal occlusion, an effect that was not prevented by tadalafil treatment. In the AI group, there was an obvious epithelial atrophy and a statistically significant increase in collagen fibers compared with the controls. Immunohistochemically, there was an up-regulation of smooth muscle α-actin (SMA). Contractile responses of prostate strips to KCl, electrical field stimulation (EFS), and phenylephrine (PE) were significantly higher after AI than in controls. Chronic treatment with tadalafil prevented the increase in contractile responses in ischemic tissue, and decreased the collagen deposition compared with the AI group. In this rat model, chronic pelvic ischemia caused distinct functional and morphological changes in the prostate. Prostatic tissue from ischemic animals showed an increased contractile response to electrical and pharmacological stimulation, an increase in SMA, and an increased deposition of collagen. All these changes could be prevented by treatment with the PDE5 inhibitor, tadalafil, suggesting an involvement of cyclic guanosine monophosphate (cGMP). © 2014 The Authors. The Prostate Published by Wiley Periodicals, Inc.

  17. Lead and aluminum bonding in Pb-AI metaphosphate glasses.

    PubMed

    Tsuchida, J E; Schneider, J; Pizani, P S; Oliveira, S L

    2008-01-21

    The bonding properties of cations in phosphate glasses determine many short- and medium-range structural features in the glass network, hence influencing bulk properties. In this work, Pb-Al-metaphosphate glasses (1 - x)Pb(PO(3))(2).xAI(PO(3))(3) with 0 < or = x < or = 1 were analyzed to determine the effect of the substitution of Pb by AI on the glass structure in the metaphosphate composition. The glass transition temperature and density were measured as a function of the Al concentration. The vibrational and structural properties were probed by Raman spectroscopy and nuclear magnetic resonance of (31)P, (27)AI, and (207)Pb. Aluminum incorporates homogeneously in the glass creating a stiffer and less packed network. The average coordination number for AI decreases from 5.9 to 5.0 as x increases from 0.1 to 1, indicating more covalent AI-O bonds. The coordination number of Pb in these glasses is greater than 8, showing an increasing ionic behavior for compositions richer in AI. A quantitative analysis of the phosphate speciation shows definite trends in the bonding of AIO(n) groups and phosphate tetrahedra. In glasses with x < 0.48, phosphate groups share preferentially only one nonbridging O corner with an AIO(n) coordination polyhedron. For x > 0.48 more than one nonbridging O can be linked to AIO(n) polyhedra. There is no corner sharing of O between AIO(n) and PbO(n) polyhedra nor between AIO(n) themselves throughout the compositional range. The PbO(n) coordination polyhedra show considerable nonbridging O sharing, with each O participating in the coordination sphere of at least two Pb. The bonding preferences determined for Al are consistent with the behavior observed in Na-AI and Ca-AI metaphosphates, indicating this may be a general behavior for ternary phosphate glasses.

  18. Morphological, structural, and spectral characteristics of amorphous iron sulfates

    PubMed Central

    Sklute, E. C.; Jensen, H. B.; Rogers, A. D.; Reeder, R. J.

    2018-01-01

    Current or past brine hydrologic activity on Mars may provide suitable conditions for the formation of amorphous ferric sulfates. Once formed, these phases would likely be stable under current Martian conditions, particularly at low- to mid-latitudes. Therefore, we consider amorphous iron sulfates (AIS) as possible components of Martian surface materials. Laboratory AIS were created through multiple synthesis routes and characterized with total X-ray scattering, thermogravimetric analysis, scanning electron microscopy, visible/near-infrared (VNIR), thermal infrared (TIR), and Mössbauer techniques. We synthesized amorphous ferric sulfates (Fe(III)2(SO4)3 · ~ 6–8H2O) from sulfate-saturated fluids via vacuum dehydration or exposure to low relative humidity (<11%). Amorphous ferrous sulfate (Fe(II)SO4 · ~1H2O) was synthesized via vacuum dehydration of melanterite. All AIS lack structural order beyond 11 Å. The short-range (<5 Å) structural characteristics of amorphous ferric sulfates resemble all crystalline reference compounds; structural characteristics for the amorphous ferrous sulfate are similar to but distinct from both rozenite and szomolnokite. VNIR and TIR spectral data for all AIS display broad, muted features consistent with structural disorder and are spectrally distinct from all crystalline sulfates considered for comparison. Mössbauer spectra are also distinct from crystalline phase spectra available for comparison. AIS should be distinguishable from crystalline sulfates based on the position of their Fe-related absorptions in the visible range and their spectral characteristics in the TIR. In the NIR, bands associated with hydration at ~1.4 and 1.9 μm are significantly broadened, which greatly reduces their detectability in soil mixtures. AIS may contribute to the amorphous fraction of soils measured by the Curiosity rover. PMID:29675340

  19. Computational study of stability of an H-H-type pseudoknot motif.

    PubMed

    Wang, Jun; Zhao, Yunjie; Wang, Jian; Xiao, Yi

    2015-12-01

    Motifs in RNA tertiary structures are important to their structural organizations and biological functions. Here we consider an H-H-type pseudoknot (HHpk) motif that consists of two hairpins connected by a junction loop and with kissing interactions between the two hairpin loops. Such a tertiary structural motif is recurrently found in RNA tertiary structures, but is difficult to predict computationally. So it is important to understand the mechanism of its formation and stability. Here we investigate the stability of the HHpk tertiary structure by using an all-atom molecular dynamics simulation. The results indicate that the HHpk tertiary structure is stable. However, it is found that this stability is not due to the helix-helix packing, as is usually expected, but is maintained by the combined action of the kissing hairpin loops and junctions, although the former plays the main role. Stable HHpk motifs may form structural platforms for the molecules to realize their biological functions. These results are useful for understanding the construction principle of RNA tertiary structures and structure prediction.

  20. Engineering the l-Arabinose Isomerase from Enterococcus Faecium for d-Tagatose Synthesis.

    PubMed

    de Sousa, Marylane; Manzo, Ricardo M; García, José L; Mammarella, Enrique J; Gonçalves, Luciana R B; Pessela, Benevides C

    2017-12-06

    l-Arabinose isomerase (EC 5.3.1.4) (l-AI) from Enterococcus faecium DBFIQ E36 was overproduced in Escherichia coli by designing a codon-optimized synthetic araA gene. Using this optimized gene, two N- and C-terminal His-tagged-l-AI proteins were produced. The cloning of the two chimeric genes into regulated expression vectors resulted in the production of high amounts of recombinant N -His-l-AI and C -His-l-AI in soluble and active forms. Both His-tagged enzymes were purified in a single step through metal-affinity chromatography and showed different kinetic and structural characteristics. Analytical ultracentrifugation revealed that C -His-l-AI was preferentially hexameric in solution, whereas N -His-l-AI was mainly monomeric. The specific activity of the N -His-l-AI at acidic pH was higher than that of C -His-l-AI and showed a maximum bioconversion yield of 26% at 50 °C for d-tagatose biosynthesis, with Km and Vmax parameters of 252 mM and 0.092 U mg -1 , respectively. However, C -His-l-AI was more active and stable at alkaline pH than N -His-l-AI. N -His-l-AI follows a Michaelis-Menten kinetic, whereas C -His-l-AI fitted to a sigmoidal saturation curve.

  1. Text Generation: The Problem of Text Structure.

    ERIC Educational Resources Information Center

    Mann, William C.

    One of the major problems in artificial intelligence (AI) text generation is text organization; a poorly organized text can be unreadable or even misleading. A comparison of two AI approaches to text organization--McKeown's TEXT system and Rhetorical Structure Theory (RST)--shows that, although they share many assumptions about the nature of text,…

  2. Analysis of Management Practices in Lagos State Tertiary Institutions through Total Quality Management Structural Framework

    ERIC Educational Resources Information Center

    AbdulAzeez, Abbas Tunde

    2016-01-01

    This research investigated total quality management practices and quality teacher education in public tertiary institutions in Lagos State. The study was therefore designed to analyse management practices in Lagos state tertiary institutions through total quality management structural framework. The selected public tertiary institutions in Lagos…

  3. Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress

    PubMed Central

    Barron, Martin J.; Smith, Claire E.L.; Poulter, James A.; Mighell, Alan J.; Inglehearn, Chris F.; Brown, Catriona J.; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J.

    2017-01-01

    Abstract ‘Amelogenesis imperfecta’ (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype. PMID:28334996

  4. Amelogenesis imperfecta caused by N-terminal enamelin point mutations in mice and men is driven by endoplasmic reticulum stress.

    PubMed

    Brookes, Steven J; Barron, Martin J; Smith, Claire E L; Poulter, James A; Mighell, Alan J; Inglehearn, Chris F; Brown, Catriona J; Rodd, Helen; Kirkham, Jennifer; Dixon, Michael J

    2017-05-15

    'Amelogenesis imperfecta' (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel. However, enamel secreted thereafter was structurally abnormal; presumably due to the UPR modulating ameloblast behaviour and function in an attempt to relieve ER stress. Homozygous mutant mice failed to produce enamel. We also identified a novel heterozygous ENAMp.L31R mutation causing AI in humans. We hypothesize that ER stress is the aetiological factor in this case of human AI as it shared the characteristic phenotype described above for the Enamp.S55I mouse. We previously demonstrated that AI in mice carrying the Amelxp.Y64H mutation is a proteinopathy. The current data indicate that AI in Enamp.S55I mice is also a proteinopathy, and based on comparative phenotypic analysis, we suggest that human AI resulting from the ENAMp.L31R mutation is another proteinopathic disease. Identifying a common aetiology for AI resulting from mutations in two different genes opens the way for developing pharmaceutical interventions designed to relieve ER stress or modulate the UPR during enamel development to ameliorate the clinical phenotype. © The Author 2017. Published by Oxford University Press.

  5. Computational methods for efficient structural reliability and reliability sensitivity analysis

    NASA Technical Reports Server (NTRS)

    Wu, Y.-T.

    1993-01-01

    This paper presents recent developments in efficient structural reliability analysis methods. The paper proposes an efficient, adaptive importance sampling (AIS) method that can be used to compute reliability and reliability sensitivities. The AIS approach uses a sampling density that is proportional to the joint PDF of the random variables. Starting from an initial approximate failure domain, sampling proceeds adaptively and incrementally with the goal of reaching a sampling domain that is slightly greater than the failure domain to minimize over-sampling in the safe region. Several reliability sensitivity coefficients are proposed that can be computed directly and easily from the above AIS-based failure points. These probability sensitivities can be used for identifying key random variables and for adjusting design to achieve reliability-based objectives. The proposed AIS methodology is demonstrated using a turbine blade reliability analysis problem.

  6. Cultural Identity Among Urban American Indian/Alaska Native Youth: Implications for Alcohol and Drug Use.

    PubMed

    Brown, Ryan A; Dickerson, Daniel L; D'Amico, Elizabeth J

    2016-10-01

    American Indian / Alaska Native (AI/AN) youth exhibit high rates of alcohol and other drug (AOD) use, which is often linked to the social and cultural upheaval experienced by AI/ANs during the colonization of North America. Urban AI/AN youth may face unique challenges, including increased acculturative stress due to lower concentrations of AI/AN populations in urban areas. Few existing studies have explored cultural identity among urban AI/AN youth and its association with AOD use. This study used systematic qualitative methods with AI/AN communities in two urban areas within California to shed light on how urban AI/AN youth construct cultural identity and how this relates to AOD use and risk behaviors. We conducted 10 focus groups with a total of 70 youth, parents, providers, and Community Advisory Board members and used team-based structured thematic analysis in the Dedoose software platform. We identified 12 themes: intergenerational stressors, cultural disconnection, AI/AN identity as protective, pan-tribal identity, mixed racial-ethnic identity, rural vs. urban environments, the importance of AI/AN institutions, stereotypes and harassment, cultural pride, developmental trajectories, risks of being AI/AN, and mainstream culture clash. Overall, youth voiced curiosity about their AI/AN roots and expressed interest in deepening their involvement in cultural activities. Adults described the myriad ways in which involvement in cultural activities provides therapeutic benefits for AI/AN youth. Interventions that provide urban AI/AN youth with an opportunity to engage in cultural activities and connect with positive and healthy constructs in AI/AN culture may provide added impact to existing interventions.

  7. Structural features, substrate specificity, kinetic properties of insect α-amylase and specificity of plant α-amylase inhibitors.

    PubMed

    Kaur, Rimaljeet; Kaur, Narinder; Gupta, Anil Kumar

    2014-11-01

    α-Amylase is an important digestive enzyme required for the optimal growth and development of insects. Several insect α-amylases had been purified and their physical and chemical properties were characterized. Insect α-amylases of different orders display variability in structure, properties and substrate specificity. Such diverse properties of amylases could be due to different feeding habits and gut environment of insects. In this review, structural features and properties of several insect α-amylases were compared. This could be helpful in exploring the diversity in characteristics of α-amylase between the members of the same class (insecta). Properties like pH optima are reflected in enzyme structural features. In plants, α-amylase inhibitors (α-AIs) occur as part of natural defense mechanisms against pests by interfering in their digestion process and thus could also provide access to new pest management strategies. AIs are quite specific in their action; therefore, these could be employed according to their effectiveness against target amylases. Potential of transgenics with α-AIs has also been discussed for insect resistance and controlling infestation. The differences in structural features of insect α-amylases provided reasons for their efficient functioning at different pH and the specificity towards various substrates. Various proteinaceous and non-proteinaceous inhibitors discussed could be helpful in controlling pest infestation. In depth detailed studies are required on proteinaceous α-AI-α-amylase interaction at different pH's as well as the insect proteinase action on these inhibitors before selecting the α-AI for making transgenics resistant to particular insect. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Organisational Structure and Information Technology (IT): Exploring the Implications of IT for Future Military Structures

    DTIC Science & Technology

    2006-07-01

    4 Abbreviations AI Artificial Intelligence AM Artificial Memory CAD Computer Aided...memory (AM), artificial intelligence (AI), and embedded knowledge systems it is possible to expand the “effective span of competence” of...Technology J Joint J2 Joint Intelligence J3 Joint Operations NATO North Atlantic Treaty Organisation NCW Network Centric Warfare NHS National Health

  9. Acyl carrier protein structural classification and normal mode analysis

    PubMed Central

    Cantu, David C; Forrester, Michael J; Charov, Katherine; Reilly, Peter J

    2012-01-01

    All acyl carrier protein primary and tertiary structures were gathered into the ThYme database. They are classified into 16 families by amino acid sequence similarity, with members of the different families having sequences with statistically highly significant differences. These classifications are supported by tertiary structure superposition analysis. Tertiary structures from a number of families are very similar, suggesting that these families may come from a single distant ancestor. Normal vibrational mode analysis was conducted on experimentally determined freestanding structures, showing greater fluctuations at chain termini and loops than in most helices. Their modes overlap more so within families than between different families. The tertiary structures of three acyl carrier protein families that lacked any known structures were predicted as well. PMID:22374859

  10. Molecular dynamics simulations on discoidal HDL particles suggest a mechanism for rotation in the apo A-I belt model.

    PubMed

    Klon, Anthony E; Segrest, Jere P; Harvey, Stephen C

    2002-12-06

    Apolipoprotein A-I (apo A-I) is the major protein component of high-density lipoprotein (HDL) particles. Elevated levels of HDL in the bloodstream have been shown to correlate strongly with a reduced risk factor for atherosclerosis. Molecular dynamics simulations have been carried out on three separate model discoidal high-density lipoprotein particles (HDL) containing two monomers of apo A-I and 160 molecules of palmitoyloleoylphosphatidylcholine (POPC), to a time-scale of 1ns. The starting structures were on the basis of previously published molecular belt models of HDL consisting of the lipid-binding C-terminal domain (residues 44-243) wrapped around the circumference of a discoidal HDL particle. Subtle changes between two of the starting structures resulted in significantly different behavior during the course of the simulation. The results provide support for the hypothesis of Segrest et al. that helical registration in the molecular belt model of apo A-I is modulated by intermolecular salt bridges. In addition, we propose an explanation for the presence of proline punctuation in the molecular belt model, and for the presence of two 11-mer helical repeats interrupting the otherwise regular pattern of 22-mer helical repeats in the lipid-binding domain of apo A-I.

  11. Structural insight into the mechanism of synergistic autoinhibition of SAD kinases

    PubMed Central

    Wu, Jing-Xiang; Cheng, Yun-Sheng; Wang, Jue; Chen, Lei; Ding, Mei; Wu, Jia-Wei

    2015-01-01

    The SAD/BRSK kinases participate in various important life processes, including neural development, cell cycle and energy metabolism. Like other members of the AMPK family, SAD contains an N-terminal kinase domain followed by the characteristic UBA and KA1 domains. Here we identify a unique autoinhibitory sequence (AIS) in SAD kinases, which exerts autoregulation in cooperation with UBA. Structural studies of mouse SAD-A revealed that UBA binds to the kinase domain in a distinct mode and, more importantly, AIS nestles specifically into the KD-UBA junction. The cooperative action of AIS and UBA results in an ‘αC-out' inactive kinase, which is conserved across species and essential for presynaptic vesicle clustering in C. elegans. In addition, the AIS, along with the KA1 domain, is indispensable for phospholipid binding. Taken together, these data suggest a model for synergistic autoinhibition and membrane activation of SAD kinases. PMID:26626945

  12. Structural insight into the mechanism of synergistic autoinhibition of SAD kinases.

    PubMed

    Wu, Jing-Xiang; Cheng, Yun-Sheng; Wang, Jue; Chen, Lei; Ding, Mei; Wu, Jia-Wei

    2015-12-02

    The SAD/BRSK kinases participate in various important life processes, including neural development, cell cycle and energy metabolism. Like other members of the AMPK family, SAD contains an N-terminal kinase domain followed by the characteristic UBA and KA1 domains. Here we identify a unique autoinhibitory sequence (AIS) in SAD kinases, which exerts autoregulation in cooperation with UBA. Structural studies of mouse SAD-A revealed that UBA binds to the kinase domain in a distinct mode and, more importantly, AIS nestles specifically into the KD-UBA junction. The cooperative action of AIS and UBA results in an 'αC-out' inactive kinase, which is conserved across species and essential for presynaptic vesicle clustering in C. elegans. In addition, the AIS, along with the KA1 domain, is indispensable for phospholipid binding. Taken together, these data suggest a model for synergistic autoinhibition and membrane activation of SAD kinases.

  13. Cooperativity of hydrogen-bonded networks in 7-azaindole(CH3OH)n (n=2,3) clusters evidenced by IR-UV ion-dip spectroscopy and natural bond orbital analysis.

    PubMed

    Sakota, Kenji; Kageura, Yutaka; Sekiya, Hiroshi

    2008-08-07

    IR-UV ion-dip spectra of the 7-azaindole (7AI)(CH(3)OH)(n) (n=1-3) clusters have been measured in the hydrogen-bonded NH and OH stretching regions to investigate the stable structures of 7AI(CH(3)OH)(n) (n=1-3) in the S(0) state and the cooperativity of the H-bonding interactions in the H-bonded networks. The comparison of the IR-UV ion-dip spectra with IR spectra obtained by quantum chemistry calculations shows that 7AI(CH(3)OH)(n) (n=1-3) have cyclic H-bonded structures, where the NH group and the heteroaromatic N atom of 7AI act as the proton donor and proton acceptor, respectively. The H-bonded OH stretch fundamental of 7AI(CH(3)OH)(2) is remarkably redshifted from the corresponding fundamental of (CH(3)OH)(2) by 286 cm(-1), which is an experimental manifestation of the cooperativity in H-bonding interaction. Similarly, two localized OH fundamentals of 7AI(CH(3)OH)(3) also exhibit large redshifts. The cooperativity of 7AI(CH(3)OH)(n) (n=2,3) is successfully explained by the donor-acceptor electron delocalization interactions between the lone-pair orbital in the proton acceptor and the antibonding orbital in the proton donor in natural bond orbital (NBO) analyses.

  14. Cultural Identity among Urban American Indian/Native Alaskan Youth: Implications for Alcohol and Drug Use

    PubMed Central

    Brown, Ryan A.; Dickerson, Daniel L.; D’Amico, Elizabeth J.

    2016-01-01

    American Indian and Alaska Native (AI/AN) youth exhibit high rates of alcohol and other drug (AOD) use, which is often linked to the social and cultural upheaval experienced by AI/ANs during the colonization of North America. Urban AI/AN youth may face unique challenges, including increased acculturative stress due to lower concentrations of AI/AN populations in urban areas. Few existing studies have explored cultural identity among urban AI/AN youth and its association with AOD use. Objectives This study used systematic qualitative methods with AI/AN communities in two urban areas within California to shed light on how urban AI/AN youth construct cultural identity and how this relates to AOD use and risk behaviors. Methods We conducted 10 focus groups with a total of 70 youth, parents, providers, and Community Advisory Board members and used team-based structured thematic analysis in the Dedoose software platform. Results We identified 12 themes: intergenerational stressors, cultural disconnection, AI/AN identity as protective, pan-tribal identity, mixed racial-ethnic identity, rural vs. urban environments, the importance of AI/AN institutions, stereotypes and harassment, cultural pride, developmental trajectories, risks of being AI/AN, and mainstream culture clash. Overall, youth voiced curiosity about their AI/AN roots and expressed interest in deepening their involvement in cultural activities. Adults described the myriad ways in which involvement in cultural activities provides therapeutic benefits for AI/AN youth. Conclusions Interventions that provide urban AI/AN youth with an opportunity to engage in cultural activities and connect with positive and healthy constructs in AI/AN culture may provide added impact to existing interventions. PMID:27450682

  15. Automated and fast building of three-dimensional RNA structures.

    PubMed

    Zhao, Yunjie; Huang, Yangyu; Gong, Zhou; Wang, Yanjie; Man, Jianfen; Xiao, Yi

    2012-01-01

    Building tertiary structures of non-coding RNA is required to understand their functions and design new molecules. Current algorithms of RNA tertiary structure prediction give satisfactory accuracy only for small size and simple topology and many of them need manual manipulation. Here, we present an automated and fast program, 3dRNA, for RNA tertiary structure prediction with reasonable accuracy for RNAs of larger size and complex topology.

  16. DNA inversion within the apolipoproteins AI/CIII/AIV-encoding gene cluster of certain patients with premature atherosclerosis

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

    Karathanasis, S.K.; Ferris, E.; Haddad, I.A.

    1987-10-01

    The genes coding for apolipoproteins (apo) AI, CIII, and AIV, designated APOA1, APOC3, and APOA4, respectively, are closely linked and tandemly organized in the long arm of the human chromosome 11. A DNA rearrangement involving the genes encoding apoAI and apoCIII in certain patients with premature atherosclerosis has been associated with deficiency of both apoAI and apoCIII in the plasma of these patients. Structural characterization of the genes for apoAI and apoCIII in one of these patients indicates that this rearrangement consists of a DNA inversion containing portions of the 3' ends of the apoAI and apoCIII genes, including themore » DNA region between these genes. The breakpoints of this DNA inversion are located within the fourth exon of the apoAI gene and the first intron of the apoCIII gene. Thus, this DNA inversion results in reciprocal fusion of the apoAI and apoCIII gene transcriptional units. Expression of these gene fusions in cultured mammalian cells results in stable mRNA transcripts with sequences representing fusions of the apoAI and apoCIII mRNAs. These results indicate that absence of transcripts with correct apoAI and apoCIII mRNA sequences causes apoAI and apoCIII deficiency in the plasma of these patients and suggest that these apolipoproteins are involved in cholesterol homeostasis and protection against premature atherosclerosis.« less

  17. Implementing embedded artificial intelligence rules within algorithmic programming languages

    NASA Technical Reports Server (NTRS)

    Feyock, Stefan

    1988-01-01

    Most integrations of artificial intelligence (AI) capabilities with non-AI (usually FORTRAN-based) application programs require the latter to execute separately to run as a subprogram or, at best, as a coroutine, of the AI system. In many cases, this organization is unacceptable; instead, the requirement is for an AI facility that runs in embedded mode; i.e., is called as subprogram by the application program. The design and implementation of a Prolog-based AI capability that can be invoked in embedded mode are described. The significance of this system is twofold: Provision of Prolog-based symbol-manipulation and deduction facilities makes a powerful symbolic reasoning mechanism available to applications programs written in non-AI languages. The power of the deductive and non-procedural descriptive capabilities of Prolog, which allow the user to describe the problem to be solved, rather than the solution, is to a large extent vitiated by the absence of the standard control structures provided by other languages. Embedding invocations of Prolog rule bases in programs written in non-AI languages makes it possible to put Prolog calls inside DO loops and similar control constructs. The resulting merger of non-AI and AI languages thus results in a symbiotic system in which the advantages of both programming systems are retained, and their deficiencies largely remedied.

  18. Secondary structure encodes a cooperative tertiary folding funnel in the Azoarcus ribozyme

    PubMed Central

    Mustoe, Anthony M.; Al-Hashimi, Hashim M.; Brooks, Charles L.

    2016-01-01

    A requirement for specific RNA folding is that the free-energy landscape discriminate against non-native folds. While tertiary interactions are critical for stabilizing the native fold, they are relatively non-specific, suggesting additional mechanisms contribute to tertiary folding specificity. In this study, we use coarse-grained molecular dynamics simulations to explore how secondary structure shapes the tertiary free-energy landscape of the Azoarcus ribozyme. We show that steric and connectivity constraints posed by secondary structure strongly limit the accessible conformational space of the ribozyme, and that these so-called topological constraints in turn pose strong free-energy penalties on forming different tertiary contacts. Notably, native A-minor and base-triple interactions form with low conformational free energy, while non-native tetraloop/tetraloop–receptor interactions are penalized by high conformational free energies. Topological constraints also give rise to strong cooperativity between distal tertiary interactions, quantitatively matching prior experimental measurements. The specificity of the folding landscape is further enhanced as tertiary contacts place additional constraints on the conformational space, progressively funneling the molecule to the native state. These results indicate that secondary structure assists the ribozyme in navigating the otherwise rugged tertiary folding landscape, and further emphasize topological constraints as a key force in RNA folding. PMID:26481360

  19. Thioesterases: A new perspective based on their primary and tertiary structures

    PubMed Central

    Cantu, David C; Chen, Yingfei; Reilly, Peter J

    2010-01-01

    Thioesterases (TEs) are classified into EC 3.1.2.1 through EC 3.1.2.27 based on their activities on different substrates, with many remaining unclassified (EC 3.1.2.–). Analysis of primary and tertiary structures of known TEs casts a new light on this enzyme group. We used strong primary sequence conservation based on experimentally proved proteins as the main criterion, followed by verification with tertiary structure superpositions, mechanisms, and catalytic residue positions, to accurately define TE families. At present, TEs fall into 23 families almost completely unrelated to each other by primary structure. It is assumed that all members of the same family have essentially the same tertiary structure; however, TEs in different families can have markedly different folds and mechanisms. Conversely, the latter sometimes have very similar tertiary structures and catalytic mechanisms despite being only slightly or not at all related by primary structure, indicating that they have common distant ancestors and can be grouped into clans. At present, four clans encompass 12 TE families. The new constantly updated ThYme (Thioester-active enzYmes) database contains TE primary and tertiary structures, classified into families and clans that are different from those currently found in the literature or in other databases. We review all types of TEs, including those cleaving CoA, ACP, glutathione, and other protein molecules, and we discuss their structures, functions, and mechanisms. PMID:20506386

  20. Automated extraction and classification of RNA tertiary structure cyclic motifs

    PubMed Central

    Lemieux, Sébastien; Major, François

    2006-01-01

    A minimum cycle basis of the tertiary structure of a large ribosomal subunit (LSU) X-ray crystal structure was analyzed. Most cycles are small, as they are composed of 3- to 5 nt, and repeated across the LSU tertiary structure. We used hierarchical clustering to quantify and classify the 4 nt cycles. One class is defined by the GNRA tetraloop motif. The inspection of the GNRA class revealed peculiar instances in sequence. First is the presence of UA, CA, UC and CC base pairs that substitute the usual sheared GA base pair. Second is the revelation of GNR(Xn)A tetraloops, where Xn is bulged out of the classical GNRA structure, and of GN/RA formed by the two strands of interior-loops. We were able to unambiguously characterize the cycle classes using base stacking and base pairing annotations. The cycles identified correspond to small and cyclic motifs that compose most of the LSU RNA tertiary structure and contribute to its thermodynamic stability. Consequently, the RNA minimum cycles could well be used as the basic elements of RNA tertiary structure prediction methods. PMID:16679452

  1. Anterior Insula Volume and Guilt

    PubMed Central

    Belden, Andy C.; Barch, Deanna M.; Oakberg, Timothy J.; April, Laura M.; Harms, Michael P.; Botteron, Kelly N.; Luby, Joan L.

    2016-01-01

    IMPORTANCE This is the first study to date to examine volumetric alterations in the anterior insula (AI) as a potential biomarker for the course of childhood major depressive disorder (MDD). OBJECTIVES To examine whether children with a history of preschool-onset (PO) MDD show reduced AI volume, whether a specific symptom of PO MDD (pathological guilt) is related to AI volume reduction (given the known relationship between AI and guilt processing), and whether AI volumes predict subsequent likelihood of having an episode of MDD. DESIGN, SETTING, AND PARTICIPANTS In a prospective longitudinal study, 306 children (age range, 3.00–5.11 years) and caregivers completed DSM diagnostic assessments at 6 annual time points during 10 years as part of the Preschool Depression Study. Magnetic resonance imaging was completed on a subset of 145 school-age children (age range, 6.11–12.11 years). MAIN OUTCOMES AND MEASURES Whole-brain–adjusted AI volume measured using magnetic resonance imaging at school age and children’s diagnosis of MDD any time after their imaging. RESULTS Compared with children without a history of PO MDD, school-age children previously diagnosed as having PO MDD had smaller left and right AI volumes (Wilks Λ = 0.94, F2,124 = 3.37, P = .04, Cohen d = 0.23). However, the effect of PO MDD on reduced AI volumes was better explained by children’s experience of pathological guilt during preschool (Λ = 0.91, F2,120 = 6.17, P = .003, d = .30). When covarying for children’s lifetime history of MDD episodes, their experience of pathological guilt during preschool, as well as their sex and age at the time of imaging, schoolchildren’s right-side AI volume was a significant predictor of being diagnosed as having an MDD episode after imaging (odds ratio, 0.96; 95% CI, 0.01–0.75; P = .03). CONCLUSIONS AND RELEVANCE These results provide evidence that structural abnormalities in AI volume are related to the neurobiology of depressive disorders starting in early childhood. The present findings are consistent with mounting research in adult MDD suggesting that insula function and structure may be a target biomarker for major depression. PMID:25390502

  2. Anterior insula volume and guilt: neurobehavioral markers of recurrence after early childhood major depressive disorder.

    PubMed

    Belden, Andy C; Barch, Deanna M; Oakberg, Timothy J; April, Laura M; Harms, Michael P; Botteron, Kelly N; Luby, Joan L

    2015-01-01

    This is the first study to date to examine volumetric alterations in the anterior insula (AI) as a potential biomarker for the course of childhood major depressive disorder (MDD). To examine whether children with a history of preschool-onset (PO) MDD show reduced AI volume, whether a specific symptom of PO MDD (pathological guilt) is related to AI volume reduction (given the known relationship between AI and guilt processing), and whether AI volumes predict subsequent likelihood of having an episode of MDD. In a prospective longitudinal study, 306 children (age range, 3.00-5.11 years) and caregivers completed DSM diagnostic assessments at 6 annual time points during 10 years as part of the Preschool Depression Study. Magnetic resonance imaging was completed on a subset of 145 school-age children (age range, 6.11-12.11 years). Whole-brain-adjusted AI volume measured using magnetic resonance imaging at school age and children's diagnosis of MDD any time after their imaging. Compared with children without a history of PO MDD, school-age children previously diagnosed as having PO MDD had smaller left and right AI volumes (Wilks Λ = 0.94, F2,124 = 3.37, P = .04, Cohen d = 0.23). However, the effect of PO MDD on reduced AI volumes was better explained by children's experience of pathological guilt during preschool (Λ = 0.91, F2,120 = 6.17, P = .003, d = .30). When covarying for children's lifetime history of MDD episodes, their experience of pathological guilt during preschool, as well as their sex and age at the time of imaging, schoolchildren's right-side AI volume was a significant predictor of being diagnosed as having an MDD episode after imaging (odds ratio, 0.96; 95% CI, 0.01-0.75; P = .03). These results provide evidence that structural abnormalities in AI volume are related to the neurobiology of depressive disorders starting in early childhood. The present findings are consistent with mounting research in adult MDD suggesting that insula function and structure may be a target biomarker for major depression.

  3. Glasgow Coma Scale and Outcomes after Structural Traumatic Head Injury in Early Childhood

    PubMed Central

    Heather, Natasha L.; Derraik, José G. B.; Beca, John; Hofman, Paul L.; Dansey, Rangi; Hamill, James; Cutfield, Wayne S.

    2013-01-01

    Objective To assess the association of the Glasgow Coma Scale (GCS) with radiological evidence of head injury (the Abbreviated Injury Scale for the head region, AIS-HR) in young children hospitalized with traumatic head injury (THI), and the predictive value of GCS and AIS-HR scores for long-term impairment. Methods Our study involved a 10-year retrospective review of a database encompassing all patients admitted to Starship Children’s Hospital (Auckland, New Zealand, 2000–2010) with THI. Results We studied 619 children aged <5 years at the time of THI, with long-term outcome data available for 161 subjects. Both GCS and AIS-HR scores were predictive of length of intensive care unit and hospital stay (all p<0.001). GCS was correlated with AIS-HR (ρ=-0.46; p<0.001), although mild GCS scores (13–15) commonly under-estimated the severity of radiological injury: 42% of children with mild GCS scores had serious–critical THI (AIS-HR 3–5). Increasingly severe GCS or AIS-HR scores were both associated with a greater likelihood of long-term impairment (neurological disability, residual problems, and educational support). However, long-term impairment was also relatively common in children with mild GCS scores paired with structural THI more severe than a simple linear skull fracture. Conclusion Severe GCS scores will identify most cases of severe radiological injury in early childhood, and are good predictors of poor long-term outcome. However, young children admitted to hospital with structural THI and mild GCS scores have an appreciable risk of long-term disability, and also warrant long-term follow-up. PMID:24312648

  4. Predicting loop–helix tertiary structural contacts in RNA pseudoknots

    PubMed Central

    Cao, Song; Giedroc, David P.; Chen, Shi-Jie

    2010-01-01

    Tertiary interactions between loops and helical stems play critical roles in the biological function of many RNA pseudoknots. However, quantitative predictions for RNA tertiary interactions remain elusive. Here we report a statistical mechanical model for the prediction of noncanonical loop–stem base-pairing interactions in RNA pseudoknots. Central to the model is the evaluation of the conformational entropy for the pseudoknotted folds with defined loop–stem tertiary structural contacts. We develop an RNA virtual bond-based conformational model (Vfold model), which permits a rigorous computation of the conformational entropy for a given fold that contains loop–stem tertiary contacts. With the entropy parameters predicted from the Vfold model and the energy parameters for the tertiary contacts as inserted parameters, we can then predict the RNA folding thermodynamics, from which we can extract the tertiary contact thermodynamic parameters from theory–experimental comparisons. These comparisons reveal a contact enthalpy (ΔH) of −14 kcal/mol and a contact entropy (ΔS) of −38 cal/mol/K for a protonated C+•(G–C) base triple at pH 7.0, and (ΔH = −7 kcal/mol, ΔS = −19 cal/mol/K) for an unprotonated base triple. Tests of the model for a series of pseudoknots show good theory–experiment agreement. Based on the extracted energy parameters for the tertiary structural contacts, the model enables predictions for the structure, stability, and folding pathways for RNA pseudoknots with known or postulated loop–stem tertiary contacts from the nucleotide sequence alone. PMID:20100813

  5. ApoA-I/A-II-HDL positively associates with apoB-lipoproteins as a potential atherogenic indicator.

    PubMed

    Kido, Toshimi; Kondo, Kazuo; Kurata, Hideaki; Fujiwara, Yoko; Urata, Takeyoshi; Itakura, Hiroshige; Yokoyama, Shinji

    2017-11-29

    We recently reported distinct nature of high-density lipoproteins (HDL) subgroup particles with apolipoprotein (apo) A-I but not apoA-II (LpAI) and HDL having both (LpAI:AII) based on the data from 314 Japanese. While plasma HDL level almost exclusively depends on concentration of LpAI having 3 to 4 apoA-I molecules, LpAI:AII appeared with almost constant concentration regardless of plasma HDL levels having stable structure with two apoA-I and one disulfide-dimeric apoA-II molecules (Sci. Rep. 6; 31,532, 2016). The aim of this study is further characterization of LpAI:AII with respect to its role in atherogenesis. Association of LpAI, LpAI:AII and other HDL parameters with apoB-lipoprotein parameters was analyzed among the cohort data above. ApoA-I in LpAI negatively correlated with the apoB-lipoprotein parameters such as apoB, triglyceride, nonHDL-cholesterol, and nonHDL-cholesterol + triglyceride, which are apparently reflected in the relations of the total HDL parameters to apoB-lipoproteins. In contrast, apoA-I in LpAI:AII and apoA-II positively correlated to the apoB-lipoprotein parameters even within their small range of variation. These relationships are independent of sex, but may slightly be influenced by the activity-related CETP mutations. The study suggested that LpAI:AII is an atherogenic indicator rather than antiatherogenic. These sub-fractions of HDL are to be evaluated separately for estimating atherogenic risk of the patients.

  6. An evaluation of Ada for Al applications

    NASA Technical Reports Server (NTRS)

    Wallace, David R.

    1986-01-01

    Expert system technology seems to be the most promising type of Artificial Intelligence (AI) application for Ada. An expert system implemented with an expert system shell provides a highly structured approach that fits well with the structured approach found in Ada systems. The current commercial expert system shells use Lisp. In this highly structured situation a shell could be built that used Ada just as well. On the other hand, if it is necessary to deal with some AI problems that are not suited to expert systems, the use of Ada becomes more problematical. Ada was not designed as an AI development language, and is not suited to that. It is possible that an application developed in say, Common Lisp could be translated to Ada for actual use in a particular application, but this could be difficult. Some standard Ada packages could be developed to make such a translation easier. If the most general AI programs need to be dealt with, a Common Lisp system integrated with the Ada Environment is probably necessary. Aside from problems with language features, Ada, by itself, is not well suited to the prototyping and incremental development that is well supported by Lisp.

  7. NASA space station automation: AI-based technology review

    NASA Technical Reports Server (NTRS)

    Firschein, O.; Georgeff, M. P.; Park, W.; Neumann, P.; Kautz, W. H.; Levitt, K. N.; Rom, R. J.; Poggio, A. A.

    1985-01-01

    Research and Development projects in automation for the Space Station are discussed. Artificial Intelligence (AI) based automation technologies are planned to enhance crew safety through reduced need for EVA, increase crew productivity through the reduction of routine operations, increase space station autonomy, and augment space station capability through the use of teleoperation and robotics. AI technology will also be developed for the servicing of satellites at the Space Station, system monitoring and diagnosis, space manufacturing, and the assembly of large space structures.

  8. [Decomposition model of energy-related carbon emissions in tertiary industry for China].

    PubMed

    Lu, Yuan-Qing; Shi, Jun

    2012-07-01

    Tertiary industry has been developed in recent years. And it is very important to find the factors influenced the energy-related carbon emissions in tertiary industry. A decomposition model of energy-related carbon emissions for China is set up by adopting logarithmic mean weight Divisia method based on the identity of carbon emissions. The model is adopted to analyze the influence of energy structure, energy efficiency, tertiary industry structure and economic output to energy-related carbon emissions in China from 2000 to 2009. Results show that the contribution rate of economic output and energy structure to energy-related carbon emissions increases year by year. Either is the contribution rate of energy efficiency or the tertiary industry restraining to energy-related carbon emissions. However, the restrain effect is weakening.

  9. An AI-based approach to structural damage identification by modal analysis

    NASA Technical Reports Server (NTRS)

    Glass, B. J.; Hanagud, S.

    1990-01-01

    Flexible-structure damage is presently addressed by a combined model- and parameter-identification approach which employs the AI methodologies of classification, heuristic search, and object-oriented model knowledge representation. The conditions for model-space search convergence to the best model are discussed in terms of search-tree organization and initial model parameter error. In the illustrative example of a truss structure presented, the use of both model and parameter identification is shown to lead to smaller parameter corrections than would be required by parameter identification alone.

  10. Delta inulin: a novel, immunologically active, stable packing structure comprising β-D-[2 -> 1] poly(fructo-furanosyl) α-D-glucose polymers.

    PubMed

    Cooper, Peter D; Petrovsky, Nikolai

    2011-05-01

    We report a novel isoform of β-D-[2 → 1] poly(fructo-furanosyl) α-D-glucose termed delta inulin (DI), comparing it with previously described alpha (AI), beta (BI) and gamma (GI) isoforms. In vitro, DI is the most immunologically active weight/weight in human complement activation and in binding to monocytes and regulating their chemokine production and cell surface protein expression. In vivo, this translates into potent immune adjuvant activity, enhancing humoral and cellular responses against co-administered antigens. As a biocompatible polysaccharide particle, DI is safe and well tolerated by subcutaneous or intramuscular injection. Physico-chemically, DI forms as an insoluble precipitate from an aqueous solution of suitable AI, BI or GI held at 37-48°C, whereas the precipitate from the same solution at lower temperatures has the properties of AI or GI. DI can also be produced by heat conversion of GI suspensions at 56°C, whereas GI is converted from AI at 45°C. DI is distinguished from GI by its higher temperature of solution in dilute aqueous suspension and by its lower solubility in dimethyl sulfoxide, both consistent with greater hydrogen bonding in DI's polymer packing structure. DI suspensions can be dissolved by heat, re-precipitated by cooling as AI and finally re-converted back to DI by repeated heat treatment. Thus, DI, like the previously described inulin isoforms, reflects the formation of a distinct polymer aggregate packing structure via reversible noncovalent bonding. DI forms the basis for a potent new human vaccine adjuvant and further swells the growing family of carbohydrate structures with immunological activity.

  11. Application of Tryptophan Fluorescence Bandwidth-Maximum Plot in Analysis of Monoclonal Antibody Structure.

    PubMed

    Huang, Cheng-Yen; Hsieh, Ming-Ching; Zhou, Qinwei

    2017-04-01

    Monoclonal antibodies have become the fastest growing protein therapeutics in recent years. The stability and heterogeneity pertaining to its physical and chemical structures remain a big challenge. Tryptophan fluorescence has been proven to be a versatile tool to monitor protein tertiary structure. By modeling the tryptophan fluorescence emission envelope with log-normal distribution curves, the quantitative measure can be exercised for the routine characterization of monoclonal antibody overall tertiary structure. Furthermore, the log-normal deconvolution results can be presented as a two-dimensional plot with tryptophan emission bandwidth vs. emission maximum to enhance the resolution when comparing samples or as a function of applied perturbations. We demonstrate this by studying four different monoclonal antibodies, which show the distinction on emission bandwidth-maximum plot despite their similarity in overall amino acid sequences and tertiary structures. This strategy is also used to demonstrate the tertiary structure comparability between different lots manufactured for one of the monoclonal antibodies (mAb2). In addition, in the unfolding transition studies of mAb2 as a function of guanidine hydrochloride concentration, the evolution of the tertiary structure can be clearly traced in the emission bandwidth-maximum plot.

  12. Creation of metal-independent hyperthermophilic L-arabinose isomerase by homologous recombination.

    PubMed

    Hong, Young-Ho; Lee, Dong-Woo; Pyun, Yu-Ryang; Lee, Sung Haeng

    2011-12-28

    Hyperthermophilic L-arabinose isomerases (AIs) are useful in the commercial production of D-tagatose as a low-calorie bulk sweetener. Their catalysis and thermostability are highly dependent on metals, which is a major drawback in food applications. To study the role of metal ions in the thermostability and catalysis of hyperthermophilic AI, four enzyme chimeras were generated by PCR-based hybridization to replace the variable N- and C-terminal regions of hyperthermophilic Thermotoga maritima AI (TMAI) and thermophilic Geobacillus stearothermophilus AI (GSAI) with those of the homologous mesophilic Bacillus halodurans AI (BHAI). Unlike Mn(2+)-dependent TMAI, the GSAI- and TMAI-based hybrids with the 72 C-terminal residues of BHAI were not metal-dependent for catalytic activity. By contrast, the catalytic activities of the TMAI- and GSAI-based hybrids containing the N-terminus (residues 1-89) of BHAI were significantly enhanced by metals, but their thermostabilities were poor even in the presence of Mn(2+), indicating that the effects of metals on catalysis and thermostability involve different structural regions. Moreover, in contrast to the C-terminal truncate (Δ20 residues) of GSAI, the N-terminal truncate (Δ7 residues) exhibited no activity due to loss of its native structure. The data thus strongly suggest that the metal dependence of the catalysis and thermostability of hyperthermophilic AIs evolved separately to optimize their activity and thermostability at elevated temperatures. This may provide effective target regions for engineering, thereby meeting industrial demands for the production of d-tagatose.

  13. [Changes in the secondary and tertiary structure of serum albumin in interactions with ligands of various structures].

    PubMed

    Trinus, F P; Braver-Chernobul'skaia, B S; Luĭk, A I; Boldeskul, A E; Velichko, A N

    1984-01-01

    High affinity interactions between blood serum albumin and five substances of various chemical structure, exhibiting distinct physiological activity, were accompanied by alterations in the protein tertiary structure, while the albumin secondary structure was involved in conformational transformation after less effective affinity binding.

  14. Back Pain Prevalence Is Associated With Curve-type and Severity in Adolescents With Idiopathic Scoliosis: A Cross-sectional Study.

    PubMed

    Théroux, Jean; Le May, Sylvie; Hebert, Jeffrey J; Labelle, Hubert

    2017-08-01

    A cross-sectional study. The aim of this study was to investigate spinal pain prevalence in adolescents with idiopathic scoliosis (AIS) and to explore associations between pain intensity and pain-related disability with scoliosis site, severity, and spinal bracing. The causal link between spinal pain and AIS remains unclear. Spinal asymmetry has been recognized as a back pain risk factor, which is a known cause of care-seeking in adolescents. Participants were recruited from an outpatient tertiary-care scoliosis clinic. Pain intensity and pain-related disability were measured by the Brief Pain Inventory questionnaire and the Roland-Morris Disability Questionnaire. Scoliosis severity estimation was performed using Cobb angles. Associations were explored using multiple linear regressions and reported with unstandardized beta coefficients (β) adjusted for age and sex. We recruited 500 patients (85% female) with mean (SD) age of 14.2 (1.8) years. Means (SD) of thoracic and lumbar Cobb angle were 24.54(9.77) and 24.13 (12.40), respectively. Spinal pain prevalence was 68% [95% confidence interval (95% CI): 64.5-72.4] with a mean intensity of 1.63 (SD, 1.89). Spinal pain intensity was positively associated with scoliosis severity in the main thoracic (P = 0.003) and lumbar (P = 0.001) regions. The mean (SD) disability score was 1.73 (2.98). Disability was positively associated with scoliosis severity in the proximal thoracic (P = 0.035), main thoracic (P = 0.000), and lumbar (P = 0.000) regions.Spinal bracing was associated with lower spinal pain intensity in the thoracic (P = 0.000) and lumbar regions (P = 0.009). Bracing was also related with lower disability for all spinal areas (P < 0.045). Spinal pain is common among patients with AIS, and greater spinal deformity was associated with higher pain intensity. These findings should inform clinical decision-making when caring for patients with AIS. 3.

  15. Artificial Intelligence and Information Management

    NASA Astrophysics Data System (ADS)

    Fukumura, Teruo

    After reviewing the recent popularization of the information transmission and processing technologies, which are supported by the progress of electronics, the authors describe that by the introduction of the opto-electronics into the information technology, the possibility of applying the artificial intelligence (AI) technique to the mechanization of the information management has emerged. It is pointed out that althuogh AI deals with problems in the mental world, its basic methodology relies upon the verification by evidence, so the experiment on computers become indispensable for the study of AI. The authors also describe that as computers operate by the program, the basic intelligence which is concerned in AI is that expressed by languages. This results in the fact that the main tool of AI is the logical proof and it involves an intrinsic limitation. To answer a question “Why do you employ AI in your problem solving”, one must have ill-structured problems and intend to conduct deep studies on the thinking and the inference, and the memory and the knowledge-representation. Finally the authors discuss the application of AI technique to the information management. The possibility of the expert-system, processing of the query, and the necessity of document knowledge-base are stated.

  16. Obstructive Sleep-Disordered Breathing Is More Common than Central in Mild Familial Dysautonomia

    PubMed Central

    Hilz, Max J.; Moeller, Sebastian; Buechner, Susanne; Czarkowska, Hanna; Ayappa, Indu; Axelrod, Felicia B.; Rapoport, David M.

    2016-01-01

    Study Objectives: In familial dysautonomia (FD) patients, sleep-disordered breathing (SDB) might contribute to their high risk of sleep-related sudden death. Prevalence of central versus obstructive sleep apneas is controversial but may be therapeutically relevant. We, therefore, assessed sleep structure and SDB in FD-patients with no history of SDB. Methods: 11 mildly affected FD-patients (28 ± 11 years) without clinically overt SDB and 13 controls (28 ± 10 years) underwent polysomnographic recording during one night. We assessed sleep stages, obstructive and central apneas (≥ 90% air flow reduction) and hypopneas (> 30% decrease in airflow with ≥ 4% oxygen-desaturation), and determined obstructive (oAI) and central (cAI) apnea indices and the hypopnea index (HI) as count of respective apneas/hypopneas divided by sleep time. We obtained the apnea-hypopnea index (AHI4%) from the total of apneas and hypopneas divided by sleep time. We determined differences between FD-patients and controls using the U-test and within-group differences between oAIs, cAIs, and HIs using the Friedman test and Wilcoxon test. Results: Sleep structure was similar in FD-patients and controls. AHI4% and HI were significantly higher in patients than controls. In patients, HIs were higher than oAIs and oAIs were higher than cAIs. In controls, there was no difference between HIs, oAIs, and cAIs. Only patients had apneas and hypopneas during slow wave sleep. Conclusions: In our FD-patients, obstructive apneas were more common than central apneas. These findings may be related to FD-specific pathophysiology. The potential ramifications of SDB in FD-patients suggest the utility of polysomnography to unveil SDB and initiate treatment. Commentary: A commentary on this article appears in this issue on page 1583. Citation: Hilz MJ, Moeller S, Buechner S, Czarkowska H, Ayappa I, Axelrod FB, Rapoport DM. Obstructive sleep-disordered breathing is more common than central in mild familial dysautonomia. J Clin Sleep Med 2016;12(12):1607–1614. PMID:27655467

  17. Balancing Two Cultures: American Indian/Alaska Native Medical Students' Perceptions of Academic Medicine Careers.

    PubMed

    Sánchez, John Paul; Poll-Hunter, Norma; Stern, Nicole; Garcia, Andrea N; Brewster, Cheryl

    2016-08-01

    American Indians and Alaska Natives (AI/AN) remain underrepresented in the academic medicine workforce and little is known about cultivating AI/AN medical students' interest in academic medicine careers. Five structured focus groups were conducted including 20 medical students and 18 physicians. The discussion guide explored factors influencing AI/AN trainees' academic medicine career interest and recommended approaches to increase their pursuit of academia. Consensual qualitative research was employed to analyze transcripts. Our research revealed six facilitating factors, nine dissuading factors, and five recommendations towards cultivating AI/AN pursuit of academia. Facilitators included the opportunity to teach, serving as a role model/mentor, enhancing the AI/AN medical education pipeline, opportunities to influence institution, collegiality, and financial stability. Dissuading factors included limited information on academic career paths, politics, lack of credit for teaching and community service, isolation, self-doubt, lower salary, lack of positions in rural areas, lack of focus on clinical care for AI/AN communities, and research obligations. Recommendations included heighten career awareness, recognize the challenges in balancing AI/AN and academic cultures, collaborate with IHS on faculty recruitment strategies, identify concordant role models/mentors, and identify loan forgiveness programs. Similar to other diverse medical students', raising awareness of academic career opportunities especially regarding teaching and community scholarship, access to concordant role models/mentors, and supportive institutional climates can also foster AI/AN medical students' pursuit of academia. Unique strategies for AI/AN trainees include learning how to balance AI/AN and academic cultures, collaborating with IHS on faculty recruitment strategies, and increasing faculty opportunities in rural areas.

  18. Generic Features of Tertiary Chromatin Structure as Detected in Natural Chromosomes

    PubMed Central

    Müller, Waltraud G.; Rieder, Dietmar; Kreth, Gregor; Cremer, Christoph; Trajanoski, Zlatko; McNally, James G.

    2004-01-01

    Knowledge of tertiary chromatin structure in mammalian interphase chromosomes is largely derived from artificial tandem arrays. In these model systems, light microscope images reveal fibers or beaded fibers after high-density targeting of transactivators to insertional domains spanning several megabases. These images of fibers have lent support to chromonema fiber models of tertiary structure. To assess the relevance of these studies to natural mammalian chromatin, we identified two different ∼400-kb regions on human chromosomes 6 and 22 and then examined light microscope images of interphase tertiary chromatin structure when the regions were transcriptionally active and inactive. When transcriptionally active, these natural chromosomal regions elongated, yielding images characterized by a series of adjacent puncta or “beads”, referred to hereafter as beaded images. These elongated structures required transcription for their maintenance. Thus, despite marked differences in the density and the mode of transactivation, the natural and artificial systems showed similarities, suggesting that beaded images are generic features of transcriptionally active tertiary chromatin. We show here, however, that these images do not necessarily favor chromonema fiber models but can also be explained by a radial-loop model or even a simple nucleosome affinity, random-chain model. Thus, light microscope images of tertiary structure cannot distinguish among competing models, although they do impose key constraints: chromatin must be clustered to yield beaded images and then packaged within each cluster to enable decondensation into adjacent clusters. PMID:15485905

  19. Locomotor training with body weight support in SCI: EMG improvement is more optimally expressed at a low testing speed.

    PubMed

    Meyns, P; Van de Crommert, H W A A; Rijken, H; van Kuppevelt, D H J M; Duysens, J

    2014-12-01

    Case series. To determine the optimal testing speed at which the recovery of the EMG (electromyographic) activity should be assessed during and after body weight supported (BWS) locomotor training. Tertiary hospital, Sint Maartenskliniek, Nijmegen, The Netherlands. Four participants with incomplete chronic SCI were included for BWS locomotor training; one AIS-C and three AIS-D (according to the ASIA (American Spinal Injury Association) Impairment Scale or AIS). All were at least 5 years after injury. The SCI participants were trained three times a week for a period of 6 weeks. They improved their locomotor function in terms of higher walking speed, less BWS and less assistance needed. To investigate which treadmill speed for EMG assessment reflects the functional improvement most adequately, all participants were assessed weekly using the same two speeds (0.5 and 1.5 km h(-1), referred to as low and high speed, respectively) for 6 weeks. The change in root mean square EMG (RMS EMG) was assessed in four leg muscles; biceps femoris, rectus femoris, gastrocnemius medialis and tibialis anterior. The changes in RMS EMG occurred at similar phases of the step cycle for both walking conditions, but these changes were larger when the treadmill was set at a low speed (0.5 km h(-1)). Improvement in gait is feasible with BWS treadmill training even long after injury. The EMG changes after treadmill training are more optimally expressed using a low rather than a high testing treadmill speed.

  20. Canadian Association of Radiologists White Paper on Artificial Intelligence in Radiology.

    PubMed

    Tang, An; Tam, Roger; Cadrin-Chênevert, Alexandre; Guest, Will; Chong, Jaron; Barfett, Joseph; Chepelev, Leonid; Cairns, Robyn; Mitchell, J Ross; Cicero, Mark D; Poudrette, Manuel Gaudreau; Jaremko, Jacob L; Reinhold, Caroline; Gallix, Benoit; Gray, Bruce; Geis, Raym

    2018-05-01

    Artificial intelligence (AI) is rapidly moving from an experimental phase to an implementation phase in many fields, including medicine. The combination of improved availability of large datasets, increasing computing power, and advances in learning algorithms has created major performance breakthroughs in the development of AI applications. In the last 5 years, AI techniques known as deep learning have delivered rapidly improving performance in image recognition, caption generation, and speech recognition. Radiology, in particular, is a prime candidate for early adoption of these techniques. It is anticipated that the implementation of AI in radiology over the next decade will significantly improve the quality, value, and depth of radiology's contribution to patient care and population health, and will revolutionize radiologists' workflows. The Canadian Association of Radiologists (CAR) is the national voice of radiology committed to promoting the highest standards in patient-centered imaging, lifelong learning, and research. The CAR has created an AI working group with the mandate to discuss and deliberate on practice, policy, and patient care issues related to the introduction and implementation of AI in imaging. This white paper provides recommendations for the CAR derived from deliberations between members of the AI working group. This white paper on AI in radiology will inform CAR members and policymakers on key terminology, educational needs of members, research and development, partnerships, potential clinical applications, implementation, structure and governance, role of radiologists, and potential impact of AI on radiology in Canada. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  1. A scallop C-type lectin from Argopecten irradians (AiCTL5) with activities of lipopolysaccharide binding and Gram-negative bacteria agglutination.

    PubMed

    Mu, Changkao; Song, Xiaoyan; Zhao, Jianmin; Wang, Lingling; Qiu, Limei; Zhang, Huan; Zhou, Zhi; Wang, Mengqiang; Song, Linsheng; Wang, Chunlin

    2012-05-01

    C-type lectins are a family of calcium-dependent carbohydrate-binding proteins. In the present study, a C-type lectin (designated as AiCTL5) was identified and characterized from Argopecten irradians. The full-length cDNA of AiCTL5 was of 673 bp, containing a 5' untranslated region (UTR) of 24 bp, a 3' UTR of 130 bp with a poly (A) tail, and an open reading frame (ORF) of 519 bp encoding a polypeptide of 172 amino acids with a putative signal peptide of 17 amino acids. A C-type lectin-like domain (CRD) containing 6 conserved cysteines and a putative glycosylation sites were identified in the deduced amino acid sequence of AiCTL5. AiCTL5 shared 11%-27.5% identity with the previous reported C-type lectin from A. irradians. The cDNA fragment encoding the mature peptide of AiCTL5 was recombined into pET-21a (+) with a C-terminal hexa-histidine tag fused in-frame, and expressed in Escherichia coli Origami (DE3). The recombinant AiCTL5 (rAiCTL5) agglutinated Gram-negative E. coli TOP10F' and Listonella anguillarum, but did not agglutinate Gram-positive bacteria Bacillus thuringiensis and Micrococcus luteus, and the agglutination could be inhibited by EDTA, indicating that AiCTL5 was a Ca(2+)-dependent lectin. rAiCTL5 exhibited a significantly strong activity to bind LPS from E. coli, which conformed to the agglutinating activity toward Gram-negative bacteria. Moreover, rAiCTL5 also agglutinated rabbit erythrocytes. These results indicated that AiCTL5 could function as a pattern recognition receptor to protect bay scallop from Gram-negative bacterial infection, and also provide evidence to understand the structural and functional diverse of lectin. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Cooperative Interactions between 480 kDa Ankyrin-G and EB Proteins Assemble the Axon Initial Segment.

    PubMed

    Fréal, Amélie; Fassier, Coralie; Le Bras, Barbara; Bullier, Erika; De Gois, Stéphanie; Hazan, Jamilé; Hoogenraad, Casper C; Couraud, François

    2016-04-20

    The axon initial segment (AIS) is required for generating action potentials and maintaining neuronal polarity. Significant progress has been made in deciphering the basic building blocks composing the AIS, but the underlying mechanisms required for AIS formation remains unclear. The scaffolding protein ankyrin-G is the master-organizer of the AIS. Microtubules and their interactors, particularly end-binding proteins (EBs), have emerged as potential key players in AIS formation. Here, we show that the longest isoform of ankyrin-G (480AnkG) selectively associates with EBs via its specific tail domain and that this interaction is crucial for AIS formation and neuronal polarity in cultured rodent hippocampal neurons. EBs are essential for 480AnkG localization and stabilization at the AIS, whereas 480AnkG is required for the specific accumulation of EBs in the proximal axon. Our findings thus provide a conceptual framework for understanding how the cooperative relationship between 480AnkG and EBs induces the assembly of microtubule-AIS structures in the proximal axon. Neuronal polarity is crucial for the proper function of neurons. The assembly of the axon initial segment (AIS), which is the hallmark of early neuronal polarization, relies on the longest 480 kDa ankyrin-G isoform. The microtubule cytoskeleton and its interacting proteins were suggested to be early key players in the process of AIS formation. In this study, we show that the crosstalk between 480 kDa ankyrin-G and the microtubule plus-end tracking proteins, EBs, at the proximal axon is decisive for AIS assembly and neuronal polarity. Our work thus provides insight into the functional mechanisms used by 480 kDa ankyrin-G to drive the AIS formation and thereby to establish neuronal polarity. Copyright © 2016 the authors 0270-6474/16/364421-13$15.00/0.

  3. Tertiary structure-related activity of tick defensin (persulcatusin) in the taiga tick, Ixodes persulcatus.

    PubMed

    Isogai, Emiko; Isogai, Hiroshi; Okumura, Kazuhiko; Hori, Hatsuhiro; Tsuruta, Hiroki; Kurebayashi, Yoichi

    2011-01-01

    Defensins are small cysteine-rich cationic proteins found in both vertebrates and invertebrates constituting the front line of host innate immunity. To examine the importance of the tertiary structure of tick defensin in its antimicrobial activity, we synthesized two types of the peptides with tertiary structure or primary one on basis of the information of the sequence in the defensin originated from the taiga tick, Ixodes persulcatus. Chemically synthesized peptides were used to investigate the activity spectrum against Staphylococcus aureus, Borrelia garinii and flora-associated bacteria. Both synthetic peptides showed antimicrobial activity against S. aureus in short-time killing within 1 h, but they do not show the activity against B. garinii, Stenotrophomonas maltophila and Bacillus spp., which were frequently isolated from the midgut of I. persulcatus. The teriary structure brought more potent activity to S. aureus than primary one in short-time killing. We also examined its antimicrobial activity by evaluation of growth inhibition in the presence of the synthetic peptides. Minimum inhibitory concentration (MIC) was ranged from 1.2 to 5.0 μg/ml in tertiary peptide and from 10 to 40 μg/ml in primary peptide, when 10 strains of S. aureus were used. From the curve of cumulative inhibition rates, MIC50 (MIC which half of the strains showed) to S. aureus is about 1.2 μg/ml in the peptide with tertiary structure and about 10 μg/ml in the linear one. Corynebacterium renale is 10 times or more sensitive to tertiary peptide than primary one. In conclusion, the presence of 3 disulfide bridges, which stabilize the molecule and maintain the tertiary structure, is considered to have an effect on their antimicrobial activities against Gram-positive bacteria such as S. aureus.

  4. STAR- A SIMPLE TOOL FOR AUTOMATED REASONING SUPPORTING HYBRID APPLICATIONS OF ARTIFICIAL INTELLIGENCE (DEC VAX VERSION)

    NASA Technical Reports Server (NTRS)

    Borchardt, G. C.

    1994-01-01

    The Simple Tool for Automated Reasoning program (STAR) is an interactive, interpreted programming language for the development and operation of artificial intelligence (AI) application systems. STAR provides an environment for integrating traditional AI symbolic processing with functions and data structures defined in compiled languages such as C, FORTRAN and PASCAL. This type of integration occurs in a number of AI applications including interpretation of numerical sensor data, construction of intelligent user interfaces to existing compiled software packages, and coupling AI techniques with numerical simulation techniques and control systems software. The STAR language was created as part of an AI project for the evaluation of imaging spectrometer data at NASA's Jet Propulsion Laboratory. Programming in STAR is similar to other symbolic processing languages such as LISP and CLIP. STAR includes seven primitive data types and associated operations for the manipulation of these structures. A semantic network is used to organize data in STAR, with capabilities for inheritance of values and generation of side effects. The AI knowledge base of STAR can be a simple repository of records or it can be a highly interdependent association of implicit and explicit components. The symbolic processing environment of STAR may be extended by linking the interpreter with functions defined in conventional compiled languages. These external routines interact with STAR through function calls in either direction, and through the exchange of references to data structures. The hybrid knowledge base may thus be accessed and processed in general by either side of the application. STAR is initially used to link externally compiled routines and data structures. It is then invoked to interpret the STAR rules and symbolic structures. In a typical interactive session, the user enters an expression to be evaluated, STAR parses the input, evaluates the expression, performs any file input/output required, and displays the results. The STAR interpreter is written in the C language for interactive execution. It has been implemented on a VAX 11/780 computer operating under VMS, and the UNIX version has been implemented on a Sun Microsystems 2/170 workstation. STAR has a memory requirement of approximately 200K of 8 bit bytes, excluding externally compiled functions and application-dependent symbolic definitions. This program was developed in 1985.

  5. STAR- A SIMPLE TOOL FOR AUTOMATED REASONING SUPPORTING HYBRID APPLICATIONS OF ARTIFICIAL INTELLIGENCE (UNIX VERSION)

    NASA Technical Reports Server (NTRS)

    Borchardt, G. C.

    1994-01-01

    The Simple Tool for Automated Reasoning program (STAR) is an interactive, interpreted programming language for the development and operation of artificial intelligence (AI) application systems. STAR provides an environment for integrating traditional AI symbolic processing with functions and data structures defined in compiled languages such as C, FORTRAN and PASCAL. This type of integration occurs in a number of AI applications including interpretation of numerical sensor data, construction of intelligent user interfaces to existing compiled software packages, and coupling AI techniques with numerical simulation techniques and control systems software. The STAR language was created as part of an AI project for the evaluation of imaging spectrometer data at NASA's Jet Propulsion Laboratory. Programming in STAR is similar to other symbolic processing languages such as LISP and CLIP. STAR includes seven primitive data types and associated operations for the manipulation of these structures. A semantic network is used to organize data in STAR, with capabilities for inheritance of values and generation of side effects. The AI knowledge base of STAR can be a simple repository of records or it can be a highly interdependent association of implicit and explicit components. The symbolic processing environment of STAR may be extended by linking the interpreter with functions defined in conventional compiled languages. These external routines interact with STAR through function calls in either direction, and through the exchange of references to data structures. The hybrid knowledge base may thus be accessed and processed in general by either side of the application. STAR is initially used to link externally compiled routines and data structures. It is then invoked to interpret the STAR rules and symbolic structures. In a typical interactive session, the user enters an expression to be evaluated, STAR parses the input, evaluates the expression, performs any file input/output required, and displays the results. The STAR interpreter is written in the C language for interactive execution. It has been implemented on a VAX 11/780 computer operating under VMS, and the UNIX version has been implemented on a Sun Microsystems 2/170 workstation. STAR has a memory requirement of approximately 200K of 8 bit bytes, excluding externally compiled functions and application-dependent symbolic definitions. This program was developed in 1985.

  6. Quantitative tests of a reconstitution model for RNA folding thermodynamics and kinetics.

    PubMed

    Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Mabuchi, Hideo; Herschlag, Daniel

    2017-09-12

    Decades of study of the architecture and function of structured RNAs have led to the perspective that RNA tertiary structure is modular, made of locally stable domains that retain their structure across RNAs. We formalize a hypothesis inspired by this modularity-that RNA folding thermodynamics and kinetics can be quantitatively predicted from separable energetic contributions of the individual components of a complex RNA. This reconstitution hypothesis considers RNA tertiary folding in terms of ΔG align , the probability of aligning tertiary contact partners, and ΔG tert , the favorable energetic contribution from the formation of tertiary contacts in an aligned state. This hypothesis predicts that changes in the alignment of tertiary contacts from different connecting helices and junctions (ΔG HJH ) or from changes in the electrostatic environment (ΔG +/- ) will not affect the energetic perturbation from a mutation in a tertiary contact (ΔΔG tert ). Consistent with these predictions, single-molecule FRET measurements of folding of model RNAs revealed constant ΔΔG tert values for mutations in a tertiary contact embedded in different structural contexts and under different electrostatic conditions. The kinetic effects of these mutations provide further support for modular behavior of RNA elements and suggest that tertiary mutations may be used to identify rate-limiting steps and dissect folding and assembly pathways for complex RNAs. Overall, our model and results are foundational for a predictive understanding of RNA folding that will allow manipulation of RNA folding thermodynamics and kinetics. Conversely, the approaches herein can identify cases where an independent, additive model cannot be applied and so require additional investigation.

  7. Thermodynamics and kinetics of RNA tertiary structure formation in the junctionless hairpin ribozyme.

    PubMed

    White, Neil A; Hoogstraten, Charles G

    2017-09-01

    The hairpin ribozyme consists of two RNA internal loops that interact to form the catalytically active structure. This docking transition is a rare example of intermolecular formation of RNA tertiary structure without coupling to helix annealing. We have used temperature-dependent surface plasmon resonance (SPR) to characterize the thermodynamics and kinetics of RNA tertiary structure formation for the junctionless form of the ribozyme, in which loops A and B reside on separate molecules. We find docking to be strongly enthalpy-driven and to be accompanied by substantial activation barriers for association and dissociation, consistent with the structural reorganization of both internal loops upon complex formation. Comparisons with the parallel analysis of a ribozyme variant carrying a 2'-O-methyl modification at the self-cleavage site and with published data in other systems reveal a surprising diversity of thermodynamic signatures, emphasizing the delicate balance of contributions to the free energy of formation of RNA tertiary structure. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Antibacterial Activity of AI-Hemocidin 2, a Novel N-Terminal Peptide of Hemoglobin Purified from Arca inflata.

    PubMed

    Li, Chunlei; Zhu, Jianhua; Wang, Yanqing; Chen, Yuyan; Song, Liyan; Zheng, Weiming; Li, Jingjing; Yu, Rongmin

    2017-06-29

    The continued emergence of antibiotic resistant bacteria in recent years is of great concern. The search for new classes of antibacterial agents has expanded to non-traditional sources such as shellfish. An antibacterial subunit of hemoglobin (Hb-I) was purified from the mantle of Arca inflata by phosphate extraction and ion exchange chromatography. A novel antibacterial peptide, AI-hemocidin 2, derived from Hb-I, was discovered using bioinformatics analysis. It displayed antibacterial activity across a broad spectrum of microorganisms, including several Gram-positive and Gram-negative bacteria, with minimal inhibitory concentration (MIC) values ranging from 37.5 to 300 μg/mL, and it exhibited minimal hemolytic or cytotoxic activities. The antibacterial activity of AI-hemocidin 2 was thermostable (25-100 °C) and pH resistant (pH 3-10). The cellular integrity was determined by flow cytometry. AI-hemocidin 2 was capable of permeating the cellular membrane. Changes in the cell morphology were observed with a scanning electron microscope. Circular dichroism spectra suggested that AI-hemocidin 2 formed an α-helix structure in the membrane mimetic environment. The results indicated that the anti-bacterial mechanism for AI-hemocidin 2 occurred through disrupting the cell membrane. AI-hemocidin 2 might be a potential candidate for tackling antibiotic resistant bacteria.

  9. Search-based model identification of smart-structure damage

    NASA Technical Reports Server (NTRS)

    Glass, B. J.; Macalou, A.

    1991-01-01

    This paper describes the use of a combined model and parameter identification approach, based on modal analysis and artificial intelligence (AI) techniques, for identifying damage or flaws in a rotating truss structure incorporating embedded piezoceramic sensors. This smart structure example is representative of a class of structures commonly found in aerospace systems and next generation space structures. Artificial intelligence techniques of classification, heuristic search, and an object-oriented knowledge base are used in an AI-based model identification approach. A finite model space is classified into a search tree, over which a variant of best-first search is used to identify the model whose stored response most closely matches that of the input. Newly-encountered models can be incorporated into the model space. This adaptativeness demonstrates the potential for learning control. Following this output-error model identification, numerical parameter identification is used to further refine the identified model. Given the rotating truss example in this paper, noisy data corresponding to various damage configurations are input to both this approach and a conventional parameter identification method. The combination of the AI-based model identification with parameter identification is shown to lead to smaller parameter corrections than required by the use of parameter identification alone.

  10. Triblock copolyampholytes from 5-(N,N-dimethyl amino)isoprene styrene, and methacrylic acid: Synthesis and solution properties

    NASA Astrophysics Data System (ADS)

    Bieringer, R.; Abetz, V.; Müller, A. H. E.

    ABC triblock copolymers of the type poly[5-(N,N-dimethyl amino)isoprene]-block-polystyrene-block-poly(tert-butyl methacrylate) (AiST) were synthesized and hydrolyzed to yield poly[5-(N,N-dimethyl amino)isoprene]-block-polystyrene-block-poly(methacrylic acid) (AiSA) triblock copolyampholytes. Due to a complex solubility behavior the solution properties of these materials had to be investigated in THF/water solvent mixtures. Potentiometric titrations of AiSA triblock copolyampholytes showed two inflection points with the A block being deprotonated prior to the Ai hydrochloride block thus forming a polyzwitterion at the isoelectric point (iep). The aggregation behavior was studied by dynamic light scattering (DLS) and freeze-fracture/transmission electron microscopy (TEM). Large vesicular structures with almost pH-independent radii were observed.

  11. Discovery and structure activity relationships of 2-pyrazolines derived from chalcones from a pest management perspective

    USDA-ARS?s Scientific Manuscript database

    Synthesis of chalcones and 2-pyrazoline derivatives has been an active field of research due to the established pharmacological effects of these compounds. In this study, a series of chalcone (1a-i), 2-pyrazoline-1-carbothioamides (2a-i) and 2-pyrazoline-1-carboxamide derivatives (3a-g) were synthes...

  12. New directions for Artificial Intelligence (AI) methods in optimum design

    NASA Technical Reports Server (NTRS)

    Hajela, Prabhat

    1989-01-01

    Developments and applications of artificial intelligence (AI) methods in the design of structural systems is reviewed. Principal shortcomings in the current approach are emphasized, and the need for some degree of formalism in the development environment for such design tools is underscored. Emphasis is placed on efforts to integrate algorithmic computations in expert systems.

  13. Kinetic and thermodynamic framework for P4-P6 RNA reveals tertiary motif modularity and modulation of the folding preferred pathway

    PubMed Central

    Bisaria, Namita; Greenfeld, Max; Limouse, Charles; Pavlichin, Dmitri S.; Mabuchi, Hideo; Herschlag, Daniel

    2016-01-01

    The past decade has seen a wealth of 3D structural information about complex structured RNAs and identification of functional intermediates. Nevertheless, developing a complete and predictive understanding of the folding and function of these RNAs in biology will require connection of individual rate and equilibrium constants to structural changes that occur in individual folding steps and further relating these steps to the properties and behavior of isolated, simplified systems. To accomplish these goals we used the considerable structural knowledge of the folded, unfolded, and intermediate states of P4-P6 RNA. We enumerated structural states and possible folding transitions and determined rate and equilibrium constants for the transitions between these states using single-molecule FRET with a series of mutant P4-P6 variants. Comparisons with simplified constructs containing an isolated tertiary contact suggest that a given tertiary interaction has a stereotyped rate for breaking that may help identify structural transitions within complex RNAs and simplify the prediction of folding kinetics and thermodynamics for structured RNAs from their parts. The preferred folding pathway involves initial formation of the proximal tertiary contact. However, this preference was only ∼10 fold and could be reversed by a single point mutation, indicating that a model akin to a protein-folding contact order model will not suffice to describe RNA folding. Instead, our results suggest a strong analogy with a modified RNA diffusion-collision model in which tertiary elements within preformed secondary structures collide, with the success of these collisions dependent on whether the tertiary elements are in their rare binding-competent conformations. PMID:27493222

  14. Stroke mimics under the drip-and-ship paradigm.

    PubMed

    Mehta, Sonal; Vora, Nirav; Edgell, Randall C; Allam, Hesham; Alawi, Aws; Koehne, Jennifer; Kumar, Abhay; Feen, Eliahu; Cruz-Flores, Salvador; Alshekhlee, Amer

    2014-01-01

    Recent reports suggested better outcomes associated with the drip-and-ship paradigm for acute ischemic stroke (AIS) treated with thrombolysis. We hypothesized that a higher rate of stroke mimics (SM) among AIS treated in nonspecialized stroke centers that are transferred to comprehensive centers is responsible for such outcomes. Consecutive patients treated with thrombolysis according to the admission criteria were reviewed in a single comprehensive stroke center over 1 academic year (July 1, 2011 to June 30, 2012). Information on the basic demographic, hospital complications, psychiatric diagnoses, and discharge disposition was collected. We identified those patients who were treated at a facility and then transferred to the tertiary center (ie, drip-and-ship paradigm). In addition to comparative and adjusted analysis to identify predictors for SM, a stratified analysis by the drip-and-ship status was performed. One hundred twenty patients were treated with thrombolysis for AIS included in this analysis; 20 (16.7%) were discharged with the final diagnosis of SM; 14 of those had conversion syndrome and 6 patients had other syndromes (seizures, migraine, and hypoglycemia). Patients with SM were younger (55.6 ± 15.0 versus 69.4 ± 14.9, P = .0003) and more likely to harbor psychiatric diagnoses (45% versus 9%; P ≤ .0001). Eighteen of 20 SM patients (90%) had the drip-and-ship treatment paradigm compared with 65% of those with AIS (P = .02). None of the SM had hemorrhagic complications, and all were discharged to home. Predictors of SM on adjusted analysis included the drip-and-ship paradigm (odds ratio [OR] 12.8, 95% confidence interval [CI] 1.78, 92.1) and history of any psychiatric illness (OR 12.08; 95% CI 3.14, 46.4). Eighteen of 83 drip-and-ship patients (21.7%) were diagnosed with SM compared with 2 of 37 patients (5.4%) presented directly to the hub hospital (P = .02). The drip-and-ship paradigm and any psychiatric history predict the diagnosis of SM. None of the SM had thrombolysis-related complications, and all were discharged to home. These findings may explain the superior outcomes associated with the drip-and-ship paradigm in the treatment for AIS. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes.

    PubMed

    Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

    2016-05-26

    Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes.

  16. Systematic analysis of mutation distribution in three dimensional protein structures identifies cancer driver genes

    PubMed Central

    Fujimoto, Akihiro; Okada, Yukinori; Boroevich, Keith A.; Tsunoda, Tatsuhiko; Taniguchi, Hiroaki; Nakagawa, Hidewaki

    2016-01-01

    Protein tertiary structure determines molecular function, interaction, and stability of the protein, therefore distribution of mutation in the tertiary structure can facilitate the identification of new driver genes in cancer. To analyze mutation distribution in protein tertiary structures, we applied a novel three dimensional permutation test to the mutation positions. We analyzed somatic mutation datasets of 21 types of cancers obtained from exome sequencing conducted by the TCGA project. Of the 3,622 genes that had ≥3 mutations in the regions with tertiary structure data, 106 genes showed significant skew in mutation distribution. Known tumor suppressors and oncogenes were significantly enriched in these identified cancer gene sets. Physical distances between mutations in known oncogenes were significantly smaller than those of tumor suppressors. Twenty-three genes were detected in multiple cancers. Candidate genes with significant skew of the 3D mutation distribution included kinases (MAPK1, EPHA5, ERBB3, and ERBB4), an apoptosis related gene (APP), an RNA splicing factor (SF1), a miRNA processing factor (DICER1), an E3 ubiquitin ligase (CUL1) and transcription factors (KLF5 and EEF1B2). Our study suggests that systematic analysis of mutation distribution in the tertiary protein structure can help identify cancer driver genes. PMID:27225414

  17. A Structural Weight Estimation Program (SWEEP) for Aircraft. Volume 6 - Wing and Empennage Module. Appendix C: Program Flow Charts, Overlays (9.0) and (10,0)

    DTIC Science & Technology

    1974-06-01

    NQUI II.CH Uj^f^i.»! orwi MI-../f;*« MA orrrtAi IOHAI niuipi imiAi mioi tu U/IN IK «»At IB MIDI win» t np roKnAi im fx.ir...rj0lll.f<CC9>l,(DCUI.II??)l. ICKi«. TDOUIfi I, IK . >’. TlKWi Si I. l!Ü>X. lOKJrs I). ( WAV .rtXO»». ((;XW.»;)(*>.U.(KlMi)(ClH.MOP|.rt)(a’M, lWM3i

  18. Freezing-Induced Perturbation of Tertiary Structure of a Monoclonal Antibody

    PubMed Central

    LIU, LU; BRAUN, LATOYA JONES; WANG, WEI; RANDOLPH, THEODORE W.; CARPENTER, JOHN F.

    2014-01-01

    We studied the effects of pH and solution additives on freezing-induced perturbations in the tertiary structure of a monoclonal antibody (mAb) by intrinsic tryptophan fluorescence spectroscopy. In general, freezing caused perturbations in the tertiary structure of the mAb, which were reversible or irreversible depending on the pH or excipients present in the formulation. Protein aggregation occurred in freeze–thawed samples in which perturbations of the tertiary structure were observed, but the levels of protein aggregates formed were not proportional to the degree of structural perturbation. Protein aggregation also occurred in freeze–thawed samples without obvious structural perturbations, most likely because of freeze concentration of protein and salts, and thus reduced protein colloidal stability. Therefore, freezing-induced protein aggregation may or may not first involve the perturbation of its native structure, followed by the assembly processes to form aggregates. Depending on the solution conditions, either step can be rate limiting. Finally, this study demonstrates the potential of fluorescence spectroscopy as a valuable tool for screening therapeutic protein formulations subjected to freeze–thaw stress. PMID:24832730

  19. Topological constraints are major determinants of tRNA tertiary structure and dynamics and provide basis for tertiary folding cooperativity

    PubMed Central

    Mustoe, Anthony M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

    2014-01-01

    Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA's allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA's helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA's different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding. PMID:25217593

  20. Restrained Differential Growth: The Initiating Event of Adolescent Idiopathic Scoliosis?

    PubMed

    Crijns, Tom Joris; Stadhouder, Agnita; Smit, Theodoor Henri

    2017-06-15

    An experimental model study and a short review of literature. The purpose of this study was to explore a new hypothesis suggesting that the curvatures seen in adolescent idiopathic scoliosis (AIS) originate from restrained differential growth between the vertebral column and the surrounding musculo-ligamentary structures. Despite decades of research, there is no generally accepted theory on the physical origin of the severe spinal deformations seen in AIS. The prevailing theories tend to focus on left-right asymmetry, rotational instability, or the sagittal spinal profile in idiopathic scoliosis. We test our hypothesis with a physical model of the spine that simulates growth, counteracted by ligaments and muscles, modeled by tethers and springs. Growth of the spine is further restrained by an anterior band representing the thorax, the linea alba, and abdominal musculature. We also explore literature in search of molecular mechanisms that may induce differential growth. Differential growth in the restrained spine model first induces hypokyphosis and mild lateral bending of the thoracic spine, but then suddenly escalates into a scoliotic deformity, consistent with clinical observations of AIS. The band simulating the ventral structures of the body had a pivotal effect on sagittal curvature and the initiation of lateral bending and rotation. In literature, several molecular mechanisms were found that may explain the occurrence of differential growth between the spine and the musculo-ligamentary structures. While AIS is a three-dimensional deformation of the spine, it appears that restrained differential growth in the sagittal plane can result in lateral bending and rotation without a pre-existing left-right asymmetry. This supports the concept that AIS may result from a growth imbalance rather than a local anatomical defect. N/A.

  1. A Systematic Review and Methodological Evaluation of Published Cost-Effectiveness Analyses of Aromatase Inhibitors versus Tamoxifen in Early Stage Breast Cancer

    PubMed Central

    John-Baptiste, Ava A.; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M.; Bell, Chaim M.

    2013-01-01

    Background A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. Methods We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. Results We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Conclusion Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy. PMID:23671612

  2. A systematic review and methodological evaluation of published cost-effectiveness analyses of aromatase inhibitors versus tamoxifen in early stage breast cancer.

    PubMed

    John-Baptiste, Ava A; Wu, Wei; Rochon, Paula; Anderson, Geoffrey M; Bell, Chaim M

    2013-01-01

    A key priority in developing policies for providing affordable cancer care is measuring the value for money of new therapies using cost-effectiveness analyses (CEAs). For CEA to be useful it should focus on relevant outcomes and include thorough investigation of uncertainty. Randomized controlled trials (RCTs) of five years of aromatase inhibitors (AI) versus five years of tamoxifen in the treatment of post-menopausal women with early stage breast cancer, show benefit of AI in terms of disease free survival (DFS) but not overall survival (OS) and indicate higher risk of fracture with AI. Policy-relevant CEA of AI versus tamoxifen should focus on OS and include analysis of uncertainty over key assumptions. We conducted a systematic review of published CEAs comparing an AI to tamoxifen. We searched Ovid MEDLINE, EMBASE, PsychINFO, and the Cochrane Database of Systematic Reviews without language restrictions. We selected CEAs with outcomes expressed as cost per life year or cost per quality adjusted life year (QALY). We assessed quality using the Neumann checklist. Using structured forms two abstractors collected descriptive information, sources of data, baseline assumptions on effectiveness and adverse events, and recorded approaches to assessing parameter uncertainty, methodological uncertainty, and structural uncertainty. We identified 1,622 citations and 18 studies met inclusion criteria. All CE estimates assumed a survival benefit for aromatase inhibitors. Twelve studies performed sensitivity analysis on the risk of adverse events and 7 assumed no additional mortality risk with any adverse event. Sub-group analysis was limited; 6 studies examined older women, 2 examined women with low recurrence risk, and 1 examined women with multiple comorbidities. Published CEAs comparing AIs to tamoxifen assumed an OS benefit though none has been shown in RCTs, leading to an overestimate of the cost-effectiveness of AIs. Results of these CEA analyses may be suboptimal for guiding policy.

  3. Purification, developmental expression, and in silico characterization of α-amylase inhibitor from Echinochloa frumentacea.

    PubMed

    Panwar, Priyankar; Verma, A K; Dubey, Ashutosh

    2018-05-01

    Barnyard ( Echinochloa frumentacea ) and finger ( Eleusine coracana ) millet growing at northwestern Himalaya were explored for the α-amylase inhibitor (α-AI). The mature seeds of barnyard millet variety PRJ1 had maximum α-AI activity which increases in different developmental stage. α-AI was purified up to 22.25-fold from barnyard millet variety PRJ1. Semi-quantitative PCR of different developmental stages of barnyard millet seeds showed increased levels of the transcript from 7 to 28 days. Sequence analysis revealed that it contained 315 bp nucleotide which encodes 104 amino acid sequence with molecular weight 10.72 kDa. The predicted 3D structure of α-AI was 86.73% similar to a bifunctional inhibitor of ragi. In silico analysis of 71 α-AI protein sequences were carried out for biochemical features, homology search, multiple sequence alignment, phylogenetic tree construction, motif, and superfamily distribution of protein sequences. Analysis of multiple sequence alignment revealed the existence of conserved regions NPLP[S/G]CRWYVV[S/Q][Q/R]TCG[V/I] throughout sequences. Superfam analysis revealed that α-AI protein sequences were distributed among seven different superfamilies.

  4. Urban, Forest, and Agricultural AIS Data: Fine Spectral Structure

    NASA Technical Reports Server (NTRS)

    Vanderbilt, V. C.

    1985-01-01

    Spectra acquired by the Airborne Imaging Spectrometer (AIS) near Lafayette, IN, Ely, MN, and over the Stanford University campus, CA were analyzed for fine spectral structure using two techniques: the ratio of radiance of a ground target to the radiance of a standard and also the correlation coefficient of radiances at adjacent wavelengths. The results show ramp like features in the ratios. These features are due to the biochemical composition of the leaf and to the optical scattering properties of its cuticle. The size and shape of the ramps vary with ground cover.

  5. The roles of tertiary amine structure, background organic matter and chloramine species on NDMA formation.

    PubMed

    Selbes, Meric; Kim, Daekyun; Ates, Nuray; Karanfil, Tanju

    2013-02-01

    N-nitrosodimethylamine (NDMA), a probable human carcinogen, is a disinfection by-product that has been detected in chloraminated and chlorinated drinking waters and wastewaters. Formation mechanisms and precursors of NDMA are still not well understood. The main objectives of this study were to systematically investigate (i) the effect of tertiary amine structure, (ii) the effect of background natural organic matter (NOM), and (iii) the roles of mono vs. dichloramine species on the NDMA formation. Dimethylamine (DMA) and 20 different tertiary aliphatic and aromatic amines were carefully examined based on their functional groups attached to the basic DMA structure. The wide range (0.02-83.9%) of observed NDMA yields indicated the importance of the structure of tertiary amines, and both stability and electron distribution of the leaving group of tertiary amines on NDMA formation. DMA associated with branched alkyl groups or benzyl like structures having only one carbon between the ring and DMA structure consistently gave higher NDMA yields. Compounds with electron withdrawing groups (EWG) reacted preferentially with monochloramine, whereas compounds with electron donating group (EDG) showed tendency to react with dichloramine to form NDMA. When the selected amines were present in NOM solutions, NDMA formation increased for compounds with EWG while decreased for compounds with EDG. This impact was attributed to the competitions between NOM and amines for chloramine species. The results provided additional information to the commonly accepted mechanism for NDMA formation including chloramine species reacting with tertiary amines and the role of the leaving group on overall NDMA conversion. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Locomotor skills and balance strategies in adolescents idiopathic scoliosis.

    PubMed

    Mallau, Sophie; Bollini, Gérard; Jouve, Jean-Luc; Assaiante, Christine

    2007-01-01

    Locomotor balance control assessment was performed to study the effect of idiopathic scoliosis on head-trunk coordination in 17 patients with adolescent idiopathic scoliosis (AIS) and 16 control subjects. The aim of this study was to explore the functional effects of structural spinal deformations like idiopathic scoliosis on the balance strategies used during locomotion. Up to now, the repercussion of the idiopathic scoliosis on head-trunk coordination and balance strategies during locomotion is relatively unknown. Seventeen patients with AIS (mean age 14 years 3 months, 10 degrees < Cobb angle > 30 degrees) and 16 control subjects (mean age 14 years 1 month) were tested during various locomotor tasks: walking on the ground, walking on a line, and walking on a beam. Balance control was examined in terms of rotation about the vertical axis (yaw) and on a frontal plane (roll). Kinematics of foot, pelvis, trunk, shoulder, and head rotations were measured with an automatic optical TV image processor in order to calculate angular dispersions and segmental stabilizations. Decreasing the walking speed is the main adaptive strategy used in response to balance problems in control subjects as well as patients with AIS. However, patients with AIS performed walking tasks more slowly than normal subjects (around 15%). Moreover, the pelvic stabilization is preserved, despite the structural changes affecting the spine. Lastly, the biomechanical defect resulting from idiopathic scoliosis mainly affects the yaw head stabilization during locomotion. Patients with AIS show substantial similarities with control subjects in adaptive strategies relative to locomotor velocity as well as balance control based on segmental stabilization. In contrast, the loss of the yaw head stabilization strategies, mainly based on the use of vestibular information, probably reflects the presence of vestibular deficits in the patients with AIS.

  7. Artificial Intelligence: An Analysis of the Technology for Training. Training and Development Research Center Project Number Fourteen.

    ERIC Educational Resources Information Center

    Sayre, Scott Alan

    The ultimate goal of the science of artificial intelligence (AI) is to establish programs that will use algorithmic computer techniques to imitate the heuristic thought processes of humans. Most AI programs, especially expert systems, organize their knowledge into three specific areas: data storage, a rule set, and a control structure. Limitations…

  8. A theoretical approach to artificial intelligence systems in medicine.

    PubMed

    Spyropoulos, B; Papagounos, G

    1995-10-01

    The various theoretical models of disease, the nosology which is accepted by the medical community and the prevalent logic of diagnosis determine both the medical approach as well as the development of the relevant technology including the structure and function of the A.I. systems involved. A.I. systems in medicine, in addition to the specific parameters which enable them to reach a diagnostic and/or therapeutic proposal, entail implicitly theoretical assumptions and socio-cultural attitudes which prejudice the orientation and the final outcome of the procedure. The various models -causal, probabilistic, case-based etc. -are critically examined and their ethical and methodological limitations are brought to light. The lack of a self-consistent theoretical framework in medicine, the multi-faceted character of the human organism as well as the non-explicit nature of the theoretical assumptions involved in A.I. systems restrict them to the role of decision supporting "instruments" rather than regarding them as decision making "devices". This supporting role and, especially, the important function which A.I. systems should have in the structure, the methods and the content of medical education underscore the need of further research in the theoretical aspects and the actual development of such systems.

  9. Psychometric analyses to improve the Dutch ICF Activity Inventory.

    PubMed

    Bruijning, Janna E; van Rens, Ger; Knol, Dirk; van Nispen, Ruth

    2013-08-01

    In the past, rehabilitation centers for the visually impaired used unstructured or semistructured methods to assess rehabilitation needs of their patients. Recently, an extensive instrument, the Dutch ICF Activity Inventory (D-AI), was developed to systematically investigate rehabilitation needs of visually impaired adults and to evaluate rehabilitation outcomes. The purpose of this study was to investigate the underlying factor structure and other psychometric properties to shorten and improve the D-AI. The D-AI was administered to 241 visually impaired persons who recently enrolled in a multidisciplinary rehabilitation center. The D-AI uses graded scores to assess the importance and difficulty of 65 rehabilitation goals. For high-priority goals (e.g., daily meal preparation), the difficulty of underlying tasks (e.g., read recipes, cut vegetables) was assessed. To reduce underlying task items (>950), descriptive statistics were investigated and factor analyses were performed for several goals. The internal consistency reliability and test-retest reliability of the D-AI were investigated by calculating Cronbach α and Cohen (weighted) κ. Finally, consensus-based discussions were used to shorten and improve the D-AI. Except for one goal, factor analysis model parameters were at least reasonable. Internal consistency reliability was satisfactory (range, 0.74 to 0.93). In total, 60% of the 65 goal importance items and 84.4% of the goal difficulty items showed moderate to almost perfect κ values (≥0.40). After consensus-based discussions, a new D-AI was produced, containing 48 goals and less than 500 tasks. The analyses were an important step in the validation process of the D-AI and to develop a more feasible assessment tool to investigate rehabilitation needs of visually impaired persons in a systematic way. The D-AI is currently implemented in all Dutch rehabilitation centers serving all visually impaired adults with various rehabilitation needs.

  10. Antibacterial Activity of AI-Hemocidin 2, a Novel N-Terminal Peptide of Hemoglobin Purified from Arca inflata

    PubMed Central

    Li, Chunlei; Zhu, Jianhua; Wang, Yanqing; Chen, Yuyan; Song, Liyan; Zheng, Weiming; Li, Jingjing; Yu, Rongmin

    2017-01-01

    The continued emergence of antibiotic resistant bacteria in recent years is of great concern. The search for new classes of antibacterial agents has expanded to non-traditional sources such as shellfish. An antibacterial subunit of hemoglobin (Hb-I) was purified from the mantle of Arca inflata by phosphate extraction and ion exchange chromatography. A novel antibacterial peptide, AI-hemocidin 2, derived from Hb-I, was discovered using bioinformatics analysis. It displayed antibacterial activity across a broad spectrum of microorganisms, including several Gram-positive and Gram-negative bacteria, with minimal inhibitory concentration (MIC) values ranging from 37.5 to 300 μg/mL, and it exhibited minimal hemolytic or cytotoxic activities. The antibacterial activity of AI-hemocidin 2 was thermostable (25–100 °C) and pH resistant (pH 3–10). The cellular integrity was determined by flow cytometry. AI-hemocidin 2 was capable of permeating the cellular membrane. Changes in the cell morphology were observed with a scanning electron microscope. Circular dichroism spectra suggested that AI-hemocidin 2 formed an α-helix structure in the membrane mimetic environment. The results indicated that the anti-bacterial mechanism for AI-hemocidin 2 occurred through disrupting the cell membrane. AI-hemocidin 2 might be a potential candidate for tackling antibiotic resistant bacteria. PMID:28661457

  11. Correlation between the radiological observation of isolated tertiary waves on an esophagram and findings on high-resolution esophageal manometry.

    PubMed

    Halland, M; Ravi, K; Barlow, J; Arora, A

    2016-01-01

    Barium esophagrams are a frequently performed test, and radiological observations about potential abnormal esophageal motility, such as tertiary contractions, are commonly reported. We sought to assess the correlation between tertiary waves, and in particular isolated tertiary waves, on esophagrams and findings on non-synchronous high-resolution esophageal manometry. We retrospectively reviewed reports of esophagrams performed at a tertiary referral center and identified patients in whom tertiary waves were observed and a high-resolution esophageal manometry had been performed. We defined two groups; group 1 was defined as patients with isolated tertiary waves, whereas group 2 had tertiary waves and evidence of achalasia or an obstructing structural abnormality on the esophagram. We collected data on demographics, dysphagia score, associated findings on esophagram, and need for intervention. We reviewed the reports of 2100 esophagrams of which tertiary waves were noted as an isolated abnormality in 92, and in association with achalasia or a structural obstruction in 61. High-resolution manometry was performed in 17 patients in group 1, and five had evidence of a significant esophageal motility disorder and 4 required any intervention. Twenty-one patients in group 2 underwent manometry, and 18 had a significant esophageal motility disorder. An isolated finding of tertiary waves on an esophagram is rarely associated with a significant esophageal motility disorder that requires intervention. All patients with isolated tertiary waves who required intervention had a dysphagia to liquids. Tertiary contractions, in the absence of dysphagia to liquids, indicate no significant esophageal motility disorder. © 2014 International Society for Diseases of the Esophagus.

  12. Protein backbone engineering as a strategy to advance foldamers toward the frontier of protein-like tertiary structure.

    PubMed

    Reinert, Zachary E; Horne, W Seth

    2014-11-28

    A variety of non-biological structural motifs have been incorporated into the backbone of natural protein sequences. In parallel work, diverse unnatural oligomers of de novo design (termed "foldamers") have been developed that fold in defined ways. In this Perspective article, we survey foundational studies on protein backbone engineering, with a focus on alterations made in the context of complex tertiary folds. We go on to summarize recent work illustrating the potential promise of these methods to provide a general framework for the construction of foldamer mimics of protein tertiary structures.

  13. Passive acoustic source localization using sources of opportunity.

    PubMed

    Verlinden, Christopher M A; Sarkar, J; Hodgkiss, W S; Kuperman, W A; Sabra, K G

    2015-07-01

    The feasibility of using data derived replicas from ships of opportunity for implementing matched field processing is demonstrated. The Automatic Identification System (AIS) is used to provide the library coordinates for the replica library and a correlation based processing procedure is used to overcome the impediment that the replica library is constructed from sources with different spectra and will further be used to locate another source with its own unique spectral structure. The method is illustrated with simulation and then verified using acoustic data from a 2009 experiment for which AIS information was retrieved from the United States Coast Guard Navigation Center Nationwide AIS database.

  14. The application of artificial intelligence techniques to large distributed networks

    NASA Technical Reports Server (NTRS)

    Dubyah, R.; Smith, T. R.; Star, J. L.

    1985-01-01

    Data accessibility and transfer of information, including the land resources information system pilot, are structured as large computer information networks. These pilot efforts include the reduction of the difficulty to find and use data, reducing processing costs, and minimize incompatibility between data sources. Artificial Intelligence (AI) techniques were suggested to achieve these goals. The applicability of certain AI techniques are explored in the context of distributed problem solving systems and the pilot land data system (PLDS). The topics discussed include: PLDS and its data processing requirements, expert systems and PLDS, distributed problem solving systems, AI problem solving paradigms, query processing, and distributed data bases.

  15. Development of an expert based ICD-9-CM and ICD-10-CM map to AIS 2005 update 2008.

    PubMed

    Loftis, Kathryn L; Price, Janet P; Gillich, Patrick J; Cookman, Kathy J; Brammer, Amy L; St Germain, Trish; Barnes, Jo; Graymire, Vickie; Nayduch, Donna A; Read-Allsopp, Christine; Baus, Katherine; Stanley, Patsye A; Brennan, Maureen

    2016-09-01

    This article describes how maps were developed from the clinical modifications of the 9th and 10th revisions of the International Classification of Diseases (ICD) to the Abbreviated Injury Scale 2005 Update 2008 (AIS08). The development of the mapping methodology is described, with discussion of the major assumptions used in the process to map ICD codes to AIS severities. There were many intricacies to developing the maps, because the 2 coding systems, ICD and AIS, were developed for different purposes and contain unique classification structures to meet these purposes. Experts in ICD and AIS analyzed the rules and coding guidelines of both injury coding schemes to develop rules for mapping ICD injury codes to the AIS08. This involved subject-matter expertise, detailed knowledge of anatomy, and an in-depth understanding of injury terms and definitions as applied in both taxonomies. The official ICD-9-CM and ICD-10-CM versions (injury sections) were mapped to the AIS08 codes and severities, following the rules outlined in each coding manual. The panel of experts was composed of coders certified in ICD and/or AIS from around the world. In the process of developing the map from ICD to AIS, the experts created rules to address issues with the differences in coding guidelines between the 2 schemas and assure a consistent approach to all codes. Over 19,000 ICD codes were analyzed and maps were generated for each code to AIS08 chapters, AIS08 severities, and Injury Severity Score (ISS) body regions. After completion of the maps, 14,101 (74%) of the eligible 19,012 injury-related ICD-9-CM and ICD-10-CM codes were assigned valid AIS08 severity scores between 1 and 6. The remaining 4,911 codes were assigned an AIS08 of 9 (unknown) or were determined to be nonmappable because the ICD description lacked sufficient qualifying information for determining severity according to AIS rules. There were also 15,214 (80%) ICD codes mapped to AIS08 chapter and ISS body region, which allow for ISS calculations for patient data sets. This mapping between ICD and AIS provides a comprehensive, expert-designed solution for analysts to bridge the data gap between the injury descriptions provided in hospital codes (ICD-9-CM, ICD-10-CM) and injury severity codes (AIS08). By applying consistent rules from both the ICD and AIS taxonomies, the expert panel created these definitive maps, which are the only ones endorsed by the Association for the Advancement of Automotive Medicine (AAAM). Initial validation upheld the quality of these maps for the estimation of AIS severity, but future work should include verification of these maps for MAIS and ISS estimations with large data sets. These ICD-AIS maps will support data analysis from databases with injury information classified in these 2 different systems and open new doors for the investigation of injury from traumatic events using large injury data sets.

  16. Quantification of the Thermodynamically Linked Quaternary and Tertiary Structural Stabilities of Transthyretin and its Disease-Associated Variants–the Relationship between Stability and Amyloidosis†

    PubMed Central

    Hurshman Babbes, Amy R.; Powers, Evan T.; Kelly, Jeffery W.

    2009-01-01

    Urea denaturation studies were carried out as a function of transthyretin (TTR) concentration to quantify the thermodynamically linked quaternary and tertiary structural stability and to better understand the relationship between mutant folding energetics and amyloid disease phenotype. Urea denaturation of TTR involves at least two equilibria—dissociation of tetramers into folded monomers, and monomer unfolding. To deal with the thermodynamic linkage of these equilibria, we analyzed concentration-dependent denaturation data by global fitting to an equation that simultaneously accounts for the two-step denaturation process. Using this method, the quaternary and tertiary structural stabilities of well-behaved TTR sequences, wild type (WT) TTR and the disease-associated variant V122I, were scrutinized. The V122I variant is linked to late onset familial amyloid cardiomyopathy, the most common familial TTR amyloid disease. V122I TTR exhibits a destabilized quaternary structure and a stable tertiary structure relative to WT TTR. Three other variants of TTR were also examined, L55P, V30M, and A25T TTR. The L55P mutation is associated with the most aggressive familial TTR amyloid disease. L55P TTR has a complicated denaturation pathway that includes dimers and trimers, and so globally fitting its concentration-dependent urea denaturation data yielded error-laden estimates of stability parameters. Nevertheless, it is clear that L55P TTR is substantially less stable than WT TTR, primarily because its tertiary structure is unstable, although its quaternary structure is destabilized as well. V30M is the most common mutation associated with neuropathic forms of TTR amyloid disease. V30M TTR is certainly destabilized relative to WT TTR, but like L55P TTR it has a complex denaturation pathway that cannot be fit to the aforementioned two-step denaturation model. Literature data suggest that V30M TTR has stable quaternary structure but unstable tertiary structure. The A25T mutant, associated with central nervous system amyloidosis, is highly aggregation-prone and exhibits drastically reduced quaternary and tertiary structural stability. The observed differences in stability amongst the disease-associated TTR variants highlight the complexity and the heterogeneity of TTR amyloid disease, an observation having important implications for the treatment of these diseases. PMID:18537267

  17. Methodology Investigation of AI Test Officer Support Tool II

    DTIC Science & Technology

    1989-10-01

    request. B-1 This page intentionally blank B-2 APPENDIX C. ACRONYM AND AB9EVIATIONS ADP ............ Autmated Data Processing AI...longer needed. Do not return it to the originator. DISCLAIMER Information and data contained in this document are based on input available at the time...infrastructure, with subsequent incorporation of common requirements into a supporting structure (i.e., data bases, networks, geographic information

  18. Functional subdivisions in low-frequency primary auditory cortex (AI).

    PubMed

    Wallace, M N; Palmer, A R

    2009-04-01

    We wished to test the hypothesis that there are modules in low-frequency AI that can be identified by their responsiveness to communication calls or particular regions of space. Units were recorded in anaesthetised guinea pig AI and stimulated with conspecific vocalizations and a virtual motion stimulus (binaural beats) presented via a closed sound system. Recording tracks were mainly oriented orthogonally to the cortical surface. Some of these contained units that were all time-locked to the structure of the chutter call (14/22 tracks) and/or the purr call (12/22 tracks) and/or that had a preference for stimuli from a particular region of space (8/20 tracks with four contralateral, two ipsilateral and two midline), or where there was a strong asymmetry in the response to beats of different direction (two tracks). We conclude that about half of low-frequency AI is organized into modules that are consistent with separate "what" and "where" pathways.

  19. Structure of human Aichi virus and implications for receptor binding.

    PubMed

    Zhu, Ling; Wang, Xiangxi; Ren, Jingshan; Kotecha, Abhay; Walter, Thomas S; Yuan, Shuai; Yamashita, Teruo; Tuthill, Tobias J; Fry, Elizabeth E; Rao, Zihe; Stuart, David I

    2016-09-05

    Aichi virus (AiV), an unusual and poorly characterized picornavirus, classified in the genus Kobuvirus, can cause severe gastroenteritis and deaths in children below the age of five years, especially in developing countries 1,2 . The seroprevalence of AiV is approximately 60% in children under the age of ten years and reaches 90% later in life 3,4 . There is no available vaccine or effective antiviral treatment. Here, we describe the structure of AiV at 3.7 Å. This first high-resolution structure for a kobuvirus is intermediate between those of the enteroviruses and cardioviruses, with a shallow, narrow depression bounded by the prominent VP0 CD loops (linking the C and D strands of the β-barrel), replacing the depression known as the canyon, frequently the site of receptor attachment in enteroviruses. VP0 is not cleaved to form VP2 and VP4, so the 'VP2' β-barrel structure is complemented with a unique extended structure on the inside of the capsid. On the outer surface, a polyproline helix structure, not seen previously in picornaviruses is present at the C terminus of VP1, a position where integrin binding motifs are found in some other picornaviruses. A peptide corresponding to this polyproline motif somewhat attenuates virus infectivity, presumably blocking host-cell attachment. This may guide cellular receptor identification.

  20. Diversification of Tertiary Education in Switzerland.

    ERIC Educational Resources Information Center

    Crausaz, Roselyne

    The structure of Switzerland's educational system is described including the types of secondary schools and/or courses and the system of tertiary education. Fields of study, types of institutions, and characteristics of tertiary education in Switzerland are discussed. The chapter on students covers admission procedures, trends in enrollment,…

  1. Prelude and Fugue, predicting local protein structure, early folding regions and structural weaknesses.

    PubMed

    Kwasigroch, Jean Marc; Rooman, Marianne

    2006-07-15

    Prelude&Fugue are bioinformatics tools aiming at predicting the local 3D structure of a protein from its amino acid sequence in terms of seven backbone torsion angle domains, using database-derived potentials. Prelude(&Fugue) computes all lowest free energy conformations of a protein or protein region, ranked by increasing energy, and possibly satisfying some interresidue distance constraints specified by the user. (Prelude&)Fugue detects sequence regions whose predicted structure is significantly preferred relative to other conformations in the absence of tertiary interactions. These programs can be used for predicting secondary structure, tertiary structure of short peptides, flickering early folding sequences and peptides that adopt a preferred conformation in solution. They can also be used for detecting structural weaknesses, i.e. sequence regions that are not optimal with respect to the tertiary fold. http://babylone.ulb.ac.be/Prelude_and_Fugue.

  2. Altered resting state functional connectivity of anterior insula in young smokers.

    PubMed

    Bi, Yanzhi; Yuan, Kai; Guan, Yanyan; Cheng, Jiadong; Zhang, Yajuan; Li, Yangding; Yu, Dahua; Qin, Wei; Tian, Jie

    2017-02-01

    The insula has been implicated in cognitive control and craving, all of which are critical to the clinical manifestations of nicotine dependence. However, little evidence exists about the abnormalities in resting state functional connectivity (RSFC) of the insula in young smokers, which might improve our understanding of the neural mechanisms of nicotine dependence. Due to the structural and functional heterogeneity of the insula, the RSFC patterns of both left and right anterior (AI) and posterior insula (PI) were investigated in young smokers and non-smokers. Meanwhile, the relationship was assessed between the neuroimaging findings and clinical information (pack-years, FTND, and craving) as well as cognitive control deficits measured by Stroop task performance. Compared with non-smokers, young smokers showed reduced RSFC between right AI and anterior cingulate cortex (ACC), ventromedial prefrontal cortex (VMPFC), amygdala, left dorsolateral prefrontal cortex, and dorsal striatum. Additionally, left AI showed reduced RSFC with ACC. Both left and right PI network differences were not observed between two groups. Moreover, in young smokers, FTND and incongruent errors in the Stroop task were negatively correlated with the RSFC between AI and ACC. Craving scores showed a significantly negative relationship with the RSFC strength between right AI and left VMPFC. These results provide a more thorough network-level understanding the role of insula in cigarette smoking. The findings provide new insights into the roles of AI-ACC circuit in cognitive control deficits and right AI-VMPFC circuit relevant to the craving of nicotine dependence for young smokers.

  3. Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

    PubMed Central

    Sánchez-Ponce, Diana; DeFelipe, Javier; Garrido, Juan José; Muñoz, Alberto

    2012-01-01

    Axonal outgrowth and the formation of the axon initial segment (AIS) are early events in the acquisition of neuronal polarity. The AIS is characterized by a high concentration of voltage-dependent sodium and potassium channels. However, the specific ion channel subunits present and their precise localization in this axonal subdomain vary both during development and among the types of neurons, probably determining their firing characteristics in response to stimulation. Here, we characterize the developmental expression of different subfamilies of voltage-gated potassium channels in the AISs of cultured mouse hippocampal neurons, including subunits Kv1.2, Kv2.2 and Kv7.2. In contrast to the early appearance of voltage-gated sodium channels and the Kv7.2 subunit at the AIS, Kv1.2 and Kv2.2 subunits were tethered at the AIS only after 10 days in vitro. Interestingly, we observed different patterns of Kv1.2 and Kv2.2 subunit expression, with each confined to distinct neuronal populations. The accumulation of Kv1.2 and Kv2.2 subunits at the AIS was dependent on ankyrin G tethering, it was not affected by disruption of the actin cytoskeleton and it was resistant to detergent extraction, as described previously for other AIS proteins. This distribution of potassium channels in the AIS further emphasizes the heterogeneity of this structure in different neuronal populations, as proposed previously, and suggests corresponding differences in action potential regulation. PMID:23119056

  4. Cooperative Tertiary Interaction Network Guides RNA Folding

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

    Behrouzi, Reza; Roh, Joon Ho; Kilburn, Duncan

    2013-04-08

    Noncoding RNAs form unique 3D structures, which perform many regulatory functions. To understand how RNAs fold uniquely despite a small number of tertiary interaction motifs, we mutated the major tertiary interactions in a group I ribozyme by single-base substitutions. The resulting perturbations to the folding energy landscape were measured using SAXS, ribozyme activity, hydroxyl radical footprinting, and native PAGE. Double- and triple-mutant cycles show that most tertiary interactions have a small effect on the stability of the native state. Instead, the formation of core and peripheral structural motifs is cooperatively linked in near-native folding intermediates, and this cooperativity depends onmore » the native helix orientation. The emergence of a cooperative interaction network at an early stage of folding suppresses nonnative structures and guides the search for the native state. We suggest that cooperativity in noncoding RNAs arose from natural selection of architectures conducive to forming a unique, stable fold.« less

  5. Tertiary Education in Britian. National Report.

    ERIC Educational Resources Information Center

    Eggleston, J.

    Some of the major trends in British Tertiary education are reviewed. Types of schools and/or courses in British secondary education are examined in relation to student preparation for tertiary education. The present system of higher Education in Britian is described including types of institutions and academic structures, admission requirements,…

  6. Machine intelligence applications to securities production

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

    Johnson, C.K.

    1987-01-01

    The production of security documents provides a cache of interesting problems ranging across a broad spectrum. Some of the problems do not have rigorous scientific solutions available at this time and provide opportunities for less structured approaches such as AI. AI methods can be used in conjunction with traditional scientific and computational methods. The most productive applications of AI occur when this marriage of methods can be carried out without motivation to prove that one method is better than the other. Fields such as ink chemistry and technology, and machine inspection of graphic arts printing offer interesting challenges which willmore » continue to intrigue current and future generations of researchers into the 21st century.« less

  7. Knowledge, attitudes and practices (KAP) relating to avian influenza in urban and rural areas of China

    PubMed Central

    2010-01-01

    Background Studies have revealed that visiting poultry markets and direct contact with sick or dead poultry are significant risk factors for H5N1 infection, the practices of which could possibly be influenced by people's knowledge, attitudes and practices (KAPs) associated with avian influenza (AI). To determine the KAPs associated with AI among the Chinese general population, a cross-sectional survey was conducted in China. Methods We used standardized, structured questionnaires distributed in both an urban area (Shenzhen, Guangdong Province; n = 1,826) and a rural area (Xiuning, Anhui Province; n = 2,572) using the probability proportional to size (PPS) sampling technique. Results Approximately three-quarters of participants in both groups requested more information about AI. The preferred source of information for both groups was television. Almost three-quarters of all participants were aware of AI as an infectious disease; the urban group was more aware that it could be transmitted through poultry, that it could be prevented, and was more familiar with the relationship between AI and human infection. The villagers in Xiuning were more concerned than Shenzhen residents about human AI viral infection. Regarding preventative measures, a higher percentage of the urban group used soap for hand washing whereas the rural group preferred water only. Almost half of the participants in both groups had continued to eat poultry after being informed about the disease. Conclusions Our study shows a high degree of awareness of human AI in both urban and rural populations, and could provide scientific support to assist the Chinese government in developing strategies and health-education campaigns to prevent AI infection among the general population. PMID:20170542

  8. Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1.

    PubMed

    Ishikawa-Sasaki, Kumiko; Nagashima, Shigeo; Taniguchi, Koki; Sasaki, Jun

    2018-04-15

    Positive-strand RNA viruses, including picornaviruses, utilize cellular machinery for genome replication. Previously, we reported that each of the 2B, 2BC, 2C, 3A, and 3AB proteins of Aichi virus (AiV), a picornavirus, forms a complex with the Golgi apparatus protein ACBD3 and phosphatidylinositol 4-kinase IIIβ (PI4KB) at viral RNA replication sites (replication organelles [ROs]), enhancing PI4KB-dependent phosphatidylinositol 4-phosphate (PI4P) production. Here, we demonstrate AiV hijacking of the cellular cholesterol transport system involving oxysterol-binding protein (OSBP), a PI4P-binding cholesterol transfer protein. AiV RNA replication was inhibited by silencing cellular proteins known to be components of this pathway, OSBP, the ER membrane proteins VAPA and VAPB (VAP-A/B), the PI4P-phosphatase SAC1, and PI-transfer protein β. OSBP, VAP-A/B, and SAC1 were present at RNA replication sites. We also found various previously unknown interactions among the AiV proteins (2B, 2BC, 2C, 3A, and 3AB), ACBD3, OSBP, VAP-A/B, and SAC1, and the interactions were suggested to be involved in recruiting the component proteins to AiV ROs. Importantly, the OSBP-2B interaction enabled PI4P-independent recruitment of OSBP to AiV ROs, indicating preferential recruitment of OSBP among PI4P-binding proteins. Protein-protein interaction-based OSBP recruitment has not been reported for other picornaviruses. Cholesterol was accumulated at AiV ROs, and inhibition of OSBP-mediated cholesterol transfer impaired cholesterol accumulation and AiV RNA replication. Electron microscopy showed that AiV-induced vesicle-like structures were close to ER membranes. Altogether, we conclude that AiV directly recruits the cholesterol transport machinery through protein-protein interactions, resulting in formation of membrane contact sites between the ER and AiV ROs and cholesterol supply to the ROs. IMPORTANCE Positive-strand RNA viruses utilize host pathways to modulate the lipid composition of viral RNA replication sites for replication. Previously, we demonstrated that Aichi virus (AiV), a picornavirus, forms a complex comprising certain proteins of AiV, the Golgi apparatus protein ACBD3, and the lipid kinase PI4KB to synthesize PI4P lipid at the sites for AiV RNA replication. Here, we confirmed cholesterol accumulation at the AiV RNA replication sites, which are established by hijacking the host cholesterol transfer machinery mediated by a PI4P-binding cholesterol transfer protein, OSBP. We showed that the component proteins of the machinery, OSBP, VAP, SAC1, and PITPNB, are all essential host factors for AiV replication. Importantly, the machinery is directly recruited to the RNA replication sites through previously unknown interactions of VAP/OSBP/SAC1 with the AiV proteins and with ACBD3. Consequently, we propose a specific strategy employed by AiV to efficiently accumulate cholesterol at the RNA replication sites via protein-protein interactions. Copyright © 2018 American Society for Microbiology.

  9. White matter structures associated with loneliness in young adults

    PubMed Central

    Nakagawa, Seishu; Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Sekiguchi, Atsushi; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-01-01

    Lonely individuals may exhibit dysfunction, particularly with respect to social empathy and self-efficacy. White matter (WM) structures related to loneliness have not yet been identified. We investigated the association between regional WM density (rWMD) using the UCLA Loneliness Scale in 776 healthy young students aged 18–27 years old. Loneliness scores were negatively correlated with rWMD in eight clusters: the bilateral inferior parietal lobule (IPL), right anterior insula (AI), posterior temporoparietal junction (pTPJ), left posterior superior temporal sulcus (pSTS), dorsomedial prefrontal cortex (dmPFC), and rostrolateral prefrontal cortex (RLPFC). The bilateral IPL, right AI, left pSTS, pTPJ, and RLPFC were strongly associated with Empathy Quotient (EQ), whereas the bilateral IPL, right AI, left pTPJ, and dmPFC were associated with General Self-Efficacy Scale (GSES) score. The neural correlates of loneliness comprise widespread reduction in WMD in areas related to self- and social cognition as well as areas associated with empathy and self-efficacy. PMID:26585372

  10. Predicting RNA 3D structure using a coarse-grain helix-centered model

    PubMed Central

    Kerpedjiev, Peter; Höner zu Siederdissen, Christian; Hofacker, Ivo L.

    2015-01-01

    A 3D model of RNA structure can provide information about its function and regulation that is not possible with just the sequence or secondary structure. Current models suffer from low accuracy and long running times and either neglect or presume knowledge of the long-range interactions which stabilize the tertiary structure. Our coarse-grained, helix-based, tertiary structure model operates with only a few degrees of freedom compared with all-atom models while preserving the ability to sample tertiary structures given a secondary structure. It strikes a balance between the precision of an all-atom tertiary structure model and the simplicity and effectiveness of a secondary structure representation. It provides a simplified tool for exploring global arrangements of helices and loops within RNA structures. We provide an example of a novel energy function relying only on the positions of stems and loops. We show that coupling our model to this energy function produces predictions as good as or better than the current state of the art tools. We propose that given the wide range of conformational space that needs to be explored, a coarse-grain approach can explore more conformations in less iterations than an all-atom model coupled to a fine-grain energy function. Finally, we emphasize the overarching theme of providing an ensemble of predicted structures, something which our tool excels at, rather than providing a handful of the lowest energy structures. PMID:25904133

  11. Assessing the role of internal climate variability in Antarctica's contribution to future sea-level rise

    NASA Astrophysics Data System (ADS)

    Tsai, C. Y.; Forest, C. E.; Pollard, D.

    2017-12-01

    The Antarctic ice sheet (AIS) has the potential to be a major contributor to future sea-level rise (SLR). Current projections of SLR due to AIS mass loss remain highly uncertain. Better understanding of how ice sheets respond to future climate forcing and variability is essential for assessing the long-term risk of SLR. However, the predictability of future climate is limited by uncertainties from emission scenarios, model structural differences, and the internal variability that is inherently generated within the fully coupled climate system. Among those uncertainties, the impact of internal variability on the AIS changes has not been explicitly assessed. In this study, we quantify the effect of internal variability on the AIS evolutions by using climate fields from two large-ensemble experiments using the Community Earth System Model to force a three-dimensional ice sheet model. We find that internal variability of climate fields, particularly atmospheric fields, among ensemble members leads to significantly different AIS responses. Our results show that the internal variability can cause about 80 mm differences of AIS contribution to SLR by 2100 compared to the ensemble-mean contribution of 380-450 mm. Moreover, using ensemble-mean climate fields as the forcing in the ice sheet model does not produce realistic simulations of the ice loss. Instead, it significantly delays the onset of retreat of the West Antarctic Ice Sheet for up to 20 years and significantly underestimates the AIS contribution to SLR by 0.07-0.11 m in 2100 and up to 0.34 m in the 2250's. Therefore, because the uncertainty caused by internal variability is irreducible, we seek to highlight a critical need to assess the role of internal variability in projecting the AIS loss over the next few centuries. By quantifying the impact of internal variability on AIS contribution to SLR, policy makers can obtain more robust estimates of SLR and implement suitable adaptation strategies.

  12. Mapping the Typology of Transition Systems in a Liberal Market Economy: The Case of Canada

    ERIC Educational Resources Information Center

    Arnold, Christine Helen; Wheelahan, Leesa; Moodie, Gavin; Beaulieu, Jacqueline; Taylor-Cline, Jean-Claude

    2018-01-01

    This research explores links between tertiary education institutions and between tertiary education and the labour market as determinants of provincial and national transition patterns in Canada. The study consists of a provincial analysis that maps the typology of transition systems across Canada's devolved federated tertiary education structure.…

  13. The Missing Link in Australian Tertiary Education: Short-Cycle Higher Education

    ERIC Educational Resources Information Center

    Moodie, Gavin

    2003-01-01

    The blurring of the boundary between Australian vocational education and training and higher education is leading to a reconsideration of the current structure of Australian tertiary education. This paper starts with the main overlap of the Australian tertiary education sectors, diplomas and advanced diplomas. The ambiguous treatment of these…

  14. Expression, purification, crystallization and preliminary X-ray diffraction analysis of nurse shark β2-microglobulin.

    PubMed

    Lu, Shuangshuang; Yao, Shugang; Chen, Rong; Zhang, Nianzhi; Chen, Jianmin; Gao, Feng; Xia, Chun

    2012-04-01

    β(2)-Microglobulin (β(2)m) is an essential subunit of the major histocompatibility complex (MHC) class I molecule that helps to stabilize the structure of peptide-MHC I (pMHC I). It is also one of the typical immunoglobulin superfamily (IgSF) molecules in the adaptive immune system (AIS). Sharks belong to the cartilaginous fish, which are the oldest jawed vertebrate ancestors with an AIS to exist in the world. Thus, the study of cartilaginous fish β(2)m would help in understanding the evolution of IgSF molecules. In order to demonstrate this, β(2)m from a cartilaginous fish, nurse shark (Ginglymostoma cirratum), was expressed, refolded, purified and crystallized. Diffraction data were collected to a resolution of 2.3 Å. The crystal belonged to space group P3(2)21, with unit-cell parameters a = b = 88.230, c = 67.146 Å. The crystal structure contained two molecules in the asymmetric unit. The results will provide structural information for study of the evolution of β(2)m and IgSF in the AIS. © 2012 International Union of Crystallography. All rights reserved.

  15. Structure investigation of three hydrazones Schiff's bases by spectroscopic, thermal and molecular orbital calculations and their biological activities

    NASA Astrophysics Data System (ADS)

    Belal, Arafa A. M.; Zayed, M. A.; El-Desawy, M.; Rakha, Sh. M. A. H.

    2015-03-01

    Three Schiff's bases AI (2(1-hydrazonoethyl)phenol), AII (2, 4-dibromo 6-(hydrazonomethyl)phenol) and AIII (2(hydrazonomethyl)phenol) were prepared as new hydrazone compounds via condensation reactions with molar ratio (1:1) of reactants. Firstly by reaction of 2-hydroxy acetophenone solution and hydrazine hydrate; it gives AI. Secondly condensation between 3,5-dibromo-salicylaldehyde and hydrazine hydrate gives AII. Thirdly condensation between salicylaldehyde and hydrazine hydrate gives AIII. The structures of AI-AIII were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H NMR spectra, and thermal analyses (TG, DTG, and DTA). The activation thermodynamic parameters, such as, ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bond responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities have been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillissubtilies and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

  16. Atom Interferometry with Ultracold Quantum Gases in a Microgravity Environment

    NASA Astrophysics Data System (ADS)

    Williams, Jason; D'Incao, Jose; Chiow, Sheng-Wey; Yu, Nan

    2015-05-01

    Precision atom interferometers (AI) in space promise exciting technical capabilities for fundamental physics research, with proposals including unprecedented tests of the weak equivalence principle, precision measurements of the fine structure and gravitational constants, and detection of gravity waves and dark energy. Consequently, multiple AI-based missions have been proposed to NASA, including a dual-atomic-species interferometer that is to be integrated into the Cold Atom Laboratory (CAL) onboard the International Space Station. In this talk, I will discuss our plans and preparation at JPL for the proposed flight experiments to use the CAL facility to study the leading-order systematics expected to corrupt future high-precision measurements of fundamental physics with AIs in microgravity. The project centers on the physics of pairwise interactions and molecular dynamics in these quantum systems as a means to overcome uncontrolled shifts associated with the gravity gradient and few-particle collisions. We will further utilize the CAL AI for proof-of-principle tests of systematic mitigation and phase-readout techniques for use in the next-generation of precision metrology experiments based on AIs in microgravity. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.

  17. Opportunities for Maturing Precision Metrology with Ultracold Gas Studies Aboard the ISS

    NASA Astrophysics Data System (ADS)

    Williams, Jason; D'Incao, Jose

    2017-04-01

    Precision atom interferometers (AI) in space are expected to become an enabling technology for future fundamental physics research, with proposals including unprecedented tests of the validity of the weak equivalence principle, measurements of the fine structure and gravitational constants, and detection of gravity waves and dark matter/dark energy. We will discuss our preparation at JPL to use NASA's Cold Atom Lab facility (CAL) to mature the technology of precision, space-based, AIs. The focus of our flight project is three-fold: a) study the controlled dynamics of heteronuclear Feshbach molecules, at temperatures of nano-Kelvins or below, as a means to overcome uncontrolled density-profile-dependent shifts in differential AIs, b) demonstrate unprecedented atom-photon coherence times with spatially constrained AIs, c) use the imaging capabilities of CAL to detect and analyze spatial fringe patterns written onto the clouds after AI and thereby measure the rotational noise of the ISS. The impact from this work, and potential for follow-on studies, will also be reviewed in the context of future space-based fundamental physics missions. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.

  18. Pseudomonas aeruginosa mutants resistant to urea inhibition of growth on acetanilide.

    PubMed

    Gregoriou, M; Brown, P R; Tata, R

    1977-11-01

    Pseudomonas aeruginosa AI 3 was able to grow in medium containing acetanilide (N-phenylacetamide) as a carbon source when NH4+ was the nitrogen source but not when urea was the nitrogen source. AIU mutants isolated from strain AI 3 grew on either medium. Urease levels in bacteria grown in the presence of urea were 10-fold lower when NH4+ or acetanilide was also in the medium, but there were no apparent differences in urease or its synthesis between strain AI 3 and mutant AIU 1N. The first metabolic step in the acetanilide utlization is catalyzed by an amidase. Amidases in several AIU strains showed altered physiochemical properties. Urea inhibited amidase in a time-dependent reaction, but the rates of the inhibitory reaction with amidases from the AIU mutants were slower than with AI 3 amidase. The purified amidase from AIU 1N showed a marked difference in its pH/activity profile from that obtained with purified AI 3 amidase. These observations indicate that the ability of strain AIU 1N and the other mutants to grow on acetanilide/urea medium is associated with a mutation in the amidase structural gene; this was confirmed for strain AIU 1N by transduction.

  19. Quality of care in American Indian child and adolescent behavioral health: A pilot study of patient and family perspectives

    PubMed Central

    Podlogar, Matthew C.; Novins, Douglas K.

    2015-01-01

    Research regarding the quality of behavioral health care for American Indian (AI) children and adolescents is extremely limited, and no study has considered the qualitative perspectives of the AI children receiving such services or that of their families. This pilot study investigated AI patient and family perspectives of what quality of care means to them. Data were drawn from interviews of parents (n = 15), and the youth (if they were age 11 or older; n = 11) of 16 children and adolescents who received treatment at three behavioral health programs serving AI communities. Interview transcripts were coded and analyzed for key themes that related to treatment structure, process, and outcomes. According to these participants, the principal indicator of treatment quality was “being able to trust the clinician.” The most valued treatment outcomes for improvement were the youth’s “self-efficacy and self-worth,” “functioning in school,” and “relationship with the family.” Future research is needed on how to best integrate these domains into specific and objective indicators for standardized quality of care assessments of AI child and adolescent behavioral health services. PMID:25961647

  20. Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride.

    PubMed

    Sondhi, Sham M; Dinodia, Monica; Jain, Shubhi; Kumar, Ashok

    2008-12-01

    A series of substituted N-methylisonicotinamidine (2a-f), N-methylpyrazine-2-carboxamidine (2g-i) derivatives were synthesized by reaction of amidine derivatives (1a-i) with methyl iodide in presence of triethylamine. Five-membered condensed dihydroimidazolylbenzenesulfonamide derivatives (3a-i) were obtained by the reaction of amidine derivatives (1a-i) with acylating agent oxalyl chloride. All the compounds, i.e. 2a-i and 3a-i were purified by crystallization. Structures of all the synthesized compounds are supported by correct IR, (1)H NMR, mass spectral and analytical data. Anti-inflammatory activity evaluation was carried out using carrageenan-induced paw oedema assay and compounds 2e, 3a and 3d exhibited good anti-inflammatory activity (44%, 31% and 37% activity at 50 mg/kg p.o., respectively). Analgesic activity evaluation was carried out using acetic acid writhing assay and compounds 2a and 3f gave 75% activity each at 100 mg/kg p.o.; on the other hand compounds 3a and 3d exhibited 60% analgesic activity each at 50 mg/kg p.o. Compounds 3a and 3d exhibited good anti-inflammatory and analgesic activities.

  1. American Indian and Alaska Native mental health: diverse perspectives on enduring disparities.

    PubMed

    Gone, Joseph P; Trimble, Joseph E

    2012-01-01

    As descendants of the indigenous peoples of the United States, American Indians and Alaska Natives (AI/ANs) have experienced a resurgence in population and prospects since the beginning of the twentieth century. Today, tribally affiliated individuals number over two million, distributed across 565 federally recognized tribal communities and countless metropolitan and nonreservation rural areas. Although relatively little evidence is available, the existing data suggest that AI/AN adults and youth suffer a disproportionate burden of mental health problems compared with other Americans. Specifically, clear disparities have emerged for AI/AN substance abuse, posttraumatic stress, violence, and suicide. The rapid expansion of mental health services to AI/AN communities has, however, frequently preceded careful consideration of a variety of questions about critical components of such care, such as the service delivery structure itself, clinical treatment processes, and preventive and rehabilitative program evaluation. As a consequence, the mental health needs of these communities have easily outpaced and overwhelmed the federally funded agency designed to serve these populations, with the Indian Health Service remaining chronically understaffed and underfunded such that elimination of AI/AN mental health disparities is only a distant dream. Although research published during the past decade has substantially improved knowledge about AI/AN mental health problems, far fewer investigations have explored treatment efficacy and outcomes among these culturally diverse peoples. In addition to routine calls for greater clinical and research resources, however, AI/AN community members themselves are increasingly advocating for culturally alternative approaches and opportunities to address their mental health needs on their own terms.

  2. Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

    PubMed Central

    2011-01-01

    Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis. PMID:22136338

  3. Conformational analysis of processivity clamps in solution demonstrates that tertiary structure does not correlate with protein dynamics.

    PubMed

    Fang, Jing; Nevin, Philip; Kairys, Visvaldas; Venclovas, Česlovas; Engen, John R; Beuning, Penny J

    2014-04-08

    The relationship between protein sequence, structure, and dynamics has been elusive. Here, we report a comprehensive analysis using an in-solution experimental approach to study how the conservation of tertiary structure correlates with protein dynamics. Hydrogen exchange measurements of eight processivity clamp proteins from different species revealed that, despite highly similar three-dimensional structures, clamp proteins display a wide range of dynamic behavior. Differences were apparent both for structurally similar domains within proteins and for corresponding domains of different proteins. Several of the clamps contained regions that underwent local unfolding with different half-lives. We also observed a conserved pattern of alternating dynamics of the α helices lining the inner pore of the clamps as well as a correlation between dynamics and the number of salt bridges in these α helices. Our observations reveal that tertiary structure and dynamics are not directly correlated and that primary structure plays an important role in dynamics. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Anger Suppression and Subsequent Pain Behaviors among Chronic Low Back Pain Patients: Moderating Effects of Anger Regulation Style

    PubMed Central

    Quartana, Phillip; Bruehl, Stephen

    2013-01-01

    Background Suppression of anger is linked to subsequent pain intensity among chronic low back patients, but it is not clear whether anger regulation style (trait anger-out, anger-in) moderates these effects or if aroused anger accounts for links between anger regulation style and pain. Method Chronic low back pain patients (N=58) were assigned to Suppression or No Suppression conditions for a task with harassing confederate and then underwent structured pain behavior procedures. Spielberger Anger Expression Inventory tapped trait anger-out (AOS) and anger-in (AIS). Results Regressions tested Emotion Regulation condition × AOS and AIS effects on outcomes. AOS was related to grimacing and sighing for Suppression condition patients. AIS was related negatively to guarding and bracing for Suppression condition patients. Anger report partly mediated effects for AOS and AIS. Conclusions Anger regulation style moderated effects of state anger suppression on subsequent pain behaviors, effects that were partly explained by aroused anger. PMID:21544702

  5. Synchronous cardiocerebral infarction in the era of endovascular therapy: which to treat first?

    PubMed

    Yeo, Leonard L L; Andersson, Tommy; Yee, Kong Wan; Tan, Benjamin Y Q; Paliwal, Prakash; Gopinathan, Anil; Nadarajah, Mahendran; Ting, Eric; Teoh, Hock L; Cherian, Robin; Lundström, Erik; Tay, Edgar L W; Sharma, Vijay K

    2017-07-01

    A cardiocerebral ischemic attack (CCI) or a concurrent acute ischemic stroke (AIS) and myocardial infarction (AMI) is a severe event with no clear recommendations for ideal management because of the rarity of the scenario. The narrow time window for treatment and complexity of the treatment decision puts immense pressure on the treating physician. We evaluated this challenging situation at our tertiary center. Using our prospective stroke database out of a total of 555 patients with acute ischemic stroke between 2009 and 2014, we identified five consecutive cases with CCI (incidence 0.009%). Demography, risk factor characteristics, vascular occlusions and treatment approach were recorded. Good functional outcome was defined by the modified Rankin scale (mRS) score of 0-2 points. Out of five patients, AIS was treated with endovascular treatment in three cases, while two were treated with intravenous thrombolysis only. One out of three patients had embolectomy of the brain performed prior to the coronary intervention, while the other two patients underwent coronary intervention first. One patient developed sudden cardiac arrest on day-2 and passed away. CCI is an uncommon and devastating clinical scenario, further research is needed for the ideal management strategy that provides the best outcomes. However, the rarity of the disease does not lend itself to the conduct of a trial easily. We have proposed a considered treatment algorithm based on the current literature and our experience.

  6. Prevalence of Positive Troponin and Echocardiogram Findings and Association With Mortality in Acute Ischemic Stroke.

    PubMed

    Wrigley, Peter; Khoury, Jane; Eckerle, Bryan; Alwell, Kathleen; Moomaw, Charles J; Woo, Daniel; Flaherty, Mathew L; De Los Rios la Rosa, Felipe; Mackey, Jason; Adeoye, Opeolu; Martini, Sharyl; Ferioli, Simona; Kissela, Brett M; Kleindorfer, Dawn O

    2017-05-01

    Acute ischemic stroke (AIS) patients may have raised serum cardiac troponin levels on admission, although it is unclear what prognostic implications this has, and whether elevated levels are associated with cardiac causes of stroke or structural cardiac disease as seen on echocardiogram. We investigated the positivity of cardiac troponin and echocardiogram testing within a large biracial AIS population and any association with poststroke mortality. Within a catchment area of 1.3 million, we screened emergency department admissions from 2010 using International Classification of Diseases, Ninth Edition , discharge codes 430 to 436 and ascertained all physician-confirmed AIS cases by retrospective chart review. Hypertroponinemia was defined as elevation in cardiac troponin above the standard 99th percentile. Multiple logistic regression was performed, controlling for stroke severity, history of cardiac disease, and all other stroke risk factors. Of 1999 AIS cases, 1706 (85.3%) had a cardiac troponin drawn and 1590 (79.5%) had echocardiograms. Hypertroponinemia occurred in 353 of 1706 (20.7%) and 160 of 1590 (10.1%) had echocardiogram findings of interest. Among 1377 who had both tests performed, hypertroponinemia was independently associated with echocardiogram findings (odds ratio, 2.9; 95% confidence interval, 2-4.2). When concurrent myocardial infarctions (3.5%) were excluded, hypertroponinemia was also associated with increased mortality at 1 year (35%; odds ratio, 3.45; 95% confidence interval, 2.1-5.6) and 3 years (60%; odds ratio, 2.91; 95% confidence interval, 2.06-4.11). Hypertroponinemia in the context of AIS without concurrent myocardial infarction was associated with structural cardiac disease and long-term mortality. Prospective studies are needed to determine whether further cardiac evaluation might improve the long-term mortality rates seen in this group. © 2017 American Heart Association, Inc.

  7. Understanding the dynamical structure of pulsating stars: The Baade-Wesselink projection factor of the δ Scuti stars AI Velorum and β Cassiopeiae

    NASA Astrophysics Data System (ADS)

    Guiglion, G.; Nardetto, N.; Mathias, P.; Domiciano de Souza, A.; Poretti, E.; Rainer, M.; Fokin, A.; Mourard, D.; Gieren, W.

    2013-02-01

    Aims: The Baade-Wesselink method of distance determination is based on the oscillations of pulsating stars. The key parameter of this method is the projection factor used to convert the radial velocity into the pulsation velocity. Our analysis was aimed at deriving for the first time the projection factor of δ Scuti stars, using high-resolution spectra of the high-amplitude pulsator AI Vel and of the fast rotator β Cas. Methods: The geometric component of the projection factor (i.e. p0) was calculated using a limb-darkening model of the intensity distribution for AI Vel, and a fast-rotator model for β Cas. Then, using SOPHIE/OHP data for β Cas and HARPS/ESO data for AI Vel, we compared the radial velocity curves of several spectral lines forming at different levels in the atmosphere and derived the velocity gradient associated to the spectral-line-forming regions in the atmosphere of the star. This velocity gradient was used to derive a dynamical projection factor p. Results: We find a flat velocity gradient for both stars and finally p = p0 = 1.44 for AI Vel and p = p0 = 1.41 for β Cas. By comparing Cepheids and δ Scuti stars, these results bring valuable insights into the dynamical structure of pulsating star atmospheres. They suggest that the period-projection factor relation derived for Cepheids is also applicable to δ Scuti stars pulsating in a dominant radial mode. This work uses observations made with the HARPS instrument at the 3.6 m telescope (La Silla, Chile) in the framework of the LP185.D-0056 and with the SOPHIE instrument at OHP (France).

  8. S-aryl-L-cysteine sulphoxides and related organosulphur compounds alter oral biofilm development and AI-2-based cell-cell communication.

    PubMed

    Kasper, S H; Samarian, D; Jadhav, A P; Rickard, A H; Musah, R A; Cady, N C

    2014-11-01

    To design and synthesize a library of structurally related, small molecules related to homologues of compounds produced by the plant Petiveria alliacea and determine their ability to interfere with AI-2 cell-cell communication and biofilm formation by oral bacteria. Many human diseases are associated with persistent bacterial biofilms. Oral biofilms (dental plaque) are problematic as they are often associated with tooth decay, periodontal disease and systemic disorders such as heart disease and diabetes. Using a microplate-based approach, a bio-inspired small molecule library was screened for anti-biofilm activity against the oral species Streptococcus mutans UA159, Streptococcus sanguis 10556 and Actinomyces oris MG1. To complement the static screen, a flow-based BioFlux microfluidic system screen was also performed under conditions representative of the human oral cavity. Several compounds were found to display biofilm inhibitory activity in all three of the oral bacteria tested. These compounds were also shown to inhibit bioluminescence by Vibrio harveyi and were thus inferred to be quorum sensing (QS) inhibitors. Due to the structural similarity of these compounds to each other, and to key molecules in AI-2 biosynthetic pathways, we propose that these molecules potentially reduce biofilm formation via antagonism of QS or QS-related pathways. This study highlights the potential for a non-antimicrobial-based strategy, focused on AI-2 cell-cell signalling, to control the development of dental plaque. Considering that many bacterial species use AI-2 cell-cell signalling, as well as the increased concern of the use of antimicrobials in healthcare products, such an anti-biofilm approach could also be used to control biofilms in environments beyond the human oral cavity. © 2014 The Society for Applied Microbiology.

  9. Design, Synthesis, and Chemical Processing of Hierarchical Ceramic Structures for Aerospace Applications

    DTIC Science & Technology

    1993-03-30

    Massachusetts Institute of Technology, Cambridge, MA 02139I ABSTRACT polysilanes." Pyrolysis of these polymers usually The decomposition of polymeric SiC ...of soluble polymeric solids. Pyrolysis of these polymers in argon yielded The precursors were prepared by adding a TiC/A120 3 composite at 12501C...formation of soluble polymeric solids. Pyrolysis described an approach for synthesizing AI2O/ SiC of these polymers in argon yielded TiC/AI203

  10. Benefits of an exercise wellness program after spinal cord injury.

    PubMed

    Crane, Deborah A; Hoffman, Jeanne M; Reyes, Maria R

    2017-03-01

    To describe the initial benefits of a structured group exercise program on exercise frequency and intensity, perceived health, pain, mood, and television watching habits. Pre-test/post-test. Eighty-nine persons with SCI participated voluntarily in a no-cost, twice weekly physical therapy group exercise class over 3 months. Forty-five persons completed pre- and post-participation interviews on exercise frequency and intensity, perceived health, pain, mood, sleep, and television watching habits. Mean participant age of the respondents was 43.82 years. 49% had AIS C or D injuries, 24% had AIS A,B paraplegia, 9% had AIS A,B C1-C4 and 18% had AIS A,B C5-C8. 75.6% of participants were male and 84.4% had a traumatic etiology as the cause of their SCI. There was a significant improvement in days of strenuous and moderate exercise as well as health state. There was an average decrease in pain scores, depression scores, number of hours spent watching television, and days/week of mild exercise. Participation in structured, small group exercise as a component of a wellness program after SCI shows promise for improving regular exercise participation and health state, but benefits may also occur across other areas of health and function including mood, pain, and hours spent watching television. Further follow-up is needed to determine whether improvements can be maintained after program completion and across all neurological levels.

  11. Myelin Loss and Axonal Ion Channel Adaptations Associated with Gray Matter Neuronal Hyperexcitability

    PubMed Central

    Hamada, Mustafa S.

    2015-01-01

    Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons. PMID:25948275

  12. Tertiary network in mammalian mitochondrial tRNAAsp revealed by solution probing and phylogeny

    PubMed Central

    Messmer, Marie; Pütz, Joern; Suzuki, Takeo; Suzuki, Tsutomu; Sauter, Claude; Sissler, Marie; Catherine, Florentz

    2009-01-01

    Primary and secondary structures of mammalian mitochondrial (mt) tRNAs are divergent from canonical tRNA structures due to highly skewed nucleotide content and large size variability of D- and T-loops. The nonconservation of nucleotides involved in the expected network of tertiary interactions calls into question the rules governing a functional L-shaped three-dimensional (3D) structure. Here, we report the solution structure of human mt-tRNAAsp in its native post-transcriptionally modified form and as an in vitro transcript. Probing performed with nuclease S1, ribonuclease V1, dimethylsulfate, diethylpyrocarbonate and lead, revealed several secondary structures for the in vitro transcribed mt-tRNAAsp including predominantly the cloverleaf. On the contrary, the native tRNAAsp folds into a single cloverleaf structure, highlighting the contribution of the four newly identified post-transcriptional modifications to correct folding. Reactivities of nucleotides and phosphodiester bonds in the native tRNA favor existence of a full set of six classical tertiary interactions between the D-domain and the variable region, forming the core of the 3D structure. Reactivities of D- and T-loop nucleotides support an absence of interactions between these domains. According to multiple sequence alignments and search for conservation of Leontis–Westhof interactions, the tertiary network core building rules apply to all tRNAAsp from mammalian mitochondria. PMID:19767615

  13. Reproducibility of sagittal radiographic parameters in adolescent idiopathic scoliosis-a guide to reference values using serial imaging.

    PubMed

    Hey, Hwee Weng Dennis; Wong, Gordon Chengyuan; Chan, Chloe Xiaoyun; Lau, Leok-Lim; Kumar, Naresh; Thambiah, Joseph Shantakumar; Ruiz, John Nathaniel; Liu, Ka-Po Gabriel; Wong, Hee-Kit

    2017-06-01

    Knowledge of sagittal radiographic parameters in adolescent idiopathic scoliosis (AIS) patients has not yet caught up with our understanding of their roles in patients with adult spinal deformity. It is likely that more emphasis will be placed in restoring sagittal parameters for AIS patients in the future. Therefore, we need to understand how these parameters may vary in AIS to facilitate management plans. This study aimed to determine the reproducibility of sagittal spinal parameters on lateral film radiographs in patients with AIS. This was a retrospective, comparative study conducted in a tertiary health-care institution from January 2013 to February 2016 (3-year period). All AIS patients who underwent deformity correction surgery from January 2013 to February 2016 and had two preoperative serial lateral radiographs taken within the time period of a month were included in the study. Radiographic sagittal spinal parameters including sagittal vertical axis (SVA), cervical lordosis (CL), thoracic kyphosis (TK), thoracolumbar alignment (TL), lumbar lordosis (LL); standard spinopelvic measurements such as pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS); as well as end and apical vertebrae of cervical, thoracic, and lumbar curves were the outcome measures. All patient data were pooled from electronic medical records, and X-ray images were retrieved from Centricity Enterprise Web. Averaged X-ray measurements by two independent assessors were analyzed by comparing two radiographs of the same patients performed within a 1-month time period. Chi-squared and Wilcoxon signed-rank tests were used for categorical and continuous variables. The study cohort comprised 138 patients, 28 men and 110 women, with a mean age of 15 years (range 11-20). Between the two lateral X-rays, there was a mean difference of 0.79 cm in SVA (p<.001), 0.70° in LL (p=.033), and 0.73° in PT (p=.010). In the combined Lenke 1 and 2 subgroup, there was a similar 0.77 cm (p=.002), 0.79° (p=.009), and 1.49° (p=.001) mean difference in SVA, LL, and PT, respectively. Additionally, there was also a 1.85° (p=.009) and 1.76° (p=.006) mean difference seen in TL and SS, respectively. The overall profile of the sagittal curves remained largely similar, with only the lumbar apex shifting from L3 to L4 during the first and the second X-rays, respectively (p<.001). This occurred for the combined Lenke 1 and 2 subgroup as well (p<.001). Most radiographic sagittal spinal parameters in AIS patients are generally reproducible with some variations up to a maximum of 4°. This natural variation should be taken into account when interpreting these radiographic sagittal parameters so as to achieve the most accurate results in surgical planning. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Why Do Tertiary Education Graduates Regret Their Study Program? A Comparison between Spain and the Netherlands

    ERIC Educational Resources Information Center

    Kucel, Aleksander; Vilalta-Bufi, Montserrat

    2013-01-01

    In this paper we investigate the determinants of regret of study program for tertiary education graduates in Spain and the Netherlands. These two countries differ in their educational system in terms of the tracking structure in their secondary education and the strength of their education-labor market linkages in tertiary education. Therefore, by…

  15. RNA Tertiary Interactions in a Riboswitch Stabilize the Structure of a Kink Turn

    PubMed Central

    Schroeder, Kersten T.; Daldrop, Peter; Lilley, David M.J.

    2011-01-01

    Summary The kink turn is a widespread RNA motif that introduces an acute kink into the axis of duplex RNA, typically comprising a bulge followed by a G⋅A and A⋅G pairs. The kinked conformation is stabilized by metal ions, or the binding of proteins including L7Ae. We now demonstrate a third mechanism for the stabilization of k-turn structure, involving tertiary interactions within a larger RNA structure. The SAM-I riboswitch contains an essential standard k-turn sequence that kinks a helix so that its terminal loop can make a long-range interaction. We find that some sequence variations in the k-turn within the riboswitch do not prevent SAM binding, despite preventing the folding of the k-turn in isolation. Furthermore, two crystal structures show that the sequence-variant k-turns are conventionally folded within the riboswitch. This study shows that the folded structure of the k-turn can be stabilized by tertiary interactions within a larger RNA structure. PMID:21893284

  16. STRUTEX: A prototype knowledge-based system for initially configuring a structure to support point loads in two dimensions

    NASA Technical Reports Server (NTRS)

    Robers, James L.; Sobieszczanski-Sobieski, Jaroslaw

    1989-01-01

    Only recently have engineers begun making use of Artificial Intelligence (AI) tools in the area of conceptual design. To continue filling this void in the design process, a prototype knowledge-based system, called STRUTEX has been developed to initially configure a structure to support point loads in two dimensions. This prototype was developed for testing the application of AI tools to conceptual design as opposed to being a testbed for new methods for improving structural analysis and optimization. This system combines numerical and symbolic processing by the computer with interactive problem solving aided by the vision of the user. How the system is constructed to interact with the user is described. Of special interest is the information flow between the knowledge base and the data base under control of the algorithmic main program. Examples of computed and refined structures are presented during the explanation of the system.

  17. New Mexico structural zone - An analogue of the Colorado mineral belt

    USGS Publications Warehouse

    Sims, P.K.; Stein, H.J.; Finn, C.A.

    2002-01-01

    Updated aeromagnetic maps of New Mexico together with current knowledge of the basement geology in the northern part of the state (Sangre de Cristo and Sandia-Manzano Mountains)-where basement rocks were exposed in Precambrian-cored uplifts-indicate that the northeast-trending Proterozoic shear zones that controlled localization of ore deposits in the Colorado mineral belt extend laterally into New Mexico. The shear zones in New Mexico coincide spatially with known epigenetic precious- and base-metal ore deposits; thus, the mineralized belts in the two states share a common inherited basement tectonic setting. Reactivation of the basement structures in Late Cretaceous-Eocene and Mid-Tertiary times provided zones of weakness for emplacement of magmas and conduits for ore-forming solutions. Ore deposits in the Colorado mineral belt are of both Late Cretaceous-Eocene and Mid-Tertiary age; those in New Mexico are predominantly Mid-Tertiary in age, but include Late Cretaceous porphyry-copper deposits in southwestern New Mexico. The mineralized belt in New Mexico, named the New Mexico structural zone, is 250-km wide. The northwest boundary is the Jemez subzone (or the approximately equivalent Globe belt), and the southeastern boundary was approximately marked by the Santa Rita belt. Three groups (subzones) of mineral deposits characterize the structural zone: (1) Mid-Tertiary porphyry molybdenite and alkaline-precious-metal deposits, in the northeast segment of the Jemez zone; (2) Mid-Tertiary epithermal precious-metal deposits in the Tijeras (intermediate) zone; and (3) Late Cretaceous porphyry-copper deposits in the Santa Rita zone. The structural zone was inferred to extend from New Mexico into adjacent Arizona. The structural zone provides favorable sites for exploration, particularly those parts of the Jemez subzone covered by Neogene volcanic and sedimentary rocks. ?? 2002 Published by Elsevier Science B.V.

  18. Seismic lateral prediction in chalky limestone reservoirs offshore Qatar

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

    Rubbens, I.B.H.M.; Murat, R.C.; Vankeulen, J.

    Following the discovery of non-structurally trapped oil accumulations in Cretaceous chalky reservoirs on the northern flank of the North Dome offshore QATAR, a seismic lateral prediction study was carried out for QATAR GENERAL PETROLEUM CORPORATION (Offshore Operations). The objectives of this study were to assist in the appraisal of these oil accumulations by predicting their possible lateral extent and to investigate if the technique applied could be used as a basis for further exploration of similar oil prospects in the area. Wireline logs of eight wells and some 1000 km of high quality seismic data were processed into acoustic impedancemore » (A.I.) logs and seismic A.I. sections. Having obtained a satisfactory match of the A.I. well logs and the A.I. of the seismic traces at the well locations, relationships were established by the use of well log data which allowed the interpretation of the seismic A.I. in terms of reservoir quality. Measurements of the relevant A.I. characteristics were then carried out by computer along all seismic lines and porosity distribution maps prepared for some of the reservoirs. These maps, combined with detailed seismic depth contour maps at reservoir tops, lead to definition of good reservoir development areas downdip from poor reservoir quality zones i.e. of the stratigraphic trap areas, and drilling locations could thus be proposed. The system remains to be adequately calibrated when core material becomes available in the area of study.« less

  19. Aqueous Extracts of Hibiscus sabdariffa Calyces to Control Aichi Virus.

    PubMed

    D'Souza, Doris H; Dice, Lezlee; Davidson, P Michael

    2016-06-01

    Aqueous Hibiscus sabdariffa extracts possess antimicrobial properties with limited information available on their antiviral effects. Aichi virus (AiV) is an emerging foodborne pathogen that causes gastroenteritis. Vaccines are currently unavailable to prevent their disease transmission. The objective of this study was to determine the antiviral effects of aqueous H. sabdariffa extracts against AiV. AiV at ~5 log PFU/ml was incubated with undiluted (200 mg/ml), 1:1 (100 mg/ml) or 1:5 (40 mg/ml) diluted aqueous hibiscus extract (pH 3.6), phosphate-buffered saline (pH 7.2 as control), or malic acid (pH 3.0, acid control) at 37 °C over 24 h. Treatments were stopped by serially diluting in cell-culture media containing fetal bovine serum and titers were determined using plaque assays on confluent Vero cells. Each treatment was replicated thrice and assayed in duplicate. AiV did not show any significant reduction with 1:1 (100 mg/ml) or 1:5 (40 mg/ml) diluted aqueous hibiscus extracts or malic acid after 0.5, 1, or 2 h at 37 °C. However, AiV titers were reduced to non-detectable levels after 24 h with all the three tested concentrations, while malic acid showed only 0.93 log PFU/ml reduction after 24 h. AiV was reduced by 0.5 and 0.9 log PFU/ml with undiluted extracts (200 mg/ml) after 2 and 6 h, respectively. AiV treated with 1:1 (100 mg/ml) and 1:5 (40 mg/ml) diluted extracts showed a minimal ~0.3 log PFU/ml reduction after 6 h. These extracts show promise to reduce AiV titers mainly through alteration of virus structure, though higher concentrations may have improved effects.

  20. Immunological Characterization of Intraocular Lymphoid Follicles in a Spontaneous Recurrent Uveitis Model.

    PubMed

    Kleinwort, Kristina J H; Amann, Barbara; Hauck, Stefanie M; Feederle, Regina; Sekundo, Walter; Deeg, Cornelia A

    2016-08-01

    Recently, formation of tertiary lymphoid structures was demonstrated and further characterized in the R161H mouse model of spontaneous autoimmune uveitis. In the horse model of spontaneous recurrent uveitis, intraocular lymphoid follicle formation is highly characteristic, and found in all stages and scores of disease, but in depth analyses of immunologic features of these structures are lacking to date. Paraffin-embedded eye sections of cases with equine spontaneous recurrent uveitis (ERU) were characterized with immunohistochemistry to gain insight into the distribution, localization, and signaling of immune cells in intraocular tertiary lymphoid tissues. Ectopic lymphoid tissues were located preferentially in the iris, ciliary body, and retina at the ora serrata of horses with naturally-occurring ERU. The majority of cells in the tertiary lymphoid follicles were T cells with a scattered distribution of B cells and PNA+ cells interspersed. A fraction of T cells was additionally positive for memory cell marker CD45RO. Almost all cells coexpressed CD166, a molecule associated with activation and transmigration of T cells into inflamed tissues. Several transcription factors that govern immune cell responses were detectable in the tertiary lymphoid follicles, among them Zap70, TFIIB, GATA3, and IRF4. A high expression of the phosphorylated signal transducers and activators of transcription (STAT) proteins 1 and 5 were found at the margin of the structures. Cellular composition and structural organization of these inflammation-associated tertiary lymphoid tissue structures and the expression of markers of matured T and B cells point to highly organized adaptive immune responses in these follicles in spontaneous recurrent uveitis.

  1. Mapping Abbreviated Injury Scale data from 1990 to 1998 versions: a stepping-stone in the contemporary evaluation of trauma.

    PubMed

    Palmer, Cameron S; Lang, Jacelle; Russell, Glen; Dallow, Natalie; Harvey, Kathy; Gabbe, Belinda; Cameron, Peter

    2013-11-01

    Many trauma registries have used the 1990 revision of the Abbreviated Injury Scale (AIS; AIS90) to code injuries sustained by trauma patients. Due to changes made to the AIS codeset since its release, AIS90-coded data lacks currency in the assessment of injury severity. The ability to map between the 1998 revision of AIS (AIS98) and the current (2008) AIS version (AIS08) already exists. The development of a map for transforming AIS90-coded data into AIS98 would therefore enable contemporary injury severity estimates to be derived from AIS90-coded data. Differences between the AIS90 and AIS98 codesets were identified, and AIS98 maps were generated for AIS90 codes which changed or were not present in AIS98. The effectiveness of this map in describing the severity of trauma using AIS90 and AIS98 was evaluated using a large state registry dataset, which coded injury data using AIS90 over several years. Changes in Injury Severity Scores (ISS) calculated using AIS90 and mapped AIS98 codesets were assessed using three distinct methods. Forty-nine codes (out of 1312) from the AIS90 codeset changed or were not present in AIS98. Twenty-four codes required the assignment of maps to AIS98 equivalents. AIS90-coded data from 78,075 trauma cases were used to evaluate the map. Agreement in calculated ISS between coded AIS90 data and mapped AIS98 data was very high (kappa=0.971). The ISS changed in 1902 cases (2.4%), and the mean difference in ISS across all cases was 0.006 points. The number of cases classified as major trauma using AIS98 decreased by 0.8% compared with AIS90. A total of 3102 cases (4.0%) sustained at least one AIS90 injury which required mapping to AIS98. This study identified the differences between the AIS90 and AIS98 codesets, and generated maps for the conversion process. In practice, the differences between AIS90- and AIS98-coded data were very small. As a result, AIS90-coded data can be mapped to the current AIS version (AIS08) via AIS98, with little apparent impact on the functional accuracy of the mapped dataset produced. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. RNA chaperone StpA loosens interactions of the tertiary structure in the td group I intron in vivo

    PubMed Central

    Waldsich, Christina; Grossberger, Rupert; Schroeder, Renée

    2002-01-01

    Efficient splicing of the td group I intron in vivo is dependent on the ribosome. In the absence of translation, the pre-mRNA is trapped in nonnative-splicing-incompetent conformations. Alternatively, folding of the pre-mRNA can be promoted by the RNA chaperone StpA or by the group I intron-specific splicing factor Cyt-18. To understand the mechanism of action of RNA chaperones, we probed the impact of StpA on the structure of the td intron in vivo. Our data suggest that StpA loosens tertiary interactions. The most prominent structural change was the opening of the base triples, which are involved in the correct orientation of the two major intron core domains. In line with the destabilizing activity of StpA, splicing of mutant introns with a reduced structural stability is sensitive to StpA. In contrast, Cyt-18 strengthens tertiary contacts, thereby rescuing splicing of structurally compromised td mutants in vivo. Our data provide direct evidence for protein-induced conformational changes within catalytic RNA in vivo. Whereas StpA resolves tertiary contacts enabling the RNA to refold, Cyt-18 contributes to the overall compactness of the td intron in vivo. PMID:12208852

  3. AIS spectra of desert shrub canopies

    NASA Technical Reports Server (NTRS)

    Murray, R.; Isaacson, D. L.; Schrumpf, B. J.; Ripple, W. J.; Lewis, A. J.

    1986-01-01

    Airborne Imaging Spectrometer (AIS) data were collected 30 August 1985 from a desert shrub community in central Oregon. Spectra from artificial targets placed on the test site and from bare soil, big sagebrush (Artemesia tridentata wyomingensis), silver sagebrush (Artemesia cana bolander), and exposed volcanic rocks were studied. Spectral data from grating position 3 (tree mode) were selected from 25 ground positions for analysis by Principal Factor Analysis (PFA). In this grating position, as many as six factors were identified as significant in contributing to spectral structure. Channels 74 through 84 (tree mode) best characterized between-class differences. Other channels were identified as nondiscriminating and as associated with such errors as excessive atmospheric absorption and grating positin changes. The test site was relatively simple with the two species (A. tridentata and A. cana) representing nearly 95% of biomass and with only two mineral backgrounds, a montmorillonitic soil and volcanic rocks. If, as in this study, six factors of spectral structure can be extracted from a single grating position from data acquired over a simple vegetation community, then AIS data must be considered rich in information-gathering potential.

  4. Evidence of link between quorum sensing and sugar metabolism in Escherichia coli revealed via cocrystal structures of LsrK and HPr

    PubMed Central

    Eo, Yumi; Ma, Xiaochu; Stephens, Kristina; Jeong, Migyeong; Bentley, William E.

    2018-01-01

    Quorum sensing (QS), a bacterial process that regulates population-scale behavior, is mediated by small signaling molecules, called autoinducers (AIs), that are secreted and perceived, modulating a “collective” phenotype. Because the autoinducer AI-2 is secreted by a wide variety of bacterial species, its “perception” cues bacterial behavior. This response is mediated by the lsr (LuxS-regulated) operon that includes the AI-2 transporter LsrACDB and the kinase LsrK. We report that HPr, a phosphocarrier protein central to the sugar phosphotransferase system of Escherichia coli, copurifies with LsrK. Cocrystal structures of an LsrK/HPr complex were determined, and the effects of HPr and phosphorylated HPr on LsrK activity were assessed. LsrK activity is inhibited when bound to HPr, revealing new linkages between QS activity and sugar metabolism. These findings help shed new light on the abilities of bacteria to rapidly respond to changing nutrient levels at the population scale. They also suggest new means of manipulating QS activity among bacteria and within various niches. PMID:29868643

  5. Deletion of amelotin exons 3-6 is associated with amelogenesis imperfecta.

    PubMed

    Smith, Claire E L; Murillo, Gina; Brookes, Steven J; Poulter, James A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2016-08-15

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function. © The Author 2016. Published by Oxford University Press.

  6. Pseudomonas aeruginosa mutants resistant to urea inhibition of growth on acetanilide.

    PubMed Central

    Gregoriou, M; Brown, P R; Tata, R

    1977-01-01

    Pseudomonas aeruginosa AI 3 was able to grow in medium containing acetanilide (N-phenylacetamide) as a carbon source when NH4+ was the nitrogen source but not when urea was the nitrogen source. AIU mutants isolated from strain AI 3 grew on either medium. Urease levels in bacteria grown in the presence of urea were 10-fold lower when NH4+ or acetanilide was also in the medium, but there were no apparent differences in urease or its synthesis between strain AI 3 and mutant AIU 1N. The first metabolic step in the acetanilide utlization is catalyzed by an amidase. Amidases in several AIU strains showed altered physiochemical properties. Urea inhibited amidase in a time-dependent reaction, but the rates of the inhibitory reaction with amidases from the AIU mutants were slower than with AI 3 amidase. The purified amidase from AIU 1N showed a marked difference in its pH/activity profile from that obtained with purified AI 3 amidase. These observations indicate that the ability of strain AIU 1N and the other mutants to grow on acetanilide/urea medium is associated with a mutation in the amidase structural gene; this was confirmed for strain AIU 1N by transduction. PMID:410788

  7. Challenging authority during a life-threatening crisis: the effect of operating theatre hierarchy.

    PubMed

    Sydor, D T; Bould, M D; Naik, V N; Burjorjee, J; Arzola, C; Hayter, M; Friedman, Z

    2013-03-01

    Effective operating theatre (OT) communication is important for team function and patient safety. Status asymmetry between team members may contribute to communication breakdown and threaten patient safety. We investigated how hierarchy in the OT team influences an anaesthesia trainee's ability to challenge an unethical decision by a consultant anaesthetist in a simulated crisis scenario. We prospectively randomized 49 postgraduate year (PGY) 2-5 anaesthesia trainees at two academic hospitals to participate in a videotaped simulated crisis scenario with a simulated OT team practicing either a hierarchical team structure (Group H) or a non-hierarchical team structure (Group NH). The scenario allowed trainees several opportunities to challenge their consultant anaesthetist when administering blood to a Jehovah's Witness. Three independent, blinded raters scored the performances using a modified advocacy-inquiry score (AIS). The primary outcome was the comparison of the best-response AIS between Groups H vs NH. Secondary outcomes included the comparison of best AIS by PGY and the percentage in each group that checked and administered blood. The AIS did not differ between the groups (P=0.832) but significantly improved from PGY2 to PGY5 (P=0.026). The rates of checking blood (92% vs 76%, P=0.082) and administering blood (62% vs 57%, P=0.721) were high in both groups but not significantly different between the groups. This study did not show a significant effect of OT team hierarchical structure on trainee's ability to challenge authority; however, the results are concerning. The challenges were suboptimal in quality and there was an alarming high rate of blood checking and administration in both groups. This may reflect lack of training in appropriately and effectively challenging authority within the formal curriculum with implications for patient safety.

  8. Detection of groundwater conduits in limestones with gravity surveys: data from the area of the Chicxulub Impact crater, Yucatan Peninsula, Mexico.

    PubMed

    Kinsland, G L; Hurtado, M; Pope, K O

    2000-04-15

    Small negative gravity anomalies are found in gravity data from along the northwestern shoreline of the Yucatan Peninsula. These anomalies are shown to be due to elongate, shallow anomalous porosity zones in the Tertiary carbonates. These zones are caused primarily by groundwater solution and are presently active conduits for groundwater flow. The association of these small gravity anomalies with known topographic and structural features of the area, which partially overlies the Chicxulub Impact crater, indicates their development was influenced by structures, faults and/or fractures, within the Tertiary and pre-Tertiary carbonates.

  9. Detection of groundwater conduits in limestones with gravity surveys: data from the area of the Chicxulub Impact crater, Yucatan Peninsula, Mexico

    NASA Technical Reports Server (NTRS)

    Kinsland, G. L.; Hurtado, M.; Pope, K. O.; Ocampo, A. C. (Principal Investigator)

    2000-01-01

    Small negative gravity anomalies are found in gravity data from along the northwestern shoreline of the Yucatan Peninsula. These anomalies are shown to be due to elongate, shallow anomalous porosity zones in the Tertiary carbonates. These zones are caused primarily by groundwater solution and are presently active conduits for groundwater flow. The association of these small gravity anomalies with known topographic and structural features of the area, which partially overlies the Chicxulub Impact crater, indicates their development was influenced by structures, faults and/or fractures, within the Tertiary and pre-Tertiary carbonates.

  10. Trunk imbalance in adolescent idiopathic scoliosis.

    PubMed

    Fortin, Carole; Grunstein, Erin; Labelle, Hubert; Parent, Stefan; Ehrmann Feldman, Debbie

    2016-06-01

    Trunk imbalance (ie, frontal trunk shift measured with a plumb line from C7 to S1) is part of the clinical evaluation in adolescent idiopathic scoliosis (AIS), but its prevalence and relationship with scoliosis, back pain, and health-related factors are not well documented. The principal objectives are to document trunk imbalance prevalence and to explore the association between trunk imbalance and the following factors: Cobb angle, type of scoliosis, back pain, function, mental health, and self-image. The secondary objective is to determine back pain prevalence and the relationship between back pain and each of the following: Cobb angle, function, mental health, and self-image. This is a cross-sectional study in a scoliosis clinic of a tertiary university hospital center. The sample includes youth with AIS (N=55). The outcome measures were trunk imbalance prevalence and magnitude, and back pain prevalence and intensity using the Numeric Pain Rating Scale (NPRS) and the Scoliosis Research Society-22 (SRS-22) pain score, and the function, self-image, and mental health domains of the SRS-22. Trunk imbalance and back pain were assessed in 55 patients with AIS (Cobb angle: 10-60°). Patients completed the SRS-22 questionnaire and the NPRS. Correlations were done between trunk imbalance and scoliosis (Cobb angle, type of scoliosis), back pain (NPRS and SRS-22 pain score), and health-related factors using Pearson correlation coefficients (r) and logistic regression models. Trunk imbalance prevalence is 85% and back pain prevalence is 73%. We found fair to moderate significant positive correlation between trunk imbalance and Cobb angle (r=0.32-0.66, p<.05) but not with back pain, function, mental health, self-image, or type of scoliosis. Lower self-reported pain significantly correlated with lower Cobb angles (r=0.29, p=.03), higher function (r=0.55, p=.000), higher self-image (r=0.44, p=.001), and better mental health (r=0.48, p=.000). There was a trend for trunk imbalance to be related with lower pain in logistic regression models. The high prevalence of trunk imbalance in AIS highlights the importance of screening for this clinical sign in growing adolescents. Further research should be done with regard to the treatment of trunk imbalance and its implication on both Cobb angle and back pain. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A Fourth KLK4 Mutation Is Associated with Enamel Hypomineralisation and Structural Abnormalities

    PubMed Central

    Smith, Claire E. L.; Kirkham, Jennifer; Day, Peter F.; Soldani, Francesca; McDerra, Esther J.; Poulter, James A.; Inglehearn, Christopher F.; Mighell, Alan J.; Brookes, Steven J.

    2017-01-01

    “Amelogenesis imperfecta” (AI) describes a group of genetic conditions that result in defects in tooth enamel formation. Mutations in many genes are known to cause AI, including the gene encoding the serine protease, kallikrein related peptidase 4 (KLK4), expressed during the maturation stage of amelogenesis. In this study we report the fourth KLK4 mutation to be identified in autosomal recessively-inherited hypomaturation type AI, c.632delT, p.(L211Rfs*37) (NM_004917.4, NP_004908.4). This homozygous variant was identified in five Pakistani AI families and is predicted to result in a transcript with a premature stop codon that escapes nonsense mediated decay. However, the protein may misfold, as three of six disulphide bonds would be disrupted, and may be degraded or non-functional as a result. Primary teeth were obtained from one affected individual. The enamel phenotype was characterized using high-resolution computerized X-ray tomography (CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and microhardness testing (MH). Enamel from the affected individual (referred to as KLK4 enamel) was hypomineralised in comparison with matched control enamel. Furthermore, KLK4 inner enamel was hypomineralised compared with KLK4 outer enamel. SEM showed a clear structural demarcation between KLK4 inner and outer enamel, although enamel structure was similar to control tissue overall. EDX showed that KLK4 inner enamel contained less calcium and phosphorus and more nitrogen than control inner enamel and KLK4 outer enamel. MH testing showed that KLK4 inner enamel was significantly softer than KLK4 outer enamel (p < 0.001). However, the hardness of control inner enamel was not significantly different to that of control outer enamel. Overall, these findings suggest that the KLK4 c.632delT mutation may be a common cause of autosomal recessive AI in the Pakistani population. The phenotype data obtained mirror findings in the Klk4−/− mouse and suggest that KLK4 is required for the hardening and mineralization of the inner enamel layer but is less essential for hardening and mineralization of the outer enamel layer. PMID:28611678

  12. A deep learning framework for modeling structural features of RNA-binding protein targets

    PubMed Central

    Zhang, Sai; Zhou, Jingtian; Hu, Hailin; Gong, Haipeng; Chen, Ligong; Cheng, Chao; Zeng, Jianyang

    2016-01-01

    RNA-binding proteins (RBPs) play important roles in the post-transcriptional control of RNAs. Identifying RBP binding sites and characterizing RBP binding preferences are key steps toward understanding the basic mechanisms of the post-transcriptional gene regulation. Though numerous computational methods have been developed for modeling RBP binding preferences, discovering a complete structural representation of the RBP targets by integrating their available structural features in all three dimensions is still a challenging task. In this paper, we develop a general and flexible deep learning framework for modeling structural binding preferences and predicting binding sites of RBPs, which takes (predicted) RNA tertiary structural information into account for the first time. Our framework constructs a unified representation that characterizes the structural specificities of RBP targets in all three dimensions, which can be further used to predict novel candidate binding sites and discover potential binding motifs. Through testing on the real CLIP-seq datasets, we have demonstrated that our deep learning framework can automatically extract effective hidden structural features from the encoded raw sequence and structural profiles, and predict accurate RBP binding sites. In addition, we have conducted the first study to show that integrating the additional RNA tertiary structural features can improve the model performance in predicting RBP binding sites, especially for the polypyrimidine tract-binding protein (PTB), which also provides a new evidence to support the view that RBPs may own specific tertiary structural binding preferences. In particular, the tests on the internal ribosome entry site (IRES) segments yield satisfiable results with experimental support from the literature and further demonstrate the necessity of incorporating RNA tertiary structural information into the prediction model. The source code of our approach can be found in https://github.com/thucombio/deepnet-rbp. PMID:26467480

  13. Structure-Function Study of Tertiary Amines as Switchable Polarity Solvents

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

    Aaron D. Wilson; Frederick F. Stewart

    2014-02-01

    A series of tertiary amines have been screened for their function as switchable polarity solvents (SPS). The relative ratios of tertiary amine and carbonate species as well as maximum possible concentration were determined through quantitative 1H and 13C NMR spectroscopy. The viscosities of the polar SPS solutions were measured and ranged from near water in dilute systems through to gel formation at high concentrations. The van't Hoff indices for SPS solutions were measured through freezing point depression studies as a proxy for osmotic pressures. A new form of SPS with an amine : carbonate ratio significantly greater than unity hasmore » been identified. Tertiary amines that function as SPS at ambient pressures appear to be limited to molecules with fewer than 12 carbons. The N,N-dimethyl-n-alkylamine structure has been identified as important to the function of an SPS.« less

  14. Three-dimensional tertiary structure of yeast phenylalanine transfer RNA

    NASA Technical Reports Server (NTRS)

    Kim, S. H.; Sussman, J. L.; Suddath, F. L.; Quigley, G. J.; Mcpherson, A.; Wang, A. H. J.; Seeman, N. C.; Rich, A.

    1974-01-01

    Results of an analysis and interpretation of a 3-A electron density map of yeast phenylalanine transfer RNA. Some earlier detailed assignments of nucleotide residues to electron density peaks are found to be in error, even though the overall tracing of the backbone conformation of yeast phenylalanine transfer RNA was generally correct. A new, more comprehensive interpretation is made which makes it possible to define the tertiary interactions in the molecule. The new interpretation makes it possible to visualize a number of tertiary interactions which not only explain the structural role of most of the bases which are constant in transfer RNAs, but also makes it possible to understand in a direct and simple fashion the chemical modification data on transfer RNA. In addition, this pattern of tertiary interactions provides a basis for understanding the general three-dimensional folding of all transfer RNA molecules.

  15. Chemical improvement of chitosan-modified beads for the immobilization of Enterococcus faecium DBFIQ E36 L-arabinose isomerase through multipoint covalent attachment approach.

    PubMed

    Manzo, Ricardo M; de Sousa, Marylane; Fenoglio, Cecilia L; Gonçalves, Luciana Rocha Barro; Mammarella, Enrique J

    2015-10-01

    D-tagatose is produced from D-galactose by the enzyme L-arabinose isomerase (L-AI) in a commercially viable bioprocess. An active and stable biocatalyst was obtained by modifying chitosan gel structure through reaction with TNBS, D-fructose or DMF, among others. This led to a significant improvement in L-AI immobilization via multipoint covalent attachment approach. Synthetized derivatives were compared with commercial supports such as Eupergit(®) C250L and glyoxal-agarose. The best chitosan derivative for L-AI immobilization was achieved by reacting 4 % (w/v) D-fructose with 3 % (w/v) chitosan at 50 °C for 4 h. When compared to the free enzyme, the glutaraldehyde-activated chitosan biocatalyst showed an apparent activity of 88.4 U g (gel) (-1) with a 211-fold stabilization factor while the glyoxal-agarose biocatalyst gave an apparent activity of 161.8 U g (gel) (-1) with an 85-fold stabilization factor. Hence, chitosan derivatives were comparable to commercial resins, thus becoming a viable low-cost strategy to obtain high active L-AI insolubilized derivatives.

  16. Understanding the social and community support networks of American Indian women cancer survivors.

    PubMed

    Burnette, Catherine E; Liddell, Jessica; Roh, Soonhee; Lee, Yeon-Shim; Lee, Hee Yun

    2018-04-02

    Cancer is the leading cause of death among American Indian and Alaska Native (AI/AN) women, and although cancer disparities among AI women are alarming, there is little research focused on the topic of social support and cancer treatment and outcomes. A community advisory board was used to develop and administer the project, and a qualitative descriptive study methodology was used. This research was conducted in partnership with two community-based hospitals in the Northern Plains. The sample included 43 AI female cancer survivors who were interviewed with a semi-structured interview guide. The data were analyzed using content analysis. Emergent themes revealed that AI cancer survivors' non-familial support systems included friends (n = 12), support groups (n = 6), churches (n = 10), co-workers (n = 5), communities (n = 4), support from health practitioners (n = 3) and additional forms of support. Results indicate that survivors' networks are diverse, and support broad prevention programs that reach out to churches, community groups, and online forums. These sources of supports can be enhanced through sustainable community-based infrastructures.

  17. Enzymatic conversion of D-galactose to D-tagatose: cloning, overexpression and characterization of L-arabinose isomerase from Pediococcus pentosaceus PC-5.

    PubMed

    Men, Yan; Zhu, Yueming; Zhang, Lili; Kang, Zhenkui; Izumori, Ken; Sun, Yuanxia; Ma, Yanhe

    2014-01-01

    The gene encoding L-arabinose isomerase from food-grade strain Pediococcus pentosaceus PC-5 was cloned and overexpressed in Escherichia coli. The recombinant protein was purified and characterized. It was optimally active at 50 °C and pH 6.0. Furthermore, this enzyme exhibited a weak requirement for metallic ions for its maximal activity evaluated at 0.6 mM Mn(2+) or 0.8 mM Co(2+). Interestingly, this enzyme was distinguished from other L-AIs, it could not use L-arabinose as its substrate. In addition, a three-dimensional structure of L-AI was built by homology modeling and L-arabinose and D-galactose were docked into the active site pocket of PPAI model to explain the interaction between L-AI and its substrate. The purified P. pentosaceus PC-5 L-AI converted D-galactose into D-tagatose with a high conversion rate of 52% after 24 h at 50 °C, suggesting its excellent potential in D-tagatose production. Crown Copyright © 2013. Published by Elsevier GmbH. All rights reserved.

  18. Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs

    PubMed Central

    2017-01-01

    Prediction of RNA tertiary structure from sequence is an important problem, but generating accurate structure models for even short sequences remains difficult. Predictions of RNA tertiary structure tend to be least accurate in loop regions, where non-canonical pairs are important for determining the details of structure. Non-canonical pairs can be predicted using a knowledge-based model of structure that scores nucleotide cyclic motifs, or NCMs. In this work, a partition function algorithm is introduced that allows the estimation of base pairing probabilities for both canonical and non-canonical interactions. Pairs that are predicted to be probable are more likely to be found in the true structure than pairs of lower probability. Pair probability estimates can be further improved by predicting the structure conserved across multiple homologous sequences using the TurboFold algorithm. These pairing probabilities, used in concert with prior knowledge of the canonical secondary structure, allow accurate inference of non-canonical pairs, an important step towards accurate prediction of the full tertiary structure. Software to predict non-canonical base pairs and pairing probabilities is now provided as part of the RNAstructure software package. PMID:29107980

  19. Unsupervised Fault Diagnosis of a Gear Transmission Chain Using a Deep Belief Network

    PubMed Central

    He, Jun; Yang, Shixi; Gan, Chunbiao

    2017-01-01

    Artificial intelligence (AI) techniques, which can effectively analyze massive amounts of fault data and automatically provide accurate diagnosis results, have been widely applied to fault diagnosis of rotating machinery. Conventional AI methods are applied using features selected by a human operator, which are manually extracted based on diagnostic techniques and field expertise. However, developing robust features for each diagnostic purpose is often labour-intensive and time-consuming, and the features extracted for one specific task may be unsuitable for others. In this paper, a novel AI method based on a deep belief network (DBN) is proposed for the unsupervised fault diagnosis of a gear transmission chain, and the genetic algorithm is used to optimize the structural parameters of the network. Compared to the conventional AI methods, the proposed method can adaptively exploit robust features related to the faults by unsupervised feature learning, thus requires less prior knowledge about signal processing techniques and diagnostic expertise. Besides, it is more powerful at modelling complex structured data. The effectiveness of the proposed method is validated using datasets from rolling bearings and gearbox. To show the superiority of the proposed method, its performance is compared with two well-known classifiers, i.e., back propagation neural network (BPNN) and support vector machine (SVM). The fault classification accuracies are 99.26% for rolling bearings and 100% for gearbox when using the proposed method, which are much higher than that of the other two methods. PMID:28677638

  20. Targeted transcranial theta-burst stimulation alters fronto-insular network and prefrontal GABA.

    PubMed

    Iwabuchi, Sarina J; Raschke, Felix; Auer, Dorothee P; Liddle, Peter F; Lankappa, Sudheer T; Palaniyappan, Lena

    2017-02-01

    Repetitive transcranial magnetic stimulation (rTMS) has been used worldwide to treat depression. However, the exact physiological effects are not well understood. Pathophysiology of depression involves crucial limbic structures (e.g. insula), and it is still not clear if these structures can be modulated through neurostimulation of surface regions (e.g. dorsolateral prefrontal cortex, DLPFC), and whether rTMS-induced excitatory/inhibitory transmission alterations relate to fronto-limbic connectivity changes. Therefore, we sought proof-of-concept for neuromodulation of insula via prefrontal intermittent theta-burst stimulation (iTBS), and how these effects relate to GABAergic and glutamatergic systems. In 27 healthy controls, we employed a single-blind crossover randomised-controlled trial comparing placebo and real iTBS using resting-state functional MRI and magnetic resonance spectroscopy. Granger causal analysis was seeded from right anterior insula (rAI) to locate individualized left DLPFC rTMS targets. Effective connectivity coefficients within rAI and DLPFC were calculated, and levels of GABA/Glx, GABA/Cr and Glx/Cr in DLPFC and anterior cingulate voxels were also measured. ITBS significantly dampened fronto-insular connectivity and reduced GABA/Glx in both voxels. GABA/Glx had a significant mediating effect on iTBS-induced changes in DLPFC-to-rAI connectivity. We demonstrate modulation of the rAI using targeted iTBS through alterations of excitatory/inhibitory interactions, which may underlie therapeutic effects of rTMS, offering promise for rTMS treatment optimization. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Unsupervised Fault Diagnosis of a Gear Transmission Chain Using a Deep Belief Network.

    PubMed

    He, Jun; Yang, Shixi; Gan, Chunbiao

    2017-07-04

    Artificial intelligence (AI) techniques, which can effectively analyze massive amounts of fault data and automatically provide accurate diagnosis results, have been widely applied to fault diagnosis of rotating machinery. Conventional AI methods are applied using features selected by a human operator, which are manually extracted based on diagnostic techniques and field expertise. However, developing robust features for each diagnostic purpose is often labour-intensive and time-consuming, and the features extracted for one specific task may be unsuitable for others. In this paper, a novel AI method based on a deep belief network (DBN) is proposed for the unsupervised fault diagnosis of a gear transmission chain, and the genetic algorithm is used to optimize the structural parameters of the network. Compared to the conventional AI methods, the proposed method can adaptively exploit robust features related to the faults by unsupervised feature learning, thus requires less prior knowledge about signal processing techniques and diagnostic expertise. Besides, it is more powerful at modelling complex structured data. The effectiveness of the proposed method is validated using datasets from rolling bearings and gearbox. To show the superiority of the proposed method, its performance is compared with two well-known classifiers, i.e., back propagation neural network (BPNN) and support vector machine (SVM). The fault classification accuracies are 99.26% for rolling bearings and 100% for gearbox when using the proposed method, which are much higher than that of the other two methods.

  2. An Amino Acid Code for Irregular and Mixed Protein Packing

    PubMed Central

    Joo, Hyun; Chavan, Archana; Fraga, Keith; Tsai, Jerry

    2015-01-01

    To advance our understanding of protein tertiary structure, the development of the knob-socket model is completed in an analysis of the packing in irregular coil and turn secondary structure packing as well as between mixed secondary structure. The knob-socket model simplifies packing based on repeated patterns of 2 motifs: a 3 residue socket for packing within 2° structure and a 4 residue knob-socket for 3° packing. For coil and turn secondary structure, knob-sockets allow identification of a correlation between amino acid composition and tertiary arrangements in space. Coil contributes almost as much as α-helices to tertiary packing. Irregular secondary structure involves 3 residue cliques of consecutive contacting residues or XYZ sockets. In irregular sockets, Gly, Pro, Asp and Ser are favored, while Cys, His, Met and Trp are not. For irregular knobs, the preference order is Arg, Asp, Pro, Asn, Thr, Leu, and Gly, while Cys, His, Met and Trp are not. In mixed packing, the knob amino acid preferences are a function of the socket that they are packing into, whereas the amino acid composition of the sockets does not depend on the secondary structure of the knob. A unique motif of a coil knob with an XYZ β-sheet socket may potentially function to inhibit β-sheet extension. In addition, analysis of the preferred crossing angles for strands within a β-sheet and mixed α-helices/β-sheets identifies canonical packing patterns useful in protein design. Lastly, the knob-socket model abstracts the complexity of protein tertiary structure into an intuitive packing surface topology map. PMID:26370334

  3. Smart Utilization of Tertiary Instructional Modes

    ERIC Educational Resources Information Center

    Hamilton, John; Tee, Singwhat

    2010-01-01

    This empirical research surveys first year tertiary business students across different campuses regarding their perceived views concerning traditional, blended and flexible instructional approaches. A structural equation modeling approach shows traditional instructional modes deliver lower levels of student-perceived learning quality, learning…

  4. A Dutch ICF version of the Activity Inventory: results from focus groups with visually impaired persons and experts.

    PubMed

    Bruijning, Janna; van Nispen, Ruth; Verstraten, Peter; van Rens, Ger

    2010-12-01

    To develop a valid and reliable instrument to systematically investigate visual rehabilitation needs of visually impaired older adults, which is compatible with the "International Classification of Functioning, Disability and Health" (ICF) structure: a new Dutch ICF version of the Activity Inventory (D-AI). The original AI was translated, adjusted and expanded. After studying literature and investigating patient records, focus group discussions were conducted until the input was just confirmatory. Six (n = 41) and seven (n = 50) discussions with patients and professionals respectively contributed to the first draft of the D-AI, which was further improved by professionals. The D-AI now consists of 10 domains, 68 goals and 813 tasks. Goals are organized into the "Activities and Participation" domains of the ICF. The original routing was maintained; only tasks organized under important (0 [not important] to 3 [very important]) and difficult (0 [not difficult] to 4 [impossible]) goals were assessed. Rehabilitation needs can be organized in the "Activities and Participation" domains of the ICF. The D-AI offers a way of systematically assessing and measuring functional limitations and disabilities, and provides detailed information about activities that are needed to perform a certain goal. Focus group discussions with Dutch patients and experts revealed additional items that will probably be relevant for other populations. Involving patients in the first step of the developing process is important to provide face and content validity. The D-AI can prioritize rehabilitation goals by multiplying importance and difficulty scores, which is helpful in formulating a rehabilitation plan.

  5. Injury Risk for Rear-Seated Occupants in Small Overlap Crashes

    PubMed Central

    Arbogast, Kristy B.; Locey, Caitlin M.; Hammond, Rachel; Belwadi, Aditya

    2013-01-01

    Small overlap crashes, where the primary crash engagement is outboard from the longitudinal energy absorbing structures of the vehicle, have received recent interest as a crash dynamic that results in high likelihood of injury. Previous analyses of good performing vehicles showed that 24% of crashes with AIS 3+ injuries to front seat occupants were small overlap crashes. However, similar evaluations have not been conducted for those rear seated. Vehicle dynamics suggest that rear seat occupants may be at greater risk due to lack of lateral seating support and a steering wheel to hold, making them more sensitive to lateral movement seen in these crashes. Thus, the objective was to calculate injury risk for rear-seated occupants in small overlap collisions. AIS 2+ and AIS 3+ injury risk was calculated from NASS-CDS data from 2000–2011. Inclusion criteria were vehicles of model year 2000 or later, with CDC codes of “FL” or “FR”, and an occupant in the second or third row. AIS2+ injury risk was 5.1%, and AIS3+ injury risk was 2.4%. Of note, half of the occupants were <15 years of age indicating rear seat protection should emphasize the young. Occupants seated near side were nearly three times as likely to sustain an AIS2+ injury than occupants seated far side. Particular attention should be paid to the prominence of head injuries in this crash dynamic and consideration given to their mitigation. Additional research should determine whether countermeasures being implemented for front seat occupants can be beneficial to rear seat occupants. PMID:24406964

  6. The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke

    PubMed Central

    Jeanneret, Valerie; Yepes, Manuel

    2016-01-01

    Advances in neurocritical care and interventional neuroradiology have led to a significant decrease in acute ischemic stroke (AIS) mortality. In contrast, due to the lack of an effective therapeutic strategy to promote neuronal recovery among AIS survivors, cerebral ischemia is still a leading cause of disability in the world. Ischemic stroke has a harmful impact on synaptic structure and function, and plasticity-mediated synaptic recovery is associated with neurological improvement following an AIS. Dendritic spines (DSs) are specialized dendritic protrusions that receive most of the excitatory input in the brain. The deleterious effect of cerebral ischemia on DSs morphology and function has been associated with impaired synaptic transmission and neurological deterioration. However, these changes are reversible if cerebral blood flow is restored on time, and this recovery has been associated with neurological improvement following an AIS. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are two serine proteases that besides catalyzing the conversion of plasminogen into plasmin in the intravascular and pericellular environment, respectively, are also are efficient inductors of synaptic plasticity. Accordingly, recent evidence indicates that both, tPA and uPA, protect DSs from the metabolic stress associated with the ischemic injury, and promote their morphological and functional recovery during the recovery phase from an AIS. Here we will review data indicating that plasticity-induced changes in DSs and the associated post-synaptic density play a pivotal role in the recovery process from AIS, making special emphasis on the role of tPA and uPA in this process. PMID:26846991

  7. An Amino Acid Code to Define a Protein’s Tertiary Packing Surface

    PubMed Central

    Fraga, Keith J.; Joo, Hyun; Tsai, Jerry

    2015-01-01

    One difficult aspect of the protein-folding problem is characterizing the non-specific interactions that define packing in protein tertiary structure. To better understand tertiary structure, this work extends the knob-socket model by classifying the interactions of a single knob residue packed into a set of contiguous sockets, or a pocket made up of 4 or more residues. The knob-socket construct allows for a symbolic two-dimensional mapping of pockets. The two-dimensional mapping of pockets provides a simple method to investigate the variety of pocket shapes in order to understand the geometry of protein tertiary surfaces. The diversity of pocket geometries can be organized into groups of pockets that share a common core, which suggests that some interactions in pockets are ancillary to packing. Further analysis of pocket geometries displays a preferred configuration that is right-handed in α-helices and left-handed in β-sheets. The amino acid composition of pockets illustrates the importance of non-polar amino acids in packing as well as position specificity. As expected, all pocket shapes prefer to pack with hydrophobic knobs; however, knobs are not selective for the pockets they pack. Investigating side-chain rotamer preferences for certain pocket shapes uncovers no strong correlations. These findings allow a simple vocabulary based on knobs and sockets to describe protein tertiary packing that supports improved analysis, design and prediction of protein structure. PMID:26575337

  8. Patients' assessment of quality of care in public tertiary hospitals with and without accreditation: comparative cross-sectional study.

    PubMed

    Aboshaiqah, Ahmad E; Alonazi, Wadi B; Patalagsa, Joel Gonzales

    2016-11-01

    To compare patients' assessment of quality of care provided by public tertiary hospitals grouped according to accreditation status. Healthcare institutions worldwide are increasingly adopting accreditation as continuing initiative aimed at improving structures, processes and outcomes associated with quality of care. Patients being recipients of health care need to participate in assessing the quality of care they experienced while confined for therapeutic management. Comparative, cross-sectional. Data were collected from patients confined in public tertiary hospitals (n = 517 in four with accreditation and n = 542 in four without accreditation) in Riyadh, Saudi Arabia between February 2011-June 2011. Patients rated key performance indicators grouped under the dimensions of structure, process and outcome. Mann-Whitney U-test, Spearman Correlation Coefficient and coefficient of determination were used in analysing data. Patients in accredited public tertiary hospitals perceived structure, outcome and overall quality of care statistically higher than patients in non-accredited hospitals. No statistical differences were found in process (access and communication) indicators. Accreditation status is marginally associated with structure; outcome; and overall quality of care. The proportion of variance in the ranks of accreditation status explained the proportion of variance in the ranks of structure; outcome; and overall quality of care. The results apparently showed better structure, outcome and overall quality of care in accredited hospitals. Accreditation's association in the overall quality of care apparently remained unclear. Further studies are needed to appreciate the contribution of accreditation. © 2016 John Wiley & Sons Ltd.

  9. Halogen dependent symmetry change in two series of wheel cluster organic frameworks built from La18 tertiary building units.

    PubMed

    Fang, Wei-Hui; Zhang, Lei; Zhang, Jian; Yang, Guo-Yu

    2016-01-25

    Two series of wheel cluster organic frameworks (WCOFs) built from La18 tertiary building units are hydrothermally made, which show halogen-dependent structural symmetry, and demonstrate different chiral performances.

  10. VLBI survey of compact broad absorption line quasars with balnicity index BI = 0

    NASA Astrophysics Data System (ADS)

    Cegłowski, M.; Kunert-Bajraszewska, M.; Roskowiński, C.

    2015-06-01

    We present high-resolution observations, using both the European VLBI Network (EVN) at 1.7 GHz and the Very Long Baseline Array (VLBA) at 5 and 8.4 GHz, to image radio structures of 14 compact sources classified as broad absorption line (BAL) quasars based on the absorption index (AI). All sources but one were resolved, with the majority showing core-jet morphology typical for radio-loud quasars. We discuss in detail the most interesting cases. The high radio luminosities and small linear sizes of the observed objects indicate they are strong young active galactic nuclei. Nevertheless, the distribution of the radio-loudness parameter, log RI, of a larger sample of AI quasars shows that the objects observed by us constitute the most luminous, small subgroup of the AI population. Additionally, we report that for the radio-loudness parameter, the distribution of AI quasars and that for those selected using the traditional balnicity index differ significantly. Strong absorption is connected with lower log RI and thus probably larger viewing angles. Since the AI quasars have on average larger log RI, the orientation can mean that we see them less absorbed. However, we suggest that the orientation is not the only parameter that affects the detected absorption. That the strong absorption is associated with the weak radio emission is equally important and worth exploring.

  11. A neural model of mechanisms of empathy deficits in narcissism

    PubMed Central

    Jankowiak-Siuda, Kamila; Zajkowski, Wojciech

    2013-01-01

    From a multidimensional perspective, empathy is a process that includes affective sharing and imagining and understanding the emotions of others. The primary brain structures involved in mediating the components of empathy are the anterior insula (AI), the anterior cingulate cortex (ACC), and specific regions of the medial prefrontal cortex (MPFC). The AI and ACC are the main nodes in the salience network (SN), which selects and coordinates the information flow from the intero- and exteroreceptors. AI might play a role as a crucial hub – a dynamic switch between 2 separate networks of cognitive processing: the central executive network (CEN), which is concerned with effective task execution, and the default mode network (DMN), which is involved with self-reflective processes. Given various classifications, a deficit in empathy may be considered a central dysfunctional trait in narcissism. A recent fMRI study suggests that deficit in empathy is due to a dysfunction in the right AI. Based on the acquired data, we propose a theoretical model of imbalanced SN functioning in narcissism in which the dysfunctional AI hub is responsible for constant DMN activation, which, in turn, centers one’s attention on the self. This might hinder the ability to affectively share and understand the emotions of others. This review paper on neural mechanisms of empathy deficits in narcissism aims to inspire and direct future research in this area. PMID:24189465

  12. Do stigma and its psychosocial impact differ between Asian-born Chinese immigrants and Western-born Caucasians with head and neck cancer?

    PubMed

    Lebel, Sophie; Payne, Ada Y M; Mah, Kenneth; Irish, Jonathan; Rodin, Gary; Devins, Gerald M

    2016-07-01

    Stigma appears to influence emotional distress and well-being in cancer survivors, but cross-cultural differences have been ignored. Previous studies suggest that stigma may be especially relevant for survivors of Asian origin. However, their study designs (e.g. focused on female cancers, qualitative designs, and an absence of comparison groups) limit the strength of this conclusion. We hypothesized that (1) Asian-born Chinese immigrants (AI) would report more perceived cancer-related stigma than Western-born Caucasians (WBC); and (2) the impact of stigma on emotional distress and well-being would be greater in AI as compared to WBC. Head and neck cancer survivors (n = 118 AI and n = 404 WBC) completed measures of well-being, emotional distress, and a three-item indicator of stigma in structured interviews. The majority of respondents (59%) reported one or more indicators of stigma. Stigma correlated significantly with emotional distress (r = .13, p = .004) and well-being (r = -.09, p = .032). Contrary to our hypotheses, WBCs and AIs did not differ in reported stigma nor did we detect differences in its psychosocial impact. Stigma exerts a deleterious psychosocial impact on head and neck cancer survivors. It did not differ significantly between AI and WBC survivors.

  13. Space Technology - Game Changing Development NASA Facts: Autonomous Medical Operations

    NASA Technical Reports Server (NTRS)

    Thompson, David E.

    2018-01-01

    The AMO (Autonomous Medical Operations) Project is working extensively to train medical models on the reliability and confidence of computer-aided interpretation of ultrasound images in various clinical settings, and of various anatomical structures. AI (Artificial Intelligence) algorithms recognize and classify features in the ultrasound images, and these are compared to those features that clinicians use to diagnose diseases. The acquisition of clinically validated image assessment and the use of the AI algorithms constitutes fundamental baseline for a Medical Decision Support System that will advise crew on long-duration, remote missions.

  14. Proceedings of Damping Volume 2 of 3

    DTIC Science & Technology

    1993-06-01

    engineering, marine engineering, auto-industry, sporting goods, proved that the realms of application will definitely be expanding. The paper surveyed by...G13 = G13 + i Tic G13 (43a) D11 = D + i ibD (43b) (AI-All)* =(All-All) + i ql(AI1-AIl) (43c) B11 ’= Bjj + i 1d BIL (43d) (All+A11) =(Aj1 +Ajj) + i l.(A...F.: Tail Buffet Characteristics and Longitudinal Oscillation of Combat Airplanes. NAVY x Bureau of Aeronautics, Structures Project Report No. 27, Feb

  15. STAR - A computer language for hybrid AI applications

    NASA Technical Reports Server (NTRS)

    Borchardt, G. C.

    1986-01-01

    Constructing Artificial Intelligence application systems which rely on both symbolic and non-symbolic processing places heavy demands on the communication of data between dissimilar languages. This paper describes STAR (Simple Tool for Automated Reasoning), a computer language for the development of AI application systems which supports the transfer of data structures between a symbolic level and a non-symbolic level defined in languages such as FORTRAN, C and PASCAL. The organization of STAR is presented, followed by the description of an application involving STAR in the interpretation of airborne imaging spectrometer data.

  16. Quorum Sensing Signal Production and Microbial Interactions in a Polymicrobial Disease of Corals and the Coral Surface Mucopolysaccharide Layer

    PubMed Central

    Zimmer, Beth L.; May, Amanda L.; Bhedi, Chinmayee D.; Dearth, Stephen P.; Prevatte, Carson W.; Pratte, Zoe; Campagna, Shawn R.; Richardson, Laurie L.

    2014-01-01

    Black band disease (BBD) of corals is a complex polymicrobial disease considered to be a threat to coral reef health, as it can lead to mortality of massive reef-building corals. The BBD community is dominated by gliding, filamentous cyanobacteria with a highly diverse population of heterotrophic bacteria. Microbial interactions such as quorum sensing (QS) and antimicrobial production may be involved in BBD disease pathogenesis. In this study, BBD (whole community) samples, as well as 199 bacterial isolates from BBD, the surface mucopolysaccharide layer (SML) of apparently healthy corals, and SML of apparently healthy areas of BBD-infected corals were screened for the production of acyl homoserine lactones (AHLs) and for autoinducer-2 (AI-2) activity using three bacterial reporter strains. AHLs were detected in all BBD (intact community) samples tested and in cultures of 5.5% of BBD bacterial isolates. Over half of a subset (153) of the isolates were positive for AI-2 activity. AHL-producing isolates were further analyzed using LC-MS/MS to determine AHL chemical structure and the concentration of (S)-4,5-dihydroxy-2,3-pentanedione (DPD), the biosynthetic precursor of AI-2. C6-HSL was the most common AHL variant detected, followed by 3OC4-HSL. In addition to QS assays, 342 growth challenges were conducted among a subset of the isolates, with 27% of isolates eliciting growth inhibition and 2% growth stimulation. 24% of BBD isolates elicited growth inhibition as compared to 26% and 32% of the bacteria from the two SML sources. With one exception, only isolates that exhibited AI-2 activity or produced DPD inhibited growth of test strains. These findings demonstrate for the first time that AHLs are present in an active coral disease. It is possible that AI-2 production among BBD and coral SML bacteria may structure the microbial communities of both a polymicrobial infection and the healthy coral microbiome. PMID:25268348

  17. Cooperative autoinhibition and multi-level activation mechanisms of calcineurin

    PubMed Central

    Li, Sheng-Jie; Wang, Jue; Ma, Lei; Lu, Chang; Wang, Jie; Wu, Jia-Wei; Wang, Zhi-Xin

    2016-01-01

    The Ca2+/calmodulin-dependent protein phosphatase calcineurin (CN), a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus (FK506) and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN (β isoform), which revealed a novel autoinhibitory segment (AIS) in addition to the well-known autoinhibitory domain (AID). The AIS nestles in a hydrophobic intersubunit groove, which overlaps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation. PMID:26794871

  18. Autoinducer 2 controls biofilm formation in Escherichia coli through a novel motility quorum-sensing regulator (MqsR, B3022).

    PubMed

    González Barrios, Andrés F; Zuo, Rongjun; Hashimoto, Yoshifumi; Yang, Li; Bentley, William E; Wood, Thomas K

    2006-01-01

    The cross-species bacterial communication signal autoinducer 2 (AI-2), produced by the purified enzymes Pfs (nucleosidase) and LuxS (terminal synthase) from S-adenosylhomocysteine, directly increased Escherichia coli biofilm mass 30-fold. Continuous-flow cells coupled with confocal microscopy corroborated these results by showing the addition of AI-2 significantly increased both biofilm mass and thickness and reduced the interstitial space between microcolonies. As expected, the addition of AI-2 to cells which lack the ability to transport AI-2 (lsr null mutant) failed to stimulate biofilm formation. Since the addition of AI-2 increased cell motility through enhanced transcription of five motility genes, we propose that AI-2 stimulates biofilm formation and alters its architecture by stimulating flagellar motion and motility. It was also found that the uncharacterized protein B3022 regulates this AI-2-mediated motility and biofilm phenotype through the two-component motility regulatory system QseBC. Deletion of b3022 abolished motility, which was restored by expressing b3022 in trans. Deletion of b3022 also decreased biofilm formation significantly, relative to the wild-type strain in three media (46 to 74%) in 96-well plates, as well as decreased biomass (8-fold) and substratum coverage (19-fold) in continuous-flow cells with minimal medium (growth rate not altered and biofilm restored by expressing b3022 in trans). Deleting b3022 changed the wild-type biofilm architecture from a thick (54-mum) complex structure to one that contained only a few microcolonies. B3022 positively regulates expression of qseBC, flhD, fliA, and motA, since deleting b3022 decreased their transcription by 61-, 25-, 2.4-, and 18-fold, respectively. Transcriptome analysis also revealed that B3022 induces crl (26-fold) and flhCD (8- to 27-fold). Adding AI-2 (6.4 muM) increased biofilm formation of wild-type K-12 MG1655 but not that of the isogenic b3022, qseBC, fliA, and motA mutants. Adding AI-2 also increased motA transcription for the wild-type strain but did not stimulate motA transcription for the b3022 and qseB mutants. Together, these results indicate AI-2 induces biofilm formation in E. coli through B3022, which then regulates QseBC and motility; hence, b3022 has been renamed the motility quorum-sensing regulator gene (the mqsR gene).

  19. Social determinants that lead to poor knowledge about, and inappropriate precautionary practices towards, avian influenza among butchers in Kathmandu, Nepal

    PubMed Central

    2013-01-01

    Background Avian influenza (AI) is a global public health threat. Understanding the knowledge that butchers have about it and the precautionary practices they take against it is crucial for designing future preparedness programs. This study aimed to identify the social determinants of knowledge and precautionary measures of AI among butchers in the Kathmandu district in Nepal. Methods The study was based on a cross-sectional study design using structured interview questionnaires and checklists to observe social determinants and the precautionary measures of 120 butchers aged 15 years and above from the Kathmandu district. Results The majority of the respondents were male (69.2%) and more than half (53.3%) were from the age group of 25–39 years (mean: 31.08, SD: ±9.82). Nearly two-thirds (61.3%) of the respondents had a ‘poor knowledge’, and the remaining had ‘some knowledge’, about AI. More than half (55.4%) of the respondents were in the category of displaying ‘poor practice’ towards AI and the remaining half were in the ‘satisfactory practice’ category. None of the respondents had ‘adequate knowledge’ or displayed ‘good practice’. The respondents in the >25 years of age group were less likely [OR 0.169; 95% CI (0.056-0.512)] compared to those in the <25 years age group to have a poor knowledge about AI; and the respondents with ‘primary education’ were more likely [OR 3.265; 95% CI (1.326-8.189)] to have a poor knowledge about AI as compared to those who had a secondary or above level of education. Respondents who did not know the correct definition of AI were more likely to follow poor practices [OR 4.265; 95% CI (1.193-15.242)]; and the respondents who did not know the risk groups associated with AI were also more likely to follow poor practices [OR 3.103; 95% CI (1.191-8.083)]. Conclusion This study points out the need to address butchers to improve their knowledge of, and more importantly their compliance with, the precautionary measures to prevent avian influenza. PMID:23849460

  20. Structural relationships of pre-Tertiary rocks in the Nevada Test Site region, southern Nevada

    USGS Publications Warehouse

    Cole, James C.; Cashman, Patricia Hughes

    1999-01-01

    This report contains a synthesis and interpretation of structural and stratigraphic data for pre-Tertiary rocks in a large area of southern Nevada within and near the Nevada Test Site. Its presents descriptive and interpretive information from discontinuously exposed localities in the context of a regional model that integrates stratigraphy, sedimentology, crustal structure, and deformational style and timing. Evidence is given for substantial strike-slip faults, for modest excursion on low-angle faults, and for pre-Oligocene formation of the regional oroclinal flexure in neighboring mountain ranges.

  1. αII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function.

    PubMed

    Huang, Claire Yu-Mei; Zhang, Chuansheng; Ho, Tammy Szu-Yu; Oses-Prieto, Juan; Burlingame, Alma L; Lalonde, Joshua; Noebels, Jeffrey L; Leterrier, Christophe; Rasband, Matthew N

    2017-11-22

    Spectrins form a submembranous cytoskeleton proposed to confer strength and flexibility to neurons and to participate in ion channel clustering at axon initial segments (AIS) and nodes of Ranvier. Neuronal spectrin cytoskeletons consist of diverse β subunits and αII spectrin. Although αII spectrin is found in neurons in both axonal and somatodendritic domains, using proteomics, biochemistry, and superresolution microscopy, we show that αII and βIV spectrin interact and form a periodic AIS cytoskeleton. To determine the role of spectrins in the nervous system, we generated Sptan1 f/f mice for deletion of CNS αII spectrin. We analyzed αII spectrin-deficient mice of both sexes and found that loss of αII spectrin causes profound reductions in all β spectrins. αII spectrin-deficient mice die before 1 month of age and have disrupted AIS and many other neurological impairments including seizures, disrupted cortical lamination, and widespread neurodegeneration. These results demonstrate the importance of the spectrin cytoskeleton both at the AIS and throughout the nervous system. SIGNIFICANCE STATEMENT Spectrin cytoskeletons play diverse roles in neurons, including assembly of excitable domains such as the axon initial segment (AIS) and nodes of Ranvier. However, the molecular composition and structure of these cytoskeletons remain poorly understood. Here, we show that αII spectrin partners with βIV spectrin to form a periodic cytoskeleton at the AIS. Using a new αII spectrin conditional knock-out mouse, we show that αII spectrin is required for AIS assembly, neuronal excitability, cortical lamination, and to protect against neurodegeneration. These results demonstrate the broad importance of spectrin cytoskeletons for nervous system function and development and have important implications for nervous system injuries and diseases because disruption of the spectrin cytoskeleton is a common molecular pathology. Copyright © 2017 the authors 0270-6474/17/3711311-12$15.00/0.

  2. Predicting areas of sustainable error growth in quasigeostrophic flows using perturbation alignment properties

    NASA Astrophysics Data System (ADS)

    Rivière, G.; Hua, B. L.

    2004-10-01

    A new perturbation initialization method is used to quantify error growth due to inaccuracies of the forecast model initial conditions in a quasigeostrophic box ocean model describing a wind-driven double gyre circulation. This method is based on recent analytical results on Lagrangian alignment dynamics of the perturbation velocity vector in quasigeostrophic flows. More specifically, it consists in initializing a unique perturbation from the sole knowledge of the control flow properties at the initial time of the forecast and whose velocity vector orientation satisfies a Lagrangian equilibrium criterion. This Alignment-based Initialization method is hereafter denoted as the AI method.In terms of spatial distribution of the errors, we have compared favorably the AI error forecast with the mean error obtained with a Monte-Carlo ensemble prediction. It is shown that the AI forecast is on average as efficient as the error forecast initialized with the leading singular vector for the palenstrophy norm, and significantly more efficient than that for total energy and enstrophy norms. Furthermore, a more precise examination shows that the AI forecast is systematically relevant for all control flows whereas the palenstrophy singular vector forecast leads sometimes to very good scores and sometimes to very bad ones.A principal component analysis at the final time of the forecast shows that the AI mode spatial structure is comparable to that of the first eigenvector of the error covariance matrix for a "bred mode" ensemble. Furthermore, the kinetic energy of the AI mode grows at the same constant rate as that of the "bred modes" from the initial time to the final time of the forecast and is therefore characterized by a sustained phase of error growth. In this sense, the AI mode based on Lagrangian dynamics of the perturbation velocity orientation provides a rationale of the "bred mode" behavior.

  3. Geophysical Investigation of Avon Valley, West-Central Montana, using Gravity and Seismic Reflection Profiling

    NASA Astrophysics Data System (ADS)

    Knatterud, L.; Mosolf, J.; Speece, M. A.; Zhou, X.

    2014-12-01

    The Avon Valley and adjacent mountains in west-central Montana lie within the Lewis and Clark Line, a major system of WNW-striking faults and folds that transect the more northerly structural grain of the northern Rockies and represent alternating episodes of transtensional and transpressional deformation. The northwest-trending valley has been previously interpreted as an extensional half graben filled with Tertiary sedimentary and volcanic deposits; however, little-to-no geophysical constraints on basin architecture or the thickness of Tertiary fill have been reported. A major northwest-striking fault with significant normal displacement clearly bounds the valley to the northeast, juxtaposing Tertiary sedimentary deposits against Proterozoic-Mesozoic units deformed by shortening structures and crosscut by Cretaceous granitic intrusions. Tertiary volcanic deposits unconformably overlying faulted and folded Phanerozoic-Proterozoic sequences in the eastern Garnet Range bound the valley to the southwest, but in the past no faults had been mapped along this margin. New mapping by the Montana Bureau of Mines and Geology (MBMG) has identified a system of high-angle, northwest- and northeast-striking, oblique-slip faults along the southwest border of the Avon calling into question if the valley is a half, full, or asymmetrical graben. Geophysical data has recently been acquired by Montana Tech to help define the structural architecture of the Avon Valley and the thickness of its Tertiary fill. Gravity data and a short seismic reflection profile have been collected and a preliminary interpretation of these data indicates a half graben with a series of normal faults bounding the western side of the valley. Ongoing gravity data collection throughout 2014 should refine this interpretation by better defining the bedrock-Tertiary interface at depth.

  4. Double coding and mapping using Abbreviated Injury Scale 1998 and 2005: identifying issues for trauma data.

    PubMed

    Palmer, Cameron S; Niggemeyer, Louise E; Charman, Debra

    2010-09-01

    The 2005 version of the Abbreviated Injury Scale (AIS05) potentially represents a significant change in injury spectrum classification, due to a substantial increase in the codeset size and alterations to the agreed severity of many injuries compared to the previous version (AIS98). Whilst many trauma registries around the world are moving to adopt AIS05 or its 2008 update (AIS08), its effect on patient classification in existing registries, and the optimum method of comparing existing data collections with new AIS05 collections are unknown. The present study aimed to assess the potential impact of adopting the AIS05 codeset in an established trauma system, and to identify issues associated with this change. A current subset of consecutive major trauma patients admitted to two large hospitals in the Australian state of Victoria were double-coded in AIS98 and AIS05. Assigned codesets were also mapped to the other AIS version using code lists supplied in the AIS05 manual, giving up to four AIS codes per injury sustained. Resulting codesets were assessed for agreement in codes used, injury severity and calculated severity scores. 602 injuries sustained by 109 patients were compared. Adopting AIS05 would lead to a decrease in the number of designated major trauma patients in Victoria, estimated at 22% (95% confidence interval, 15-31%). Differences in AIS level between versions were significantly more likely to occur amongst head and chest injuries. Data mapped to a different codeset performed better in paired comparisons than raw AIS98 and AIS05 codesets, with data mapping of AIS05 codes back to AIS98 giving significantly higher levels of agreement in AIS level, ISS and NISS than other potential comparisons, and resulting in significantly fewer conversion problems than attempting to map AIS98 codes to AIS05. This study provides new insights into AIS codeset change impact. Adoption of AIS05 or AIS08 in established registries will decrease major trauma patient numbers. Code mapping between AIS versions can improve comparisons between datasets in different AIS versions, although the injury profile of a trauma population will affect the degree of comparability. At present, mapping AIS05 data back to AIS98 is recommended. 2009 Elsevier Ltd. All rights reserved.

  5. Architecture of a Diels-Alderase ribozyme with a preformed catalytic pocket.

    PubMed

    Keiper, Sonja; Bebenroth, Dirk; Seelig, Burckhard; Westhof, Eric; Jäschke, Andres

    2004-09-01

    Artificial ribozymes catalyze a variety of chemical reactions. Their structures and reaction mechanisms are largely unknown. We have analyzed a ribozyme catalyzing Diels-Alder cycloaddition reactions by comprehensive mutation analysis and a variety of probing techniques. New tertiary interactions involving base pairs between nucleotides of the 5' terminus and a large internal loop forming a pseudoknot fold were identified. The probing data indicate a preformed tertiary structure that shows no major changes on substrate or product binding. Based on these observations, a molecular architecture featuring a Y-shaped arrangement is proposed. The tertiary structure is formed in a rather unusual way; that is, the opposite sides of the asymmetric internal loop are clamped by the four 5'-terminal nucleotides, forming two adjacent two base-pair helices. It is proposed that the catalytic pocket is formed by a wedge within one of these helices.

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

    Xiong, J.-P.; Stehle, T.; Zhang, R.

    The structural basis for the divalent cation-dependent binding of heterodimeric alpha beta integrins to their ligands, which contain the prototypical Arg-Gly-Asp sequence, is unknown. Interaction with ligands triggers tertiary and quaternary structural rearrangements in integrins that are needed for cell signaling. Here we report the crystal structure of the extracellular segment of integrin alpha Vbeta 3 in complex with a cyclic peptide presenting the Arg-Gly-Asp sequence. The ligand binds at the major interface between the alpha V and beta 3 subunits and makes extensive contacts with both. Both tertiary and quaternary changes are observed in the presence of ligand. Themore » tertiary rearrangements take place in beta A, the ligand-binding domain of beta 3; in the complex, beta A acquires two cations, one of which contacts the ligand Asp directly and the other stabilizes the ligand-binding surface. Ligand binding induces small changes in the orientation of alpha V relative to beta 3.« less

  7. Growth and characterization of epitaxial silver indium diselenide

    NASA Astrophysics Data System (ADS)

    Pena Martin, Pamela

    Photovoltaics (solar cells) are a key player in the renewable energy frontier, and will become increasingly important as their cost per watt continues to drop, especially if fossil fuel costs increase. One particularly promising photovoltaic technology is based on chalcopyrite-structure semiconductors. Within the chalcopyrite compounds the highest efficiency thin film solar cell absorber material to date is Cu(In,Ga)Se2 (CIGS). While current efficiency records are over 21% for single-junction cells, there is still room for improvement. Replacing some of the Cu with Ag has been shown to be beneficial in CIGS devices. However, the Ag- containing chalcopyrites are still relatively unknown in terms of their growth mechanism, energetics, and surface atomic and electronic properties. These are best inferred through study of epitaxial films, yet they have little mention in literature and have not been the subject of a detailed study. This work describes the growth of epitaxial AgInSe2 (AIS) on GaAs substrates, studying the morphology, structure, and surface properties to understand how growth takes place. It also seeks to experimentally determine the surface electronic and atomic structure at the atomic scale to gain insight into the part of the material that forms the heterojunction that collects photon energy in the device. Finally, this work seeks to compare and contrast these findings with what is known about CIGS to determine where similarities and, more importantly, the differences may lie. This study has found that single phase tetragonal AIS can be epitaxially grown on GaAs, as illustrated by x-ray diffraction (XRD), transmission electron microscope (TEM), and surface morphology data. Like CIGS, the close packed polar (112) planes have the lowest energy. The morphology points to a difference in step dynamics, leading to less faceted, straight edged island shapes compared to CIGS. Epitaxial temperature as a function of growth direction shows a different trend in AIS than in CIGS. Interdiffusion of the group III elements across the substrate interface was found to result in an epitaxial intermixed layer between the film and substrate in some cases, which may help mediate the lattice mismatch. At the atomic scale, scanning tunneling microscopy (STM) was used to observe details of the surface morphology, which indicated growth of the (112)A orientation of AIS by a screw dislocation mechanism (other surfaces were not examined by STM but are expected to show similar results). The surface atomic structure was directly imaged for the first time, revealing an arrangement similar to that expected from a bulk terminated surface. The electronic structure shows a gap in surface electronic states with a width comparable to bulk AIS, n-type conduction, and a tail of states near the valence band edge that decay well into the gap. The conduction and valence bands show fluctuations as a function of position on the surface, with greater magnitude in the valence band. The fluctuations in both bands are less than those observed on the surface of CIS by STM. It seems to indicate a reduction in band tails, both in magnitude and spacial extent, in AIS compared to CIS, likely tied to a reduction in point defect concentration at the surface.

  8. Tertiary structure-based analysis of microRNA–target interactions

    PubMed Central

    Gan, Hin Hark; Gunsalus, Kristin C.

    2013-01-01

    Current computational analysis of microRNA interactions is based largely on primary and secondary structure analysis. Computationally efficient tertiary structure-based methods are needed to enable more realistic modeling of the molecular interactions underlying miRNA-mediated translational repression. We incorporate algorithms for predicting duplex RNA structures, ionic strength effects, duplex entropy and free energy, and docking of duplex–Argonaute protein complexes into a pipeline to model and predict miRNA–target duplex binding energies. To ensure modeling accuracy and computational efficiency, we use an all-atom description of RNA and a continuum description of ionic interactions using the Poisson–Boltzmann equation. Our method predicts the conformations of two constructs of Caenorhabditis elegans let-7 miRNA–target duplexes to an accuracy of ∼3.8 Å root mean square distance of their NMR structures. We also show that the computed duplex formation enthalpies, entropies, and free energies for eight miRNA–target duplexes agree with titration calorimetry data. Analysis of duplex–Argonaute docking shows that structural distortions arising from single-base-pair mismatches in the seed region influence the activity of the complex by destabilizing both duplex hybridization and its association with Argonaute. Collectively, these results demonstrate that tertiary structure-based modeling of miRNA interactions can reveal structural mechanisms not accessible with current secondary structure-based methods. PMID:23417009

  9. Rapid search for tertiary fragments reveals protein sequence–structure relationships

    PubMed Central

    Zhou, Jianfu; Grigoryan, Gevorg

    2015-01-01

    Finding backbone substructures from the Protein Data Bank that match an arbitrary query structural motif, composed of multiple disjoint segments, is a problem of growing relevance in structure prediction and protein design. Although numerous protein structure search approaches have been proposed, methods that address this specific task without additional restrictions and on practical time scales are generally lacking. Here, we propose a solution, dubbed MASTER, that is both rapid, enabling searches over the Protein Data Bank in a matter of seconds, and provably correct, finding all matches below a user-specified root-mean-square deviation cutoff. We show that despite the potentially exponential time complexity of the problem, running times in practice are modest even for queries with many segments. The ability to explore naturally plausible structural and sequence variations around a given motif has the potential to synthesize its design principles in an automated manner; so we go on to illustrate the utility of MASTER to protein structural biology. We demonstrate its capacity to rapidly establish structure–sequence relationships, uncover the native designability landscapes of tertiary structural motifs, identify structural signatures of binding, and automatically rewire protein topologies. Given the broad utility of protein tertiary fragment searches, we hope that providing MASTER in an open-source format will enable novel advances in understanding, predicting, and designing protein structure. PMID:25420575

  10. Design, synthesis, and spectroscopic study of some new flavones containing two azo linkages

    NASA Astrophysics Data System (ADS)

    Ayoob, Mzgin Mohammed; Hawaiz, Farouq Emam

    2017-09-01

    In the present study; 5-(4-chlorophenyl azo) -2-hydroxy acetophenone (1) was prepared by diazotization of 4-chloro aniline and its coupling reaction with 2-hydroxy acetophenone, then reacted with different azo benzyloxy benzaldehydes(3a-i) to give new synthesized 2-hydroxy chalcones(4a-i). The later compounds were subjected to oxidative cyclization by catalytic amount of I2 in DMSO affording the target molecules new flavones bearing two azo-linkages (5a-i). The structures of the newly synthesized compounds were identified on the bases of their FT-IR, 1H-NMR, 13C-NMR and DEPT-135 spectra. The synthesized Flavone derivatives were evaluated against two types of bacteria gram positive (Staphylococcus aurous) and gram negative (Pseudomonas aeruginosa). The results showed that most of the synthesized flavones are more sensitive against (G -ve) bacteria than (G +ve) bacteria.

  11. Induction of Female-to-Male Sex Change in Adult Zebrafish by Aromatase Inhibitor Treatment

    NASA Astrophysics Data System (ADS)

    Takatsu, Kanae; Miyaoku, Kaori; Roy, Shimi Rani; Murono, Yuki; Sago, Tomohiro; Itagaki, Hideyuki; Nakamura, Masaru; Tokumoto, Toshinobu

    2013-12-01

    This study investigated whether undifferentiated germ and/or somatic stem cells remain in the differentiated ovary of a species that does not undergo sex changes under natural conditions and retain their sexual plasticity. The effect of aromatase inhibitor (AI)-treatment on sexually mature female zebrafish was examined. A 5-month AI treatment caused retraction of the ovaries after which testes-like organs appeared, and cyst structures filled with spermatozoa-like cells were observed in sections of these tissues. Electron microscopic observations revealed that these cells appeared as large sperm heads without tails. Sperm formation was re-examined after changing the diet to an AI-free food. A large number of normal sperm were obtained after eight weeks, and no formation of ovarian tissue was observed. Artificial fertilization using sperm from the sex-changed females was successful. These results demonstrated that sex plasticity remains in the mature ovaries of this species.

  12. Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

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

    Neiditch,M.; Federle, M.; Pompeani, A.

    2006-01-01

    Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement inmore » which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.« less

  13. High-Resolution Triple Resonance Autoionization of Uranium Isotopes

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

    Schumann, Philipp G.; Wendt, K; Bushaw, Bruce A.

    2005-11-01

    The near-threshold autoionization (AI) spectrum of uranium has been investigated by triple-resonance excitation with single-mode continuous lasers. Spectra were recorded over the first {approx}30 cm-1 above the first ionization limit at a resolution of 3x10-4 cm 1 using intermediate states with different J values (6, 7, 8) to assign AI level total angular momentum JAI = 5 to 9. Resonances with widths ranging from 8 MHz to 30 GHz were observed; the strongest ones have JAI = 9 and widths of {approx} 60 MHz. Hyperfine structures for 235U and isotope shifts for 234,235U have been measured in the two intermediatemore » levels and in the final AI level for the most favorable excitation path. These measurements were performed using aqueous samples containing sub-milligram quantities of uranium at natural isotopic abundances, indicating the potential of this approach for trace isotope ratio determinations.« less

  14. Artificial intelligence approaches for rational drug design and discovery.

    PubMed

    Duch, Włodzisław; Swaminathan, Karthikeyan; Meller, Jarosław

    2007-01-01

    Pattern recognition, machine learning and artificial intelligence approaches play an increasingly important role in rational drug design, screening and identification of candidate molecules and studies on quantitative structure-activity relationships (QSAR). In this review, we present an overview of basic concepts and methodology in the fields of machine learning and artificial intelligence (AI). An emphasis is put on methods that enable an intuitive interpretation of the results and facilitate gaining an insight into the structure of the problem at hand. We also discuss representative applications of AI methods to docking, screening and QSAR studies. The growing trend to integrate computational and experimental efforts in that regard and some future developments are discussed. In addition, we comment on a broader role of machine learning and artificial intelligence approaches in biomedical research.

  15. AI tools in computer based problem solving

    NASA Technical Reports Server (NTRS)

    Beane, Arthur J.

    1988-01-01

    The use of computers to solve value oriented, deterministic, algorithmic problems, has evolved a structured life cycle model of the software process. The symbolic processing techniques used, primarily in research, for solving nondeterministic problems, and those for which an algorithmic solution is unknown, have evolved a different model, much less structured. Traditionally, the two approaches have been used completely independently. With the advent of low cost, high performance 32 bit workstations executing identical software with large minicomputers and mainframes, it became possible to begin to merge both models into a single extended model of computer problem solving. The implementation of such an extended model on a VAX family of micro/mini/mainframe systems is described. Examples in both development and deployment of applications involving a blending of AI and traditional techniques are given.

  16. A modified artificial immune system based pattern recognition approach -- an application to clinic diagnostics

    PubMed Central

    Zhao, Weixiang; Davis, Cristina E.

    2011-01-01

    Objective This paper introduces a modified artificial immune system (AIS)-based pattern recognition method to enhance the recognition ability of the existing conventional AIS-based classification approach and demonstrates the superiority of the proposed new AIS-based method via two case studies of breast cancer diagnosis. Methods and materials Conventionally, the AIS approach is often coupled with the k nearest neighbor (k-NN) algorithm to form a classification method called AIS-kNN. In this paper we discuss the basic principle and possible problems of this conventional approach, and propose a new approach where AIS is integrated with the radial basis function – partial least square regression (AIS-RBFPLS). Additionally, both the two AIS-based approaches are compared with two classical and powerful machine learning methods, back-propagation neural network (BPNN) and orthogonal radial basis function network (Ortho-RBF network). Results The diagnosis results show that: (1) both the AIS-kNN and the AIS-RBFPLS proved to be a good machine leaning method for clinical diagnosis, but the proposed AIS-RBFPLS generated an even lower misclassification ratio, especially in the cases where the conventional AIS-kNN approach generated poor classification results because of possible improper AIS parameters. For example, based upon the AIS memory cells of “replacement threshold = 0.3”, the average misclassification ratios of two approaches for study 1 are 3.36% (AIS-RBFPLS) and 9.07% (AIS-kNN), and the misclassification ratios for study 2 are 19.18% (AIS-RBFPLS) and 28.36% (AIS-kNN); (2) the proposed AIS-RBFPLS presented its robustness in terms of the AIS-created memory cells, showing a smaller standard deviation of the results from the multiple trials than AIS-kNN. For example, using the result from the first set of AIS memory cells as an example, the standard deviations of the misclassification ratios for study 1 are 0.45% (AIS-RBFPLS) and 8.71% (AIS-kNN) and those for study 2 are 0.49% (AIS-RBFPLS) and 6.61% (AIS-kNN); and (3) the proposed AIS-RBFPLS classification approaches also yielded better diagnosis results than two classical neural network approaches of BPNN and Ortho-RBF network. Conclusion In summary, this paper proposed a new machine learning method for complex systems by integrating the AIS system with RBFPLS. This new method demonstrates its satisfactory effect on classification accuracy for clinical diagnosis, and also indicates its wide potential applications to other diagnosis and detection problems. PMID:21515033

  17. Theoretical studies for excited-state tautomerization in the 7-azaindole-(CH3OH)n (n = 1 and 2) complexes in the gas phase.

    PubMed

    Fang, Hua; Kim, Yongho

    2011-12-01

    The excited-state tautomerization of 7-azaindole (7AI) complexes bonded with either one or two methanol molecule(s) was studied by systematic quantum mechanical calculations in the gas phases. Electronic structures and energies for the reactant, transition state (TS), and product were computed at the complete active space self-consistent field (CASSCF) levels with the second-order multireference perturbation theory (MRPT2) to consider the dynamic electron correlation. The time-dependent density functional theory (TDDFT) was also used for comparison. The excited-state double proton transfer (ESDPT) in 7AI-CH(3)OH occurs in a concerted but asynchronous mechanism. Similarly, such paths are also found in the two transition states during the excited-state triple proton transfer (ESTPT) of the 7AI-(CH(3)OH)(2) complex. In the first TS, the pyrrole ring proton first migrated to methanol, while in the second the methanol proton moved first to the pyridine ring. The CASSCF level with the MRPT2 correction showed that the former path was much preferable to the latter, and the ESDPT is much slower than the ESTPT. Additionally, the vibrational-mode enhanced tautomerization in the 7AI-(CH(3)OH)(2) complex was also studied. We found that the excitation of the low-frequency mode shortens the reaction path to increase the tautomerization rate. Overall, most TDDFT methods used in this study predicted different TS structures and barriers from the CASSCF methods with MRPT2 corrections. © 2011 American Chemical Society

  18. Development and validation of a complementary map to enhance the existing 1998 to 2008 Abbreviated Injury Scale map

    PubMed Central

    2011-01-01

    Introduction Many trauma registries have used the Abbreviated Injury Scale 1990 Revision Update 98 (AIS98) to classify injuries. In the current AIS version (Abbreviated Injury Scale 2005 Update 2008 - AIS08), injury classification and specificity differ substantially from AIS98, and the mapping tools provided in the AIS08 dictionary are incomplete. As a result, data from different AIS versions cannot currently be compared. The aim of this study was to develop an additional AIS98 to AIS08 mapping tool to complement the current AIS dictionary map, and then to evaluate the completed map (produced by combining these two maps) using double-coded data. The value of additional information provided by free text descriptions accompanying assigned codes was also assessed. Methods Using a modified Delphi process, a panel of expert AIS coders established plausible AIS08 equivalents for the 153 AIS98 codes which currently have no AIS08 map. A series of major trauma patients whose injuries had been double-coded in AIS98 and AIS08 was used to assess the maps; both of the AIS datasets had already been mapped to another AIS version using the AIS dictionary maps. Following application of the completed (enhanced) map with or without free text evaluation, up to six AIS codes were available for each injury. Datasets were assessed for agreement in injury severity measures, and the relative performances of the maps in accurately describing the trauma population were evaluated. Results The double-coded injuries sustained by 109 patients were used to assess the maps. For data conversion from AIS98, both the enhanced map and the enhanced map with free text description resulted in higher levels of accuracy and agreement with directly coded AIS08 data than the currently available dictionary map. Paired comparisons demonstrated significant differences between direct coding and the dictionary maps, but not with either of the enhanced maps. Conclusions The newly-developed AIS98 to AIS08 complementary map enabled transformation of the trauma population description given by AIS98 into an AIS08 estimate which was statistically indistinguishable from directly coded AIS08 data. It is recommended that the enhanced map should be adopted for dataset conversion, using free text descriptions if available. PMID:21548991

  19. Development and validation of a complementary map to enhance the existing 1998 to 2008 Abbreviated Injury Scale map.

    PubMed

    Palmer, Cameron S; Franklyn, Melanie; Read-Allsopp, Christine; McLellan, Susan; Niggemeyer, Louise E

    2011-05-08

    Many trauma registries have used the Abbreviated Injury Scale 1990 Revision Update 98 (AIS98) to classify injuries. In the current AIS version (Abbreviated Injury Scale 2005 Update 2008 - AIS08), injury classification and specificity differ substantially from AIS98, and the mapping tools provided in the AIS08 dictionary are incomplete. As a result, data from different AIS versions cannot currently be compared. The aim of this study was to develop an additional AIS98 to AIS08 mapping tool to complement the current AIS dictionary map, and then to evaluate the completed map (produced by combining these two maps) using double-coded data. The value of additional information provided by free text descriptions accompanying assigned codes was also assessed. Using a modified Delphi process, a panel of expert AIS coders established plausible AIS08 equivalents for the 153 AIS98 codes which currently have no AIS08 map. A series of major trauma patients whose injuries had been double-coded in AIS98 and AIS08 was used to assess the maps; both of the AIS datasets had already been mapped to another AIS version using the AIS dictionary maps. Following application of the completed (enhanced) map with or without free text evaluation, up to six AIS codes were available for each injury. Datasets were assessed for agreement in injury severity measures, and the relative performances of the maps in accurately describing the trauma population were evaluated. The double-coded injuries sustained by 109 patients were used to assess the maps. For data conversion from AIS98, both the enhanced map and the enhanced map with free text description resulted in higher levels of accuracy and agreement with directly coded AIS08 data than the currently available dictionary map. Paired comparisons demonstrated significant differences between direct coding and the dictionary maps, but not with either of the enhanced maps. The newly-developed AIS98 to AIS08 complementary map enabled transformation of the trauma population description given by AIS98 into an AIS08 estimate which was statistically indistinguishable from directly coded AIS08 data. It is recommended that the enhanced map should be adopted for dataset conversion, using free text descriptions if available.

  20. Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

    PubMed Central

    Marques, João C.; Lamosa, Pedro; Russell, Caitlin; Ventura, Rita; Maycock, Christopher; Semmelhack, Martin F.; Miller, Stephen T.; Xavier, Karina B.

    2011-01-01

    The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsible for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior. PMID:21454635

  1. Role of urea on recombinant Apo A-I stability and its utilization in anion exchange chromatography.

    PubMed

    Angarita, Monica; Arosio, Paolo; Müller-Späth, Thomas; Baur, Daniel; Falkenstein, Roberto; Kuhne, Wolfgang; Morbidelli, Massimo

    2014-08-08

    Apolipoprotein A-I (Apo A-I) is an important lipid-binding protein involved in the transport and metabolism of cholesterol. High protein purity, in particular with respect to endotoxins is required for therapeutic applications. The use of urea during the purification process of recombinant Apo A-I produced in Escherichia coli has been suggested so as to provide high endotoxin clearance. In this work, we show that urea can be used as a sole modifier during the ion exchange chromatographic purification of Apo A-I and we investigate the molecular mechanism of elution by correlating the effect of urea on self-association, conformation and adsorption equilibrium properties of a modified model Apo A-I. In the absence of urea the protein was found to be present as a population of oligomers represented mainly by trimers, hexamers and nonamers. The addition of urea induced oligomer dissociation and protein structure unfolding. We correlated the changes in protein association and conformation with variations of the adsorption equilibrium of the protein on a strong anion exchanger. It was confirmed that the adsorption isotherms, described by a Langmuir model, were dependent on both protein and urea concentrations. Monomers, observed at low urea concentration (0.5M), were characterized by larger binding affinity and adsorption capacity compared to both protein oligomers (0M) and unfolded monomers (2-8M). The reduction of both the binding strength and maximum adsorption capacity at urea concentrations larger than 0.5M explains the ability of urea of inducing elution of the protein from the ion exchange resin. The dissociation of the protein complexes occurring during the elution could likely be the origin of the effective clearance of endotoxins originally trapped inside the oligomers. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Apoptotic mechanisms after repeated noise trauma in the mouse medial geniculate body and primary auditory cortex.

    PubMed

    Fröhlich, Felix; Ernst, Arne; Strübing, Ira; Basta, Dietmar; Gröschel, Moritz

    2017-12-01

    A correlation between noise-induced apoptosis and cell loss has previously been shown after a single noise exposure in the cochlear nucleus, inferior colliculus, medial geniculate body (MGB) and primary auditory cortex (AI). However, repeated noise exposure is the most common situation in humans and a major risk factor for the induction of noise-induced hearing loss (NIHL). The present investigation measured cell death pathways using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in the dorsal, medial and ventral MGB (dMGB, mMGB and vMGB) and six layers of the AI (AI-1 to AI-6) in mice (NMRI strain) after a second noise exposure (double-exposure group). Therefore, a single noise exposure group has been investigated 7 (7-day-group-single) or 14 days (14-day-group-single) after noise exposure (3 h, 5-20 kHz, 115 dB SPL peak-to-peak). The double-exposure group received the same noise trauma for a second time 7 days after the initial exposure and was either TUNEL-stained immediately (7-day-group-double) or 1 week later (14-day-group-double) and data were compared to the corresponding single-trauma group as well as to an unexposed control group. It was shown that TUNEL increased immediately after the second noise exposure in AI-3 and stayed upregulated in the 14-day-group-double. A significant increase in TUNEL was also seen in the 14-day-group-double in vMGB, mMGB and AI-1. The present results show for the first time the influence of a repeated noise trauma on cell death mechanisms in thalamic and cortical structures and might contribute to the understanding of pathophysiological findings and psychoacoustic phenomena accompanying NIHL.

  3. Processing the Interspecies Quorum-sensing Signal Autoinducer-2 (AI-2)

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

    J Marques; P Lamosa; C Russell

    The molecule (S)-4,5-dihydroxy-2,3-pentanedione (DPD) is produced by many different species of bacteria and is the precursor of the signal molecule autoinducer-2 (AI-2). AI-2 mediates interspecies communication and facilitates regulation of bacterial behaviors such as biofilm formation and virulence. A variety of bacterial species have the ability to sequester and process the AI-2 present in their environment, thereby interfering with the cell-cell communication of other bacteria. This process involves the AI-2-regulated lsr operon, comprised of the Lsr transport system that facilitates uptake of the signal, a kinase that phosphorylates the signal to phospho-DPD (P-DPD), and enzymes (like LsrG) that are responsiblemore » for processing the phosphorylated signal. Because P-DPD is the intracellular inducer of the lsr operon, enzymes involved in P-DPD processing impact the levels of Lsr expression. Here we show that LsrG catalyzes isomerization of P-DPD into 3,4,4-trihydroxy-2-pentanone-5-phosphate. We present the crystal structure of LsrG, identify potential catalytic residues, and determine which of these residues affects P-DPD processing in vivo and in vitro. We also show that an lsrG deletion mutant accumulates at least 10 times more P-DPD than wild type cells. Consistent with this result, we find that the lsrG mutant has increased expression of the lsr operon and an altered profile of AI-2 accumulation and removal. Understanding of the biochemical mechanisms employed by bacteria to quench signaling of other species can be of great utility in the development of therapies to control bacterial behavior.« less

  4. Double insemination and gonadotropin-releasing hormone treatment of repeat-breeding dairy cattle.

    PubMed

    Stevenson, J S; Call, E P; Scoby, R K; Phatak, A P

    1990-07-01

    Our objective was to determine if double inseminations during the same estrous period of dairy cattle eligible for their third or fourth service (repeat breeders) would improve pregnancy rates equivalent to injections of GnRH given at the time of AI. Repeat-breeding, lactating cows from six herds (five herds in the San Joaquin Valley of central California and one herd in northeast Kansas) were assigned randomly to four treatment groups when detected in estrus: 1) single AI plus no injection, 2) single AI plus 100 micrograms GnRH at AI, 3) double AI plus no injection, or 4) double AI plus 100 micrograms of GnRH at AI. Inseminations were performed according to the a.m.-p.m. rule. The second AI for the double AI treatment was given 12 to 16 h after the first AI. Injections of GnRH were given intramuscularly immediately following the single AI or the first AI of the double AI. Pregnancy rates of cows given a single AI and hormone injection were numerically higher in all six herds than those of their herdmates given only a single AI. In five of six herds, the pregnancy rates of cows given a double AI and hormone injection were numerically higher than pregnancy rates of their herdmates given only a double AI. Overall pregnancy rates for the four treatments were 1) 112/353 (32.1%), 2) 165/406 (41.6%), 3) 119/364 (33.5%), and 4) 135/359 (37.5%). Gonadotropin-releasing hormone increased pregnancy rates of repeat breeders compared with controls given only a single AI. No further benefit beyond the single AI was accrued from the double AI treatment, with or without concurrent hormone administration.

  5. Growing our own: building a native research team.

    PubMed

    Gray, Jacqueline S; Carter, Paula M

    2012-01-01

    In 2006, American Indian/Alaska Natives (AI/AN) made up less than 1% of the science, engineering and health doctorates in the U.S. Early introduction of AI/AN students to research and continued opportunities are necessary to develop successful AI/AN researchers who can better serve their communities. This team was developed to form a cohort of American Indian students, staff and faculty interested in research and becoming researchers. Since implementation, the program grew from one student to over 20 AI students ranging from freshmen just entering college to doctoral students working to complete their dissertations. This article highlights the team growth, increasing structure, student needs and the faculty and staff involved. It further addresses the support and educational aspects of growing an ongoing, multidisciplinary research team committed to ethical research in Native communities. The team addresses substance use prevalence, the relationship of substance abuse to other mental health diagnoses, and treatment issues. The team includes weekly team meetings, a Blackboard site on the Internet that is populated with resources and focused on sharing materials and information, a weekly journal club discussion of research articles, and collaborative discussions on each project and the barriers and challenges that need to be addressed to move forward.

  6. Experimental results of sodium-water reaction test No. 3 in LLTR

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

    Miller, A.E.; Neely, H.H.

    1977-08-01

    Computer-generated plots of the transient data obtained during the third sodium-water reaction test (SWR-3) and observations made after the test are presented. Similar to the first two tests of Series I, a double-ended guillotine rupture was produced in a water tube of the Atomics International Modular Steam Generator (AI-MSG). Prior to tube rupture, the temperature distribution in the vertical AI-MSG was linear from 600/sup 0/F at the bottom to 800/sup 0/F at the top. The rupture was located in the horizontal section 1.75 in. from the upper tubesheet. Peak pressures generated in this test were somewhat lower than the 400more » psi and 500 psi measured in the prior tests; while peak temperatures, about 1600/sup 0/F, were higher than were measured previously. The interest examinations revealed no structural damage, material wastage, stress corrosion cracking, or dimensional changes. Additional reaction products have been accumulated in the bottom of the AI-MSG up to Spacer 3, so that the flow path in the AI-MSG to both the lower relief line and the drain line is restricted. The relief lines are relatively clear.« less

  7. Aesthetic and Functional Rehabilitation of the Primary Dentition Affected by Amelogenesis Imperfecta

    PubMed Central

    Marquezin, Maria Carolina Salomé; Zancopé, Bruna Raquel; Pacheco, Larissa Ferreira; Gavião, Maria Beatriz Duarte; Pascon, Fernanda Miori

    2015-01-01

    The objective of this case report was to describe the oral rehabilitation of a five-year-old boy patient diagnosed with amelogenesis imperfecta (AI) in the primary dentition. AI is a group of hereditary disorders that affects the enamel structure. The patient was brought to the dental clinic complaining of tooth hypersensitivity during meals. The medical history and clinical examination were used to arrive at the diagnosis of AI. The treatment was oral rehabilitation of the primary molars with stainless steel crowns and resin-filled celluloid forms. The main objectives of the selected treatment were to enhance the esthetics, restore masticatory function, and eliminate the teeth sensitivity. The child was monitored in the pediatric dentistry clinic at four-month intervals until the mixed dentition stage. Treatment not only restored function and esthetic, but also showed a positive psychological impact and thereby improved perceived quality of life. The preventive, psychological, and curative measures of a young child with AI were successful. This result can encourage the clinicians to seek a cost-effective technique such as stainless steel crowns, and resin-filled celluloid forms to reestablish the oral functions and improve the child's psychosocial development. PMID:25705526

  8. The AIS-2005 Revision in Severe Traumatic Brain Injury: Mission Accomplished or Problems for Future Research?

    PubMed Central

    Carroll, Christopher P.; Cochran, Joseph A.; Price, Janet P.; Guse, Clare E.; Wang, Marjorie C.

    2010-01-01

    The Abbreviated Injury Scale (AIS) is commonly used to score injury severity and describe types of injuries. In 2005, the AIS-Head section was revised to capture more detailed information about head injuries and to better reflect their clinical severity, but the impact of these changes is largely unknown. The purpose of this study was to compare AIS-1998 and AIS-2005 coding of traumatic brain injuries (TBI) using medical records at a single Level I trauma center. We included patients with severe TBI (Glasgow Coma Scale 3–8) after blunt injury, excluding those who were missing medical records. Detailed descriptions of injuries were collected, then manually coded into AIS-1998 and AIS-2005 by the same Certified AIS Specialist. Compared to AIS-1998, AIS-2005 coded the same injuries with lower severity scores [p<0.01] and with decreased mean and maximum AIS-Head scores [p<0.01]. Of the types of traumatic brain injuries, most of the changes occurred among cerebellar and cerebral injuries. Traumatic hypoxic brain injury secondary to systemic dysfunction was captured by AIS-2005 but not by AIS-1998. However, AIS-2005 captured fewer loss of consciousness cases due to changes in criteria for coding concussive injury. In conclusion, changes from AIS-1998 to AIS-2005 result in significant differences in severity scores and types of injuries captured. This may complicate future TBI research by precluding direct comparison to datasets using AIS-1998. TBIs should be coded into the same AIS-version for comparison or evaluation of trends, and specify which AIS-version is used. PMID:21050606

  9. The AIS-2005 Revision in Severe Traumatic Brain Injury: Mission Accomplished or Problems for Future Research?

    PubMed

    Carroll, Christopher P; Cochran, Joseph A; Price, Janet P; Guse, Clare E; Wang, Marjorie C

    2010-01-01

    The Abbreviated Injury Scale (AIS) is commonly used to score injury severity and describe types of injuries. In 2005, the AIS-Head section was revised to capture more detailed information about head injuries and to better reflect their clinical severity, but the impact of these changes is largely unknown. The purpose of this study was to compare AIS-1998 and AIS-2005 coding of traumatic brain injuries (TBI) using medical records at a single Level I trauma center. We included patients with severe TBI (Glasgow Coma Scale 3-8) after blunt injury, excluding those who were missing medical records. Detailed descriptions of injuries were collected, then manually coded into AIS-1998 and AIS-2005 by the same Certified AIS Specialist. Compared to AIS-1998, AIS-2005 coded the same injuries with lower severity scores [p<0.01] and with decreased mean and maximum AIS-Head scores [p<0.01]. Of the types of traumatic brain injuries, most of the changes occurred among cerebellar and cerebral injuries. Traumatic hypoxic brain injury secondary to systemic dysfunction was captured by AIS-2005 but not by AIS-1998. However, AIS-2005 captured fewer loss of consciousness cases due to changes in criteria for coding concussive injury. In conclusion, changes from AIS-1998 to AIS-2005 result in significant differences in severity scores and types of injuries captured. This may complicate future TBI research by precluding direct comparison to datasets using AIS-1998. TBIs should be coded into the same AIS-version for comparison or evaluation of trends, and specify which AIS-version is used.

  10. Distinct Tertiary Lymphoid Structure Associations and Their Prognostic Relevance in HER2 Positive and Negative Breast Cancers.

    PubMed

    Liu, Xia; Tsang, Julia Y S; Hlaing, Thazin; Hu, Jintao; Ni, Yun-Bi; Chan, Siu Ki; Cheung, Sai Yin; Tse, Gary M

    2017-11-01

    The presence of tumor infiltrating lymphocytes (TIL) is associated with favorable prognosis. Recent evidence suggested that not only their density, but also the spatial organization as tertiary lymphoid structures (TLS), play a key role in determining patient survival. In a cohort of 248 breast cancers, the clinicopathologic association and prognostic role of TLS was examined. Tertiary lymphoid structures were associated with higher tumor grade, apocrine phenotype, necrosis, extensive in situ component, lymphovascular invasion (LVI), and high TIL. For biomarkers, TLS were associated with hormone receptors negativity, HER2 positivity, and c-kit expression. Tertiary lymphoid structures were significantly related to better disease-free survival (DFS) in HER2 positive (HER2+) breast cancers (log-rank = 4.054), which was not dependent on high TIL status. The combined TLS and TIL status was an independent favorable factor associated with DFS in those cases. Interestingly, tumor cell infiltration into the TLS was found in 41.9% of TLS positive cases. It was associated with LVI in HER2 negative (HER2-) TLS positive (particularly estrogen receptor positive [ER+] HER2-) cases. In the ER+ HER2- cases, tumor cell infiltration into TLS was also associated with increased pathologic nodal stage (pN) stage and nodal involvement. Tertiary lymphoid structures showed a similar relationship with clinicopathologic features and biomarkers as TIL. The presence of TLS, irrespective of TIL level, could be an important favorable prognostic indicator in HER2+ breast cancer patients. Given the significance of TLS in promoting effective antitumor immunity, further understanding of its organization and induction may provide new opportunities to improve the current immunotherapy strategies. Despite recent interest on the clinical value of tumor infiltrating lymphocyte (TIL), little was known on the clinical significance on their spatial organization as tertiary lymphoid structures (TLS). Although TLS showed similar relationships with clinicopathologic features and biomarkers as TIL, the prognostic value of TLS, particularly in HER2 positive cancers, was independent of TIL. Moreover, tumor infiltration could be present in TLS which appears to be related to tumor invasion in HER2 negative cancers. Overall, the results demonstrated the additional value for TLS in HER2 cancer subtypes. Further investigations and its standardized evaluation will enhance its use as standard practice. © AlphaMed Press 2017.

  11. Assessment of the effects and limitations of the 1998 to 2008 Abbreviated Injury Scale map using a large population-based dataset.

    PubMed

    Palmer, Cameron S; Franklyn, Melanie

    2011-01-07

    Trauma systems should consistently monitor a given trauma population over a period of time. The Abbreviated Injury Scale (AIS) and derived scores such as the Injury Severity Score (ISS) are commonly used to quantify injury severities in trauma registries. To reflect contemporary trauma management and treatment, the most recent version of the AIS (AIS08) contains many codes which differ in severity from their equivalents in the earlier 1998 version (AIS98). Consequently, the adoption of AIS08 may impede comparisons between data coded using different AIS versions. It may also affect the number of patients classified as major trauma. The entire AIS98-coded injury dataset of a large population based trauma registry was retrieved and mapped to AIS08 using the currently available AIS98-AIS08 dictionary map. The percentage of codes which had increased or decreased in severity, or could not be mapped, was examined in conjunction with the effect of these changes to the calculated ISS. The potential for free text information accompanying AIS coding to improve the quality of AIS mapping was explored. A total of 128280 AIS98-coded injuries were evaluated in 32134 patients, 15471 patients of whom were classified as major trauma. Although only 4.5% of dictionary codes decreased in severity from AIS98 to AIS08, this represented almost 13% of injuries in the registry. In 4.9% of patients, no injuries could be mapped. ISS was potentially unreliable in one-third of patients, as they had at least one AIS98 code which could not be mapped. Using AIS08, the number of patients classified as major trauma decreased by between 17.3% and 30.3%. Evaluation of free text descriptions for some injuries demonstrated the potential to improve mapping between AIS versions. Converting AIS98-coded data to AIS08 results in a significant decrease in the number of patients classified as major trauma. Many AIS98 codes are missing from the existing AIS map, and across a trauma population the AIS08 dataset estimates which it produces are of insufficient quality to be used in practice. However, it may be possible to improve AIS98 to AIS08 mapping to the point where it is useful to established registries.

  12. Assessment of the effects and limitations of the 1998 to 2008 Abbreviated Injury Scale map using a large population-based dataset

    PubMed Central

    2011-01-01

    Background Trauma systems should consistently monitor a given trauma population over a period of time. The Abbreviated Injury Scale (AIS) and derived scores such as the Injury Severity Score (ISS) are commonly used to quantify injury severities in trauma registries. To reflect contemporary trauma management and treatment, the most recent version of the AIS (AIS08) contains many codes which differ in severity from their equivalents in the earlier 1998 version (AIS98). Consequently, the adoption of AIS08 may impede comparisons between data coded using different AIS versions. It may also affect the number of patients classified as major trauma. Methods The entire AIS98-coded injury dataset of a large population based trauma registry was retrieved and mapped to AIS08 using the currently available AIS98-AIS08 dictionary map. The percentage of codes which had increased or decreased in severity, or could not be mapped, was examined in conjunction with the effect of these changes to the calculated ISS. The potential for free text information accompanying AIS coding to improve the quality of AIS mapping was explored. Results A total of 128280 AIS98-coded injuries were evaluated in 32134 patients, 15471 patients of whom were classified as major trauma. Although only 4.5% of dictionary codes decreased in severity from AIS98 to AIS08, this represented almost 13% of injuries in the registry. In 4.9% of patients, no injuries could be mapped. ISS was potentially unreliable in one-third of patients, as they had at least one AIS98 code which could not be mapped. Using AIS08, the number of patients classified as major trauma decreased by between 17.3% and 30.3%. Evaluation of free text descriptions for some injuries demonstrated the potential to improve mapping between AIS versions. Conclusions Converting AIS98-coded data to AIS08 results in a significant decrease in the number of patients classified as major trauma. Many AIS98 codes are missing from the existing AIS map, and across a trauma population the AIS08 dataset estimates which it produces are of insufficient quality to be used in practice. However, it may be possible to improve AIS98 to AIS08 mapping to the point where it is useful to established registries. PMID:21214906

  13. Prediction of protein tertiary structure from sequences using a very large back-propagation neural network

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

    Liu, X.; Wilcox, G.L.

    1993-12-31

    We have implemented large scale back-propagation neural networks on a 544 node Connection Machine, CM-5, using the C language in MIMD mode. The program running on 512 processors performs backpropagation learning at 0.53 Gflops, which provides 76 million connection updates per second. We have applied the network to the prediction of protein tertiary structure from sequence information alone. A neural network with one hidden layer and 40 million connections is trained to learn the relationship between sequence and tertiary structure. The trained network yields predicted structures of some proteins on which it has not been trained given only their sequences.more » Presentation of the Fourier transform of the sequences accentuates periodicity in the sequence and yields good generalization with greatly increased training efficiency. Training simulations with a large, heterologous set of protein structures (111 proteins from CM-5 time) to solutions with under 2% RMS residual error within the training set (random responses give an RMS error of about 20%). Presentation of 15 sequences of related proteins in a testing set of 24 proteins yields predicted structures with less than 8% RMS residual error, indicating good apparent generalization.« less

  14. Long-range AIS message analysis based on the TianTuo-3 micro satellite

    NASA Astrophysics Data System (ADS)

    Li, Shiyou; Chen, Lihu; Chen, Xiaoqian; Zhao, Yong; Bai, Yuzhu

    2017-07-01

    The "Type-27 AIS message" is the long-range AIS broadcast message, which is primarily intended for the long-range detection of AIS typically by satellite. The TT3-AIS uses a four-frequency receiver scheme which includes two frequency channels conventionally applied by the AIS system and two new frequency channels allocated to the long-range AIS broadcast message. To the end of April 2016, the TT3-AIS has already received more than 11,400 packets of Type-27 AIS messages. In this paper, a detailed analysis of the Type-27 AIS messages is performed. Firstly, an eavesdropper diagram of the space-borne AIS received from the worldwide vessels is obtained. Secondly, the analysis to the trend of the number and the ratio of the new-type vessels is performed based on the Type-27 AIS message. The detection probability of the new-type vessels is also discussed. The result would be helpful on the usage of the long-range AIS message both for data application and for the improvement in designing the next space-based AIS receiver.

  15. Secondary and tertiary isoquinoline alkaloids from Xylopia parviflora.

    PubMed

    Nishiyama, Yumi; Moriyasu, Masataka; Ichimaru, Momoyo; Iwasa, Kinuko; Kato, Atsushi; Mathenge, Simon G; Chalo Mutiso, Patrick B; Juma, Francis D

    2006-12-01

    From the secondary and tertiary alkaloidal fractions of the root and the bark of Xylopia parviflora (Annonaceae), the isoquinoline alkaloids, 10,11-dihydroxy-1,2-dimethoxynoraporphine and parvinine were isolated, along with 39 known alkaloids. Their structures were determined on the basis of analysis of spectroscopic data.

  16. Tractography-Based Score for Learning Effective Connectivity From Multimodal Imaging Data Using Dynamic Bayesian Networks.

    PubMed

    Dang, Shilpa; Chaudhury, Santanu; Lall, Brejesh; Roy, Prasun K

    2018-05-01

    Effective connectivity (EC) is the methodology for determining functional-integration among the functionally active segregated regions of the brain. By definition EC is "the causal influence exerted by one neuronal group on another" which is constrained by anatomical connectivity (AC) (axonal connections). AC is necessary for EC but does not fully determine it, because synaptic communication occurs dynamically in a context-dependent fashion. Although there is a vast emerging evidence of structure-function relationship using multimodal imaging studies, till date only a few studies have done joint modeling of the two modalities: functional MRI (fMRI) and diffusion tensor imaging (DTI). We aim to propose a unified probabilistic framework that combines information from both sources to learn EC using dynamic Bayesian networks (DBNs). DBNs are probabilistic graphical temporal models that learn EC in an exploratory fashion. Specifically, we propose a novel anatomically informed (AI) score that evaluates fitness of a given connectivity structure to both DTI and fMRI data simultaneously. The AI score is employed in structure learning of DBN given the data. Experiments with synthetic-data demonstrate the face validity of structure learning with our AI score over anatomically uninformed counterpart. Moreover, real-data results are cross-validated by performing classification-experiments. EC inferred on real fMRI-DTI datasets is found to be consistent with previous literature and show promising results in light of the AC present as compared to other classically used techniques such as Granger-causality. Multimodal analyses provide a more reliable basis for differentiating brain under abnormal/diseased conditions than the single modality analysis.

  17. Changing to AIS 2005 and agreement of injury severity scores in a trauma registry with scores based on manual chart review.

    PubMed

    Stewart, Kenneth E; Cowan, Linda D; Thompson, David M

    2011-09-01

    The Abbreviated Injury Scale (AIS) recently underwent a major revision from AIS 98 to AIS 05. AIS injury codes form the basis of widely used injury severity scores such as the injury severity score (ISS). ISS thresholds are often used in trauma case definitions and ISS is widely used in injury research to adjust for injury severity. This study evaluated changes from AIS 98 to AIS 05, the changes' effect on ISS distributions, and presents an application of the results. Injury descriptions from medical records of 137 randomly selected patients in the Oklahoma Trauma Registry (OTR) were obtained. A single trained coder used AIS 98 and AIS 05 to code each injury. ISS values were calculated and grouped into 4 categories: 1-8, 9-14, 16-24, >24. Paired ISS was compared using Kappa statistics and tests of symmetry. We identified common injury diagnoses for which AIS severity changed between versions. Estimates of the proportion of patients changing ISS groups were applied to the entire OTR to assess the impact on reporting and on a model for reimbursement. OTR AIS 98 and manual AIS 98-based ISS values had a weighted Kappa of 0.71. OTR AIS 98 and manual AIS 05-based ISS values had a Kappa of 0.58. Manual AIS 98 and manual AIS 05 ISS had the highest Kappa of 0.81, however, though the scores differed by only 1 ISS category, there were 30 discordant pairs. The distribution of these discordant pairs was not symmetrical (Bowker's S=30; df=6; p<0.0001) with AIS 05-based ISS values consistently shifted to a lower ISS category. Reductions in AIS severity and ISS values using AIS 05 were common for extremity fractures and thorax injuries. The results suggest fewer patients would be reported to the OTR or be eligible for reimbursement. Changing from AIS 98 to AIS 05 injury coding resulted in systematic changes in AIS codes and ISS. Specific injuries and body regions were differentially affected. Trauma registries and injury researchers that use AIS based injury coding can use this information to evaluate the potential impact of changes in AIS 2005. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. inhibitory effects of citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella enteritidis.

    PubMed

    Zhang, Hongmei; Zhou, Wenyuan; Zhang, Wenyan; Yang, Anlin; Liu, Yanlan; Jiang, Yan; Huang, Shaosong; Su, Jianyu

    2014-06-01

    Biofilms are significant hazards in the food industry. In this study, we investigated the effects of food additive such as citral, cinnamaldehyde, and tea polyphenols on mixed biofilm formation by foodborne Staphylococcus aureus and Salmonella serotype Enteritidis. The adhesion rates of mixed strains in sub-MIC of additives were determined by a microtiter plate assay and bacterial communication signal autoinducer 2 (AI-2) production via a bioluminescence reporter Vibrio harveyi BB170. The structure of mixed biofilm was analyzed using scanning electron microscopy. The effect of the disinfectants hydrogen peroxide, sodium hypochlorite, and peracetic acid was tested on the mixed biofilm. Our results demonstrated that citral, cinnamaldehyde, and tea polyphenols were able to significantly inhibit mixed biofilm formation, while citral could reduce the synthesis of AI-2. Conversely, we observed a significant increase in AI-2 mediated by cinnamaldehyde. Tea polyphenols at lower concentrations induced AI-2 synthesis; however, AI-2 synthesis was significantly inhibited at higher concentrations (300 m g/ml). Food additives inhibited the adhesion of mixed bacteria on stainless steel chips and increased the sensitivity of the mixed biofilm to disinfectants. In conclusion, citral, cinnamaldehyde, and tea polyphenols had strong inhibitory effects on mixed biofilm formation and also enhanced the effect of disinfectant on mixed biofilm formation. This study provides a scientific basis for the application of natural food additives to control biofilm formation of foodborne bacteria.

  19. The Baade-Wesselink projection factor of the δ-Scuti stars AI Vel and β Cas

    NASA Astrophysics Data System (ADS)

    Guiglion, G.; Nardetto, N.; Domiciano de Souza, A.; Mathias, P.; Mourard, D.; Poretti, E.

    2012-12-01

    The Baade-Wesselink method of distance determination is based on the oscillations of pulsating stars. After determining the angular diameter and the linear radius variations, the distance is derived by a simple ratio. The linear radius variation is measured by integrating the pulsation velocity (hereafter V_{puls}) over one pulsating cycle. However, from observations we have only access to the radial velocity (V_{rad}) because of the projection along the line-of-sight. The projection factor, used to convert the radial velocity into the pulsation velocity, is defined by: p = V_{puls} / V_{rad}. We aim to derive the projection factor for two δ-Scuti stars, the high amplitude pulsator AI Vel and the fast rotator β Cas. The geometric component of the projection factor is derived using a limb-darkening model of the intensity distribution of AI Vel, and a fast rotator model for β Cas. Then, by comparing the radial velocity curves of several spectral lines forming at different levels in the atmosphere, we derive directly the velocity gradient (in a part of the atmosphere of the star) using SOPHIE/OHP data for β Cas and HARPS/ESO data for AI Vel, which is used to derive a dynamical projection factor for both stars. We find p = 1.44 ± 0.05 for AI Vel and p = 1.41 ± 0.25 for β Cas. By comparing Cepheids and δ-Scuti stars, these results bring valuable insights into the dynamical structure of pulsating star atmospheres.

  20. Deletion of the steroid-binding domain of the human androgen receptor gene in one family with complete androgen insensitivity syndrome: Evidence for further genetic heterogeneity in this syndrome

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

    Brown, T.R.; Lubahn, D.B.; Wilson, E.M.

    1988-11-01

    The cloning of a cDNA for the human androgen receptor gene has resulted in the availability for cDNA probes that span various parts of the gene, including the entire steroid-binding domain and part of the DNA-binding domain, as well as part of the 5' region of the gene. The radiolabeled probes were used to screen for androgen receptor mutations on Southern blots prepared by restriction endonuclease digestion of genomic DNA from human subjects with complete androgen insensitivity syndrome (AIS). In this investigation, the authors considered only patients presenting complete AIS and with the androgen receptor (-) form as the mostmore » probably subjects to show a gene deletion. One subject from each of six unrelated families with the receptor (-) form of complete AIS and 10 normal subjects were studied. In the 10 normal subjects and in 5 of the 6 patients, identical DNA restriction fragment patterns were observed with EcoRI and BamHI. Analysis of other members of this family confirmed the apparent gene deletion. The data provide direct proof that complete AIS in some families can result from a deletion of the androgen receptor structural gene. However, other families do not demonstrate such a deletion, suggesting that point mutations may also result in the receptor (-) form of complete AIS, adding further to the genetic heterogeneity of this syndrome.« less

  1. Chilean Universities in the Transition to a Market-Driven Policy Regime

    ERIC Educational Resources Information Center

    Katz, Jorge; Spence, Randy

    2009-01-01

    This paper briefly reviews the historical development of the university system in Chile, and describes the current structure of funding, supply and demand for tertiary education, research and university services. Both public and private universities in Chile have expanded and restructured, access to tertiary education has improved, and…

  2. Structural basis of DNA folding and recognition in an AMP-DNA aptamer complex: distinct architectures but common recognition motifs for DNA and RNA aptamers complexed to AMP.

    PubMed

    Lin, C H; Patel, D J

    1997-11-01

    Structural studies by nuclear magnetic resonance (NMR) of RNA and DNA aptamer complexes identified through in vitro selection and amplification have provided a wealth of information on RNA and DNA tertiary structure and molecular recognition in solution. The RNA and DNA aptamers that target ATP (and AMP) with micromolar affinity exhibit distinct binding site sequences and secondary structures. We report below on the tertiary structure of the AMP-DNA aptamer complex in solution and compare it with the previously reported tertiary structure of the AMP-RNA aptamer complex in solution. The solution structure of the AMP-DNA aptamer complex shows, surprisingly, that two AMP molecules are intercalated at adjacent sites within a rectangular widened minor groove. Complex formation involves adaptive binding where the asymmetric internal bubble of the free DNA aptamer zippers up through formation of a continuous six-base mismatch segment which includes a pair of adjacent three-base platforms. The AMP molecules pair through their Watson-Crick edges with the minor groove edges of guanine residues. These recognition G.A mismatches are flanked by sheared G.A and reversed Hoogsteen G.G mismatch pairs. The AMP-DNA aptamer and AMP-RNA aptamer complexes have distinct tertiary structures and binding stoichiometries. Nevertheless, both complexes have similar structural features and recognition alignments in their binding pockets. Specifically, AMP targets both DNA and RNA aptamers by intercalating between purine bases and through identical G.A mismatch formation. The recognition G.A mismatch stacks with a reversed Hoogsteen G.G mismatch in one direction and with an adenine base in the other direction in both complexes. It is striking that DNA and RNA aptamers selected independently from libraries of 10(14) molecules in each case utilize identical mismatch alignments for molecular recognition with micromolar affinity within binding-site pockets containing common structural elements.

  3. Conformational changes of a chemically modified HRP: formation of a molten globule like structure at pH 5

    PubMed Central

    Bamdad, Kourosh; Ranjbar, Bijan; Naderi-Manesh, Hossein; Sadeghi, Mehdi

    2014-01-01

    Horseradish peroxidase is an all alpha-helical enzyme, which widely used in biochemistry applications mainly because of its ability to enhance the weak signals of target molecules. This monomeric heme-containing plant peroxidase is also used as a reagent for the organic synthesis, biotransformation, chemiluminescent assays, immunoassays, bioremediation, and treatment of wastewaters as well. Accordingly, enhancing stability and catalytic activity of this protein for biotechnological uses has been one of the important issues in the field of biological investigations in recent years. In this study, pH-induced structural alterations of native (HRP), and modified (MHRP) forms of Horseradish peroxidase have been investigated. Based on the results, dramatic loss of the tertiary structure and also the enzymatic activity for both forms of enzymes recorded at pH values lower than 6 and higher than 8. Ellipticiy measurements, however, indicated very slight variations in the secondary structure for MHRP at pH 5. Spectroscopic analysis also indicated that melting of the tertiary structure of MHRP at pH 5 starts at around 45 °C, which is associated to the pKa of His 42 that has a serious role in keeping of the heme prostethic group in its native position through natural hydrogen bond network in the enzyme structure. According to our data, a molten globule like structure of a chemically modified form of Horseradish peroxidase at pH 5 with initial steps of conformational transition in tertiary structure with almost no changes in the secondary structure has been detected. Despite of some conformational changes in the tertiary structure of MHRP at pH 5, this modified form still keeps its catalytic activity to some extent besides enhanced thermal stability. These findings also indicated that a molten globular state does not necessarily preclude efficient catalytic activity. PMID:26417287

  4. Modeling Current-Voltage Charateristics of Proteorhodopsin and Bacteriorhodopsin: Towards an Optoelectronics Based on Proteins.

    PubMed

    Alfinito, Eleonora; Reggiani, Lino

    2016-10-01

    Current-voltage characteristics of metal-protein-metal structures made of proteorhodopsin and bacteriorhodopsin are modeled by using a percolation-like approach. Starting from the tertiary structure pertaining to the single protein, an analogous resistance network is created. Charge transfer inside the network is described as a sequential tunneling mechanism and the current is calculated for each value of the given voltage. The theory is validated with available experiments, in dark and light. The role of the tertiary structure of the single protein and of the mechanisms responsible for the photo-activity is discussed.

  5. Space-based detection of spoofing AIS signals using Doppler frequency

    NASA Astrophysics Data System (ADS)

    Guo, Shanzeng

    2014-05-01

    The Automatic Identification System (AIS) is a self-reporting system based on VHF radio to transmit a vessel's identity, position, speed, heading and other parameters to improve maritime domain awareness. However, AIS information can be programmatically spoofed by terrorists or other criminals, who often choose to masquerade as innocent civilians and exploit the vulnerabilities of military and civilian infrastructures for their purposes. Therefore, detecting and localizing a spoofing AIS ship become a critical and challenging issue for maritime security. This paper presents an algorithm to detect and geolocalize a spoofing AIS emitter using space-based AIS signals with its Doppler frequency. With an AIS signal sensor on a fast orbiting satellite, the measured AIS Doppler frequency of an AIS emitter can be used to define a double-napped cone of which the satellite is at its vertex and satellite velocity coincides with its axis, such that the theoretical Doppler frequency derived from the radial velocity to the AIS emitter matches the measured Doppler frequency. All such matches can only lie on either cone extending out from the satellite, which cuts the Earth's surface in two curves, so we know that the AIS emitter must lie somewhere on these curves. Two such AIS Doppler frequency measurements for the same stationary AIS emitter produce two valid curves which intersect at the position of the AIS emitter. Multiple Doppler frequency measurements can be used to better estimate the position fix of an AIS emitter, hence determine the spoofing AIS ship if the estimated position fix unreasonably differs from the position carried in its AIS message. A set of formulas are derived which relate an AIS emitter position to its Doppler frequency measurements.

  6. Supplemental progesterone and timing of resynchronization on pregnancy outcomes in lactating dairy cows.

    PubMed

    Bilby, T R; Bruno, R G S; Lager, K J; Chebel, R C; Moraes, J G N; Fricke, P M; Lopes, G; Giordano, J O; Santos, J E P; Lima, F S; Stevenson, J S; Pulley, S L

    2013-01-01

    The objective was to determine the effect of exogenous progesterone (P4) in a timed artificial insemination (TAI) protocol initiated at 2 different times post-AI on pregnancies per AI (P/AI) in lactating dairy cows. Cows (n=1,982) in 5 dairy herds were assigned randomly at a nonpregnancy diagnosis 32 ± 3 d post-AI to 1 of 4 resynchronization (RES) treatments arranged in a 2 × 2 factorial design using the Ovsynch-56 (GnRH, 7d later PGF2α, 56 h later GnRH, 16 h later TAI) protocol. Treatments were as follows: cows initiating RES 32 ± 3 d after AI with no supplemental P4 (d 32 RES-CON; n=516); same as d 32 RES-CON plus a controlled internal drug release (CIDR) insert containing P4 at the onset of Ovsynch-56 (d 32 RES-CIDR; n=503); cows initiating RES 39 ± 3 d after AI (d 39 RES-CON; n=494); and same as d 39 RES-CON plus a CIDR (d 39 RES-CIDR; n=491). Cows were inseminated if observed in estrus before TAI. The P/AI was determined 32 and 60 d after TAI. In a subgroup of cows (n=1,152), blood samples were collected and ovarian structures examined by ultrasonography on the days of the first GnRH (G1) and PGF2α of Ovsynch-56. Percentage of cows with a corpus luteum (CL) at G1 was unaffected by timing of treatments, but percentage of cows with a CL at PGF2α was greater for d 32 than for d 39 cows (87.9 vs. 79.4%). In addition, percentage of cows with P4 ≥ 1 ng/mL at G1 was unaffected by timing of treatments, but was increased for d 32 compared with d 39 RES cows on the day of the PGF2α of the RES protocols (86.5 vs. 74.3%). Treatment did not affect ovulation to G1 or P/AI 32 d after RES TAI (d 32 RES-CON=30.1%, d 32 RES-CIDR=28.8%, d 39 RES-CON=27.5%, d 39 RES-CIDR=30.5%). A greater percentage of d 39 RES cows underwent premature luteolysis during the RES protocol compared with d 32 RES cows. An interaction was detected between day of RES initiation and CIDR treatment, in which the CIDR increased P/AI 60 d after TAI for d 39 (CON=23.7% vs. CIDR=28.0%), but not for d 32 (CON=26.9% and CIDR=24.2%) cows. Pregnancy loss was unaffected by treatment. In addition, cows had improved P/AI 60 d after TAI when they received a CIDR and did not have a CL (CON-CL=28.2%, CON-No CL=19.2%, CIDR-CL=27.0%, and CIDR-No CL=26.5%) or had P4 <1 ng/mL (CON-High P4=27.8%, CON-Low P4=15.0%, CIDR-High P4=25.0%, and CIDR-Low P4=29.4%) at G1, but not if a CL was present or P4 was ≥ 1 ng/mL at G1. In conclusion, addition of a CIDR insert to supplement P4 during the RES protocol increased P/AI for cows initiating RES 39 ± 3 d after AI but not 32 ± 3 d after AI. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  7. The impact of the AIS 2005 revision on injury severity scores and clinical outcome measures.

    PubMed

    Salottolo, Kristin; Settell, April; Uribe, Phyllis; Akin, Shelley; Slone, Denetta Sue; O'Neal, Erika; Mains, Charles; Bar-Or, David

    2009-09-01

    The abbreviated injury scale (AIS) was updated in 2005 from the AIS 1998 version. The purpose of this study is to describe the effects of this change on injury severity scoring and outcome measures. Analyses were performed on all trauma patients consecutively admitted over a 6-month period at two geographically separate Level I trauma centers. Injuries were manually double-coded according to the AIS 05 and the AIS 98. Changes in AIS, ISS, and new ISS (NISS) were analysed using paired t-tests. Apparent differences in outcome by ISS strata (<16, 16-24, >24) were compared for AIS 05 versus AIS 98 using the Wald-type statistic. Lastly, the percent of patients with a change in ISS strata are reported. There were 2250 patients included in the study. Nearly half (46.4%) of AIS codes changed, resulting in a different AIS score for 18.9% of all codes. The mean ISS was significantly lower using the AIS 05 (11.7) versus the AIS 98 (13.3, p<0.001). Similarly, the mean NISS was significantly lower (16.3 versus 18.7, p<0.001). In the ISS strata 16-24 an apparent increase in mortality, length of stay, and percent of patients not discharged home was observed for the AIS 05 versus AIS 98. Changes in outcome measures for this stratum were as follows (AIS 98 versus AIS 05): mortality, 4.3% versus 7.7% (p=0.002); hospital length of stay, 5.2 days versus 7.3 days (p<0.001); percent of patients not discharged home, 39.2% versus 49.3% (p<0.001). Finally, there was a 20.5% reduction in patients with an ISS>or=16 and a 26.2% reduction in patients with an ISS>or=25 using the AIS 05. The AIS revision had a significant impact on overall injury severity measures, clinical outcome measures, and percent of patients in each ISS strata. Therefore, the AIS revision affects the ability to directly compare data generated using AIS 05 and AIS 98 which has implications in trauma research, reimbursement and ACS accreditation.

  8. From Ramachandran Maps to Tertiary Structures of Proteins.

    PubMed

    DasGupta, Debarati; Kaushik, Rahul; Jayaram, B

    2015-08-27

    Sequence to structure of proteins is an unsolved problem. A possible coarse grained resolution to this entails specification of all the torsional (Φ, Ψ) angles along the backbone of the polypeptide chain. The Ramachandran map quite elegantly depicts the allowed conformational (Φ, Ψ) space of proteins which is still very large for the purposes of accurate structure generation. We have divided the allowed (Φ, Ψ) space in Ramachandran maps into 27 distinct conformations sufficient to regenerate a structure to within 5 Å from the native, at least for small proteins, thus reducing the structure prediction problem to a specification of an alphanumeric string, i.e., the amino acid sequence together with one of the 27 conformations preferred by each amino acid residue. This still theoretically results in 27(n) conformations for a protein comprising "n" amino acids. We then investigated the spatial correlations at the two-residue (dipeptide) and three-residue (tripeptide) levels in what may be described as higher order Ramachandran maps, with the premise that the allowed conformational space starts to shrink as we introduce neighborhood effects. We found, for instance, for a tripeptide which potentially can exist in any of the 27(3) "allowed" conformations, three-fourths of these conformations are redundant to the 95% confidence level, suggesting sequence context dependent preferred conformations. We then created a look-up table of preferred conformations at the tripeptide level and correlated them with energetically favorable conformations. We found in particular that Boltzmann probabilities calculated from van der Waals energies for each conformation of tripeptides correlate well with the observed populations in the structural database (the average correlation coefficient is ∼0.8). An alpha-numeric string and hence the tertiary structure can be generated for any sequence from the look-up table within minutes on a single processor and to a higher level of accuracy if secondary structure can be specified. We tested the methodology on 100 small proteins, and in 90% of the cases, a structure within 5 Å is recovered. We thus believe that the method presented here provides the missing link between Ramachandran maps and tertiary structures of proteins. A Web server to convert a tertiary structure to an alphanumeric string and to predict the tertiary structure from the sequence of a protein using the above methodology is created and made freely accessible at http://www.scfbio-iitd.res.in/software/proteomics/rm2ts.jsp.

  9. A new way to see RNA

    PubMed Central

    Keating, Kevin S.; Humphris, Elisabeth L.; Pyle, Anna Marie

    2015-01-01

    Unlike proteins, the RNA backbone has numerous degrees of freedom (eight, if one counts the sugar pucker), making RNA modeling, structure building and prediction a multidimensional problem of exceptionally high complexity. And yet RNA tertiary structures are not infinite in their structural morphology; rather, they are built from a limited set of discrete units. In order to reduce the dimensionality of the RNA backbone in a physically reasonable way, a shorthand notation was created that reduced the RNA backbone torsion angles to two (η and θ, analogous to ϕ and ψ in proteins). When these torsion angles are calculated for nucleotides in a crystallographic database and plotted against one another, one obtains a plot analogous to a Ramachandran plot (the η/θ plot), with highly populated and unpopulated regions. Nucleotides that occupy proximal positions on the plot have identical structures and are found in the same units of tertiary structure. In this review, we describe the statistical validation of the η/θ formalism and the exploration of features within the η/θ plot. We also describe the application of the η/θ formalism in RNA motif discovery, structural comparison, RNA structure building and tertiary structure prediction. More than a tool, however, the η/θ formalism has provided new insights into RNA structure itself, revealing its fundamental components and the factors underlying RNA architectural form. PMID:21729350

  10. Convergence Insufficiency, Accommodative Insufficiency, Visual Symptoms, and Astigmatism in Tohono O'odham Students

    PubMed Central

    Twelker, J. Daniel; Miller, Joseph M.; Campus, Irene

    2016-01-01

    Purpose. To determine rate of convergence insufficiency (CI) and accommodative insufficiency (AI) and assess the relation between CI, AI, visual symptoms, and astigmatism in school-age children. Methods. 3rd–8th-grade students completed the Convergence Insufficiency Symptom Survey (CISS) and binocular vision testing with correction if prescribed. Students were categorized by astigmatism magnitude (no/low: <1.00 D, moderate: 1.00 D to <3.00 D, and high: ≥3.00 D), presence/absence of clinical signs of CI and AI, and presence of symptoms. Analyses determine rate of clinical CI and AI and symptomatic CI and AI and assessed the relation between CI, AI, visual symptoms, and astigmatism. Results. In the sample of 484 students (11.67 ± 1.81 years of age), rate of symptomatic CI was 6.2% and symptomatic AI 18.2%. AI was more common in students with CI than without CI. Students with AI only (p = 0.02) and with CI and AI (p = 0.001) had higher symptom scores than students with neither CI nor AI. Moderate and high astigmats were not at increased risk for CI or AI. Conclusions. With-the-rule astigmats are not at increased risk for CI or AI. High comorbidity rates of CI and AI and higher symptoms scores with AI suggest that research is needed to determine symptomatology specific to CI. PMID:27525112

  11. Use of terbium as a probe of tRNA tertiary structure and folding.

    PubMed Central

    Hargittai, M R; Musier-Forsyth, K

    2000-01-01

    Lanthanide metals such as terbium have previously been shown to be useful for mapping metal-binding sites in RNA. Terbium binds to the same sites on RNA as magnesium, however, with a much higher affinity. Thus, low concentrations of terbium ions can easily displace magnesium and promote phosphodiester backbone scission. At higher concentrations, terbium cleaves RNA in a sequence-independent manner, with a preference for single-stranded, non-Watson-Crick base-paired regions. Here, we show that terbium is a sensitive probe of human tRNALys,3 tertiary structure and folding. When 1 microM tRNA is used, the optimal terbium ion concentration for detecting Mg2+-induced tertiary structural changes is 50-60 microM. Using these concentrations of RNA and terbium, a magnesium-dependent folding transition with a midpoint (KMg) of 2.6 mM is observed for unmodified human tRNALys,3. At lower Tb3+ concentrations, cleavage is restricted to nucleotides that constitute specific metal-binding pockets. This small chemical probe should also be useful for detecting protein induced structural changes in RNA. PMID:11105765

  12. Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

    PubMed

    Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

    2017-08-01

    Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

  13. Artificial intelligence and design: Opportunities, research problems and directions

    NASA Technical Reports Server (NTRS)

    Amarel, Saul

    1990-01-01

    The issues of industrial productivity and economic competitiveness are of major significance in the U.S. at present. By advancing the science of design, and by creating a broad computer-based methodology for automating the design of artifacts and of industrial processes, we can attain dramatic improvements in productivity. It is our thesis that developments in computer science, especially in Artificial Intelligence (AI) and in related areas of advanced computing, provide us with a unique opportunity to push beyond the present level of computer aided automation technology and to attain substantial advances in the understanding and mechanization of design processes. To attain these goals, we need to build on top of the present state of AI, and to accelerate research and development in areas that are especially relevant to design problems of realistic complexity. We propose an approach to the special challenges in this area, which combines 'core work' in AI with the development of systems for handling significant design tasks. We discuss the general nature of design problems, the scientific issues involved in studying them with the help of AI approaches, and the methodological/technical issues that one must face in developing AI systems for handling advanced design tasks. Looking at basic work in AI from the perspective of design automation, we identify a number of research problems that need special attention. These include finding solution methods for handling multiple interacting goals, formation problems, problem decompositions, and redesign problems; choosing representations for design problems with emphasis on the concept of a design record; and developing approaches for the acquisition and structuring of domain knowledge with emphasis on finding useful approximations to domain theories. Progress in handling these research problems will have major impact both on our understanding of design processes and their automation, and also on several fundamental questions that are of intrinsic concern to AI. We present examples of current AI work on specific design tasks, and discuss new directions of research, both as extensions of current work and in the context of new design tasks where domain knowledge is either intractable or incomplete. The domains discussed include Digital Circuit Design, Mechanical Design of Rotational Transmissions, Design of Computer Architectures, Marine Design, Aircraft Design, and Design of Chemical Processes and Materials. Work in these domains is significant on technical grounds, and it is also important for economic and policy reasons.

  14. Altering the time of the second gonadotropin-releasing hormone injection and artificial insemination (AI) during Ovsynch affects pregnancies per AI in lactating dairy cows.

    PubMed

    Brusveen, D J; Cunha, A P; Silva, C D; Cunha, P M; Sterry, R A; Silva, E P B; Guenther, J N; Wiltbank, M C

    2008-03-01

    Based on previous research, we hypothesized that Cosynch at 72 h [GnRH-7 d-PGF(2alpha)-72 h-GnRH + artificial insemination (AI)] would result in a greater number of pregnancies per AI (P/AI) than Cosynch at 48 h. Further, we hypothesized that P/AI would be improved to a greater extent when GnRH was administered at 56 h after PGF(2alpha) before AI at 72 h due to a more optimal interval between the LH surge and AI. Nine hundred twenty-seven lactating dairy cows (n = 1,507 AI) were blocked by pen, and pens rotated through treatments. All cows received GnRH followed 7 d later by PGF(2alpha) and then received one of the following: 1) GnRH + timed AI 48 h after PGF(2alpha) (Cosynch-48); 2) GnRH 56 h after PGF(2alpha) + timed AI 72 h after PGF(2alpha) (Ovsynch-56); or 3) GnRH + timed AI 72 h after PGF(2alpha) (Cosynch-72). Pregnancy diagnoses were performed by ultrasound at 31 to 33 d post-AI and again at 52 to 54 d post-AI. Overall P/AI were similar for the Cosynch-48 (29.2%) and Cosynch-72 (25.4%) groups. The Ovsynch-56 group had a greater P/AI (38.6%) than Cosynch-48 or Cosynch-72. Presynchronized first-service animals had greater P/AI than cows at later services in Cosynch-48 (36.2 vs. 23.0%) and Ovsynch-56 (44.8 vs. 32.7%) but not in Cosynch-72 (24.6 vs. 26.2%). Similarly, primiparous cows had greater P/AI than multiparous cows in Cosynch-48 (34.1 vs. 22.9%) and Ovsynch-56 (41.3 vs. 32.6%), but not Cosynch-72 (29.8 vs. 25.3%). In conclusion, we found no advantage to Cosynch at 72 h vs. 48 h. In contrast, we found a clear advantage to treating with GnRH at 56 h, 16 h before a 72-h AI, probably because of more-optimal timing of AI before ovulation.

  15. Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008).

    PubMed

    Tohira, Hideo; Jacobs, Ian; Mountain, David; Gibson, Nick; Yeo, Allen

    2011-01-01

    The Abbreviated Injury Scale (AIS) was revised in 2005 and updated in 2008 (AIS 2008). We aimed to compare the outcome prediction performance of AIS-based injury severity scoring tools by using AIS 2008 and AIS 98. We used all major trauma patients hospitalized to the Royal Perth Hospital between 1994 and 2008. We selected five AIS-based injury severity scoring tools, including Injury Severity Score (ISS), New Injury Severity Score (NISS), modified Anatomic Profile (mAP), Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). We selected survival after injury as a target outcome. We used the area under the Receiver Operating Characteristic curve (AUROC) as a performance measure. First, we compared the five tools using all cases whose records included all variables for the TRISS (complete dataset) using a 10-fold cross-validation. Second, we compared the ISS and NISS for AIS 98 and AIS 2008 using all subjects (whole dataset). We identified 1,269 and 4,174 cases for a complete dataset and a whole dataset, respectively. With the 10-fold cross-validation, there were no clear differences in the AUROCs between the AIS 98- and AIS 2008-based scores. With the second comparison, the AIS 98-based ISS performed significantly worse than the AIS 2008-based ISS (p<0.0001), while there was no significant difference between the AIS 98- and AIS 2008-based NISSs. Researchers should be aware of these findings when they select an injury severity scoring tool for their studies.

  16. High-Throughput, Data-Rich Cellular RNA Device Engineering

    PubMed Central

    Townshend, Brent; Kennedy, Andrew B.; Xiang, Joy S.; Smolke, Christina D.

    2015-01-01

    Methods for rapidly assessing sequence-structure-function landscapes and developing conditional gene-regulatory devices are critical to our ability to manipulate and interface with biology. We describe a framework for engineering RNA devices from preexisting aptamers that exhibit ligand-responsive ribozyme tertiary interactions. Our methodology utilizes cell sorting, high-throughput sequencing, and statistical data analyses to enable parallel measurements of the activities of hundreds of thousands of sequences from RNA device libraries in the absence and presence of ligands. Our tertiary interaction RNA devices exhibit improved performance in terms of gene silencing, activation ratio, and ligand sensitivity as compared to optimized RNA devices that rely on secondary structure changes. We apply our method to building biosensors for diverse ligands and determine consensus sequences that enable ligand-responsive tertiary interactions. These methods advance our ability to develop broadly applicable genetic tools and to elucidate understanding of the underlying sequence-structure-function relationships that empower rational design of complex biomolecules. PMID:26258292

  17. Bilateral adrenal masses: a single-centre experience

    PubMed Central

    Bandgar, Tushar; Khare, Shruti; Jadhav, Swati; Lila, Anurag; Goroshi, Manjunath; Kasaliwal, Rajeev; Khadilkar, Kranti; Shah, Nalini S

    2016-01-01

    Background Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited. Aims To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses. Methods Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015). Results The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001). Conclusion In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies. PMID:27037294

  18. The Development of Adult and Community Education Policy in New Zealand: Insights from Popper

    ERIC Educational Resources Information Center

    Slater, Gloria

    2009-01-01

    This paper examines the process by which all post-compulsory education in New Zealand has become integrated under one administrative structure, the Tertiary Education Commission (TEC), with the intention of developing a single coordinated system of tertiary education. In particular, adult and community education (ACE), the least formal and…

  19. PASS Student Leader and Mentor Roles: A Tertiary Leadership Pathway

    ERIC Educational Resources Information Center

    Skalicky, Jane; Caney, Annaliese

    2010-01-01

    In relation to developing leadership skills during tertiary studies, this paper considers the leadership pathway afforded by a Peer Assisted Study Sessions (PASS) program which includes the traditional PASS Leader role and a more senior PASS Mentor role. Data was collected using a structured survey with open-ended questions designed to capture the…

  20. Apolipoprotein AI Deficiency Inhibits Serum Opacity Factor Activity against Plasma High Density Lipoprotein via a Stabilization Mechanism

    PubMed Central

    Rosales, Corina; Patel, Niket; Gillard, Baiba K.; Yelamanchili, Dedipya; Yang, Yaliu; Courtney, Harry S.; Santos, Raul D.; Gotto, Antonio M.; Pownall, Henry J.

    2016-01-01

    The reaction of Streptococcal serum opacity factor (SOF) against plasma high-density lipoproteins (HDL) produces a large cholesteryl ester-rich microemulsion (CERM), a smaller neo HDL that is apolipoprotein (apo) AI-poor, and lipid-free apo AI. SOF is active vs. both human and mouse plasma HDL. In vivo injection of SOF into mice reduces plasma cholesterol ~40% in 3 hours while forming the same products observed in vitro, but at different ratios. Previous studies supported the hypothesis that labile apo AI is required for the SOF reaction vs. HDL. Here we further tested that hypothesis by studies of SOF against HDL from apo AI-null mice. When injected into apo AI-null mice, SOF reduced plasma cholesterol ~35% in three hours. The reaction of SOF vs. apo AI-null HDL in vitro produced a CERM and neo HDL, but no lipid-free apo. Moreover, according to the rate of CERM formation, the extent and rate of the SOF reaction vs. apo AI-null mouse HDL was less than that against wild-type (WT) mouse HDL. Chaotropic perturbation studies using guanidine hydrochloride showed that apo AI-null HDL was more stable than WT HDL. Human apo AI added to apo AI-null HDL was quantitatively incorporated, giving reconstituted HDL. Both SOF and guanidine hydrochloride displaced apo AI from the reconstituted HDL. These results support the conclusion that apo AI-null HDL is more stable than WT HDL because it lacks apo AI, a labile protein that is readily displaced by physico-chemical and biochemical perturbations. Thus, apo AI-null HDL is less SOF-reactive than WT HDL. The properties of apo AI-null HDL can be partially restored to those of WT HDL by the spontaneous incorporation of human apo AI. It remains to be determined what other HDL functions are affected by apo AI deletion. PMID:25790332

  1. TBS and BMD at the end of AI-therapy: A prospective study of the B-ABLE cohort.

    PubMed

    María, Rodríguez-Sanz; Marta, Pineda-Moncusí; Sonia, Servitja; Natalia, Garcia-Giralt; Tamara, Martos; Ignasi, Tusquets; Maria, Martínez-García; Jaime, Rodriguez-Morera; Adolfo, Diez-Perez; Joan, Albanell; Xavier, Nogués

    2016-11-01

    Patients with breast cancer under aromatase inhibitor (AI) treatment often develop osteoporosis and their average bone loss rate is twice that of natural reduction during menopause, increasing fracture risk. As the current diagnostic technique based on bone mineral density (BMD) provides no information on bone quality, the Trabecular Bone Score (TBS) has been proposed to reflect bone microarchitecture status. The present study was designed to assess prospective changes in TBS and lumbar spine (LS) BMD in postmenopausal women with breast cancer at completion of AI treatment. B-ABLE is a prospective cohort of 735 women with breast cancer treated with AIs according to American Society of Clinical Oncology recommendations: 5years of AI starting within 6weeks post-surgery or 1month after the last cycle of chemotherapy (5y-AI group), or switching to an AI to complete 5-year therapy after 2-3years of tamoxifen (pTMX-AI group). Patients with osteoporosis were treated with oral bisphosphonates (BP). TBS and LS-BMD changes at completion of AI therapy were evaluated by Student t-test for paired samples. Pearson correlation coefficients were computed for correlations between LS-BMD and TBS. AI treatment was completed by 277 women. Of these, 70 (25.3%) were allocated to BP therapy. The non-BP-treated patients (74.7%) showed significant decreases in TBS (-2.94% in pTMX-AI and -2.93% in 5y-AI groups) and in LS-BMD (-4.14% in pTMX-AI and -2.28% in 5y-AI groups) at the end of AI treatment. In BP-treated patients, TBS remained stable at the end of AI treatment, whereas LS-BMD showed significant increases (+2.30% in pTMX-AI and +5.33% in 5y-AI groups). Moderate associations between TBS and LS-BMD values at baseline and at the end of AI treatment (r=0.4; P<0.001) were observed. At the end of treatment, changes in spine BMD and TBS were weakly correlated (r=0.1, P<0.01). AI therapy induces significant decreases in TBS, comparable to BMD loss. BP-treated patients maintained TBS values, whereas BMD increased. AI treatment leads to deterioration of bone microarchitecture, which seems to be attenuated by BP therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Bhageerath-H: A homology/ab initio hybrid server for predicting tertiary structures of monomeric soluble proteins

    PubMed Central

    2014-01-01

    Background The advent of human genome sequencing project has led to a spurt in the number of protein sequences in the databanks. Success of structure based drug discovery severely hinges on the availability of structures. Despite significant progresses in the area of experimental protein structure determination, the sequence-structure gap is continually widening. Data driven homology based computational methods have proved successful in predicting tertiary structures for sequences sharing medium to high sequence similarities. With dwindling similarities of query sequences, advanced homology/ ab initio hybrid approaches are being explored to solve structure prediction problem. Here we describe Bhageerath-H, a homology/ ab initio hybrid software/server for predicting protein tertiary structures with advancing drug design attempts as one of the goals. Results Bhageerath-H web-server was validated on 75 CASP10 targets which showed TM-scores ≥0.5 in 91% of the cases and Cα RMSDs ≤5Å from the native in 58% of the targets, which is well above the CASP10 water mark. Comparison with some leading servers demonstrated the uniqueness of the hybrid methodology in effectively sampling conformational space, scoring best decoys and refining low resolution models to high and medium resolution. Conclusion Bhageerath-H methodology is web enabled for the scientific community as a freely accessible web server. The methodology is fielded in the on-going CASP11 experiment. PMID:25521245

  3. Validation of the "HAMP" mapping algorithm: a tool for long-term trauma research studies in the conversion of AIS 2005 to AIS 98.

    PubMed

    Adams, Derk; Schreuder, Astrid B; Salottolo, Kristin; Settell, April; Goss, J Richard

    2011-07-01

    There are significant changes in the abbreviated injury scale (AIS) 2005 system, which make it impractical to compare patients coded in AIS version 98 with patients coded in AIS version 2005. Harborview Medical Center created a computer algorithm "Harborview AIS Mapping Program (HAMP)" to automatically convert AIS 2005 to AIS 98 injury codes. The mapping was validated using 6 months of double-coded patient injury records from a Level I Trauma Center. HAMP was used to determine how closely individual AIS and injury severity scores (ISS) were converted from AIS 2005 to AIS 98 versions. The kappa statistic was used to measure the agreement between manually determined codes and HAMP-derived codes. Seven hundred forty-nine patient records were used for validation. For the conversion of AIS codes, the measure of agreement between HAMP and manually determined codes was [kappa] = 0.84 (95% confidence interval, 0.82-0.86). The algorithm errors were smaller in magnitude than the manually determined coding errors. For the conversion of ISS, the agreement between HAMP versus manually determined ISS was [kappa] = 0.81 (95% confidence interval, 0.78-0.84). The HAMP algorithm successfully converted injuries coded in AIS 2005 to AIS 98. This algorithm will be useful when comparing trauma patient clinical data across populations coded in different versions, especially for longitudinal studies.

  4. Effect of sequence of insemination after simultaneous thawing of multiple semen straws on conception rate to timed AI in suckled multiparous Nelore cows.

    PubMed

    Oliveira, L Z; Arruda, R P; de Andrade, A F C; Santos, R M; Beletti, M E; Peres, R F G; Martins, J P N; de Lima, V F M Hossepian

    2012-11-01

    The objective was to determine the effect of sequence of insemination after simultaneous thawing of multiple 0.5 mL semen straws on conception rate in suckled multiparous Nelore cows. The effect of this thawing procedure on in vitro sperm characteristics was also evaluated. All cows (N = 944) received the same timed AI protocol. Ten straws (0.5 mL) of frozen semen from the same batch were simultaneously thawed at 36 °C, for a minimum of 30 sec. One straw per cow was used for timed AI. Frozen semen from three Angus bulls was used. Timed AI records included sequence of insemination (first to tenth) and time of semen removal from thawing bath. For laboratory analyses, the same semen batches used in the field experiment were evaluated. Ten frozen straws from the same batch were thawed simultaneously in a thawing unit identical to that used in the field experiment. The following sperm characteristics were analyzed: sperm motility parameters, sperm thermal resistance, plasma and acrosomal membrane integrity, lipid peroxidation, chromatin structure, and sperm morphometry. Based on logistic regression, there were no significant effects of breeding group, body condition score, AI technician, and sire on conception rate, but there was an interaction between sire and straw group (P = 0.002). Semen from only one bull had decreased (P < 0.05) field fertility for the group of straws associated with the longest interval from thawing to AI. However, the results of the laboratory experiment were unable to explain the findings of the field experiment. Sperm width:length ratio of morphometric analysis was the single sperm characteristic with a significant interaction between sire and straw group (P = 0.02). It was concluded that sequence of insemination after simultaneous thawing of 10 semen straws can differently affect conception rates at timed AI, depending on the sire used. Nevertheless, the effects of this thawing environment on in vitro sperm characteristics, remain to be further investigated. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Developing adaptive interventions for adolescent substance use treatment settings: protocol of an observational, mixed-methods project.

    PubMed

    Grant, Sean; Agniel, Denis; Almirall, Daniel; Burkhart, Q; Hunter, Sarah B; McCaffrey, Daniel F; Pedersen, Eric R; Ramchand, Rajeev; Griffin, Beth Ann

    2017-12-19

    Over 1.6 million adolescents in the United States meet criteria for substance use disorders (SUDs). While there are promising treatments for SUDs, adolescents respond to these treatments differentially in part based on the setting in which treatments are delivered. One way to address such individualized response to treatment is through the development of adaptive interventions (AIs): sequences of decision rules for altering treatment based on an individual's needs. This protocol describes a project with the overarching goal of beginning the development of AIs that provide recommendations for altering the setting of an adolescent's substance use treatment. This project has three discrete aims: (1) explore the views of various stakeholders (parents, providers, policymakers, and researchers) on deciding the setting of substance use treatment for an adolescent based on individualized need, (2) generate hypotheses concerning candidate AIs, and (3) compare the relative effectiveness among candidate AIs and non-adaptive interventions commonly used in everyday practice. This project uses a mixed-methods approach. First, we will conduct an iterative stakeholder engagement process, using RAND's ExpertLens online system, to assess the importance of considering specific individual needs and clinical outcomes when deciding the setting for an adolescent's substance use treatment. Second, we will use results from the stakeholder engagement process to analyze an observational longitudinal data set of 15,656 adolescents in substance use treatment, supported by the Substance Abuse and Mental Health Services Administration, using the Global Appraisal of Individual Needs questionnaire. We will utilize methods based on Q-learning regression to generate hypotheses about candidate AIs. Third, we will use robust statistical methods that aim to appropriately handle casemix adjustment on a large number of covariates (marginal structural modeling and inverse probability of treatment weights) to compare the relative effectiveness among candidate AIs and non-adaptive decision rules that are commonly used in everyday practice. This project begins filling a major gap in clinical and research efforts for adolescents in substance use treatment. Findings could be used to inform the further development and revision of influential multi-dimensional assessment and treatment planning tools, or lay the foundation for subsequent experiments to further develop or test AIs for treatment planning.

  6. When Machines Think: Radiology's Next Frontier.

    PubMed

    Dreyer, Keith J; Geis, J Raymond

    2017-12-01

    Artificial intelligence (AI), machine learning, and deep learning are terms now seen frequently, all of which refer to computer algorithms that change as they are exposed to more data. Many of these algorithms are surprisingly good at recognizing objects in images. The combination of large amounts of machine-consumable digital data, increased and cheaper computing power, and increasingly sophisticated statistical models combine to enable machines to find patterns in data in ways that are not only cost-effective but also potentially beyond humans' abilities. Building an AI algorithm can be surprisingly easy. Understanding the associated data structures and statistics, on the other hand, is often difficult and obscure. Converting the algorithm into a sophisticated product that works consistently in broad, general clinical use is complex and incompletely understood. To show how these AI products reduce costs and improve outcomes will require clinical translation and industrial-grade integration into routine workflow. Radiology has the chance to leverage AI to become a center of intelligently aggregated, quantitative, diagnostic information. Centaur radiologists, formed as a synergy of human plus computer, will provide interpretations using data extracted from images by humans and image-analysis computer algorithms, as well as the electronic health record, genomics, and other disparate sources. These interpretations will form the foundation of precision health care, or care customized to an individual patient. © RSNA, 2017.

  7. Relationship between thoracic hypokyphosis, lumbar lordosis and sagittal pelvic parameters in adolescent idiopathic scoliosis.

    PubMed

    Clément, Jean-Luc; Geoffray, Anne; Yagoubi, Fatima; Chau, Edouard; Solla, Federico; Oborocianu, Ioana; Rampal, Virginie

    2013-11-01

    Sagittal spine and pelvic alignment of adolescent idiopathic scoliosis (AIS) is poorly described in the literature. It generally reports the sagittal alignment with regard to the type of curve and never correlated to the thoracic kyphosis. The objective of this study is to investigate the relationship between thoracic kyphosis, lumbar lordosis and sagittal pelvic parameters in thoracic AIS. Spinal and pelvic sagittal parameters were evaluated on lateral radiographs of 86 patients with thoracic AIS; patients were separated into hypokyphosis group (n = 42) and normokyphosis group (n = 44). Results were statistically analyzed. The lumbar lordosis was lower in the hypokyphosis group, due to the low proximal lordosis. The thoracic kyphosis was not correlated with any pelvic parameters but with the proximal lordosis. The pelvic incidence was correlated with sacral slope, pelvic tilt, lumbar lordosis and highly correlated with distal lumbar lordosis in the two groups. There was a significant linear regression between thoracic kyphosis and proximal lordosis and between pelvic incidence and distal lordosis. We can consider that the proximal part of the lordosis depends on the thoracic kyphosis and the distal part depends on the pelvic incidence. The hypokyphosis in AIS is independent of the pelvic parameters and could be described as a structural parameter, characteristic of the scoliotic deformity.

  8. AIS ASM Operational Integration Plan

    DTIC Science & Technology

    2013-08-01

    al. | Public August 2013 This page intentionally left blank. AIS ASM Operational Integration Plan v ...that supply AIS Routers as part of their AIS shoreside network software : Kongsberg C-Scope, Gatehouse AIS, Transas AIS Network, and CNS DataSwitch...commercial systems would be suitable for the current USCG traffic conditions. The ASM Manager is software that adds the required queuing and

  9. Optics and Symbolic Computing

    DTIC Science & Technology

    1987-03-01

    applicatior for AI are in variation of classification parameters for knowledge acquisition ( changing of classes into which objects are placed), and...computation. The well-structured data formats of vectors, matrices, etc. used in numeric computing give way to data structures that can change their shapes...by "flexible data structures. The semantic meanings of objects are readily changed by adding and deleting the variable lists of attributes. Another

  10. Comparisons of the Outcome Prediction Performance of Injury Severity Scoring Tools Using the Abbreviated Injury Scale 90 Update 98 (AIS 98) and 2005 Update 2008 (AIS 2008)

    PubMed Central

    Tohira, Hideo; Jacobs, Ian; Mountain, David; Gibson, Nick; Yeo, Allen

    2011-01-01

    The Abbreviated Injury Scale (AIS) was revised in 2005 and updated in 2008 (AIS 2008). We aimed to compare the outcome prediction performance of AIS-based injury severity scoring tools by using AIS 2008 and AIS 98. We used all major trauma patients hospitalized to the Royal Perth Hospital between 1994 and 2008. We selected five AIS-based injury severity scoring tools, including Injury Severity Score (ISS), New Injury Severity Score (NISS), modified Anatomic Profile (mAP), Trauma and Injury Severity Score (TRISS) and A Severity Characterization of Trauma (ASCOT). We selected survival after injury as a target outcome. We used the area under the Receiver Operating Characteristic curve (AUROC) as a performance measure. First, we compared the five tools using all cases whose records included all variables for the TRISS (complete dataset) using a 10-fold cross-validation. Second, we compared the ISS and NISS for AIS 98 and AIS 2008 using all subjects (whole dataset). We identified 1,269 and 4,174 cases for a complete dataset and a whole dataset, respectively. With the 10-fold cross-validation, there were no clear differences in the AUROCs between the AIS 98- and AIS 2008-based scores. With the second comparison, the AIS 98-based ISS performed significantly worse than the AIS 2008-based ISS (p<0.0001), while there was no significant difference between the AIS 98- and AIS 2008-based NISSs. Researchers should be aware of these findings when they select an injury severity scoring tool for their studies. PMID:22105401

  11. Structural and Functional Alterations in Neocortical Circuits after Mild Traumatic Brain Injury

    NASA Astrophysics Data System (ADS)

    Vascak, Michal

    National concern over traumatic brain injury (TBI) is growing rapidly. Recent focus is on mild TBI (mTBI), which is the most prevalent injury level in both civilian and military demographics. A preeminent sequelae of mTBI is cognitive network disruption. Advanced neuroimaging of mTBI victims supports this premise, revealing alterations in activation and structure-function of excitatory and inhibitory neuronal systems, which are essential for network processing. However, clinical neuroimaging cannot resolve the cellular and molecular substrates underlying such changes. Therefore, to understand the full scope of mTBI-induced alterations it is necessary to study cortical networks on the microscopic level, where neurons form local networks that are the fundamental computational modules supporting cognition. Recently, in a well-controlled animal model of mTBI, we demonstrated in the excitatory pyramidal neuron system, isolated diffuse axonal injury (DAI), in concert with electrophysiological abnormalities in nearby intact (non-DAI) neurons. These findings were consistent with altered axon initial segment (AIS) intrinsic activity functionally associated with structural plasticity, and/or disturbances in extrinsic systems related to parvalbumin (PV)-expressing interneurons that form GABAergic synapses along the pyramidal neuron perisomatic/AIS domains. The AIS and perisomatic GABAergic synapses are domains critical for regulating neuronal activity and E-I balance. In this dissertation, we focus on the neocortical excitatory pyramidal neuron/inhibitory PV+ interneuron local network following mTBI. Our central hypothesis is that mTBI disrupts neuronal network structure and function causing imbalance of excitatory and inhibitory systems. To address this hypothesis we exploited transgenic and cre/lox mouse models of mTBI, employing approaches that couple state-of-the-art bioimaging with electrophysiology to determine the structuralfunctional alterations of excitatory and inhibitory systems in the neocortex.

  12. Experimental and theoretical investigation of three-dimensional nitrogen-doped aluminum clusters AI 8N - and AI 8N

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

    Wang, Leiming; Huang, Wei; Wang, Lai S.

    The structure and electronic properties of the Al 8N - and Al 8N clusters were investigated by combined photoelectron spectroscopy and ab initio studies. Congested photoelectron spectra were observed and experimental evidence was obtained for the presence of multiple isomers for Al 8N - Global minimum searches revealed several structures for Al 8N - with close energies. The calculated vertical detachment energies of the two lowest-lying isomers, which are of C 2v and C s symmetry, respectively, were shown to agree well with the experimental data. Unlike the three-dimensional structures of Al 6N - and Al 7N -, in whichmore » the dopant N atom has a high coordination number of 6,the dopant N atom in the two low-lying isomers of Al 8N - has a lower coordination number of 4 and 5, respectively. The competition between the Al–Al and Al–N interactions are shown to determine the global minimum structures of the doped aluminum clusters and results in the structural diversity for both Al 8N - and Al8N. © 2009 American Institute of Physics« less

  13. Minor Structural Change to Tertiary Sulfonamide RORc Ligands Led to Opposite Mechanisms of Action

    PubMed Central

    2014-01-01

    A minor structural change to tertiary sulfonamide RORc ligands led to distinct mechanisms of action. Co-crystal structures of two compounds revealed mechanistically consistent protein conformational changes. Optimized phenylsulfonamides were identified as RORc agonists while benzylsulfonamides exhibited potent inverse agonist activity. Compounds behaving as agonists in our biochemical assay also gave rise to an increased production of IL-17 in human PBMCs whereas inverse agonists led to significant suppression of IL-17 under the same assay conditions. The most potent inverse agonist compound showed >180-fold selectivity over the ROR isoforms as well as all other nuclear receptors that were profiled. PMID:25815138

  14. The Design of a Multi-component Intervention to Promote Screening Mammography in an American Indian Community: The Native Women's Health Project

    PubMed Central

    Tolma, Eleni L.; Engelman, Kimberly; Stoner, Julie A.; Thomas, Cara; Joseph, Stephanie; Li, Ji; Blackwater, Cecily; Henderson, J. Neil; Carson, L. D.; Neely, Norma; Edwards, Tewanna

    2016-01-01

    Background Breast cancer is an important public health issue among American Indian/Alaska Native (AI/AN) women in the US. This article describes the design and implementation of a culturally sensitive intervention to promote breast health among AI/AN women through a hybrid model that incorporates clinical and community-based approaches. This is one of the first studies using this model addressing breast cancer disparities among AI/AN populations in the US. Methods The Theory of Planned Behavior was used as the guiding framework of the intervention and Community Based Participatory Research was the primary vehicle for the intervention planning and implementation. Three preliminary studies took place that aimed to identify qualitatively and quantitatively what deterred or encouraged AI women to get past or future mammograms. The research results were shared with community members who, through a prioritization process, identified the theoretical focus of the intervention and its corresponding activities. The priority population consisted of AI women ages 40–74, with no recent mammogram, and no breast cancer history. Results The intervention centered on the promotion of social modeling and physician recommendation. The main corresponding activities included enhancing patient-physician communication about screening mammography through a structured dialogue, receipt of a breast cancer brochure, participation in an inter-generational discussion group, and a congratulatory bracelet upon receipt of a mammogram. Environmental and policy related changes also were developed. Conclusion Creating a theory-based, culturally-sensitive intervention through tribal participatory research is a challenging approach towards eliminating breast cancer disparities among hard-to-reach populations. PMID:29546205

  15. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in patients with primary aldosteronism.

    PubMed

    Chang, Yi-Yao; Chen, Aaron; Chen, Ying-Hsien; Hung, Chi-Sheng; Wu, Vin-Cent; Wu, Xue-Ming; Lin, Yen-Hung; Ho, Yi-Lwun; Wu, Kwan-Dun

    2015-06-01

    Hypokalemia in primary aldosteronism (PA) patients correlates with higher levels of cardiovascular events and altered left ventricular geometry. However, the influence of aldosterone on microvascular endothelial function and the effect of hypokalemia on the vascular structure still remain unclear. We investigated the peripheral arterial functions, including the endothelial function of microvasculature and arterial stiffness in PA and essential hypertension (EH) patients, and the correlation between hypokalemia and peripheral arterial function among PA patients. Twenty patients diagnosed as EH and 37 patients with PA were enrolled in this study. Reactive hyperemia index (RHI) and the augmentation index (AI) were obtained by non-invasive peripheral arterial tonometry. Twenty EH patients and a total of 37 PA patients, including 21 patients with normokalemia and 16 patients with hypokalemia, were enrolled and divided into groups 1, 2 and 3 respectively. PA patients had significantly higher AI (p=0.024) but not RHI than EH patients. RHI showed no difference between groups 1, 2 and 3. Group 3 had higher AI than either group 1 or group 2. In the whole study population, serum potassium level, after multivariate regression analysis testing, was the only factor associated with AI (ß= -0.102; p=0.002). In PA patients, serum potassium level was the only significant factor correlated with AI. (r= -0.458; p=0.004) CONCLUSIONS: PA patients had higher arterial stiffness but comparable microvascular endothelial function to EH patients. Hypokalemia correlated with arterial stiffness but not microvascular endothelial function in PA patients. © The Author(s) 2014.

  16. An Opening Chapter of the First Generation of Artificial Intelligence in Medicine: The First Rutgers AIM Workshop, June 1975

    PubMed Central

    2015-01-01

    Summary The first generation of Artificial Intelligence (AI) in Medicine methods were developed in the early 1970’s drawing on insights about problem solving in AI. They developed new ways of representing structured expert knowledge about clinical and biomedical problems using causal, taxonomic, associational, rule, and frame-based models. By 1975, several prototype systems had been developed and clinically tested, and the Rutgers Research Resource on Computers in Biomedicine hosted the first in a series of workshops on AI in Medicine that helped researchers and clinicians share their ideas, demonstrate their models, and comment on the prospects for the field. These developments and the workshops themselves benefited considerably from Stanford’s SUMEX-AIM pioneering experiment in biomedical computer networking. This paper focuses on discussions about issues at the intersection of medicine and artificial intelligence that took place during the presentations and panels at the First Rutgers AIM Workshop in New Brunswick, New Jersey from June 14 to 17, 1975. PMID:26123911

  17. Chitin: a cell-surface component of Phytomonas françai.

    PubMed

    Nakamura, C V; Esteves, M J; Andrade, A F; Alviano, C S; de Souza, W; Angluster, J

    1993-01-01

    The occurrence of chitin as a structural component of the surface of the phytopathogenic protozoan Phytomonas françai was demonstrated by paper and gas-liquid chromatographic analysis of the products of enzymatic and chemical hydrolysis of alkali-resistant polysaccharides, lectin binding, glycosidase digestion, and infrared spectra. Chitin was characterized by its insolubility in hot alkali and chromatographic immobility as well as by the release of glucosamine on hydrolysis with strong acid and of N-acetylglucosamine (GlcNAc) on hydrolysis with chitinase. The presence of chitin was also shown directly by binding of wheat-germ agglutinin (WGA), which recognizes GlcNAc units, to the parasite surface. Fluorescein-labeled WGA binding was completely abolished by treatment with chitinase. This effect was specific since it could be prevented by incubating the enzyme with chitin before treatment of the phytomonads. These findings indicate that chitin is an exposed cell-surface polysaccharide in Phytomonas françai. The data were confirmed by the infrared spectrum of an alkali-insoluble residue, which showed a pattern typical of chitin.

  18. A knowledge based software engineering environment testbed

    NASA Technical Reports Server (NTRS)

    Gill, C.; Reedy, A.; Baker, L.

    1985-01-01

    The Carnegie Group Incorporated and Boeing Computer Services Company are developing a testbed which will provide a framework for integrating conventional software engineering tools with Artifical Intelligence (AI) tools to promote automation and productivity. The emphasis is on the transfer of AI technology to the software development process. Experiments relate to AI issues such as scaling up, inference, and knowledge representation. In its first year, the project has created a model of software development by representing software activities; developed a module representation formalism to specify the behavior and structure of software objects; integrated the model with the formalism to identify shared representation and inheritance mechanisms; demonstrated object programming by writing procedures and applying them to software objects; used data-directed and goal-directed reasoning to, respectively, infer the cause of bugs and evaluate the appropriateness of a configuration; and demonstrated knowledge-based graphics. Future plans include introduction of knowledge-based systems for rapid prototyping or rescheduling; natural language interfaces; blackboard architecture; and distributed processing

  19. An Opening Chapter of the First Generation of Artificial Intelligence in Medicine: The First Rutgers AIM Workshop, June 1975.

    PubMed

    Kulikowski, C A

    2015-08-13

    The first generation of Artificial Intelligence (AI) in Medicine methods were developed in the early 1970's drawing on insights about problem solving in AI. They developed new ways of representing structured expert knowledge about clinical and biomedical problems using causal, taxonomic, associational, rule, and frame-based models. By 1975, several prototype systems had been developed and clinically tested, and the Rutgers Research Resource on Computers in Biomedicine hosted the first in a series of workshops on AI in Medicine that helped researchers and clinicians share their ideas, demonstrate their models, and comment on the prospects for the field. These developments and the workshops themselves benefited considerably from Stanford's SUMEX-AIM pioneering experiment in biomedical computer networking. This paper focuses on discussions about issues at the intersection of medicine and artificial intelligence that took place during the presentations and panels at the First Rutgers AIM Workshop in New Brunswick, New Jersey from June 14 to 17, 1975.

  20. Recent developments of artificial intelligence in drying of fresh food: A review.

    PubMed

    Sun, Qing; Zhang, Min; Mujumdar, Arun S

    2018-03-01

    Intellectualization is an important direction of drying development and artificial intelligence (AI) technologies have been widely used to solve problems of nonlinear function approximation, pattern detection, data interpretation, optimization, simulation, diagnosis, control, data sorting, clustering, and noise reduction in different food drying technologies due to the advantages of self-learning ability, adaptive ability, strong fault tolerance and high degree robustness to map the nonlinear structures of arbitrarily complex and dynamic phenomena. This article presents a comprehensive review on intelligent drying technologies and their applications. The paper starts with the introduction of basic theoretical knowledge of ANN, fuzzy logic and expert system. Then, we summarize the AI application of modeling, predicting, and optimization of heat and mass transfer, thermodynamic performance parameters, and quality indicators as well as physiochemical properties of dried products in artificial biomimetic technology (electronic nose, computer vision) and different conventional drying technologies. Furthermore, opportunities and limitations of AI technique in drying are also outlined to provide more ideas for researchers in this area.

  1. Machine intelligence and autonomy for aerospace systems

    NASA Technical Reports Server (NTRS)

    Heer, Ewald (Editor); Lum, Henry (Editor)

    1988-01-01

    The present volume discusses progress toward intelligent robot systems in aerospace applications, NASA Space Program automation and robotics efforts, the supervisory control of telerobotics in space, machine intelligence and crew/vehicle interfaces, expert-system terms and building tools, and knowledge-acquisition for autonomous systems. Also discussed are methods for validation of knowledge-based systems, a design methodology for knowledge-based management systems, knowledge-based simulation for aerospace systems, knowledge-based diagnosis, planning and scheduling methods in AI, the treatment of uncertainty in AI, vision-sensing techniques in aerospace applications, image-understanding techniques, tactile sensing for robots, distributed sensor integration, and the control of articulated and deformable space structures.

  2. AiResearch QCGAT engine, airplane, and nacelle design features

    NASA Technical Reports Server (NTRS)

    Heldenbrand, R. W.

    1980-01-01

    The quiet, clean, general aviation turbofan engine and nacelle system was designed and tested. The engine utilized the core of the AiResearch model TFE731-3 engine and incorporated several unique noise- and emissions-reduction features. Components that were successfully adapted to this core include the fan, gearbox, combustor, low-pressure turbine, and associated structure. A highly versatile workhorse nacelle incorporating interchangeable acoustic and hardwall duct liners, showed that large-engine attenuation technology could be applied to small propulsion engines. The application of the mixer compound nozzle demonstrated both performance and noise advantages on the engine. Major performance, emissions, and noise goals were demonstrated.

  3. Microtropins A-I: 6'-O-(2″S,3″R)-2″-ethyl-2″,3″-dihydroxybutyrates of aliphatic alcohol β-D-glucopyranosides from the branches of Microtropis japonica.

    PubMed

    Uemura, Yuka; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Takeda, Yoshio; Kawahata, Masatoshi; Yamaguchi, Kentaro

    2013-03-01

    From the branches of Microtropis japonica (Celastraceae), nine aliphatic glucosides, named microtropins A-I, were isolated. The 6-position of glucose was esterified with (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid. Microtropins A-D contained a rare natured product nitrile functional group in their aglycones. The absolute structures of the (2S,3R)-2-ethyl-2,3-dihydroxybutyric acid moiety and aglycone of microtropin A were determined by an X-ray crystallographic method. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Characterization of a Novel Composite Staphylococcal Cassette Chromosome mec in Methicillin-Resistant Staphylococcus pseudintermedius from Thailand

    PubMed Central

    Chanchaithong, Pattrarat; Prapasarakul, Nuvee; Schwendener, Sybille

    2015-01-01

    A novel staphylococcal cassette chromosome mec (SCCmec) composite island (SCCmecAI16-SCCczrAI16-CI) was identified in Staphylococcus pseudintermedius. Four integration site sequences for SCC subdivided the 60,734-bp island into 41,232-bp SCCmecAI16, 19,400-bp SCCczrAI16, and 102-bp SCC-likeAI16 elements. SCCmecAI16 represents a new combination of ccrA1B3 genes with a class A mec complex. SCCczrAI16 contains ccrA1B6 and genes related to restriction modification and heavy metal resistance. SCCmecAI16-SCCczrAI16-CI was found in methicillin-resistant S. pseudintermedius sequence type 112 (ST112) and ST111 isolated from dogs and veterinarians in Thailand. PMID:26643350

  5. Application Architecture of Avian Influenza Research Collaboration Network in Korea e-Science

    NASA Astrophysics Data System (ADS)

    Choi, Hoon; Lee, Junehawk

    In the pursuit of globalization of the AI e-Science environment, KISTI is fostering to extend the AI research community to the AI research institutes of neighboring countries and to share the AI e-Science environment with them in the near future. In this paper we introduce the application architecture of AI research collaboration network (AIRCoN). AIRCoN is a global e-Science environment for AI research conducted by KISTI. It consists of AI virus sequence information sharing system for sufficing data requirement of research community, integrated analysis environment for analyzing the mutation pattern of AI viruses and their risks, epidemic modeling and simulation environment for establishing national effective readiness strategy against AI pandemics, and knowledge portal for sharing expertise of epidemic study and unpublished research results with community members.

  6. Transdiagnostic and diagnosis-specific dynamic functional connectivity anchored in the right anterior insula in major depressive disorder and bipolar depression.

    PubMed

    Pang, Yajing; Chen, Heng; Wang, Yifeng; Long, Zhiliang; He, Zongling; Zhang, Huangbin; Liao, Wei; Cui, Qian; Chen, Huafu

    2018-07-13

    Dysfunctional and abnormal functional connectivity in the right anterior insula (rAI) may underlie the pathophysiology of depression episode in bipolar disorder (BD) and of major depressive disorder (MDD). In this study, we examined the dynamic functional connectivity (dFC) of the rAI of 30 patients with BD, 30 patients with MDD, and 30 healthy controls. In the functional separation of rAI, the right dorsal AI (rdAI) and ventral AI (rvAI) were defined as seed regions. Sliding-window correlation of rAI subregions was implemented to measure the variance of dFC. BD and MDD shared abnormality in dFC, such as the decreased dFC between the rvAI and right ventrolateral prefrontal cortex. Others were disorder-specific and included MDD-related increases in dFC between the rvAI and right precuneus, temporal pole, and left dorsolateral prefrontal cortex. This observation is in stark contrast to BD-related increases in the dFC between the rdAI and left inferior parietal lobule and right middle occipital gyrus. The abnormal dFC of rAI shared by BD and MDD supports the importance of rAI in the common pathophysiology of these disorders. Meanwhile, disorder-specific abnormalities that attribute to the dorsal and ventral divisions of rAI can be used as biomarkers to differentiate BD from MDD. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Neuron Morphology Influences Axon Initial Segment Plasticity.

    PubMed

    Gulledge, Allan T; Bravo, Jaime J

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation.

  8. Neuron Morphology Influences Axon Initial Segment Plasticity123

    PubMed Central

    2016-01-01

    In most vertebrate neurons, action potentials are initiated in the axon initial segment (AIS), a specialized region of the axon containing a high density of voltage-gated sodium and potassium channels. It has recently been proposed that neurons use plasticity of AIS length and/or location to regulate their intrinsic excitability. Here we quantify the impact of neuron morphology on AIS plasticity using computational models of simplified and realistic somatodendritic morphologies. In small neurons (e.g., dentate granule neurons), excitability was highest when the AIS was of intermediate length and located adjacent to the soma. Conversely, neurons having larger dendritic trees (e.g., pyramidal neurons) were most excitable when the AIS was longer and/or located away from the soma. For any given somatodendritic morphology, increasing dendritic membrane capacitance and/or conductance favored a longer and more distally located AIS. Overall, changes to AIS length, with corresponding changes in total sodium conductance, were far more effective in regulating neuron excitability than were changes in AIS location, while dendritic capacitance had a larger impact on AIS performance than did dendritic conductance. The somatodendritic influence on AIS performance reflects modest soma-to-AIS voltage attenuation combined with neuron size-dependent changes in AIS input resistance, effective membrane time constant, and isolation from somatodendritic capacitance. We conclude that the impact of AIS plasticity on neuron excitability will depend largely on somatodendritic morphology, and that, in some neurons, a shorter or more distally located AIS may promote, rather than limit, action potential generation. PMID:27022619

  9. Measurement level AIS/radar fusion for maritime surveillance

    NASA Astrophysics Data System (ADS)

    Habtemariam, Biruk K.; Tharmarasa, R.; Meger, Eric; Kirubarajan, T.

    2012-05-01

    Using the Automatic Identification System (AIS) ships identify themselves intermittently by broadcasting their location information. However, traditionally radars are used as the primary source of surveillance and AIS is considered as a supplement with a little interaction between these data sets. The data from AIS is much more accurate than radar data with practically no false alarms. But unlike the radar data, the AIS measurements arrive unpredictably, depending on the type and behavior of a ship. The AIS data includes target IDs that can be associated to initialized tracks. In multitarget maritime surveillance environment, for some targets the revisit interval form the AIS could be very large. In addition, the revisit intervals for various targets can be different. In this paper, we proposed a joint probabilistic data association based tracking algorithm that addresses the aforementioned issues to fuse the radar measurements with AIS data. Multiple AIS IDs are assigned to a track, with probabilities updated by both AIS and radar measurements to resolve the ambiguity in the AIS ID source. Experimental results based on simulated data demonstrate the performance the proposed technique.

  10. Effects of different five-day progesterone-based fixed-time AI protocols on follicular/luteal dynamics and fertility in dairy cows

    PubMed Central

    GARCIA-ISPIERTO, Irina; LÓPEZ-GATIUS, Fernando

    2014-01-01

    This study compares in two experiments the responses of lactating dairy cows to four different progesterone-based protocols for fixed-time artificial insemination (FTAI) in terms of their effects on follicular/luteal dynamics and fertility. The protocols consisted of a progesterone intravaginal device fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone, equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I, the data were derived from 232 lactating cows. Binary logistic regression identified no effects of treatment on ovulation failure or multiple ovulation 10 days post artificial insemination (AI). Based on the odds ratio, the likelihood of ovulation failure was lower (by a factor of 0.1) in cows showing at least one corpus luteum (CL) upon treatment than in cows lacking a CL; repeat breeders (> 3 AI) and cows with multiple CLs at treatment showed lower (by a factor of 0.44) and higher (by a factor of 9.0) risks of multiple ovulation, respectively, than the remaining animals. In Experiment II, the data were derived from 5173 AIs. The independent variable treatment failed to affect the conception rate 28–34 days post AI, twin pregnancy or early fetal loss 58–64 days post AI. The results of this study demonstrate the efficacy of 5-day progesterone-based protocols for FTAI. All four protocols examined were able to induce ovulation in both cyclic and non-cyclic animals so that FTAI returned a similar pregnancy rate to spontaneous estrus. Our results suggest that the ovarian response and fertility resulting from each treatment are due more to the effect of ovarian structures at treatment than to the different combinations of hormones investigated. PMID:25196275

  11. Insular dysfunction within the salience network is associated with severity of symptoms and aberrant inter-network connectivity in major depressive disorder

    PubMed Central

    Manoliu, Andrei; Meng, Chun; Brandl, Felix; Doll, Anselm; Tahmasian, Masoud; Scherr, Martin; Schwerthöffer, Dirk; Zimmer, Claus; Förstl, Hans; Bäuml, Josef; Riedl, Valentin; Wohlschläger, Afra M.; Sorg, Christian

    2014-01-01

    Major depressive disorder (MDD) is characterized by altered intrinsic functional connectivity within (intra-iFC) intrinsic connectivity networks (ICNs), such as the Default Mode- (DMN), Salience- (SN) and Central Executive Network (CEN). It has been proposed that aberrant switching between DMN-mediated self-referential and CEN-mediated goal-directed cognitive processes might contribute to MDD, possibly explaining patients' difficulties to disengage the processing of self-focused, often negatively biased thoughts. Recently, it has been shown that the right anterior insula (rAI) within the SN is modulating DMN/CEN interactions. Since structural and functional alterations within the AI have been frequently reported in MDD, we hypothesized that aberrant intra-iFC in the SN's rAI is associated with both aberrant iFC between DMN and CEN (inter-iFC) and severity of symptoms in MDD. Twenty-five patients with MDD and 25 healthy controls were assessed using resting-state fMRI (rs-fMRI) and psychometric examination. High-model-order independent component analysis (ICA) of rs-fMRI data was performed to identify ICNs including DMN, SN, and CEN. Intra-iFC within and inter-iFC between distinct subsystems of the DMN, SN, and CEN were calculated, compared between groups and correlated with the severity of symptoms. Patients with MDD showed (1) decreased intra-iFC within the SN's rAI, (2) decreased inter-iFC between the DMN and CEN, and (3) increased inter-iFC between the SN and DMN. Moreover, decreased intra-iFC in the SN's rAI was associated with severity of symptoms and aberrant DMN/CEN interactions, with the latter losing significance after correction for multiple comparisons. Our results provide evidence for a relationship between aberrant intra-iFC in the salience network's rAI, aberrant DMN/CEN interactions and severity of symptoms, suggesting a link between aberrant salience mapping, abnormal coordination of DMN/CEN based cognitive processes and psychopathology in MDD. PMID:24478665

  12. Curriculum Development in Outdoor Education: Tasmanian Teachers' Perspectives on the New Pre-Tertiary Outdoor Leadership Course

    ERIC Educational Resources Information Center

    Dyment, Janet; Morse, Marcus; Shaw, Simon; Smith, Heidi

    2014-01-01

    The paper examines how outdoor education teachers in Tasmania, Australia have implemented and perceive a new pre-tertiary Outdoor Leadership curriculum document. It draws on an analysis of in-depth semi-structured interviews with 11 outdoor education teachers. The results revealed that teachers were generally welcoming of the new higher-order…

  13. Asian Students' Perceptions of Group Work and Group Assignments in a New Zealand Tertiary Institution

    ERIC Educational Resources Information Center

    Li, Mingsheng; Campbell, Jacqui

    2008-01-01

    This study, conducted in 2005 in a New Zealand tertiary institution, examines Asian students' perceptions of the much-promulgated cooperative learning concepts in the form of group work and group assignments. Twenty-two Asian students participated in one-hour individual face-to-face semi-structured interviews. The study found that Asian students…

  14. Role of extensional structures on the location of folds and thrusts during tectonic inversion (northern Iberian Chain, Spain)

    NASA Astrophysics Data System (ADS)

    Cortés, Angel L.; Liesa, Carlos L.; Soria, Ana R.; Meléndez, Alfonso

    1999-03-01

    The Aguilón Subbasin (NE Spain) was originated daring the Late Jurassic-Early Cretaceous rifting due to the action of large normal faults, probably inherited from Late Variscan fracturing. WNW-ESE normal faults limit two major troughs filled by continental deposits (Valanginian to Early Barremian). NE-SW faults control the location of subsidiary depocenters within these troughs. These basins were weakly inverted during the Tertiary with folds and thrusts striking E-W to WNW-ESE involving the Mesozoic-Tertiary cover with a maximum estimated shortening of about 12 %. Tertiary compression did not produce the total inversion of the Mesozoic basin but extensional structures are responsible for the location of major Tertiary folds. Shortening of the cover during the Tertiary involved both reactivation of some normal faults and development of folds and thrusts nucleated on basement extensional steps. The inversion style depends mainly on the occurrence and geometry of normal faults limiting the basin. Steep normal faults were not reactivated but acted as buttresses to the cover translation. Around these faults, affecting both basement and cover, folds and thrusts were nucleated due to the stress rise in front of major faults. Within the cover, the buttressing against normal faults consists of folding and faulting implying little shortening without development of ceavage or other evidence of internal deformation.

  15. Increasing atrial fibrillation prevalence in acute ischemic stroke and TIA.

    PubMed

    Otite, Fadar Oliver; Khandelwal, Priyank; Chaturvedi, Seemant; Romano, Jose G; Sacco, Ralph L; Malik, Amer M

    2016-11-08

    To evaluate trends in atrial fibrillation (AF) prevalence in acute ischemic stroke (AIS) and TIA in the United States. We used the Nationwide Inpatient Sample to retrospectively compute weighted prevalence of AF in AIS (n = 4,355,140) and TIA (n = 1,816,459) patients admitted to US hospitals from 2004 to 2013. Multivariate-adjusted models were used to evaluate the association of AF with clinical factors, mortality, length of stay, and cost. From 2004 to 2013, AF prevalence increased by 22% in AIS (20%-24%) and by 38% in TIA (12%-17%). AF prevalence varied by age (AIS: 6% in 50-59 vs 37% in ≥80 years; TIA: 4% in 50-59 vs 24% in ≥80 years), sex (AIS: male 19% vs female 25%; TIA: male 15% vs female 14%), race (AIS: white 26% vs black 12%), and region (AIS: Northeast 25% vs South 20%). Advancing age, female sex, white race, high income, and large hospital size were associated with increased odds of AF in AIS. AF in AIS was a risk factor for in-hospital death (odds ratio 1.93, 95% confidence interval 1.89-1.98) but mortality in AIS with AF decreased from 11.6% to 8.3% (p < 0.001). Compared to no AF, AF was associated with increased cost of $2,310 and length of stay 1.1 days in AIS. AF prevalence in AIS and TIA has continued to increase. Disparity in AF prevalence in AIS and TIA exists by patient and hospital factors. AF is associated with increased mortality in AIS. Innovative AIS preventive strategies are needed in patients with AF, especially in the elderly. © 2016 American Academy of Neurology.

  16. Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study

    PubMed Central

    Hsu, Tai-Yi; Shih, Hong-Mo; Wang, Yu-Chiao; Lin, Leng-Chieh; He, Guan-Yi; Chen, Chih-Yu; Kao, Chia-Hung; Chen, Chao-Hsien

    2016-01-01

    Purpose This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan. Methods This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI. Results The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19–4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001). Conclusion The risk of IBD was higher in patients with AI and increased with the length of hospital stay. PMID:27802288

  17. Do antibiotic-impregnated shunts in hydrocephalus therapy reduce the risk of infection? An observational study in 258 patients

    PubMed Central

    Ritz, Rainer; Roser, Florian; Morgalla, Matthias; Dietz, Klaus; Tatagiba, Marcos; Will, Bernd E

    2007-01-01

    Background Shunt infection in hydrocephalus patients is a severe, even life-threatening complication. Antibiotic-impregnated shunts (AIS) have been developed in an attempt to reduce rate of shunt infection. The study was performed to analyze if AIS can diminish the rate of shunt infection. The pathogenic nature of shunt infection in patients with AIS systems and those without antibiotic impregnated shunts (non-AIS) was compared. Methods Over a period of 24 months in the Department of Neurosurgery at University Hospital of Tübingen shunt surgery was performed in 258 patients. In 86 patients AIS systems were implanted. Shunt catheters were commercially impregnated with clindamycin and rifampicin. Analysis of the clinical data included sex, age, classification of hydrocephalus, shunt types and risk factors for shunt infection [age (< 1 year and > 80 years), prematurely born patients, external ventricular drainage, former shunt infection, former systemic infection, disturbance of consciousness, former radiation-/chemotherapy]. Infection rates and underlying bacterial pathogens of patients with AIS were compared to patients with implanted non-AIS systems (172 patients). Results AIS and non-AIS patients did not differ in sex, etiology of hydrocephalus and the shunt type. In the AIS group 72 out of 86 patients had at least one risk factor (83.7 %), compared to 126 patients in the non-AIS group (73.3 %). There was no significant difference between the two groups (p = 0.0629; Fisher's exact test). In patients with no risk factors, only one patient with non-AIS suffered from shunt infection. In patients with one or more risk factors the rate for shunt infection was 7.14 % in patients with non-AIS and 6.94 % in patients with AIS. Former shunt infection (p = 0.0124) was related to higher risk for shunt infection. The use of AIS had therefore no significant advantage (p = 0.8611; multiple logistic regression). Significantly related to a shunt infection was the number of shunt surgeries. 190 interventions in the AIS group (2.21 interventions per patient) and 408 in the non-AIS group (2.37 interventions per patient) had been performed (p = 0.3063; Wilcoxon). There was no shunt infection in the group of patients on whom only one shunt surgery was performed. In patients with at least two shunt surgeries the infection rate was 9%. The infection rate in AIS patients was 5/52 (9.6 %) and in the non-AIS 10/114 (8.77 %), (p = 1.0; Fisher's exact test). Staphylococcus epidermidis was the most frequent pathogen for shunt infection. Fourteen out of 15 infections occurred within the first 6 months of surgery. The most frequent pathogen for shunt infection was S. epidermidis. No toxic or allergic complications were seen using the AIS shunt systems. The presented data show a remarkably low infection rate of 5.8 % in the non-AIS group compared to other studies which demonstrated a significant decrease in the infection rate by AIS. Conclusion AIS did not significantly reduce shunt infection in hydrocephalus patients in the presented study. In the AIS group three patients suffered from shunt infections caused by skin ulceration or neurosurgical procedures with exposure of the cerebrospinal liquor after shunt implantation. AIS was not developed to prevent infection in such cases, therefore an advantage of AIS can not be excluded. In view of the presented data and the small number of reported studies a prospective randomized multicenter study is required. PMID:17488498

  18. Effect of education on ability of AI professionals and herd-owner inseminators to detect cows not in oestrus and its relation with progesterone concentration on day of re-insemination.

    PubMed

    Vartia, K; Taponen, J; Heikkinen, J; Lindeberg, H

    2017-10-15

    The effect of training background of persons performing artificial insemination (AI) (herd-owner inseminators (OWNER), AI technicians (AI-T), and fertility consultants (FC)) on pregnancy rate and their ability to detect cows not in oestrus were studied. A total of 1584 re-AI occasions on 754 dairy farms were included. Milk samples for progesterone (P4) analysis in all cases were collected, as were data on the herd, previous breeding attempts, oestrous signs, uterine tone, slipperiness of cervix, and co-operation of the cow. Further breeding attempts and next calving or culling date were sought from registers. The cases were distributed into three categories based on P4 concentrations; <6 nmol/l (no luteal activity, could be in oestrus), 6-10 nmol/l (some luteal activity), and >10 nmol/l (high luteal activity, not in oestrus). Of cows offered for re-AI 7.7% had P4 concentration >10 nmol/l, with no difference between OWNER farms and farms using AI service. OWNERs chose for AI more cows having intermediate P4 than farms using AI service (9.8% vs. 5.9%, p < 0.05). AI-Ts recommended no AI significantly less often than FCs (1.6% vs. 4.9%, p < 0.01). Both groups were equally right: 71% and 68% of cows that were recommended to have no AI had high P4 concentration. Due to courageous and correct rejection of cows with high P4, FCs inseminated proportionally more cows in low P4 and less cows in intermediate P4 than OWNERs (p < 0.05). Of cows finally inseminated, 36.7% became pregnant, with no difference between OWNER farms and farms using AI service. Fertility consultants had higher pregnancy rates than AI-Ts (39.6% vs. 32.6%, p < 0.05). Toneless uterus and sticky cervix at AI significantly correlated with AI occurring at the wrong time (p < 0.001). Behaviour of the cow at AI did not predict P4 concentration. In conclusion, 7.7% of cows offered for re-AI had high P4 concentration. Training of AI personnel increased their ability to detect and reject these cows. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Formation mechanism of NDMA from ranitidine, trimethylamine, and other tertiary amines during chloramination: a computational study.

    PubMed

    Liu, Yong Dong; Selbes, Meric; Zeng, Chengchu; Zhong, Rugang; Karanfil, Tanju

    2014-01-01

    Chloramination of drinking waters has been associated with N-nitrosodimethylamine (NDMA) formation as a disinfection byproduct. NDMA is classified as a probable carcinogen and thus its formation during chloramination has recently become the focus of considerable research interest. In this study, the formation mechanisms of NDMA from ranitidine and trimethylamine (TMA), as models of tertiary amines, during chloramination were investigated by using density functional theory (DFT). A new four-step formation pathway of NDMA was proposed involving nucleophilic substitution by chloramine, oxidation, and dehydration followed by nitrosation. The results suggested that nitrosation reaction is the rate-limiting step and determines the NDMA yield for tertiary amines. When 45 other tertiary amines were examined, the proposed mechanism was found to be more applicable to aromatic tertiary amines, and there may be still some additional factors or pathways that need to be considered for aliphatic tertiary amines. The heterolytic ONN(Me)2-R(+) bond dissociation energy to release NDMA and carbocation R(+) was found to be a criterion for evaluating the reactivity of aromatic tertiary amines. A structure-activity study indicates that tertiary amines with benzyl, aromatic heterocyclic ring, and diene-substituted methenyl adjacent to the DMA moiety are potentially significant NDMA precursors. The findings of this study are helpful for understanding NDMA formation mechanism and predicting NDMA yield of a precursor.

  20. Quantifying the tracking capability of space-based AIS systems

    NASA Astrophysics Data System (ADS)

    Skauen, Andreas Nordmo

    2016-01-01

    The Norwegian Defence Research Establishment (FFI) has operated three Automatic Identification System (AIS) receivers in space. Two are on dedicated nano-satellites, AISSat-1 and AISSat-2. The third, the NORAIS Receiver, was installed on the International Space Station. A general method for calculating the upper bound on the tracking capability of a space-based AIS system has been developed and the results from the algorithm applied to AISSat-1 and the NORAIS Receiver individually. In addition, a constellation of AISSat-1 and AISSat-2 is presented. The tracking capability is defined as the probability of re-detecting ships as they move around the globe and is explained to represent and upper bound on a space-based AIS system performance. AISSat-1 and AISSat-2 operates on the nominal AIS1 and AIS2 channels, while the NORAIS Receiver data used are from operations on the dedicated space AIS channels, AIS3 and AIS4. The improved tracking capability of operations on the space AIS channels is presented.

  1. Prevalence and Frequency of Heterosexual Anal Intercourse Among Young People: A Systematic Review and Meta-analysis.

    PubMed

    Owen, Branwen N; Brock, Patrick M; Butler, Ailsa R; Pickles, Michael; Brisson, Marc; Baggaley, Rebecca F; Boily, Marie-Claude

    2015-07-01

    We aim to assess if heterosexual anal intercourse (AI) is commonly practiced and how frequently it is practiced by young people. We searched PubMed for articles published 1975 to July 2014 reporting data on the proportion of young people (mean age <25) practicing heterosexual AI (AI prevalence) and on number of AI acts (AI frequency). Stratified random-effects meta-analysis and meta-regression were used to produce summary estimates and assess the influence of participant and study characteristics on AI prevalence. Eighty-three and thirteen of the 136 included articles reported data on lifetime AI prevalence and monthly AI frequency, respectively. Estimates were heterogenous. Overall summary estimates of lifetime AI prevalence were 22 % (95 % confidence interval 20-24) among sexually active young people, with no statistically significant differences by gender, continent or age. Prevalence increased significantly with confidentiality of interview method and, among males and in Europe, by survey year. Prevalence did not significantly differ by recall period. An estimated 3-24 % of all reported sex acts were AI. Reported heterosexual AI is common but variable among young people worldwide. To fully understand its impact on STI spread, more and better quality data on frequency of unprotected AI, and trends over time are required.

  2. Structural controls on Carlin-type gold mineralization in the gold bar district, Eureka County, Nevada

    USGS Publications Warehouse

    Yigit, O.; Nelson, E.P.; Hitzman, M.W.; Hofstra, A.H.

    2003-01-01

    The Gold Bar district in the southern Roberts Mountains, 48 km northwest of Eureka, Nevada, contains one main deposit (Gold Bar), five satellite deposits, and other resources. Approximately 0.5 Moz of gold have been recovered from a resource of 1,639,000 oz of gold in Carlin-type gold deposits in lower plate, miogeoclinal carbonate rocks below the Roberts Mountains thrust. Host rocks are unit 2 of the Upper Member of the Devonian Denay Formation and the Bartine Member of the McColley Canyon Formation. Spatial and temporal relations between structures and gold mineralization indicate that both pre-Tertiary and Tertiary structures were important controls on gold mineralization. Gold mineralization occurs primarily along high-angle Tertiary normal faults, some of which are reactivated reverse faults of Paleozoic or Mesozoic age. Most deposits are localized at the intersection of northwest- and northeast-striking faults. Alteration includes decalcification, and to a lesser extent, silicification along high-angle faults. Jasperoid (pervasive silicification), which formed along most faults and in some strata-bound zones, accounts for a small portion of the ore in every deposit. In the Gold Canyon deposit, a high-grade jasperoid pipe formed along a Tertiary normal fault which was localized along a zone of overturned fault-propagation folds and thrust faults of Paleozoic or Mesozoic age.

  3. Geology and tectonic development of the continental margin north of Alaska

    USGS Publications Warehouse

    Grantz, A.; Eittreim, S.; Dinter, D.A.

    1979-01-01

    The continental margin north of Alaska, as interpreted from seismic reflection profiles, is of the Atlantic type and consists of three sectors of contrasting structure and stratigraphy. The Chukchi sector, on the west, is characterized by the deep late Mesozoic and Tertiary North Chukchi basin and the Chukchi Continental Borderland. The Barrow sector of central northern Alaska is characterized by the Barrow arch and a moderately thick continental terrace build of Albian to Tertiary clastic sediment. The terrace sedimentary prism is underlain by lower Paleozoic metasedimentary rocks. The Barter Island sector of northeastern Alaska and Yukon Territory is inferred to contain a very thick prism of Jurassic, Cretaceous and Tertiary marine and nonmarine clastic sediment. Its structure is dominated by a local deep Tertiary depocenter and two regional structural arches. We postulate that the distinguishing characteristics of the three sectors are inherited from the configuration of the rift that separated arctic Alaska from the Canadian Arctic Archipelago relative to old pre-rift highlands, which were clastic sediment sources. Where the rift lay relatively close to northern Alaska, in the Chukchi and Barter Island sectors, and locally separated Alaska from the old source terranes, thick late Mesozoic and Tertiary sedimentary prisms extend farther south beneath the continental shelf than in the intervening Barrow sector. The boundary between the Chukchi and Barrow sectors is relatively well defined by geophysical data, but the boundary between the Barrow and Barter Island sectors can only be inferred from the distribution and thickness of Jurassic and Cretaceous sedimentary rocks. These boundaries may be extensions of oceanic fracture zones related to the rifting that is postulated to have opened the Canada Basin, probably beginning during the Early Jurassic. ?? 1979.

  4. Long-term adherence to apomorphine infusion in patients with Parkinson disease: a 10-year observational study.

    PubMed

    Kimber, Thomas E; Fang, Jing; Huddy, Lynda J; Thompson, Philip D

    2017-05-01

    Patients with Parkinson disease (PD) commonly experience motor fluctuations and dyskinesias in response to oral dopaminergic medications. Affected patients may benefit from device-assisted therapy, such as medication infusion or deep brain stimulation surgery. This is the first Australian study of the long-term adherence to apomorphine infusion (AI) in patients with PD. To assess the adherence to AI in patients with PD in a single centre over a 10-year period and to find the reasons for discontinuation in patients who discontinued AI. This is an observational study of patients with PD treated with AI between 2004 and 2014. Outcome measures included changes in motor function and quality of life following AI, change in dose of other dopaminergic medications following AI, duration of infusion, adverse effects, reasons for cessation of AI and subsequent treatment after cessation. Mean duration of AI was 21.65 months. No patient achieved apomorphine monotherapy, and the mean reduction in the levodopa-equivalent dose of other dopaminergic medications after AI was 22.7%. The benefit of AI on motor function and quality of life was rated as 'much improved' or 'better' in 83% of patients. The most common reasons for discontinuation of AI were adverse effects and inadequate motor benefit. Most patients who discontinued AI were subsequently treated with another device-assisted therapy. AI is an effective therapy for severe motor response complications in PD, especially in the short and medium term. However, many patients cannot be maintained on AI in the longer term. © 2017 Royal Australasian College of Physicians.

  5. Amorphous Iron Borides: Preparation, Structure and Magnetic Properties.

    DTIC Science & Technology

    1982-09-28

    temperature. External magnetic field experiments were performed in a superconducting solenoid with both source and absor- ber at 4.2 K. The observed...D-Ai20 919 AMORPHOUS IRON BORIDES: PREPARATION STRUCTURE AND i/i MAGNETIC PROPERTIES(U) JOHNS HOPKINS UNIV LAUREL NO APPLIED PHYSICS LRB K MOORJRNI...NATIONAL BUREAU OF STANOANOS-93-A 10 AMORPHOUS IRON BORIDES: PREPARATION, STRUCTURE ~AND MAGNETIC PROPERTIES FINAL REPORT Kishin Moorjani September 1982 U

  6. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: ALTERNATIVE.

    PubMed

    Johnston, Stephen R D; Hegg, Roberto; Im, Seock-Ah; Park, In Hae; Burdaeva, Olga; Kurteva, Galina; Press, Michael F; Tjulandin, Sergei; Iwata, Hiroji; Simon, Sergio D; Kenny, Sarah; Sarp, Severine; Izquierdo, Miguel A; Williams, Lisa S; Gradishar, William J

    2018-03-10

    Purpose Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)-positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. Methods Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) + TRAS + AI, TRAS + AI, or LAP + AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP + TRAS + AI versus TRAS + AI. Secondary end points were PFS (comparison of other arms), overall survival, overall response rate, clinical benefit rate, and safety. Results Three hundred fifty-five patients were included in this analysis: LAP + TRAS + AI (n = 120), TRAS + AI (n = 117), and LAP + AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP + TRAS + AI versus TRAS + AI (median PFS, 11 v 5.7 months; hazard ratio, 0.62; 95% CI, 0.45 to 0.88; P = .0064). Consistent PFS benefit was observed in predefined subgroups. Overall response rate, clinical benefit rate, and overall survival also favored LAP + TRAS + AI. The median PFS with LAP + AI versus TRAS + AI was 8.3 versus 5.7 months (hazard ratio, 0.71; 95% CI, 0.51 to 0.98; P = .0361). Common adverse events (AEs; ≥ 15%) with LAP + TRAS + AI, TRAS + AI, and LAP + AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the three groups, and AEs leading to discontinuation were lower with LAP + TRAS + AI. Conclusion Dual HER2 blockade with LAP + TRAS + AI showed superior PFS benefit versus TRAS + AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population.

  7. Evaporite geometries and diagenetic traps, lower San Andres, Northwest shelf, New Mexico

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

    Keller, D.R.

    An east-west-trending belt of lower San Andres oil fields extends 80 mi across southeastern New Mexico from the Pecos River near Roswell to the Texas-New Mexico border. These fields are along a porosity pinch-out zone where porous carbonates grade laterally into bedded anhydrite and halite. The lower San Andres traps are associated with pre-Tertiary structural or stratigraphic traps. Oil and water production relationships from these fields are not consistent with present-day structure. These fields have been commonly interpreted to be hydrodynamic traps created by the eastern flow of fresh surface water that enters the lower San Andres outcrops west ofmore » Pecos River. There is no evidence, however, that surface water has moved through the lower San Andres in this area. This conclusion is supported by the fact that formation-water resistivities are uniform throughout the producing trend, no significant dissolution of carbonates or evaporites has occurred, and there has been no increase in biogradation of oils adjacent to the lower San Andres outcrops. These fields actually are diagenetic traps created by porosity occlusion in the water column beneath the oil accumulations. Hydrocarbons originally were trapped in pre-Tertiary structural and structural-stratigraphic traps. Bedded evaporites were effective barriers to vertical and lateral hydrocarbon migration. Eastward tilting of the Northwest shelf during the Tertiary opened these traps, but the oil remained in these structurally unfavorable positions because of the diagenetic sealing. The gas-solution drive in these reservoirs is a result of this sealing. The sequence of events leading to diagenetic entrapment include (1) Triassic and Jurassic migration of hydrocarbons into broad, low-relief post-San Andres structural and structural-stratigraphic traps; (2) rapid occlusion of porosity in the water column beneath oil reservoirs, and (3) Tertiary tilt-out traps.« less

  8. Discovery of Tertiary Sulfonamides as Potent Liver X Receptor Antagonists

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

    Zuercher, William J.; Buckholz†, Richard G.; Campobasso, Nino

    2010-08-12

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  9. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    PubMed

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  10. Tertiary alphabet for the observable protein structural universe.

    PubMed

    Mackenzie, Craig O; Zhou, Jianfu; Grigoryan, Gevorg

    2016-11-22

    Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence-a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure.

  11. Tertiary alphabet for the observable protein structural universe

    PubMed Central

    Mackenzie, Craig O.; Zhou, Jianfu; Grigoryan, Gevorg

    2016-01-01

    Here, we systematically decompose the known protein structural universe into its basic elements, which we dub tertiary structural motifs (TERMs). A TERM is a compact backbone fragment that captures the secondary, tertiary, and quaternary environments around a given residue, comprising one or more disjoint segments (three on average). We seek the set of universal TERMs that capture all structure in the Protein Data Bank (PDB), finding remarkable degeneracy. Only ∼600 TERMs are sufficient to describe 50% of the PDB at sub-Angstrom resolution. However, more rare geometries also exist, and the overall structural coverage grows logarithmically with the number of TERMs. We go on to show that universal TERMs provide an effective mapping between sequence and structure. We demonstrate that TERM-based statistics alone are sufficient to recapitulate close-to-native sequences given either NMR or X-ray backbones. Furthermore, sequence variability predicted from TERM data agrees closely with evolutionary variation. Finally, locations of TERMs in protein chains can be predicted from sequence alone based on sequence signatures emergent from TERM instances in the PDB. For multisegment motifs, this method identifies spatially adjacent fragments that are not contiguous in sequence—a major bottleneck in structure prediction. Although all TERMs recur in diverse proteins, some appear specialized for certain functions, such as interface formation, metal coordination, or even water binding. Structural biology has benefited greatly from previously observed degeneracies in structure. The decomposition of the known structural universe into a finite set of compact TERMs offers exciting opportunities toward better understanding, design, and prediction of protein structure. PMID:27810958

  12. Topological Constraints and Their Conformational Entropic Penalties on RNA Folds.

    PubMed

    Mak, Chi H; Phan, Ethan N H

    2018-05-08

    Functional RNAs can fold into intricate structures using a number of different secondary and tertiary structural motifs. Many factors contribute to the overall free energy of the target fold. This study aims at quantifying the entropic costs coming from the loss of conformational freedom when the sugar-phosphate backbone is subjected to constraints imposed by secondary and tertiary contacts. Motivated by insights from topology theory, we design a diagrammatic scheme to represent different types of RNA structures so that constraints associated with a folded structure may be segregated into mutually independent subsets, enabling the total conformational entropy loss to be easily calculated as a sum of independent terms. We used high-throughput Monte Carlo simulations to simulate large ensembles of single-stranded RNA sequences in solution to validate the assumptions behind our diagrammatic scheme, examining the entropic costs for hairpin initiation and formation of many multiway junctions. Our diagrammatic scheme aids in the factorization of secondary/tertiary constraints into distinct topological classes and facilitates the discovery of interrelationships among multiple constraints on RNA folds. This perspective, which to our knowledge is novel, leads to useful insights into the inner workings of some functional RNA sequences, demonstrating how they might operate by transforming their structures among different topological classes. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  13. Alteration of human serum albumin tertiary structure induced by glycation. Spectroscopic study

    NASA Astrophysics Data System (ADS)

    Szkudlarek, A.; Maciążek-Jurczyk, M.; Chudzik, M.; Równicka-Zubik, J.; Sułkowska, A.

    2016-01-01

    The modification of human serum albumin (HSA) structure by non-enzymatic glycation is one of the underlying factors that contribute to the development of complications of diabetes and neurodegenerative diseases. The aim of the present work was to estimate how glycation of HSA altered its tertiary structure. Changes of albumin conformation were investigated by comparison of glycated (gHSA) and non-glycated human serum albumin (HSA) absorption spectra, red edge excitation shift (REES) and synchronous spectra. Effect of glycation on human serum albumin tertiary structure was also investigated by 1H NMR spectroscopy. Formation of gHSA Advanced Glycation End-products (AGEs) caused absorption of UV-VIS light between 310 nm and 400 nm while for non-glycated HSA in this region no absorbance has been registered. Analysis of red edge excitation shift effect allowed for observation of structural changes of gHSA in the hydrophobic pocket containing the tryptophanyl residue. Moreover changes in the microenvironment of tryptophanyl and tyrosyl residues brought about AGEs on the basis of synchronous fluorescence spectroscopy have been confirmed. The influence of glycation process on serum albumin binding to 5-dimethylaminonaphthalene-1-sulfonamide (DNSA), 2-(p-toluidino) naphthalene-6-sulfonic acid (TNS), has been studied. Fluorescence analysis showed that environment of both binding site I and II is modified by galactose glycation.

  14. American Indians/Native Alaskans with Traumatic Brain Injury: Examining the Impairments of Traumatic Brain Injury, Disparities in Service Provision, and Employment Outcomes

    ERIC Educational Resources Information Center

    Whitfield, Harold Wayne; Lloyd, Rosalind

    2008-01-01

    The researchers analyzed data from fiscal year 2006 and found that American Indians/Native Alaskans (AI/NA) with traumatic brain injury experienced similar functional limitations at application as did non-AI/NA. Fewer funds were expended on purchased services for AI/NA than for non-AI/NA. The wages of AI/NA were equitable to those of non-AI/NA at…

  15. Laser-ranging long-baseline differential atom interferometers for space

    NASA Astrophysics Data System (ADS)

    Chiow, Sheng-wey; Williams, Jason; Yu, Nan

    2015-12-01

    High-sensitivity differential atom interferometers (AIs) are promising for precision measurements in science frontiers in space, including gravity-field mapping for Earth science studies and gravitational wave detection. Difficulties associated with implementing long-baseline differential AIs have previously included the need for a high optical power, large differential Doppler shifts, and narrow dynamic range. We propose a configuration of twin AIs connected by a laser-ranging interferometer (LRI-AI) to provide precise information of the displacements between the two AI reference mirrors and also to phase-lock the two independent interferometer lasers over long distances, thereby drastically improving the practical feasibility of long-baseline differential AI measurements. We show that a properly implemented LRI-AI can achieve equivalent functionality to the conventional differential AI measurement configuration.

  16. Results from service tests on AI-91 gasoline

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

    Turovskii, F.V.; Bakaleinik, A.M.; Belyaev, A.A.

    1988-01-01

    Research was conducted to establish whether the operational reliability of engines will be affected by the use of a gasoline with an octane number two points lower than that of commercial AI-93 leaded gasoline with knock resistance in acceleration that is better than that of the AI-93 by approximately the same amount. Extended road tests were run in VAZ-2106 and Moskvich-2140 automobiles using gasoline with a research octane number of 91, containing an antiknock additive based on tetramethyl lead, and AI-93. The experimental AI-91 and the commercial AI-93 gasolines were prepared from the same base blend. Average specific fuel consumptionsmore » were identical for automobiles using AI-93 and AI-91 with the tetramethyl lead additive. For automobiles using AI-91 with the additive and with ethyl bromide as a lead scavenger the fuel consumption was 2% lower.« less

  17. Novel cross-linked alcohol-insoluble solid (CL-AIS) affinity gel from pea pod for pectinesterase purification.

    PubMed

    Wu, Ming-Chang; Lin, Guan-Hui; Wang, Yuh-Tai; Jiang, Chii-Ming; Chang, Hung-Min

    2005-10-05

    Alcohol-insoluble solids (AIS) from pea pod were cross-linked (CL-AIS) and used as an affinity gel matrix to isolate pectin esterases (PEs) from tendril shoots of chayote (TSC) and jelly fig achenes (JFA), and the results were compared with those isolated by ion-exchange chromatography with a commercial resin. CL-AIS gel matrix in a column displayed poor absorption and purification fold of PE; however, highly methoxylated CL-AIS (HM-CL-AIS), by exposing CL-AIS to methanolic sulfuric acid to increase the degree of esterification (DE) to 92%, facilitated the enzyme purification. The purified TSC PE and JFA PE by the HM-CL-AIS column were proofed as a single band on an SDS-PAGE gel, showing that the HM-CL-AIS column was a good matrix for purification of PE, either with alkaline isoelectric point (pI) (TSC PE) or with acidic pI (JFA PE).

  18. Mapping AIS coverage for trusted surveillance

    NASA Astrophysics Data System (ADS)

    Lapinski, Anna-Liesa S.; Isenor, Anthony W.

    2010-10-01

    Automatic Identification System (AIS) is an unattended vessel reporting system developed for collision avoidance. Shipboard AIS equipment automatically broadcasts vessel positional data at regular intervals. The real-time position and identity data from a vessel is received by other vessels in the area thereby assisting with local navigation. As well, AIS broadcasts are beneficial to those concerned with coastal and harbour security. Land-based AIS receiving stations can also collect the AIS broadcasts. However, reception at the land station is dependent upon the ship's position relative to the receiving station. For AIS to be used as a trusted surveillance system, the characteristics of the AIS coverage area in the vicinity of the station (or stations) should be understood. This paper presents some results of a method being investigated at DRDC Atlantic, Canada) to map the AIS coverage characteristics of a dynamic AIS reception network. The method is shown to clearly distinguish AIS reception edges from those edges caused by vessel traffic patterns. The method can also be used to identify temporal changes in the coverage area, an important characteristic for local maritime security surveillance activities. Future research using the coverage estimate technique is also proposed to support surveillance activities.

  19. Abnormal skeletal growth patterns in adolescent idiopathic scoliosis--a longitudinal study until skeletal maturity.

    PubMed

    Yim, Annie P Y; Yeung, Hiu-Yan; Hung, Vivian W Y; Lee, Kwong-Man; Lam, Tsz-Ping; Ng, Bobby K W; Qiu, Yong; Cheng, Jack C Y

    2012-08-15

    A cross-sectional and prospective longitudinal study on the anthropometric parameters and growth pattern of girls with adolescent idiopathic scoliosis (AIS). To investigate the growth pattern of girls with AIS with different severities, using cross-sectional and prospective longitudinal data set in comparison with age-matched healthy controls. AIS occurs in children during their pubertal growth spurt. Although there is no clear consensus on the difference in body height between girls with AIS and healthy controls, it is generally thought that the development and curve progression in girls with AIS is closely associated with their growth rate. There is no concrete prospective longitudinal study to document clearly the growth pattern and growth rate of subjects with AIS . A total of 611 girls with AIS and 296 healthy age-matched controls were included in the study and among them, 194 girls with AIS and 116 healthy controls were followed up until skeletal maturity. The girls with AIS were grouped into moderate (AIS20) and severe curve (AIS40) groups on the basis of maximum curve magnitude at skeletal maturity. Clinical data and detailed anthropometric parameters were recorded. In the cross-sectional analysis, the groups of subjects were compared within different age groups (from the age of 12-16 yr). In the longitudinal study, linear mixed modeling with respect to age or years since menarche was employed to formulate the growth trajectory of different anthropometric parameters. In the cross-sectional analysis, the girls with AIS were generally taller, with longer arm span and lower body mass index than the healthy controls. The girls with AIS40 were found to be significantly shorter in height (P = 0.006) and arm span (P = 0.025) at the age of 12 years but caught up and overtook the control group at the age of 14 to 16 years. In the longitudinal study, the average growth rate of arm span in girls with AIS40 was significantly higher than that in girls with AIS20 (> 30%) (P = 0.004) and controls (> 70%) (P = 0.0004). The age of menarche of girls with AIS40 was significantly delayed by 5.9 months and 3.8 months when compared with the control group and girls with AIS20, respectively (P < 0.05). The growth patterns of girls with AIS with confirmed curve severities were significantly different from healthy age-matched controls. Girls with severe AIS had delayed menarche with faster skeletal growth rate during the age of 12 to 16 years. Monitoring the rate of change of arm span of girls with AIS could be an important additional clinical parameter in helping predict curve severity in girls with AIS.

  20. Measuring case-mix complexity of tertiary care hospitals using DRGs.

    PubMed

    Park, Hayoung; Shin, Youngsoo

    2004-02-01

    The objectives of the study were to develop a model that measures and evaluates case-mix complexity of tertiary care hospitals, and to examine the characteristics of such a model. Physician panels defined three classes of case complexity and assigned disease categories represented by Adjacent Diagnosis Related Groups (ADRGs) to one of three case complexity classes. Three types of scores, indicating proportions of inpatients in each case complexity class standardized by the proportions at the national level, were defined to measure the case-mix complexity of a hospital. Discharge information for about 10% of inpatient episodes at 85 hospitals with bed size larger than 400 and their input structure and research and education activity were used to evaluate the case-mix complexity model. Results show its power to predict hospitals with the expected functions of tertiary care hospitals, i.e. resource intensive care, expensive input structure, and high levels of research and education activities.

  1. Unique local bone tissue characteristics in iliac crest bone biopsy from adolescent idiopathic scoliosis with severe spinal deformity

    PubMed Central

    Wang, Zhiwei; Chen, Huanxiong; Yu, Y. Eric; Zhang, Jiajun; Cheuk, Ka-Yee; Ng, Bobby K. W.; Qiu, Yong; Guo, X. Edward; Cheng, Jack C. Y.; Lee, Wayne Y. W.

    2017-01-01

    Adolescent idiopathic scoliosis is a complex disease with unclear etiopathogenesis. Systemic and persistent low bone mineral density is an independent prognostic factor for curve progression. The fundamental question of how bone quality is affected in AIS remains controversy because there is lack of site-matched control for detailed analysis on bone-related parameters. In this case-control study, trabecular bone biopsies from iliac crest were collected intra-operatively from 28 severe AIS patients and 10 matched controls with similar skeletal and sexual maturity, anthropometry and femoral neck BMD Z-score to control confounding effects. In addition to static histomorphometry, micro-computed tomography (μCT) and real time-PCR (qPCR) analyses, individual trabecula segmentation (ITS)-based analysis, finite element analysis (FEA), energy dispersive X-ray spectroscopy (EDX) were conducted to provide advanced analysis of structural, mechanical and mineralization features. μCT and histomorphometry showed consistently reduced trabecular number and connectivity. ITS revealed predominant change in trabecular rods, and EDX confirmed less mineralization. The structural and mineralization abnormality led to slight reduction in apparent modulus, which could be attributed to differential down-regulation of Runx2, and up-regulation of Spp1 and TRAP. In conclusion, this is the first comprehensive study providing direct evidence of undefined unique pathological changes at different bone hierarchical levels in AIS. PMID:28054655

  2. Cytotoxicity and structure activity relationship studies of maplexins A-I, gallotannins from red maple (Acer rubrum).

    PubMed

    González-Sarrías, Antonio; Yuan, Tao; Seeram, Navindra P

    2012-05-01

    Maplexins A-I are a series of structurally related gallotannins recently isolated from the red maple (Acer rubrum) species. They differ in number and location of galloyl derivatives attached to 1,5-anhydro-glucitol. Here, maplexins A-I were evaluated for anticancer effects against human tumorigenic (colon, HCT-116; breast, MCF-7) and non-tumorigenic (colon, CCD-18Co) cell lines. The maplexins which contained two (maplexins C-D) or three (maplexins E-I) galloyl derivatives each, inhibited cancer cell growth while those with only one galloyl group (maplexins A-B) did not. Moreover, maplexins C-D showed greater antiproliferative effects than maplexins E-I (IC(50)=59.8-67.9 and 95.5-108.5 μM vs. 73.7-165.2 and 115.5-182.5 μM against HCT-116 and MCF-7 cells, respectively). Notably, the cancer cells were up to 2.5-fold more sensitive to the maplexins than the normal cells. In further mechanistic studies, maplexins C-D (at 75 μM concentrations) induced apoptosis and arrested cell cycle (in the S-phase) of the cancer cells. These results suggest that the number of galloyl groups attached to the 1,5-anhydro-glucitol moiety in these gallotannins are important for antiproliferative activity. Also, this is the first in vitro anticancer study of maplexins. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex.

    PubMed

    Stehberg, Jimmy; Dang, Phat T; Frostig, Ron D

    2014-01-01

    Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed.

  4. Unimodal primary sensory cortices are directly connected by long-range horizontal projections in the rat sensory cortex

    PubMed Central

    Stehberg, Jimmy; Dang, Phat T.; Frostig, Ron D.

    2014-01-01

    Research based on functional imaging and neuronal recordings in the barrel cortex subdivision of primary somatosensory cortex (SI) of the adult rat has revealed novel aspects of structure-function relationships in this cortex. Specifically, it has demonstrated that single whisker stimulation evokes subthreshold neuronal activity that spreads symmetrically within gray matter from the appropriate barrel area, crosses cytoarchitectural borders of SI and reaches deeply into other unimodal primary cortices such as primary auditory (AI) and primary visual (VI). It was further demonstrated that this spread is supported by a spatially matching underlying diffuse network of border-crossing, long-range projections that could also reach deeply into AI and VI. Here we seek to determine whether such a network of border-crossing, long-range projections is unique to barrel cortex or characterizes also other primary, unimodal sensory cortices and therefore could directly connect them. Using anterograde (BDA) and retrograde (CTb) tract-tracing techniques, we demonstrate that such diffuse horizontal networks directly and mutually connect VI, AI and SI. These findings suggest that diffuse, border-crossing axonal projections connecting directly primary cortices are an important organizational motif common to all major primary sensory cortices in the rat. Potential implications of these findings for topics including cortical structure-function relationships, multisensory integration, functional imaging, and cortical parcellation are discussed. PMID:25309339

  5. Tertiary structural propensities reveal fundamental sequence/structure relationships.

    PubMed

    Zheng, Fan; Zhang, Jian; Grigoryan, Gevorg

    2015-05-05

    Extracting useful generalizations from the continually growing Protein Data Bank (PDB) is of central importance. We hypothesize that the PDB contains valuable quantitative information on the level of local tertiary structural motifs (TERMs). We show that by breaking a protein structure into its constituent TERMs, and querying the PDB to characterize the natural ensemble matching each, we can estimate the compatibility of the structure with a given amino acid sequence through a metric we term "structure score." Considering submissions from recent Critical Assessment of Structure Prediction (CASP) experiments, we found a strong correlation (R = 0.69) between structure score and model accuracy, with poorly predicted regions readily identifiable. This performance exceeds that of leading atomistic statistical energy functions. Furthermore, TERM-based analysis of two prototypical multi-state proteins rapidly produced structural insights fully consistent with prior extensive experimental studies. We thus find that TERM-based analysis should have considerable utility for protein structural biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Infectious Disease Hospitalizations Among American Indian/Alaska Native and Non–American Indian/Alaska Native Persons in Alaska, 2010-2011

    PubMed Central

    Holman, Robert C.; Seeman, Sara M.; Rarig, Alice J.; McEwen, Mary; Steiner, Claudia A.; Bartholomew, Michael L.; Hennessy, Thomas W.

    2016-01-01

    Objective: Reports about infectious disease (ID) hospitalization rates among American Indian/Alaska Native (AI/AN) persons have been constrained by data limited to the tribal health care system and by comparisons with the general US population. We used a merged state database to determine ID hospitalization rates in Alaska. Methods: We combined 2010 and 2011 hospital discharge data from the Indian Health Service and the Alaska State Inpatient Database. We used the merged data set to calculate average annual age-adjusted and age-specific ID hospitalization rates for AI/AN and non-AI/AN persons in Alaska. We stratified the ID hospitalization rates by sex, age, and ID diagnosis. Results: ID diagnoses accounted for 19% (6501 of 34 160) of AI/AN hospitalizations, compared with 12% (7397 of 62 059) of non-AI/AN hospitalizations. The average annual age-adjusted hospitalization rate was >3 times higher for AI/AN persons (2697 per 100 000 population) than for non-AI/AN persons (730 per 100 000 population; rate ratio = 3.7, P < .001). Lower respiratory tract infection (LRTI), which occurred in 38% (2486 of 6501) of AI/AN persons, was the most common reason for ID hospitalization. AI/AN persons were significantly more likely than non-AI/AN persons to be hospitalized for LRTI (rate ratio = 5.2, P < .001). Conclusions: A substantial disparity in ID hospitalization rates exists between AI/AN and non-AI/AN persons, and the most common reason for ID hospitalization among AI/AN persons was LRTI. Public health programs and policies that address the risk factors for LRTI are likely to benefit AI/AN persons. PMID:28005485

  7. Data Continuity of Aerosol Index from Suomi NPP/OMPS Observations

    NASA Astrophysics Data System (ADS)

    Ahn, C.; Torres, O.; Tiruchirapalli, R.; Taylor, S.; Jethva, H. T.

    2017-12-01

    Since the development of the Aerosol Index (AI) concept from Nimubs-7 TOMS near-UV measurements, the AI product has been widely used by the aerosol community in a variety of applications including monitoring of the sources and sinks of carbonaceous and desert dust aerosols. The AI uses a pair of near-UV radiances to detect the presence of absorbing particles even over bright backgrounds such as clouds and snow/ice covered areas. Since its inception in the mid 90's, the AI has been available as a by-product of the total ozone product. Due to the implementation of a new total ozone algorithm, the standard AI product will no longer be available starting in 2018. To assure the continuity of the AI record, we have developed an improved AI algorithm that uses a better forward modeling method of the top of atmosphere radiances. The enhanced modelling capability accounts for the scattering of clouds using Mie theory, and includes the effect of wavelength and angle dependent surface reflectance effects. By doing this, we have significantly reduced angular dependent false AI signals such as sun glint over the ocean. We will discuss the improved AI algorithm and present the long term AI record from various UV space borne sensors including TOMS, OMI, OMPS, and EPIC with consistent AI algorithms, followed by future plans for near-real time processing and operational production of a new OMPS AI product.

  8. The Relevance of English Language Instruction in a Changing Linguistic Environment in Iceland: The L2 Self of Young Icelanders

    ERIC Educational Resources Information Center

    Jeeves, Anna

    2014-01-01

    In this study perceptions of post-compulsory school studies in Iceland were investigated through semi-structured interviews. While colloquial English suffices for entertainment, hobbies and Internet use in Iceland, a high level of proficiency is required for employment and tertiary study. School learners and young people in tertiary study and…

  9. Diagnosis and management of pediatric adrenal insufficiency.

    PubMed

    Uçar, Ahmet; Baş, Firdevs; Saka, Nurçin

    2016-08-01

    Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

  10. Geology of drill hole UE25p No. 1: A test hole into pre-Tertiary rocks near Yucca Mountain, southern Nevada

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

    Carr, M.D.; Waddell, S.J.; Vick, G.S.

    1986-12-31

    Yucca Mountain in southern Nye County, Nevada, has been proposed as a potential site for the underground disposal of high-level nuclear waste. An exploratory drill hole designated UE25p No. 1 was drilled 3 km east of the proposed repository site to investigate the geology and hydrology of the rocks that underlie the Tertiary volcanic and sedimentary rock sequence forming Yucca Mountain. Silurian dolomite assigned to the Roberts Mountain and Lone Mountain Formations was intersected below the Tertiary section between a depth of approximately 1244 m (4080 ft) and the bottom of the drill hole at 1807 m (5923 ft). Thesemore » formations are part of an important regional carbonate aquifer in the deep ground-water system. Tertiary units deeper than 1139 m (3733 ft) in drill hole UE25p No. 1 are stratigraphically older than any units previously penetrated by drill holes at Yucca Mountain. These units are, in ascending order, the tuff of Yucca Flat, an unnamed calcified ash-flow tuff, and a sequence of clastic deposits. The upper part of the Tertiary sequence in drill hole UE25p No. 1 is similar to that found in other drill holes at Yucca Mountain. The Tertiary sequence is in fault contact with the Silurian rocks. This fault between Tertiary and Paleozoic rocks may correlate with the Fran Ridge fault, a steeply westward-dipping fault exposed approximately 0.5 km east of the drill hole. Another fault intersects UE25p No. 1 at 873 m (2863 ft), but its surface trace is concealed beneath the valley west of the Fran Ridge fault. The Paintbrush Canyon fault, the trace of which passes less than 100 m (330 ft) east of the drilling site, intersects drill hole UE25p No. 1 at a depth of approximately 78 m (255 ft). The drill hole apparently intersected the west flank of a structural high of pre-Tertiary rocks, near the eastern edge of the Crater Flat structural depression.« less

  11. Protein sectors: evolutionary units of three-dimensional structure

    PubMed Central

    Halabi, Najeeb; Rivoire, Olivier; Leibler, Stanislas; Ranganathan, Rama

    2011-01-01

    Proteins display a hierarchy of structural features at primary, secondary, tertiary, and higher-order levels, an organization that guides our current understanding of their biological properties and evolutionary origins. Here, we reveal a structural organization distinct from this traditional hierarchy by statistical analysis of correlated evolution between amino acids. Applied to the S1A serine proteases, the analysis indicates a decomposition of the protein into three quasi-independent groups of correlated amino acids that we term “protein sectors”. Each sector is physically connected in the tertiary structure, has a distinct functional role, and constitutes an independent mode of sequence divergence in the protein family. Functionally relevant sectors are evident in other protein families as well, suggesting that they may be general features of proteins. We propose that sectors represent a structural organization of proteins that reflects their evolutionary histories. PMID:19703402

  12. Regulation of bacteria population behaviors by AI-2 "consumer cells" and "supplier cells".

    PubMed

    Quan, Yufen; Meng, Fankang; Ma, Xinyu; Song, Xinhao; Liu, Xiao; Gao, Weixia; Dang, Yulei; Meng, Yao; Cao, Mingfeng; Song, Cunjiang

    2017-09-19

    Autoinducer-2 (AI-2) is a universal signal molecule and enables an individual bacteria to communicate with each other and ultimately control behaviors of the population. Harnessing the character of AI-2, two kinds of AI-2 "controller cells" ("consumer cells" and "supplier cells") were designed to "reprogram" the behaviors of entire population. For the consumer cells, genes associated with the uptake and processing of AI-2, which includes LsrACDB, LsrFG, LsrK, were overexpressed in varying combinations. Four consumer cell strains were constructed: Escherichia coli MG1655 pLsrACDB (NK-C1), MG1655 pLsrACDBK (NK-C2), MG1655 pLsrACDBFG (NK-C3) and MG1655 pLsrACDBFGK (NK-C4). The key enzymes responsible for production of AI-2, LuxS and Mtn, were also overexpressed, yielding strains MG1655 pLuxS (NK-SU1), and MG1655 pLuxS-Mtn (NK-SU2). All the consumer cells could decrease the environmental AI-2 concentration. NK-C2 and NK-C4 were most effective in AI-2 uptake and inhibited biofilm formation. While suppliers can increase the environmental AI-2 concentration and NK-SU2 was most effective in supplying AI-2 and facilitated biofilm formation. Further, reporter strain, MG1655 pLGFP was constructed. The expression of green fluorescent protein (GFP) in reporter cells was initiated and guided by AI-2. Mixture of consumer cells and reporter cells suggest that consumer cells can decrease the AI-2 concentration. And the supplier cells were co-cultured with reporter cells, indicating that supplier cells can provide more AI-2 compared to the control. The consumer cells and supplier cells could be used to regulate environmental AI-2 concentration and the biofilm formation. They can also modulate the AI-2 concentration when they were co-cultured with reporter cells. It can be envisioned that this system will become useful tools in synthetic biology and researching new antimicrobials.

  13. Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature.

    PubMed

    Mauras, Nelly; Ross, Judith L; Gagliardi, Priscila; Yu, Y Miles; Hossain, Jobayer; Permuy, Joseph; Damaso, Ligeia; Merinbaum, Debbie; Singh, Ravinder J; Gaete, Ximena; Mericq, Veronica

    2016-12-01

    Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. To compare: 1) the efficacy and safety of aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and 2) differences in body composition among groups. Randomized three-arm open-label comparator. Outpatient clinical research. Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), -2.3 (0.0)]. Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24-36 months. Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. Height gain [mean (SE)] at 24 months was: AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006, analysis of covariance). Height SDS was: AI, -1.73 (0.12); GH, -1.43 (0.14); AI/GH, -1.25 (0.12) (P < .0012). Those treated through 36 months grew more. Regardless of treatment duration, height SDS at near-final height [n = 71; age, 17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ∼97.6%] was: AI, -1.4 (0.1); GH, -1.4 (0.2); AI/GH, -1.0 (0.1) (P = .06). Absolute height change was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01) (expected height gain at -2.0 height SDS, +13.0 cm). AI/GH had higher fat free mass accrual. Measures of bone health, safety labs, and adverse events were similar in all groups. Letrozole caused higher T and lower estradiol than anastrozole. Combination therapy with AI/GH increases height potential in pubertal boys with ISS more than GH and AI alone treated for 24-36 months with a strong safety profile.

  14. Role of the Axon Initial Segment in the Control of Spontaneous Frequency of Nigral Dopaminergic Neurons In Vivo.

    PubMed

    Meza, Rodrigo C; López-Jury, Luciana; Canavier, Carmen C; Henny, Pablo

    2018-01-17

    The spontaneous tonic discharge activity of nigral dopamine neurons plays a fundamental role in dopaminergic signaling. To investigate the role of neuronal morphology and architecture with respect to spontaneous activity in this population, we visualized the 3D structure of the axon initial segment (AIS) along with the entire somatodendritic domain of adult male mouse dopaminergic neurons, previously recorded in vivo We observed a positive correlation of the firing rate with both proximity and size of the AIS. Computational modeling showed that the size of the AIS, but not its position within the somatodendritic domain, is the major causal determinant of the tonic firing rate in the intact model, by virtue of the higher intrinsic frequency of the isolated AIS. Further mechanistic analysis of the relationship between neuronal morphology and firing rate showed that dopaminergic neurons function as a coupled oscillator whose frequency of discharge results from a compromise between AIS and somatodendritic oscillators. Thus, morphology plays a critical role in setting the basal tonic firing rate, which in turn could control striatal dopaminergic signaling that mediates motivation and movement. SIGNIFICANCE STATEMENT The frequency at which nigral dopamine neurons discharge action potentials sets baseline dopamine levels in the brain, which enables activity in motor, cognitive, and motivational systems. Here, we demonstrate that the size of the axon initial segment, a subcellular compartment responsible for initiating action potentials, is a key determinant of the firing rate in these neurons. The axon initial segment and all the molecular components that underlie its critical function may provide a novel target for the regulation of dopamine levels in the brain. Copyright © 2018 the authors 0270-6474/18/380733-12$15.00/0.

  15. Axonal Membranes and Their Domains: Assembly and Function of the Axon Initial Segment and Node of Ranvier

    PubMed Central

    Nelson, Andrew D.; Jenkins, Paul M.

    2017-01-01

    Neurons are highly specialized cells of the nervous system that receive, process and transmit electrical signals critical for normal brain function. Here, we review the intricate organization of axonal membrane domains that facilitate rapid action potential conduction underlying communication between complex neuronal circuits. Two critical excitable domains of vertebrate axons are the axon initial segment (AIS) and the nodes of Ranvier, which are characterized by the high concentrations of voltage-gated ion channels, cell adhesion molecules and specialized cytoskeletal networks. The AIS is located at the proximal region of the axon and serves as the site of action potential initiation, while nodes of Ranvier, gaps between adjacent myelin sheaths, allow rapid propagation of the action potential through saltatory conduction. The AIS and nodes of Ranvier are assembled by ankyrins, spectrins and their associated binding partners through the clustering of membrane proteins and connection to the underlying cytoskeleton network. Although the AIS and nodes of Ranvier share similar protein composition, their mechanisms of assembly are strikingly different. Here we will cover the mechanisms of formation and maintenance of these axonal excitable membrane domains, specifically highlighting the similarities and differences between them. We will also discuss recent advances in super resolution fluorescence imaging which have elucidated the arrangement of the submembranous axonal cytoskeleton revealing a surprising structural organization necessary to maintain axonal organization and function. Finally, human mutations in axonal domain components have been associated with a growing number of neurological disorders including severe cognitive dysfunction, epilepsy, autism, neurodegenerative diseases and psychiatric disorders. Overall, this review highlights the assembly, maintenance and function of axonal excitable domains, particularly the AIS and nodes of Ranvier, and how abnormalities in these processes may contribute to disease. PMID:28536506

  16. Effects of a T'ai Chi-Based Health Promotion Program on Metabolic Syndrome Markers, Health Behaviors, and Quality of Life in Middle-Aged Male Office Workers: A Randomized Trial.

    PubMed

    Choi, Ye-Sook; Song, Rhayun; Ku, Bon Jeong

    2017-12-01

    To determine the effects of a t'ai chi-applied worksite health promotion program on metabolic syndrome markers, health behaviors, and quality of life in middle-aged male office workers at a high risk of metabolic syndrome. A prospective randomized controlled study. Health center of a government office building in Korea. Forty-three male office workers with two or more metabolic syndrome markers. The office workers were randomly assigned either to an experimental group that received t'ai chi combined with health education twice weekly for 12 weeks, or to a control group that received health education only. Blood sampling for metabolic syndrome markers and structured questionnaires for health behaviors and quality of life. The experimental group showed significant reductions in systolic (t = -3.103, p = 0.003) and diastolic (t = -2.159, p = 0.037) blood pressures and the triglyceride level (t = -2.451, p = 0.019) compared with the control group. Those in the experimental group also performed health behaviors more frequently (t = 4.047, p < 0.001) and reported a significantly better quality of life (t = 3.193, p = 0.003) than those in the control group. The study findings show that t'ai chi was an effective adjunctive intervention in a worksite health promotion program for middle-aged office workers at a high risk of metabolic syndrome. Future studies should examine the long-term effects of t'ai chi-applied worksite health promotion programs in individuals with confirmed metabolic syndrome.

  17. Genome-wide association studies of adolescent idiopathic scoliosis suggest candidate susceptibility genes

    PubMed Central

    Sharma, Swarkar; Gao, Xiaochong; Londono, Douglas; Devroy, Shonn E.; Mauldin, Kristen N.; Frankel, Jessica T.; Brandon, January M.; Zhang, Dongping; Li, Quan-Zhen; Dobbs, Matthew B.; Gurnett, Christina A.; Grant, Struan F.A.; Hakonarson, Hakon; Dormans, John P.; Herring, John A.; Gordon, Derek; Wise, Carol A.

    2011-01-01

    Adolescent idiopathic scoliosis (AIS) is an unexplained and common spinal deformity seen in otherwise healthy children. Its pathophysiology is poorly understood despite intensive investigation. Although genetic underpinnings are clear, replicated susceptibility loci that could provide insight into etiology have not been forthcoming. To address these issues, we performed genome-wide association studies (GWAS) of ∼327 000 single nucleotide polymorphisms (SNPs) in 419 AIS families. We found strongest evidence of association with chromosome 3p26.3 SNPs in the proximity of the CHL1 gene (P < 8 × 10−8 for rs1400180). We genotyped additional chromosome 3p26.3 SNPs and tested replication in two follow-up case–control cohorts, obtaining strongest results when all three cohorts were combined (rs10510181 odds ratio = 1.49, 95% confidence interval = 1.29–1.73, P = 2.58 × 10−8), but these were not confirmed in a separate GWAS. CHL1 is of interest, as it encodes an axon guidance protein related to Robo3. Mutations in the Robo3 protein cause horizontal gaze palsy with progressive scoliosis (HGPPS), a rare disease marked by severe scoliosis. Other top associations in our GWAS were with SNPs in the DSCAM gene encoding an axon guidance protein in the same structural class with Chl1 and Robo3. We additionally found AIS associations with loci in CNTNAP2, supporting a previous study linking this gene with AIS. Cntnap2 is also of functional interest, as it interacts directly with L1 and Robo class proteins and participates in axon pathfinding. Our results suggest the relevance of axon guidance pathways in AIS susceptibility, although these findings require further study, particularly given the apparent genetic heterogeneity in this disease. PMID:21216876

  18. Applying AI systems in the T and D arena. [Artificial Intelligence, Transmission and Distribution

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

    Venkata, S.S.; Liu, Chenching; Sumic, Z.

    1993-04-01

    The power engineering community has capitalized on various computer technologies since the early 1960s, with most successful application to solving well-defined problems that are capable of being modeled. Although computing methods have made notable progress in the power engineering arena, there is still a class of problems that is not easy to define or formulate to apply conventional computerized methods. In addition to being difficult to express in a closed mathematical form, these problems are often characterized by the absence of one or both of the following features: a predetermined decision path from the initial state to goal (ill-structured problem);more » a well-defined criteria for whether an obtained solution is acceptable (open-ended problem). Power engineers have been investigating the application of AI-based methodologies to power system problems. Most of the work in the past has been geared towards the development of expert systems as an operator's aid in energy control centers for bulk power transmission systems operating under abnormal conditions. Alarm processing, fault diagnosis, system restoration, and voltage/var control are a few key areas where significant research work has progressed to date. Results of this research have effected more than 100 prototype expert systems for power systems throughout the US, Japan, and Europe. The objectives of this article are to: expose engineers to the benefits of using AI methods for a host of transmission and distribution (T and D) problems that need immediate attention; identify problems that could be solved more effectively by applying AI approaches; summarize recent developments and successful AI applications in T and D.« less

  19. Assessing the Impact of Retreat Mechanisms in a Simple Antarctic Ice Sheet Model Using Bayesian Calibration.

    PubMed

    Ruckert, Kelsey L; Shaffer, Gary; Pollard, David; Guan, Yawen; Wong, Tony E; Forest, Chris E; Keller, Klaus

    2017-01-01

    The response of the Antarctic ice sheet (AIS) to changing climate forcings is an important driver of sea-level changes. Anthropogenic climate change may drive a sizeable AIS tipping point response with subsequent increases in coastal flooding risks. Many studies analyzing flood risks use simple models to project the future responses of AIS and its sea-level contributions. These analyses have provided important new insights, but they are often silent on the effects of potentially important processes such as Marine Ice Sheet Instability (MISI) or Marine Ice Cliff Instability (MICI). These approximations can be well justified and result in more parsimonious and transparent model structures. This raises the question of how this approximation impacts hindcasts and projections. Here, we calibrate a previously published and relatively simple AIS model, which neglects the effects of MICI and regional characteristics, using a combination of observational constraints and a Bayesian inversion method. Specifically, we approximate the effects of missing MICI by comparing our results to those from expert assessments with more realistic models and quantify the bias during the last interglacial when MICI may have been triggered. Our results suggest that the model can approximate the process of MISI and reproduce the projected median melt from some previous expert assessments in the year 2100. Yet, our mean hindcast is roughly 3/4 of the observed data during the last interglacial period and our mean projection is roughly 1/6 and 1/10 of the mean from a model accounting for MICI in the year 2100. These results suggest that missing MICI and/or regional characteristics can lead to a low-bias during warming period AIS melting and hence a potential low-bias in projected sea levels and flood risks.

  20. Integrated use of remotely sensed imagery and other data sets to infer the tectonics, structural style, and hydrocarbon habitats of the basins of the Tien Shan orogenic belt, Western China: A case study

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

    Berry, J.L.; Nishidai, T.

    1996-08-01

    Remotely sensed imagery and various other published regional data sets (gravity, magnetics, earthquake data) were integrated in order to interpret the structural style, both at deep crustal levels and at the relatively shallow levels of interest to explorationists, of the Tien Shan. Cross-sections through the range were systematically prepared, and then palinspastically restored, constrained by the remote sensing interpretation, potential fields data, and published microplate movement vectors. Since large portions of the area are covered by late Tertiary orogenic sediments, the resulting interpretation focused on these areas, and what and how much geology lies concealed beneath them. We were ablemore » to demonstrate the likely consumption in the late Tertiary of over 100 km of Tarim Basin west along a broad front south of the Tien Shan, as well as within the Kuruktag area, where basins are compressional rather than extensional. There are also local areas of extension within the orogenic zone, and these can be explained using the known microplate boundaries, backward extrapolation of present microplate motions, and the type and extent of late Tertiary deformation within the plates as constraints. Relative and absolute microplate motions have to change greatly through Tertiary time in order to comply with these constraints. The results of this work allow one to infer the affinities, and hence something of the hydrocarbon potential, of fragmentary plates by reconstructing their motions. They also allow one to infer the nature of the stratigraphy, the likely depth of burial, and something of the maturation history of pre-Tertiary rocks buried by Tertiary sediments deposited in both compressional and extensional regimes.« less

  1. Deceleration energy and change in velocity on impact: key factors in fatal versus potentially survivable motor vehicle crash (mvc) aortic injuries (AI): the role of associated injuries as determinants of outcome.

    PubMed

    Siegel, John H; Smith, Joyce A; Tenenbaum, Nadegda; McCammon, Laurie; Siddiqi, Shabana Q; Presswalla, Faruk; Pierre-Louis, Phito; Williams, Wayne; Zaretski, Leonard; Hutchins, Kenneth; Perez, Lyla; Shaikh, J; Natarajan, Geetha

    2002-01-01

    To examine the difference in force mechanisms between fatal and potentially survivable MVC aortic injuries (AI) compared to non-AI severe thoracic injuries (ST). Of 324 autopsied MVC driver or front seat passenger fatalities (1997-2000), there were 43 fatal AI (36 scene deaths, 7 hospital deaths) and 5 additional AI survivors. Of the 48 AI, there was only a 42% survival for those reaching hospital alive. 80% of AI survivors had isthmus lesions and all had no or minimal brain injury (GCS >= 13), no cardiac injury and only 20% ribs 1-4 fx or shock; of AI non-survivors reaching hospital alive, 67% had GCS <= 12, 50% cardiac injury, 83% ribs 1-4 fx and 83% shock; AI scene deaths had 78% severe brain injury, 56% cardiac injury, 69% lung injury and 78% ribs 1-4 fx. Quantifying forces in AI scene mortality: the Instantaneous Velocity on Impact of the subject vehicle (delta V1) and the Impact Energy Dissipated (IE) on the subject vehicle (V1) in joules demonstrated a linear regression in fatal car MVC AIs: Energy dissipated (joules) = -56.65 x (delta V1)(2) + 15972 x delta V1 - 454661, r(2) = 0.83. However, for 27 patients with non-AI but severe thoracic (ST) injury (AIS>=3), the relationship of IE to delta V1 had a linear regression of Energy dissipated (joules) = -5.0787 x (delta V1)(2) + 4282.1 x delta V1 - 57182 1, r(2) = 0.84, with the slope difference between the regression for AI scene deaths and that of ST and AI survivors being significant (p<0.05). Based on these relationships, a Critical Zone limited by MVC Impact Energy level of 336000 joules and a delta V1 of 64 kph appears to be the limit of potential survivability in MVCs producing aortic injuries. All AI above these thresholds died. In contrast, ST had greater use of seatbelts (AI 10% vs all ST 60%) and airbags (AI 50% vs all ST 72%), and an 83% survival. The data suggest different mechanisms of force delivery and injury patterns in fatal vs potentially survivable AI, and vs ST MVCs. They suggest that an approach to improving vehicle safety measures for AI may involve better safety devices and mechanisms for reducing that fraction of Impact Energy dissipated on V1 for a given delta V1 which is focused on the upper portion of the subject's thoracic cage between the levels of ribs1-8.

  2. The Psychopathological Influence of Adolescent Idiopathic Scoliosis in Korean Male : An Analysis of Multiphasic Personal Inventory Test Results

    PubMed Central

    Oh, Chang Hyun; Shim, Yu Shik; Park, Hyeong-chun; Park, Chong Oon; Lee, Myoung Seok

    2013-01-01

    Objective There are few published studies which have documented psychopathological abnormalities in patients with of adolescent idiopathic scoliosis (AIS) The aim of this study was to evaluate the psychopathological influence of AIS in Korean 19-year-old males. Methods The authors compared the Korean military multiphasic personal inventory (KMPI) military profiles of 105 AIS cases (more than 10 degrees of Cobb's angle without surgical treatment) with the KMPI profiles of 108 normal controls. The AIS group was split depending on Cobb's angle to further evaluate this relation by the severity of AIS. Results A significantly decreased result on the faking-good response scale and an significantly increased result on the faking-bad response were observed in the AIS group compared to the control (p<0.012). The neurosis scale results, including anxiety, depression and somatization symptoms, were significantly increased in the AIS group compared to the control (p<0.010). The severity level of personality disorder and schizophrenia were also significantly increased in the AIS group (p<0.010). Differences in KMPI scale scores were not related to the severity of AIS. Conclusion Young males with AIS tend to have abnormal results on the multiphasic personal inventory test compared to normal volunteers, suggesting that AIS may be related to psychopathology in the young male group in Korea. Although these psychopathology in AIS were differently observed compared to normal controls, but not interfered with military life. Clinicians are recommended to pay attention the psychopathological traits of patients with AIS. PMID:23440382

  3. Quality of head injury coding from autopsy reports with AIS © 2005 update 2008.

    PubMed

    Schick, Sylvia; Humrich, Anton; Graw, Matthias

    2018-02-28

    ABSTACT Objective: Coding injuries from autopsy reports of traffic accident victims according to Abbreviated Injury Scale AIS © 2005 update 2008 [1] is quite time consuming. The suspicion arose, that many issues leading to discussion between coder and control reader were based on information required by the AIS that was not documented in the autopsy reports. To quantify this suspicion, we introduced an AIS-detail-indicator (AIS-DI). To each injury in the AIS Codebook one letter from A to N was assigned indicating the level of detail. Rules were formulated to receive repeatable assignments. This scheme was applied to a selection of 149 multiply injured traffic fatalities. The frequencies of "not A" codes were calculated for each body region and it was analysed, why the most detailed level A had not been coded. As a first finding, the results of the head region are presented. 747 AIS head injury codes were found in 137 traffic fatalities, and 60% of these injuries were coded with an AIS-DI of level A. There are three different explanations for codes of AIS-DI "not A": Group 1 "Missing information in autopsy report" (5%), Group 2 "Clinical data required by AIS" (20%), and Group 3 "AIS system determined" (15%). Groups 1 and 2 show consequences for the ISS in 25 cases. Other body regions might perform differently. The AIS-DI can indicate the quality of the underlying data basis and, depending on the aims of different AIS users it can be a helpful tool for quality checks.

  4. Impact of the version of the abbreviated injury scale on injury severity characterization and quality assessment of trauma care.

    PubMed

    Tohira, Hideo; Jacobs, Ian; Matsuoka, Tetsuya; Ishikawa, Kazuo

    2011-07-01

    The Abbreviated Injury Scale (AIS) was updated in 2008 (AIS 2008). We aimed to investigate the impact of AIS 2008 on the characterization of injury severity and quality assessment of trauma care. We identified all blunt trauma patients in the Japan Trauma Data Bank. First, we converted AIS 98 codes to AIS 2008 codes using a mapping table. Next, we compared Injury Severity Scores (ISSs) and New ISSs (NISSs) based on AIS 98 and AIS 2008. We compared the proportion of major trauma (ISS >15) between the two AISs. We derived risk-adjusted models using the two AISs and separately ranked hospitals according to the observed-to-expected death (OE) ratio. We counted the number of performance outliers for the two rankings. We analyzed the association between the percent change in OE ratios and the proportion of NISS outliers (change in NISS of <-12). There were 19,899 subjects. The ISSs and NISSs based on AIS 2008 were significantly less than those based on AIS 98. The proportion of major trauma was 46.3% and 38.9% for AIS 98 and AIS 2008, respectively (p < 0.001). The numbers of performance outliers were different between the two rankings. There was a significant positive linear relationship between the percent change in the OE ratio and the proportion of NISS outliers. The use of different AIS versions influenced the selection of major trauma patients and affected the quality assessment of the trauma care. Researchers should be aware of these findings when selecting the version of the AIS.

  5. Effects of Housing Conditions on Stress Responses, Feeding, and Drinking in Male and Female Rats

    DTIC Science & Technology

    1995-02-07

    and biochemical changes indicative of a stress response (Singh, D’Souza, & Singh, 1991 ; Peng, Lang, Drozdowicz, & Ohlsson-Wilhelm, 1989; Armario ...immunological, and biochemical changes indicative of stress (Peng et aI., 1989; Armario et aI. , 1987; Gamallo et aI. , 1986; Armario , Ortiz...et aI. , 19~9; Armario et aI. , 1987; Gamallo et aI. , 1986; Calhoun, 1962). Hypothesis 2. It was hypothesized that male rats would decrease food

  6. Mineral features of connective dental hard tissues in hypoplastic amelogenesis imperfecta.

    PubMed

    Kammoun, R; Behets, C; Mansour, L; Ghoul-Mazgar, S

    2018-04-01

    To explore the mineral features of dentin and cementum in hypoplastic Amelogenesis imperfecta AI teeth. Forty-four (44) teeth cleaned and free of caries were used: 20 control and 24 affected by hypoplastic amelogenesis imperfecta. Thirty-two teeth were studied by pQCT, cut in sections, and analyzed under microradiography, polarized light microscopy, and confocal Raman spectroscopy. Eight teeth were observed under scanning electron microscope. Four teeth were used for an X-ray diffraction. The mineral density data were analyzed statistically with the Mann-Whitney U test, using GraphPad InStat software. Both coronal dentin and radicular dentin were less mineralized in AI teeth when compared to control (respectively 6.2% and 6.8%; p < .001). Root dentinal walls were thin and irregular, while the cellular cementum layers were thick, reaching sometimes the cervical region of the tooth. Regular dentinal tubules and sclerotic dentin areas were noticed. Partially tubular or cellular dysplastic dentin and hyper-, normo-, or hypomineralized areas were noticed in the inter-radicular areas of hypoplastic AI teeth. The main mineral component was carbonate hydroxyapatite as explored by Raman spectroscopy and X-ray diffraction. Dentin and cementum in hypoplastic AI teeth are (i) hypomineralized, (ii) constituted of carbonate hydroxyapatite, and (iii) of non-homogenous structure. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  7. Oral Rehabilitation of Young Adult with Amelogenesis Imperfecta.

    PubMed

    Leung, Vincent Ws; Low, Bernard; Yang, Yanqi; Botelho, Michael G

    2018-05-01

    Amelogenesis imperfecta is a heterogeneous group of hereditary disorders that affect the enamel formation of the primary and permanent dentitions while the remaining tooth structure is normal. Appropriate patient care is necessary to prevent adverse effects on dental oral health, dental disfigurement, and psychological well-being. This clinical report presents a 27-year-old Chinese male with amelogenesis imperfecta (AI) and his restorative management. This clinical report presents a 27-year-old Chinese male with AI and his restorative management. Extraoral examination showed a skeletal class III profile and increased lower facial proportion. Intraorally, all the permanent dentition was hypoplastic with noticeable tooth surface loss and a yellow-brown appearance. This was complicated with a mild maloc-clusion and food packing on his posterior teeth. The patient wanted to improve his appearance and masticatory efficiency. Orthodontic treatment was performed to treat the mild malocclu-sion and create physiological interproximal spacing to minimize tooth preparation and facilitate oral hygiene. This report demonstrates how a multidisciplinary approach for the management of AI can achieve a predictable, functional, and esthetic outcome. Orthodontic treatment facilitated a conservative prosthodontic treatment outcome by selectively increasing interproximal space, minimizing tooth preparation, correcting posterior bilateral cross-bite, as well as an anterior reverse overjet and derotation of the canines. This case report demonstrates the effective restoration of AI using a multidisciplinary approach to overcome crowding using a relatively conservative approach.

  8. Amelogenesis imperfecta

    PubMed Central

    Crawford, Peter JM; Aldred, Michael; Bloch-Zupan, Agnes

    2007-01-01

    Amelogenesis imperfecta (AI) represents a group of developmental conditions, genomic in origin, which affect the structure and clinical appearance of enamel of all or nearly all the teeth in a more or less equal manner, and which may be associated with morphologic or biochemical changes elsewhere in the body. The prevalence varies from 1:700 to 1:14,000, according to the populations studied. The enamel may be hypoplastic, hypomineralised or both and teeth affected may be discoloured, sensitive or prone to disintegration. AI exists in isolation or associated with other abnormalities in syndromes. It may show autosomal dominant, autosomal recessive, sex-linked and sporadic inheritance patterns. In families with an X-linked form it has been shown that the disorder may result from mutations in the amelogenin gene, AMELX. The enamelin gene, ENAM, is implicated in the pathogenesis of the dominant forms of AI. Autosomal recessive AI has been reported in families with known consanguinity. Diagnosis is based on the family history, pedigree plotting and meticulous clinical observation. Genetic diagnosis is presently only a research tool. The condition presents problems of socialisation, function and discomfort but may be managed by early vigorous intervention, both preventively and restoratively, with treatment continued throughout childhood and into adult life. In infancy, the primary dentition may be protected by the use of preformed metal crowns on posterior teeth. The longer-term care involves either crowns or, more frequently these days, adhesive, plastic restorations. PMID:17408482

  9. The bark of Robinia pseudoacacia contains a complex mixture of lectins.Characterization of the proteins and the cDNA clones.

    PubMed Central

    Van Damme, E J; Barre, A; Smeets, K; Torrekens, S; Van Leuven, F; Rougé, P; Peumans, W J

    1995-01-01

    Two lectins were isolated from the inner bark of Robinia pseudoacacia (black locust). The first (and major) lectin (called RPbAI) is composed of five isolectins that originate from the association of 31.5- and 29-kD polypeptides into tetramers. In contrast, the second (minor) lectin (called RPbAII) is a hometetramer composed of 26-kD subunits. The cDNA clones encoding the polypeptides of RPbAI and RPbAII were isolated and their sequences determined. Apparently all three polypeptides are translated from mRNAs of approximately 1.2 kb. Alignment of the deduced amino acid sequences of the different clones indicates that the 31.5- and 29-kD RPbAI polypeptides show approximately 80% sequence identity and are homologous to the previously reported legume seed lectins, whereas the 26-kD RPbAII polypeptide shows only 33% sequence identity to the previously described legume lectins. Modeling the 31.5-kD subunit of RPbAI predicts that its three-dimensional structure is strongly related to the three-dimensional models that have been determined thus far for a few legume lectins. Southern blot analysis of genomic DNA isolated from Robinia has revealed that the Robinia bark lectins are the result of the expression of a small family of lectin genes. PMID:7716244

  10. Neurophysiological basis of rehabilitation of adolescent idiopathic scoliosis.

    PubMed

    Smania, Nicola; Picelli, Alessandro; Romano, Michele; Negrini, Stefano

    2008-01-01

    Knowledge on mechanisms of neurophysiological control of trunk movement and posture could help in the development of rehabilitation programs and brace treatment in adolescent idiopathic scoliosis (AIS). Reviewing up-to-date research on neurophysiology of movement and posture control with the aim of providing basis for new researches in the field of AIS rehabilitation and background understanding for clinicians engaged in management of AIS. Review of literature. We considered several neurophysiological issues relevant for AIS rehabilitation, namely, the peculiar organization of patterns of trunk muscle recruitment, the structure of the neural hardware subserving axial and arm muscle control, and the relevance of cognitive systems allowing mapping of spatial coordinates and building of body schema. We made clear the reason why trunk control is generally carried out by means of very fast, feedforward or feedback driven patterns of muscle activation which are deeply rooted in our neural control system and very difficult to modify by training. We hypothesized that augmented sensory feedback and strength exercises could be an important stage in a rehabilitation program aimed at hindering, or possibly reversing, scoliosis progression. In this context we considered bracing not only as a corrective biomechanical device but also as a tool for continuous sensory stimulation that could help awareness of body misalignment. Future research aimed at developing strategies of trunk postural control learning is essential in the rehabilitation of adolescent idiopathic scoliosis.

  11. Heterogeneity of the Axon Initial Segment in Interneurons and Pyramidal Cells of Rodent Visual Cortex

    PubMed Central

    Höfflin, Felix; Jack, Alexander; Riedel, Christian; Mack-Bucher, Julia; Roos, Johannes; Corcelli, Corinna; Schultz, Christian; Wahle, Petra; Engelhardt, Maren

    2017-01-01

    The microdomain that orchestrates action potential initiation in neurons is the axon initial segment (AIS). It has long been considered to be a rather homogeneous domain at the very proximal axon hillock with relatively stable length, particularly in cortical pyramidal cells. However, studies in other brain regions paint a different picture. In hippocampal CA1, up to 50% of axons emerge from basal dendrites. Further, in about 30% of thick-tufted layer V pyramidal neurons in rat somatosensory cortex, axons have a dendritic origin. Consequently, the AIS is separated from the soma. Recent in vitro and in vivo studies have shown that cellular excitability is a function of AIS length/position and somatodendritic morphology, undermining a potentially significant impact of AIS heterogeneity for neuronal function. We therefore investigated neocortical axon morphology and AIS composition, hypothesizing that the initial observation of seemingly homogeneous AIS is inadequate and needs to take into account neuronal cell types. Here, we biolistically transfected cortical neurons in organotypic cultures to visualize the entire neuron and classify cell types in combination with immunolabeling against AIS markers. Using confocal microscopy and morphometric analysis, we investigated axon origin, AIS position, length, diameter as well as distance to the soma. We find a substantial AIS heterogeneity in visual cortical neurons, classified into three groups: (I) axons with somatic origin with proximal AIS at the axon hillock; (II) axons with somatic origin with distal AIS, with a discernible gap between the AIS and the soma; and (III) axons with dendritic origin (axon-carrying dendrite cell, AcD cell) and an AIS either starting directly at the axon origin or more distal to that point. Pyramidal cells have significantly longer AIS than interneurons. Interneurons with vertical columnar axonal projections have significantly more distal AIS locations than all other cells with their prevailing phenotype as an AcD cell. In contrast, neurons with perisomatic terminations display most often an axon originating from the soma. Our data contribute to the emerging understanding that AIS morphology is highly variable, and potentially a function of the cell type. PMID:29170630

  12. Major structural controls on the distribution of pre-Tertiary rocks, Nevada Test Site vicinity, southern Nevada

    USGS Publications Warehouse

    Cole, James C.

    1997-01-01

    The lateral and vertical distributions of Proterozoic and Paleozoic sedimentary rocks in southern Nevada are the combined products of original stratigraphic relationships and post-depositional faults and folds. This map compilation shows the distribution of these pre-Tertiary rocks in the region including and surrounding the Nevada Test Site. It is based on considerable new evidence from detailed geologic mapping, biostratigraphic control, sedimentological analysis, and a review of regional map relationships.Proterozoic and Paleozoic rocks of the region record paleogeographic transitions between continental shelf depositional environments on the east and deeper-water slopefacies depositional environments on the west. Middle Devonian and Mississippian sequences, in particular, show strong lateral facies variations caused by contemporaneous changes in the western margin of North America during the Antler orogeny. Sections of rock that were originally deposited in widely separated facies localities presently lie in close proximity. These spatial relationships chiefly result from major east- and southeastdirected thrusts that deformed the region in Permian or later time.Somewhat younger contractional structures are identified within two irregular zones that traverse the region. These folds and thrusts typically verge toward the west and northwest and overprint the relatively simple pattern of the older contractional terranes. Local structural complications are significant near these younger structures due to the opposing vergence and due to irregularities in the previously folded and faulted crustal section.Structural and stratigraphic discontinuities are identified on opposing sides of two north-trending fault zones in the central part of the compilation region north of Yucca Flat. The origin and significance of these zones are enigmatic because they are largely covered by Tertiary and younger deposits. These faults most likely result from significant lateral offset, most likely in the sinistral sense.Low-angle normal faults that are at least older than Oligocene, and may pre-date Late Cretaceous time, are also present in the region. These faults are shown to locally displace blocks of pre-Tertiary rock by several kilometers. However, none of these structures can be traced for significant distances beyond its outcrop extent, and the inference is made that they do not exert regional influence on the distribution of pre-Tertiary rocks. The extensional strain accommodated by these low-angle normal faults appears to be local and highly irregular.

  13. In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL.

    PubMed

    Gan, Chaoye; Wang, Zhexuan; Chen, Yong

    2017-04-01

    The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Artificial Intelligence in Surgery: Promises and Perils.

    PubMed

    Hashimoto, Daniel A; Rosman, Guy; Rus, Daniela; Meireles, Ozanan R

    2018-07-01

    The aim of this review was to summarize major topics in artificial intelligence (AI), including their applications and limitations in surgery. This paper reviews the key capabilities of AI to help surgeons understand and critically evaluate new AI applications and to contribute to new developments. AI is composed of various subfields that each provide potential solutions to clinical problems. Each of the core subfields of AI reviewed in this piece has also been used in other industries such as the autonomous car, social networks, and deep learning computers. A review of AI papers across computer science, statistics, and medical sources was conducted to identify key concepts and techniques within AI that are driving innovation across industries, including surgery. Limitations and challenges of working with AI were also reviewed. Four main subfields of AI were defined: (1) machine learning, (2) artificial neural networks, (3) natural language processing, and (4) computer vision. Their current and future applications to surgical practice were introduced, including big data analytics and clinical decision support systems. The implications of AI for surgeons and the role of surgeons in advancing the technology to optimize clinical effectiveness were discussed. Surgeons are well positioned to help integrate AI into modern practice. Surgeons should partner with data scientists to capture data across phases of care and to provide clinical context, for AI has the potential to revolutionize the way surgery is taught and practiced with the promise of a future optimized for the highest quality patient care.

  15. Tectonic history of Sweetgrass Arch, Montana and Alberta-key to finding new hydrocarbons

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

    Shepard, W. Shepard, B.

    1985-05-01

    The Sweetgrass arch of northwestern Montana and southern Alberta is a major ancient structural feature. Initial anticlinal emplacement occurred during the early Paleozoic and was parallel with the cratonic margin. Strong uplift followed by peneplanation occurred during the Late Jurassic and basal Cretaceous during the westward drifting of the North American plate following the breakup of Pangea. During Cretaceous and early Tertiary times, the Sweetgrass arch was quiescent, but was rejuvenated in mid to late Tertiary, upwarped by a basement flexure to its present structural configuration: a 200 mi (322 km) long, north-plunging anticline showing 10,000 ft (350 m) ofmore » structural relief. Midway down its plunge, the anticline is offset 30 mi (48 km) by a right-lateral transcurrent fault. During Late Cretaceous and early Tertiary, plutonic uplifts were emplaced on the east flank, forming traps for oil then migrating updip from the Williston and Alberta basins. Oil and gas accumulated in Mississippian, Jurassic, and basal Cretaceous reservoirs in structural and stratigraphic traps around these plutonic uplifts. Subsequent late Tertiary doming of the Sweetgrass arch tilted the earlier structural traps and drained them, resulting in remigration of much of the oil and gas to the crest of the arch. The tilting failed to destroy many of the stratigraphic traps. As a result, down the flanks of the Sweetgrass arch are many frozen stratigraphic traps including Cut Bank field, the largest single-pay stratigraphic trap in the north Rockies. On the crest are large structure accumulations of remigrated oil at Kevin Sunburst and Pondera. Evidence of remigration is recorded by live oil show tracks in the reservoirs and remnant gas caps throughout the area of earlier accumulations. A potential exists for finding new frozen traps on the flanks and remigrated oil accumulations on or near the crest of the Sweetgrass arch.« less

  16. Contrasting effects of progesterone on fertility of dairy and beef cows.

    PubMed

    Stevenson, J S; Lamb, G C

    2016-07-01

    The role of progesterone in maintaining pregnancy is well known in the bovine. Subtle differences exist between dairy and beef cows because of differing concentrations of progesterone during recrudescence of postpartum estrous cycles, rate of follicular growth and maturation, proportions of 2- and 3-follicular wave cycles, and other effects on pregnancy outcomes per artificial insemination (P/AI). Because proportions of anovulatory cows before the onset of the artificial insemination (AI) period are greater and more variable in beef (usually ranging from 30 to 70%) than dairy (25%) cows, AI programs were developed to accommodate anovulatory and cycling beef cows enrolled therein. Incorporating a progestin as part of an AI program in beef cows improved P/AI by reducing the proportion of cows having premature luteal regression and short post-AI luteal phases. In both genotypes, prolonged dominant follicle growth in a reduced progesterone milieu resulted in increased (1) LH pulses, (2) preovulatory follicle diameter, and (3) concentrations of estradiol and a subsequently larger corpora lutea (CL). In contrast, the progesterone milieu during growth of the ovulatory follicle in an ovulation control program does not seem to affect subsequent P/AI in beef cows, whereas in dairy cows follicle development in an elevated compared with a low progesterone environment increases P/AI. Progesterone status in beef cows at the onset of ovulation synchronization is not related to P/AI in multiparous cows, whereas P/AI was suppressed in primiparous cows that began a timed AI program in a low-progesterone environment. In timed AI programs, elevated concentrations of progesterone just before PGF2α and reduced concentrations at AI are critical to maximizing subsequent P/AI in dairy cows, but seemingly much less important in beef cows. By inducing ancillary CL and increasing concentrations of progesterone, human chorionic gonadotropin may increase P/AI when administered to beef cows 7d after AI or at embryo transfer, and its success seems to depend on induction of ancillary CL, whereas in dairy cows increased fertility was detected in cows with multiple CL, human chorionic gonadotropin-enhanced progesterone from original CL, or both. Pregnancy losses after AI are less frequent in beef cows and are not associated with pre-AI progesterone or cycling status, whereas losses in dairy cows are inversely related to progesterone and adversely affected in anovular dairy cows. Genotype and nutritional management likely influence several physiological differences including circulating concentrations of progesterone and responses to supplemental progesterone. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  17. The secreted L-arabinose isomerase displays anti-hyperglycemic effects in mice.

    PubMed

    Rhimi, Moez; Bermudez-Humaran, Luis G; Huang, Yuan; Boudebbouze, Samira; Gaci, Nadia; Garnier, Alexandrine; Gratadoux, Jean-Jacques; Mkaouar, Héla; Langella, Philippe; Maguin, Emmanuelle

    2015-12-21

    The L-arabinose isomerase is an intracellular enzyme which converts L-arabinose into L-ribulose in living systems and D-galactose into D-tagatose in industrial processes and at industrial scales. D-tagatose is a natural ketohexose with potential uses in pharmaceutical and food industries. The D-galactose isomerization reaction is thermodynamically equilibrated, and leads to secondary subproducts at high pH. Therefore, an attractive L-arabinose isomerase should be thermoactive and acidotolerant with high catalytic efficiency. While many reports focused on the set out of a low cost process for the industrial production of D-tagatose, these procedures remain costly. When compared to intracellular enzymes, the production of extracellular ones constitutes an interesting strategy to increase the suitability of the biocatalysts. The L-arabinose isomerase (L-AI) from Lactobacillus sakei was expressed in Lactococcus lactis in fusion with the signal peptide of usp45 (SP(Usp45)). The L-AI protein and activity were detected only in the supernatant of the induced cultures of the recombinant L. lactis demonstrating the secretion in the medium of the intracellular L. sakei L-AI in an active form. Moreover, we showed an improvement in the enzyme secretion using either (1) L. lactis strains deficient for their two major proteases, ClpP and HtrA, or (2) an enhancer of protein secretion in L. lactis fused to the recombinant L-AI with the SP(Usp45). Th L-AI enzyme secreted by the recombinant L. lactis strains or produced intracellularly in E. coli, showed the same functional properties than the native enzyme. Furthermore, when mice are fed with the L. lactis strain secreting the L-AI and galactose, tagatose was produced in vivo and reduced the glycemia index. We report for the first time the secretion of the intracellular L-arabinose isomerase in the supernatant of food grade L. lactis cultures with hardly display other secreted proteins. The secreted L-AI originated from the food grade L. sakei 23 K was active and showed the same catalytic and structural properties as the intracellular enzyme. The L. lactis strains secreting the L-arabinose isomerase has the ability to produce D-tagatose in vivo and conferred an anti-hyperglycemic effect to mice.

  18. Vitamin D Receptor gene (VDR) transcripts in bone, cartilage, muscles and blood and microarray analysis of vitamin D responsive genes expression in paravertebral muscles of Juvenile and Adolescent Idiopathic Scoliosis patients

    PubMed Central

    2012-01-01

    Background VDR may be considered as a candidate gene potentially related to Idiopathic Scoliosis susceptibility and natural history. Transcriptional profile of VDR mRNA isoforms might be changed in the structural tissues of the scoliotic spine and potentially influence the expression of VDR responsive genes. The purpose of the study was to determine differences in mRNA abundance of VDR isoforms in bone, cartilage and paravertebral muscles between tissues from curve concavity and convexity, between JIS and AIS and to identify VDR responsive genes differentiating Juvenile and Adolescent Idiopathic Scoliosis in paravertebral muscles. Methods In a group of 29 patients with JIS and AIS, specimens of bone, cartilage, paravertebral muscles were harvested at the both sides of the curve apex together with peripheral blood samples. Extracted total RNA served as a matrix for VDRs and VDRl mRNA quantification by QRT PCR. Subsequent microarray analysis of paravertebral muscular tissue samples was performed with HG U133A chips (Affymetrix). Quantitative data were compared by a nonparametric Mann Whitney U test. Microarray results were analyzed with GeneSpring 11GX application. Matrix plot of normalized log-intensities visualized the degree of differentiation between muscular tissue transcriptomes of JIS and AIS group. Fold Change Analysis with cutoff of Fold Change ≥2 identified differentially expressed VDR responsive genes in paravertebral muscles of JIS and AIS. Results No significant differences in transcript abundance of VDR isoforms between tissues of the curve concavity and convexity were found. Statistically significant difference between JIS and AIS group in mRNA abundance of VDRl isoform was found in paravertebral muscles of curve concavity. Higher degree of muscular transcriptome differentiation between curve concavity and convexity was visualized in JIS group. In paravertebral muscles Tob2 and MED13 were selected as genes differentially expressed in JIS and AIS group. Conclusions In Idiopathic Scolioses transcriptional activity and alternative splicing of VDR mRNA in osseous, cartilaginous, and paravertebral muscular tissues are tissue specific and equal on both sides of the curve. The number of mRNA copies of VDRl izoform in concave paravertebral muscles might be one of the factors differentiating JIS and AIS. In paravertebral muscles Tob2 and Med13 genes differentiate Adolescent and Juvenile type of Idiopathic Scoliosis. PMID:23259508

  19. U.S. EPA, Pesticide Product Label, 20% GRANULAR 2,4-D LOW VOLATILE, 01/14/1994

    EPA Pesticide Factsheets

    2011-04-14

    ... 1lI"AiAI '~";PIR'AI UIN wilA '~t5 ,,,sa ... , Vie., 'Y' ,N.,stiaR fI'. Mill" IF .'et,. ... 181, .A" wat.r .5 IIIR iii 'l5&i~l. Itllr ",i.iAI. laa"iAIJ IIF 1"I)I'iAI'''i' ,Fa"W". 'I:'.,h hIA"'. ...

  20. The implementation of AI technologies in computer wargames

    NASA Astrophysics Data System (ADS)

    Tiller, John A.

    2004-08-01

    Computer wargames involve the most in-depth analysis of general game theory. The enumerated turns of a game like chess are dwarfed by the exponentially larger possibilities of even a simple computer wargame. Implementing challenging AI is computer wargames is an important goal in both the commercial and military environments. In the commercial marketplace, customers demand a challenging AI opponent when they play a computer wargame and are frustrated by a lack of competence on the part of the AI. In the military environment, challenging AI opponents are important for several reasons. A challenging AI opponent will force the military professional to avoid routine or set-piece approaches to situations and cause them to think much deeper about military situations before taking action. A good AI opponent would also include national characteristics of the opponent being simulated, thus providing the military professional with even more of a challenge in planning and approach. Implementing current AI technologies in computer wargames is a technological challenge. The goal is to join the needs of AI in computer wargames with the solutions of current AI technologies. This talk will address several of those issues, possible solutions, and currently unsolved problems.

  1. Acid lipase inhibitor in chicken plasma identified as apolipoprotein A-I.

    PubMed

    Fujii, M; Higuchi, T; Mukai, S; Yonekura, M; Yano, T; Kawaguchi, H; Nonaka, K; Fukunaga, T; Sugimoto, Y; Yamada, S

    1996-10-01

    We have reported a inhibitor of acid lipases in liver lysosomes and erythrocytes from chickens [M. Fujii et al., Int. J. Biochem., 22, 895-898 (1990)]. In this paper, the properties of the inhibitor were described in comparison with those of apo A-I of chicken. The purified inhibitor migrated with the same mobility on SDS-PAGE as apo A-I, and had a molecular weight of 27,000. The peptide map from the lipase inhibitor was similar to that of apo A-I. Antibodies to the acid lipase inhibitor also reacted with apo A-I. Apo A-I inhibited the acid lipase activities of liver lysosomes and erythrocytes from chickens as strongly as the lipase inhibitor. The N-terminal amino acid sequence of lipase inhibitor was identical to that of apo A-I as far as residue 20. The amino acid sequence of peptides obtained from the inhibitor by cleavage with CNBr corresponded to internal sequence of apo A-I, and so the CNBr-peptides were derived by cleavage after the methionine residues in apo A-I. The findings showed that the inhibitor of the acid lipases in liver lysosomes and erythrocytes from chickens was identical to apo A-I.

  2. Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999-2009.

    PubMed

    Jacobs-Wingo, Jasmine L; Espey, David K; Groom, Amy V; Phillips, Leslie E; Haverkamp, Donald S; Stanley, Sandte L

    2016-05-01

    To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999-2009 and compared those with corresponding urban White and rural AI/AN death rates. The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities.

  3. Pregnancy rates in lactating Holstein-Friesian cows after artificial insemination with sexed sperm.

    PubMed

    Andersson, M; Taponen, J; Kommeri, M; Dahlbom, M

    2006-04-01

    The effects of artificial insemination (AI) using sexed sperm on pregnancy rates have seldom been studied in lactating dairy cows on commercial dairy farms. We evaluated pregnancy results after AI of 306 lactating dairy cows, of which 157 were inseminated with 2x10(6) frozen/thawed sexed sperm and 149 with 15x10(6) frozen/thawed unsexed sperm. The average pregnancy and calving rates were 21.0% and 20% for the sexed-sperm AIs and 46% and 45% for the unseparated control-sperm AIs respectively (p<0.001). The proportion of female calves derived from sexed-sperm AI was 82% compared with 49% for control AI (p<0.01). The proportion of live and healthy calves in single births was 100% for sexed-sperm AI and 97% for control AI (p>0.05). Our results indicate that AI with low-dose sexed sperm under field conditions in commercial dairy herds without oestrus synchronization results in significantly reduced pregnancy rates compared with normal-dose AI. Improved insemination strategies combined with increased sperm doses are needed before the use of sexed sperm can be of any significant benefit for the dairy and beef industry.

  4. Administrative Information Systems Plan for FY89

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

    Not Available

    1988-11-01

    The Administrative Information Systems (AIS) Plan was developed to prioritize, track, and control the cost of AIS activities. This annually published plan, in conjunction with quarterly status reports, measures projected AIS activities and progress. The AIS Plan and quarterly reporting are administered jointly by the Director of Computing and an Organization 30 director. Priority development projects are clearly defined and closely managed efforts that consume significant resources. Directorate supplementals describe other AIS activity within each directorate, which may include: production support; technical support; development activity; and other AIS effort.

  5. About Student's Media Use for Learning in Tertiary Education Influence Factors and Structures of Usage Behavior

    ERIC Educational Resources Information Center

    Grosch, Michael

    2014-01-01

    The rise of the web 2.0 led to dramatic changes in media usage behavior of students in tertiary education. Services such as Google and Facebook are most accepted amongst students not only in pastime but also for learning. A representative survey was made at Karlsruhe Institute of Technology (KIT). About 1,400 students were asked 150 questions to…

  6. Genetic diversity, genetic structure, and mating system of brewer spruce (Pinaceae), a relict of the acto-tertiary forest

    Treesearch

    F. Thomas Ledig; Paul D. Hodgskiss; David R. Johnson

    2005-01-01

    Brewer spruce (Picea breweriana), a relict of the widespread Arcto-Tertiary forests, is now restricted to a highly fragmented range in the Klamath Region of California and Oregon. Expected heterozygosity for 26 isozyme loci, averaged over 10 populations, was 0.121. More notable than the relatively high level of diversity when compared to other woody...

  7. Lithospheric mantle structure beneath Northern Scotland: Pre-plume remnant or syn-plume signature?

    NASA Astrophysics Data System (ADS)

    Knapp, J.

    2003-04-01

    Upper mantle reflectors (Flannan and W) beneath the northwestern British Isles are some of the best-known and most-studied examples of preserved structure within the continental mantle lithosphere, and are spatially coincident with the surface location of early Iceland plume volcanism in the British Tertiary Province. First observed on BIRPS (British Institutions Reflection Profiling Syndicate) marine deep seismic reflection profiles in the early 1980's, these reflectors have subsequently been imaged and correlated on additional reflection and refraction profiles in the offshore area of northern and western Scotland. The age and tectonic significance of these reflectors remains a subject of wide debate, due in part to the absence of robust characterization of the upper mantle velocity structure in this tectonically complex area. Interpretations advanced over the past two decades for the dipping Flannan reflector range from fossilized subduction complex to large-scale extensional shear zone, and span ages from Proterozoic to early Mesozoic. Crustal geology of the region records early Paleozoic continental collision and late Paleozoic to Mesozoic extension. Significant modification of the British lithosphere in early Tertiary time, including dramatic thinning and extensive basaltic intrusion associated with initiation and development of the Iceland plume, suggests either (1) an early Tertiary age for the Flannan reflector or (2) preservation of ancient features within the mantle lithosphere despite such pervasive modification. Exisitng constraints are consistent with a model for early Tertiary origin of the Flannan reflector as the downdip continuation of the Rockall Trough extensional system of latest Cretaceous to earliest Tertiary age during opening of the northern Atlantic Ocean and initiation of the Iceland plume. Lithopsheric thinning beneath present-day northern Scotland could have served to focus the early expression of plume volcanism (British Tertiary Province), despite the inferred distant locus of the initial plume head. Alternatively, preservation of large-scale pre-plume fabric in the Scottish mantle would imply long-lived tectonic heredity in the continental lithospheric mantle, and place important constraints on the plume-related effects (or lack thereof) in the mantle lithosphere.

  8. Heterologous expression of an α-amylase inhibitor from common bean (Phaseolus vulgaris) in Kluyveromyces lactis and Saccharomyces cerevisiae.

    PubMed

    Brain-Isasi, Stephanie; Álvarez-Lueje, Alejandro; Higgins, Thomas Joseph V

    2017-06-15

    Phaseolamin or α-amylase inhibitor 1 (αAI) is a glycoprotein from common beans (Phaseolus vulgaris L.) that inhibits some insect and mammalian α-amylases. Several clinical studies support the beneficial use of bean αAI for control of diabetes and obesity. Commercial extracts of P. vulgaris are available but their efficacy is still under question, mainly because some of these extracts contain antinutritional impurities naturally present in bean seeds and also exhibit a lower specific activity αAI. The production of recombinant αAI allows to overcome these disadvantages and provides a platform for the large-scale production of pure and functional αAI protein for biotechnological and pharmaceutical applications. A synthetic gene encoding αAI from the common bean (Phaseolus vulgaris cv. Pinto) was codon-optimised for expression in yeasts (αAI-OPT) and cloned into the protein expression vectors pKLAC2 and pYES2. The yeasts Kluyveromyces lactis GG799 (and protease deficient derivatives such as YCT390) and Saccharomyces cerevisiae YPH499 were transformed with the optimised genes and transformants were screened for expression by antibody dot blot. Recombinant colonies of K. lactis YCT390 that expressed and secreted functional αAI into the culture supernatants were selected for further analyses. Recombinant αAI from K. lactis YCT390 was purified using anion-exchange and affinity resins leading to the recovery of a functional inhibitor. The identity of the purified αAI was confirmed by mass spectrometry. Recombinant clones of S. cerevisiae YPH499 expressed functional αAI intracellularly, but did not secrete the protein. This is the first report describing the heterologous expression of the α-amylase inhibitor 1 (αAI) from P. vulgaris in yeasts. We demonstrated that recombinant strains of K. lactis and S. cerevisiae expressed and processed the αAI precursor into mature and active protein and also showed that K. lactis secretes functional αAI.

  9. Defining major trauma using the 2008 Abbreviated Injury Scale.

    PubMed

    Palmer, Cameron S; Gabbe, Belinda J; Cameron, Peter A

    2016-01-01

    The Injury Severity Score (ISS) is the most ubiquitous summary score derived from Abbreviated Injury Scale (AIS) data. It is frequently used to classify patients as 'major trauma' using a threshold of ISS >15. However, it is not known whether this is still appropriate, given the changes which have been made to the AIS codeset since this threshold was first used. This study aimed to identify appropriate ISS and New Injury Severity Score (NISS) thresholds for use with the 2008 AIS (AIS08) which predict mortality and in-hospital resource use comparably to ISS >15 using AIS98. Data from 37,760 patients in a state trauma registry were retrieved and reviewed. AIS data coded using the 1998 AIS (AIS98) were mapped to AIS08. ISS and NISS were calculated, and their effects on patient classification compared. The ability of selected ISS and NISS thresholds to predict mortality or high-level in-hospital resource use (the need for ICU or urgent surgery) was assessed. An ISS >12 using AIS08 was similar to an ISS >15 using AIS98 in terms of both the number of patients classified major trauma, and overall major trauma mortality. A 10% mortality level was only seen for ISS 25 or greater. A NISS >15 performed similarly to both of these ISS thresholds. However, the AIS08-based ISS >12 threshold correctly classified significantly more patients than a NISS >15 threshold for all three severity measures assessed. When coding injuries using AIS08, an ISS >12 appears to function similarly to an ISS >15 in AIS98 for the purposes of identifying a population with an elevated risk of death after injury. Where mortality is a primary outcome of trauma monitoring, an ISS >12 threshold could be adopted to identify major trauma patients. Level II evidence--diagnostic tests and criteria. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Algeria: structural evolution and hydrocarbon potential of a complicated Tectonic province

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

    Knudsen, H.W.

    1985-02-01

    During most of the pre-Carboniferous, Algeria was part of a stable foreland platform on which a thick clastic sequence was deposited. Caledonian tectonics were primarily epeirogenic, but they established structural alignments that were further reinforced by the much stronger movements of the Carboniferous Hercynian orogeny. In northern and eastern Algeria, a variable basal sandstone and a thick sequence of Triassic and Lower Jurassic evaporites were deposited over the eroded Hercynian surface. This provided a seal for subsequent hydrocarbon migration from the underlying Silurian and Devonian source rocks. Important epeirogenic events and tensional faulting occurred during the Jurassic and Cretaceous. Compressionalmore » forces in the tertiary culminated in the Alpine orogeny. A broad zone of uplift and southward-directed imbricate thrusting formed along the northern margins of Algeria obscuring much of the sub-Tertiary depositional and structural features. Hydrocarbon accumulation in Algeria has been predominantly controlled by the relationships among the Silurian-Devonian source rocks, the Hercynian unconformity, and the distribution of the overlying Triassic clastic and evaporite sequence. More than 65% of the recoverable oil reserves and 90% of the gas reserves are trapped immediately below or above the Hercynian unconformity, with the evaporites providing the seal. Heretofore, the complex geology of the Tertiary overthrust zone has been a deterrent to exploration in both the autochthonous Miocene basins and the sub-Tertiary sequence. However, improved seismic techniques and renewed interest in the potential of overthrust provinces point to increased activity in this area.« less

  11. The tolerance to exchanges of the Watson–Crick base pair in the hammerhead ribozyme core is determined by surrounding elements

    PubMed Central

    Przybilski, Rita; Hammann, Christian

    2007-01-01

    Tertiary interacting elements are important features of functional RNA molecules, for example, in all small nucleolytic ribozymes. The recent crystal structure of a tertiary stabilized type I hammerhead ribozyme revealed a conventional Watson–Crick base pair in the catalytic core, formed between nucleotides C3 and G8. We show that any Watson–Crick base pair between these positions retains cleavage competence in two type III ribozymes. In the Arabidopsis thaliana sequence, only moderate differences in cleavage rates are observed for the different base pairs, while the peach latent mosaic viroid (PLMVd) ribozyme exhibits a preference for a pyrimidine at position 3 and a purine at position 8. To understand these differences, we created a series of chimeric ribozymes in which we swapped sequence elements that surround the catalytic core. The kinetic characterization of the resulting ribozymes revealed that the tertiary interacting loop sequences of the PLMVd ribozyme are sufficient to induce the preference for Y3–R8 base pairs in the A. thaliana hammerhead ribozyme. In contrast to this, only when the entire stem–loops I and II of the A. thaliana sequences are grafted on the PLMVd ribozyme is any Watson–Crick base pair similarly tolerated. The data provide evidence for a complex interplay of secondary and tertiary structure elements that lead, mediated by long-range effects, to an individual modulation of the local structure in the catalytic core of different hammerhead ribozymes. PMID:17666711

  12. Validating the Hamilton Anatomy of Risk Management-Forensic Version and the Aggressive Incidents Scale.

    PubMed

    Cook, Alana N; Moulden, Heather M; Mamak, Mini; Lalani, Shams; Messina, Katrina; Chaimowitz, Gary

    2018-06-01

    The Hamilton Anatomy of Risk Management-Forensic Version (HARM-FV) is a structured professional judgement tool of violence risk developed for use in forensic inpatient psychiatric settings. The HARM-FV is used with the Aggressive Incidents Scale (AIS), which provides a standardized method of recording aggressive incidents. We report the findings of the concurrent validity of the HARM-FV and the AIS with widely used measures of violence risk and aggressive acts, the Historical, Clinical, Risk Management-20, Version 3 (HCR-20 V3 ) and a modified version of the Overt Aggression Scale. We also present findings on the predictive validity of the HARM-FV in the short term (1-month follow-up periods) for varying severities of aggressive acts. The results indicated strong support for the concurrent validity of the HARM-FV and AIS and promising support for the predictive accuracy of the tool for inpatient aggression. This article provides support for the continued clinical use of the HARM-FV within an inpatient forensic setting and highlights areas for further research.

  13. Discriminating semiarid vegetation using airborne imaging spectrometer data - A preliminary assessment

    NASA Technical Reports Server (NTRS)

    Thomas, Randall W.; Ustin, Susan L.

    1987-01-01

    A preliminary assessment was made of Airborne Imaging Spectrometer (AIS) data for discriminating and characterizing vegetation in a semiarid environment. May and October AIS data sets were acquired over a large alluvial fan in eastern California, on which were found Great Basin desert shrub communities. Maximum likelihood classification of a principal components representation of the May AIS data enabled discrimination of subtle spatial detail in images relating to vegetation and soil characteristics. The spatial patterns in the May AIS classification were, however, too detailed for complete interpretation with existing ground data. A similar analysis of the October AIS data yielded poor results. Comparison of AIS results with a similar analysis of May Landsat Thematic Mapper data showed that the May AIS data contained approximately three to four times as much spectrally coherent information. When only two shortwave infrared TM bands were used, results were similar to those from AIS data acquired in October.

  14. QML-AiNet: An immune network approach to learning qualitative differential equation models

    PubMed Central

    Pang, Wei; Coghill, George M.

    2015-01-01

    In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG. PMID:25648212

  15. QML-AiNet: An immune network approach to learning qualitative differential equation models.

    PubMed

    Pang, Wei; Coghill, George M

    2015-02-01

    In this paper, we explore the application of Opt-AiNet, an immune network approach for search and optimisation problems, to learning qualitative models in the form of qualitative differential equations. The Opt-AiNet algorithm is adapted to qualitative model learning problems, resulting in the proposed system QML-AiNet. The potential of QML-AiNet to address the scalability and multimodal search space issues of qualitative model learning has been investigated. More importantly, to further improve the efficiency of QML-AiNet, we also modify the mutation operator according to the features of discrete qualitative model space. Experimental results show that the performance of QML-AiNet is comparable to QML-CLONALG, a QML system using the clonal selection algorithm (CLONALG). More importantly, QML-AiNet with the modified mutation operator can significantly improve the scalability of QML and is much more efficient than QML-CLONALG.

  16. AI and cognitive science: the past and next 30 years.

    PubMed

    Forbus, Kenneth D

    2010-07-01

    Artificial Intelligence (AI) is a core area of Cognitive Science, yet today few AI researchers attend the Cognitive Science Society meetings. This essay examines why, how AI has changed over the last 30 years, and some emerging areas of potential interest where AI and the Society can go together in the next 30 years, if they choose. Copyright © 2010 Cognitive Science Society, Inc.

  17. Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature

    PubMed Central

    Ross, Judith L.; Gagliardi, Priscila; Yu, Y. Miles; Hossain, Jobayer; Permuy, Joseph; Damaso, Ligeia; Merinbaum, Debbie; Singh, Ravinder J.; Gaete, Ximena; Mericq, Veronica

    2016-01-01

    Context: Growth of short children in puberty is limited by the effect of estrogen on epiphyseal fusion. Objectives: To compare: 1) the efficacy and safety of aromatase inhibitors (AIs) vs GH vs AI/GH on increasing adult height potential in pubertal boys with severe idiopathic short stature (ISS); and 2) differences in body composition among groups. Design: Randomized three-arm open-label comparator. Setting: Outpatient clinical research. Patients: Seventy-six pubertal boys [mean (SE) age, 14.1 (0.1) years] with ISS [height SD score (SDS), −2.3 (0.0)]. Intervention: Daily AIs (anastrozole or letrozole), GH, or AI/GH for 24–36 months. Outcomes: Anthropometry, bone ages, dual x-ray absorptiometry, spine x-rays, hormones, safety labs. Results: Height gain [mean (SE)] at 24 months was: AI, +14.0 (0.8) cm; GH, +17.1 (0.9) cm; AI/GH, +18.9 (0.8) cm (P < .0006, analysis of covariance). Height SDS was: AI, −1.73 (0.12); GH, −1.43 (0.14); AI/GH, −1.25 (0.12) (P < .0012). Those treated through 36 months grew more. Regardless of treatment duration, height SDS at near-final height [n = 71; age, 17.4 (0.2) years; bone age, 15.3 (0.1) years; height achieved, ∼97.6%] was: AI, −1.4 (0.1); GH, −1.4 (0.2); AI/GH, −1.0 (0.1) (P = .06). Absolute height change was: AI, +18.2 (1.6) cm; GH, +20.6 (1.5) cm; AI/GH, +22.5 (1.4) cm (P = .01) (expected height gain at −2.0 height SDS, +13.0 cm). AI/GH had higher fat free mass accrual. Measures of bone health, safety labs, and adverse events were similar in all groups. Letrozole caused higher T and lower estradiol than anastrozole. Conclusions: Combination therapy with AI/GH increases height potential in pubertal boys with ISS more than GH and AI alone treated for 24–36 months with a strong safety profile. PMID:27710241

  18. Assessing the success of invasive species prevention efforts at changing the behaviors of recreational boaters.

    PubMed

    Cole, Ellen; Keller, Reuben P; Garbach, Kelly

    2016-12-15

    Aquatic invasive species (AIS) pose major conservation challenges in freshwater ecosystems. In response, conservation organizations invest considerable resources in outreach to encourage AIS prevention behaviors among recreational boaters. Despite this, remarkably little is known about whether these efforts catalyze significant changes in boaters' perceptions, or whether they cause changes in behaviors that reduce AIS risk. We interviewed managers at the 14 Illinois organizations active in AIS outreach to determine regional priorities for, and investment in, AIS outreach. The results show a network of collaboration that reinforces a limited set of conservation messages. Next, we surveyed 515 recreational boaters to evaluate access to outreach, knowledge of AIS, and consistency of prevention behavior. Boater recognition of prevention slogans and knowledge of AIS and AIS prevention behavior was similar across Illinois regions despite large regional differences in investment in outreach. Most boaters (94%) report never intentionally moving organisms among waterbodies. Fewer reported that they Always perform recommended actions to reduce risk of AIS spread on their boat interior (68%), boat exterior (63%), or fishing tackle (47%). Recognition of prevention slogans and the number of AIS recognized were significantly, positively, associated with Always performing AIS prevention behavior on the vectors of the boat exterior, and fishing tackle, respectively. Our results suggest that increasing knowledge may be a necessary condition for higher adoption of AIS prevention behaviors, but that this alone may not be sufficient. Instead, efforts targeted at boaters who do not currently practice the recommended actions are likely to be necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Artificial insemination of Holstein heifers with sex-sorted semen during the hot season in a subtropical region.

    PubMed

    Chang, Lian-Ben; Chou, Chih-Jen; Shiu, Jia-Shian; Tu, Po-An; Gao, Shi-Xuan; Peng, Shao-Yu; Wu, Shinn-Chih

    2017-08-01

    Our aim was to investigate insemination techniques in order to improve pregnancy rates of artificial insemination (AI) using sex-sorted semen (sexed AI) in cattle in tropical and subtropical (T/ST) regions. In T/ST regions, the pregnancy rates by sexed AI are reportedly the lowest in the hottest months of the year, with less than 15% in cows and 35-40% in heifers (PMID 24048822). We compared sexed AI by depositing the semen into the uterine body (UB-AI, n = 12) versus the unilateral uterine horn (UUH-AI, n = 14) of pre-ovulation heifers. The ovary and follicle were assessed by rectal ultrasound before AI. After insemination, pregnancy was determined by ultrasound at approximately 40 days and approximately 70 days. In the present study, we demonstrated that high pregnancy rates (>70%) by sexed AI in the hottest season in a subtropical region such as Taiwan can be achieved when heifers with pre-ovulation follicles are used. The overall pregnancy rates were 54% higher in the UUH-AI (71%) group than in the UB-AI (42%) group (P = 0.06), examined on approximately 40 days post-sexed AI. Surprisingly, however, the pregnancy outcome appeared to be higher in the hot season (62%) than in the cool season (46%) although this difference was not statistically significant. Based on the present study, we recommend that cattle breeders perform UUH-AI using sex-sorted semen for heifers with pre-ovulation follicles in order to achieve satisfactory pregnancy outcome in the hot seasons in T/ST regions.

  20. Artificial intelligence applications in space and SDI: A survey

    NASA Technical Reports Server (NTRS)

    Fiala, Harvey E.

    1988-01-01

    The purpose of this paper is to survey existing and planned Artificial Intelligence (AI) applications to show that they are sufficiently advanced for 32 percent of all space applications and SDI (Space Defense Initiative) software to be AI-based software. To best define the needs that AI can fill in space and SDI programs, this paper enumerates primary areas of research and lists generic application areas. Current and planned NASA and military space projects in AI will be reviewed. This review will be largely in the selected area of expert systems. Finally, direct applications of AI to SDI will be treated. The conclusion covers the importance of AI to space and SDI applications, and conversely, their importance to AI.

  1. 47 CFR 80.393 - Frequencies for AIS stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... (AIS 1) and 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In... carriage requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46...

  2. 47 CFR 80.393 - Frequencies for AIS stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (AIS 1) and 162.025 MHz (AIS 2), each with a 25 kHz bandwidth, may be authorized only for AIS. In... carriage requirements for non-Federal Government ships. These requirements are codified at 33 CFR 164.46...

  3. Helix A Stabilization Precedes Amino-terminal Lobe Activation upon Calcium Binding to Calmodulin

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

    Chen, Baowei; Lowry, David; Mayer, M. Uljana

    2008-08-09

    The structural coupling between opposing domains of CaM was investigated using the conformationally sensitive biarsenical probe 4,5-bis(1,3,2-dithioarsolan-2-yl)-resorufin (ReAsH), which upon binding to an engineered tetracysteine binding motif near the end of helix A (Thr-5 to Phe-19) becomes highly fluorescent. Changes in conformation and dynamics are reflective of the native CaM structure, as there is no change in the 1H- 15N HSQC NMR spectrum in comparison to wild-type CaM. We find evidence of a conformational intermediate associated with CaM activation, where calcium occupancy of sites in the amino-terminal and carboxyl-terminal lobes of CaM differentially affect the fluorescence intensity of bound ReAsH.more » Insight into the structure of the conformational intermediate is possible from a consideration of calcium-dependent changes in rates of ReAsH binding and helix A mobility, which respectively distinguish secondary structural changes associated with helix A stabilization from the tertiary structural reorganization of the amino-terminal lobe of CaM necessary for high-affinity binding to target proteins. Helix A stabilization is associated with calcium occupancy of sites in the carboxyl-terminal lobe (Kd = 0.36 ± 0.04 μM), which results in a reduction in the rate of ReAsH binding from 4900 M -1 sec -1 to 370 M -1 sec -1. In comparison, tertiary structural changes involving helix A and other structural elements in the amino-terminal lobe requires calcium-occupancy of amino-terminal sites (Kd = 18 ± 3 μM). Observed secondary and tertiary structural changes involving helix A in response to the sequential calcium occupancy of carboxyl- and amino-terminal lobe calcium binding sites suggest an important involvement of helix A in mediating the structural coupling between the opposing domains of CaM. These results are discussed in terms of a model in which carboxyl-terminal lobe calcium activation induces secondary structural changes within the interdomain linker that release helix A, thereby facilitating the formation of calcium binding sites in the amino-terminal lobe and linked tertiary structural rearrangements to form a high-affinity binding cleft that can associate with target proteins.« less

  4. [Application prospect of human-artificial intelligence system in future manned space flight].

    PubMed

    Wei, Jin-he

    2003-01-01

    To make the manned space flight more efficient and safer, a concept of human-artificial (AI) system is proposed in the present paper. The task of future manned space flight and the technique requirement with respect to the human-AI system development were analyzed. The main points are as follows: 1)Astronaut and AI are complementary to each other functionally; 2) Both symbol AI and connectionist AI should be included in the human-AI system, but expert system and Soar-like system are used mainly inside the cabin, the COG-like robots are mainly assigned for EVA either in LEO flight or on the surface of Moon or Mars; 3) The human-AI system is hierarchical in nature with astronaut at the top level; 4) The complex interfaces between astronaut and AI are the key points for running the system reliably and efficiently. As the importance of human-AI system in future manned space flight and the complexity of related technology, it is suggested that the R/D should be planned as early as possible.

  5. Integration of herbicides with manual weeding for controlling the weeds in rice under saline environment.

    PubMed

    Hakim, M A; Juraimi, Abdul Shukor; Hanafi, M M; Rafii, Mohd Y; Ismail, Mohd Razi; Karim, S M Rezaul; Kausar, H

    2015-11-01

    The pot experiment was conducted to select appropriate integrated weed management method in rice under different salinity levels (0, 4 and 8 dS m(-1)). All the parameters including rice and weed measured were significantly influenced by weed control treatments at all salinity levels. Treatments including weed-free condition, Pretilachlor @0.375 kg ai ha(-1) + hand weeding, Propanil + Thiobencarb @ 0.9 kg ai ha(-1) and 1.8 kg ai ha(-1)+ hand weeding performed better under all salinity levels. Pretilachlor @ 0.375 kg ai ha(-1) with one round of hand weeding and propanil + thiobencarb 0.9 kg ai ha(-1) + 1.8 kg ai ha(-1) with one round of hand weeding were comparable to weed-free yields, and were superior to other treatments under salinity condition. Considering all the parameters, pretilachlor @ 0.375 kg ai ha(-1) + one round of hand weeding (at 65 DAT), propanil + thiobencarb 0.9 kg ai ha(-1) +1.8 kg ai ha(-1) + one round of hand weeding (at 65 DAT) gave the most effective control of weeds in rice under saline environments.

  6. Comparison of injury severity between AIS 2005 and AIS 1990 in a large injury database

    PubMed Central

    Barnes, J; Hassan, A; Cuerden, R; Cookson, R; Kohlhofer, J

    2009-01-01

    The aim of this study is to investigate the differences in car occupant injury severity recorded in AIS 2005 compared to AIS 1990 and to outline the likely effects on future data analysis findings. Occupant injury data in the UK Cooperative Crash Injury Study Database (CCIS) were coded for the period February 2006 to November 2007 using both AIS 1990 and AIS 2005. Data for 1,994 occupants with over 6000 coded injuries were reviewed at the AIS and MAIS level of severities and body regions to determine changes between the two coding methodologies. Overall there was an apparent general trend for fewer injuries to be coded at the AIS 4+ severity and more injuries to be coded at the AIS 2 severity. When these injury trends were reviewed in more detail it was found that the body regions which contributed the most to these changes in severity were the head, thorax and extremities. This is one of the first studies to examine the implications for large databases when changing to an updated method for coding injuries. PMID:20184835

  7. Molecular surface representation using 3D Zernike descriptors for protein shape comparison and docking.

    PubMed

    Kihara, Daisuke; Sael, Lee; Chikhi, Rayan; Esquivel-Rodriguez, Juan

    2011-09-01

    The tertiary structures of proteins have been solved in an increasing pace in recent years. To capitalize the enormous efforts paid for accumulating the structure data, efficient and effective computational methods need to be developed for comparing, searching, and investigating interactions of protein structures. We introduce the 3D Zernike descriptor (3DZD), an emerging technique to describe molecular surfaces. The 3DZD is a series expansion of mathematical three-dimensional function, and thus a tertiary structure is represented compactly by a vector of coefficients of terms in the series. A strong advantage of the 3DZD is that it is invariant to rotation of target object to be represented. These two characteristics of the 3DZD allow rapid comparison of surface shapes, which is sufficient for real-time structure database screening. In this article, we review various applications of the 3DZD, which have been recently proposed.

  8. Effects of topographic position and geology on shaking damage to residential wood-framed structures during the 2003 San Simeon earthquake, western San Luis obispo county, California

    USGS Publications Warehouse

    McCrink, T.P.; Wills, C.J.; Real, C.R.; Manson, M.W.

    2010-01-01

    A statistical evaluation of shaking damage to wood-framed houses caused by the 2003 M6.5 San Simeon earthquake indicates that both the rate and severity of damage, independent of structure type, are significantly greater on hilltops compared to hill slopes when underlain by Cretaceous or Tertiary sedimentary rocks. This increase in damage is interpreted to be the result of topographic amplification. An increase in the damage rate is found for all structures built on Plio-Pleistocene rocks independent of topographic position, and this is interpreted to be the result of amplified shaking caused by geologic site response. Damage rate and severity to houses built on Tertiary rocks suggest that amplification due to both topographic position and geologic site response may be occurring in these rocks, but effects from other topographic parameters cannot be ruled out. For all geologic and topographic conditions, houses with raised foundations are more frequently damaged than those with slab foundations. However, the severity of damage to houses on raised foundations is only significantly greater for those on hill slopes underlain by Tertiary rocks. Structures with some damage-resistant characteristics experienced greater damage severity on hilltops, suggesting a spectral response to topographic amplification. ?? 2010, Earthquake Engineering Research Institute.

  9. --No Title--

    Science.gov Websites

    -well{position:absolute;left:0;top:0;width:55%}.ai-feat-sm-well{margin-bottom:1em}.ai-feat-well h4{color ,.btn-ai:link,.btn-ai:visited{background-color:#0079C5;font-weight:500;margin:.5em 0 1em;text -align:center;color:#fff}.ai{-webkit-border-radius:4px;-moz-border-radius:4px;border-radius:4px;font-size:1.3em

  10. Causes and Disparities in Death Rates Among Urban American Indian and Alaska Native Populations, 1999–2009

    PubMed Central

    Espey, David K.; Groom, Amy V.; Phillips, Leslie E.; Haverkamp, Donald S.; Stanley, Sandte L.

    2016-01-01

    Objectives. To characterize the leading causes of death for the urban American Indian/Alaska Native (AI/AN) population and compare with urban White and rural AI/AN populations. Methods. We linked Indian Health Service patient registration records with the National Death Index to reduce racial misclassification in death certificate data. We calculated age-adjusted urban AI/AN death rates for the period 1999–2009 and compared those with corresponding urban White and rural AI/AN death rates. Results. The top-5 leading causes of death among urban AI/AN persons were heart disease, cancer, unintentional injury, diabetes, and chronic liver disease and cirrhosis. Compared with urban White persons, urban AI/AN persons experienced significantly higher death rates for all top-5 leading causes. The largest disparities were for diabetes and chronic liver disease and cirrhosis. In general, urban and rural AI/AN persons had the same leading causes of death, although urban AI/AN persons had lower death rates for most conditions. Conclusions. Urban AI/AN persons experience significant disparities in death rates compared with their White counterparts. Public health and clinical interventions should target urban AI/AN persons to address behaviors and conditions contributing to health disparities. PMID:26890168

  11. Using design science and artificial intelligence to improve health communication: ChronologyMD case example.

    PubMed

    Neuhauser, Linda; Kreps, Gary L; Morrison, Kathleen; Athanasoulis, Marcos; Kirienko, Nikolai; Van Brunt, Deryk

    2013-08-01

    This paper describes how design science theory and methods and use of artificial intelligence (AI) components can improve the effectiveness of health communication. We identified key weaknesses of traditional health communication and features of more successful eHealth/AI communication. We examined characteristics of the design science paradigm and the value of its user-centered methods to develop eHealth/AI communication. We analyzed a case example of the participatory design of AI components in the ChronologyMD project intended to improve management of Crohn's disease. eHealth/AI communication created with user-centered design shows improved relevance to users' needs for personalized, timely and interactive communication and is associated with better health outcomes than traditional approaches. Participatory design was essential to develop ChronologyMD system architecture and software applications that benefitted patients. AI components can greatly improve eHealth/AI communication, if designed with the intended audiences. Design science theory and its iterative, participatory methods linked with traditional health communication theory and methods can create effective AI health communication. eHealth/AI communication researchers, developers and practitioners can benefit from a holistic approach that draws from theory and methods in both design sciences and also human and social sciences to create successful AI health communication. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  12. Unintentional Injury Mortality Among American Indians and Alaska Natives in the United States, 1990–2009

    PubMed Central

    Pokhrel, Pallavi; Worthington, Anne; Billie, Holly; Sewell, Mack; Bill, Nancy

    2014-01-01

    Objectives. We describe the burden of unintentional injury (UI) deaths among American Indian and Alaska Native (AI/AN) populations in the United States. Methods. National Death Index records for 1990 to 2009 were linked with Indian Health Service registration records to identify AI/AN deaths misclassified as non-AI/AN deaths. Most analyses were restricted to Contract Health Service Delivery Area counties in 6 geographic regions of the United States. We compared age-adjusted death rates for AI/AN persons with those for Whites; Hispanics were excluded. Results. From 2005 to 2009, the UI death rate for AI/AN people was 2.4 times higher than for Whites. Death rates for the 3 leading causes of UI death—motor vehicle traffic crashes, poisoning, and falls—were 1.4 to 3 times higher among AI/AN persons than among Whites. UI death rates were higher among AI/AN males than among females and highest among AI/AN persons in Alaska, the Northern Plains, and the Southwest. Conclusions. AI/AN persons had consistently higher UI death rates than did Whites. This disparity in overall rates coupled with recent increases in unintentional poisoning deaths requires that injury prevention be a major priority for improving health and preventing death among AI/AN populations. PMID:24754624

  13. Frequency dependent hub role of the dorsal and ventral right anterior insula.

    PubMed

    Wang, Yifeng; Zhu, Lixia; Zou, Qijun; Cui, Qian; Liao, Wei; Duan, Xujun; Biswal, Bharat; Chen, Huafu

    2018-01-15

    The right anterior insula (rAI) plays a crucial role in generating adaptive behavior by orchestrating multiple brain networks. Based on functional separation findings of the insula and spectral fingerprints theory of cognitive functions, we hypothesize that the hub role of the rAI is region and frequency dependent. Using the Human Connectome Project dataset and backtracking approach, we segregate the rAI into dorsal and ventral parts at frequency bands from slow 6 to slow 3, indicating the frequency dependent functional separation of the rAI. Functional connectivity analysis shows that, within lower than 0.198 Hz frequency range, the dorsal and ventral parts of rAI form a complementary system to synchronize with externally and internally-oriented networks. Moreover, the relationship between the dorsal and ventral rAIs predicts the relationship between anti-correlated networks associated with the dorsal rAI at slow 6 and slow 5, suggesting a frequency dependent regulation of the rAI to brain networks. These findings could improve our understanding of the rAI by supporting the region and frequency dependent function of rAI and its essential role in coordinating brain systems relevant to internal and external environments. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Mineralogy of Cretaceous/Tertiary boundary clays in the Chicxulub structure in northern Yucatan

    NASA Technical Reports Server (NTRS)

    Ming, D. W.; Sharpton, Virgil L.; Schuraytz, B. C.

    1991-01-01

    The Cretaceous/Tertiary (K/T) boundary clay layer is thought to be derived from ejecta material from meteorite impact, based on the anomalous concentrations of noble metals in the layer. Because of recent findings of a half-meter thick ejecta deposit at the K/T boundary in Haiti, efforts have focused on locating a large impact feature in the Caribbean and the Gulf of Mexico. One of the leading candidates for the site of a large impact is the Chicxulub structure located on the northern Yucatan Peninsula in Mexico. The Chicxulub structure is a subsurface zone of upper Cretaceous igneous rocks, carbonates, and breccias. The structure has been interpreted to be a 200 km diameter; however, there is some question to the size of the structure or to the fact that it even is an impact feature. Little is known about the mineralogy of this structure; the objective of this study was to determine the clay mineralogy of core samples from within the Chicxulub structure.

  15. Both Reversible Self-Association and Structural Changes Underpin Molecular Viscoelasticity of mAb Solutions.

    PubMed

    Sarangapani, Prasad S; Weaver, Justin; Parupudi, Arun; Besong, Tabot M D; Adams, Gary G; Harding, Stephen E; Manikwar, Prakash; Castellanos, Maria M; Bishop, Steven M; Pathak, Jai A

    2016-12-01

    The role of antibody structure (conformation) in solution rheology is probed. It is demonstrated here that pH-dependent changes in the tertiary structure of 2 mAb solutions lead to viscoelasticity and not merely a shear viscosity (η) increase. Steady shear flow curves on mAb solutions are reported over broad pH (3.0 ≤ pH ≤ 8.7) and concentration (2 mg/mL ≤ c ≤ 120 mg/mL) ranges to comprehensively characterize their rheology. Results are interpreted using size exclusion chromatography, differential scanning calorimetry, analytical ultracentrifugation, near-UV circular dichroism, and dynamic light scattering. Changes in tertiary structure with concentration lead to elastic yield stress and increased solution viscosity in solution of "mAb1." These findings are supported by dynamic light scattering and differential scanning calorimetry, which show increased hydrodynamic radius of mAb1 at low pH and a reduced melting temperature T m , respectively. Conversely, another molecule at 120 mg/mL solution concentration is a strong viscoelastic gel due to perturbed tertiary structure (seen in circular dichroism) at pH 3.0, but the same molecule responds as a viscous liquid due to reversible self-association at pH 7.4 (verified by analytical ultracentrifugation). Both protein-protein interactions and structural perturbations govern pH-dependent viscoelasticity of mAb solutions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

    PubMed

    Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

    2018-05-02

    Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

  17. Chemorepulsion from the Quorum Signal Autoinducer-2 Promotes Helicobacter pylori Biofilm Dispersal

    PubMed Central

    Anderson, Jeneva K.; Huang, Julie Y.; Wreden, Christopher; Sweeney, Emily Goers; Goers, John; Remington, S. James

    2015-01-01

    ABSTRACT The gastric pathogen Helicobacter pylori forms biofilms on abiotic and biotic surfaces. We have shown previously that H. pylori perceives the quorum signal autoinducer-2 (AI-2) as a chemorepellent. We report here that H. pylori chemorepulsion from endogenous AI-2 influences the proportions and spatial organization of cells within biofilms. Strains that fail to produce AI-2 (∆luxS strains) or are defective for chemotaxis (∆cheA strains) formed more spatially homogenous biofilms with a greater proportion of adherent versus planktonic cells than wild-type biofilms. Reciprocally, a strain that overproduced AI-2 (luxSOP) formed biofilms with proportionally fewer adherent cells. Along with the known AI-2 chemoreceptor, TlpB, we identified AibA and AibB, two novel periplasmic binding proteins that are required for the AI-2 chemorepulsion response. Disruptions in any of the proteins required for AI-2 chemotaxis recapitulated the biofilm adherence and spatial organization phenotype of the ∆luxS mutant. Furthermore, exogenous administration of AI-2 was sufficient to decrease the proportion of adherent cells in biofilms and promote dispersal of cells from biofilms in a chemotaxis-dependent manner. Finally, we found that disruption of AI-2 production or AI-2 chemotaxis resulted in increased clustering of cells in microcolonies on cultured epithelial cells. We conclude that chemotaxis from AI-2 is a determinant of H. pylori biofilm spatial organization and dispersal. PMID:26152582

  18. Superacid synthesized tertiary benzenesulfonamides and benzofuzed sultams act as selective hCA IX inhibitors: toward understanding a new mode of inhibition by tertiary sulfonamides.

    PubMed

    Métayer, Benoît; Martin-Mingot, Agnès; Vullo, Daniella; Supuran, Claudiu T; Thibaudeau, Sébastien

    2013-11-21

    A series of tertiary (fluorinated) benzenesulfonamides was synthesized in superacid HF-SbF5. To circumvent the problem of the in situ iminium ion formation, proved by low temperature NMR experiments, a tandem superacid catalysed cross-coupling reaction was employed to synthesize the benzofuzed sultams analogues. These tertiary benzenesulfonamides were tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). These compounds did not inhibit the widespread off target hCA II isoform and showed strong selectivity toward tumor-associated carbonic anhydrase isoform IX. A dramatic effect of the electronic and structural shape of the inhibitors on selectivity was demonstrated, confirming the non-zinc-bonding mode of inhibition of this class of sulfonamides. This work allowed identifying a highly selective hCA IX inhibitor lead in this series.

  19. Network biology discovers pathogen contact points in host protein-protein interactomes.

    PubMed

    Ahmed, Hadia; Howton, T C; Sun, Yali; Weinberger, Natascha; Belkhadir, Youssef; Mukhtar, M Shahid

    2018-06-13

    In all organisms, major biological processes are controlled by complex protein-protein interactions networks (interactomes), yet their structural complexity presents major analytical challenges. Here, we integrate a compendium of over 4300 phenotypes with Arabidopsis interactome (AI-1 MAIN ). We show that nodes with high connectivity and betweenness are enriched and depleted in conditional and essential phenotypes, respectively. Such nodes are located in the innermost layers of AI-1 MAIN and are preferential targets of pathogen effectors. We extend these network-centric analyses to Cell Surface Interactome (CSI LRR ) and predict its 35 most influential nodes. To determine their biological relevance, we show that these proteins physically interact with pathogen effectors and modulate plant immunity. Overall, our findings contrast with centrality-lethality rule, discover fast information spreading nodes, and highlight the structural properties of pathogen targets in two different interactomes. Finally, this theoretical framework could possibly be applicable to other inter-species interactomes to reveal pathogen contact points.

  20. "We're Changing Our Ways": Women's Coping Strategies for Obesity Risk-reducing Behaviors in American Indian Households.

    PubMed

    Gadhoke, Preety; Christiansen, Karina; Pardilla, Marla; Frick, Kevin; Gittelsohn, Joel

    2015-01-01

    This article reveals women caregivers' perceptions and coping strategies to improve households' food and physical activity habits. Results emerged from the pre-intervention formative research phase of a multi-site, multi-level obesity prevention pilot intervention on American Indian (AI) reservations. Using purposive sampling, 250 adults and children participated in qualitative research. Results reveal that having local institutional support was a key structural facilitator. 'Family connectedness' emerged as a key relational facilitator. Hegemony of systems, food deserts, transportation, and weather were key structural barriers; Childcare needs and time constraints were key relational barriers. Women's coping strategies included planning ahead, maximizing, apportioning, tempting healthy, and social support. Findings informed the development and implementation of a novel obesity prevention pilot intervention tailored for each participating AI community addressing culturally relevant messages, institutional policies, and programs. We conclude with future consideration for comparative, ethnicity-based, class-based, and gender-specific studies on women's coping strategies for household health behaviors.

  1. A study of silver species on silver-exchanged ETS-10 and mordenite by XRD, SEM and solid-state 109Ag, 29Si and 27AI NMR spectroscopy.

    PubMed

    Liu, Yan; Chen, Fu; Wasylishen, Roderick E; Xu, Zhenghe; Sawada, James; Kuznicki, Steven M

    2012-08-01

    Silver zeolites, especially Ag-ETS-10 and Ag-mordenite, actively bind xenon and iodine, two prime contaminants common to nuclear accidents. The evolution of silver species on silver exchanged ETS-10 (Ag/ETS-10) and mordenite (Ag/Mor) has been investigated by exposing the materials to a series of activation conditions in Ar, air and H2. The samples were characterized by XRD, SEM and solid-state 109Ag, 29Si and 27AI MAS NMR. The silver reduction and structural evolution have been illustrated by those techniques. The effectiveness of one sample of each type of sieve was tested for its ability to trap mercury from a gas stream. However, the results from this study demonstrate that the adsorption characteristics of silver-loaded sieves cannot necessarily be predicted using a full complement of structural characterization techniques, which highlights the importance of understanding the formation and nature of silver species on molecular sieves.

  2. Molecular mechanism for cadmium-induced anthocyanin accumulation in Azolla imbricata.

    PubMed

    Dai, Ling-Peng; Dong, Xin-Jiao; Ma, Hai-Hu

    2012-04-01

    Anthocyanins inducibly synthesized by Cd treatment showed high antioxidant activity and might be involved in internal detoxification mechanisms of Azolla imbricata against Cd toxicity. In order to understand anthocyanin biosynthesis mechanism during Cd stress, the cDNAs encoding chalcone synthase (CHS) and dihydroflavonol reductase (DFR), two key enzymes in the anthocyanin synthesis pathway, were isolated from A. imbricata. Deduced amino acid sequences of the cDNAs showed high homology to the sequences from other plants. Expression of AiDFR, and to a lesser extent AiCHS, was significantly induced in Cd treatment plant in comparison with the control. CHS and DFR enzymatic activities showed similar pattern changes with these genes expression during Cd stress. These results strongly indicate that Cd induced anthocyanin accumulation is probably mediated by up-regulation of structural genes including CHS and DFR, which might further increase the activities of enzymes encoded by these structural genes that control the anthocyanin biosynthetic steps. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. A survey of knowledge, attitudes and practices towards avian influenza in an adult population of Italy.

    PubMed

    Di Giuseppe, Gabriella; Abbate, Rossella; Albano, Luciana; Marinelli, Paolo; Angelillo, Italo F

    2008-03-17

    Several public health strategic interventions are required for effective prevention and control of avian influenza (AI) and it is necessary to create a communication plan to keep families adequately informed on how to avoid or reduce exposure. This investigation determined the knowledge, attitudes, and behaviors relating to AI among an adult population in Italy. From December 2005 to February 2006 a random sample of 1020 adults received a questionnaire about socio-demographic characteristics, knowledge of transmission and prevention about AI, attitudes towards AI, behaviors regarding use of preventive measures and food-handling practices, and sources of information about AI. A response rate of 67% was achieved. Those in higher socioeconomic classes were more likely to identify the modes of transmission and the animals' vehicles for AI. Those older, who knew the modes of transmission and the animals' vehicles for AI, and who still need information, were more likely to know that washing hands soap before and after touching raw poultry meat and using gloves is recommended to avoid spreading of AI through food. The risk of being infected was significantly higher in those from lower socioeconomic classes, if they did not know the definition of AI, if they knew that AI could be transmitted by eating and touching raw eggs and poultry foods, and if they did not need information. Compliance with the hygienic practices during handling of raw poultry meat was more likely in those who perceived to be at higher risk, who knew the hygienic practices, who knew the modes of transmission and the animals' vehicles for AI, and who received information from health professionals and scientific journals. Respondents demonstrate no detailed understanding of AI, a greater perceived risk, and a lower compliance with precautions behaviors and health educational strategies are strongly needed.

  4. Integrating Motivational Interviewing and Traditional Practices to Address Alcohol and Drug Use Among Urban American Indian/Alaska Native Youth.

    PubMed

    Dickerson, Daniel L; Brown, Ryan A; Johnson, Carrie L; Schweigman, Kurt; D'Amico, Elizabeth J

    2016-06-01

    American Indians/Alaska Natives (AI/AN) exhibit high levels of alcohol and drug (AOD) use and problems. Although approximately 70% of AI/ANs reside in urban areas, few culturally relevant AOD use programs targeting urban AI/AN youth exist. Furthermore, federally-funded studies focused on the integration of evidence-based treatments with AI/AN traditional practices are limited. The current study addresses a critical gap in the delivery of culturally appropriate AOD use programs for urban AI/AN youth, and outlines the development of a culturally tailored AOD program for urban AI/AN youth called Motivational Interviewing and Culture for Urban Native American Youth (MICUNAY). We conducted focus groups among urban AI/AN youth, providers, parents, and elders in two urban communities in northern and southern California aimed at 1) identifying challenges confronting urban AI/AN youth and 2) obtaining feedback on MICUNAY program content. Qualitative data were analyzed using Dedoose, a team-based qualitative and mixed methods analysis software platform. Findings highlight various challenges, including community stressors (e.g., gangs, violence), shortage of resources, cultural identity issues, and a high prevalence of AOD use within these urban communities. Regarding MICUNAY, urban AI/AN youth liked the collaborative nature of the motivational interviewing (MI) approach, especially with regard to eliciting their opinions and expressing their thoughts. Based on feedback from the youth, three AI/AN traditional practices (beading, AI/AN cooking, and prayer/sage ceremony) were chosen for the workshops. To our knowledge, MICUNAY is the first AOD use prevention intervention program for urban AI/AN youth that integrates evidence-based treatment with traditional practices. This program addresses an important gap in services for this underserved population. Copyright © 2015. Published by Elsevier Inc.

  5. The American Indian and Alaska Native Dentist Workforce in the United States

    PubMed Central

    Mertz, Elizabeth; Wides, Cynthia; Gates, Paul

    2017-01-01

    Objectives The purpose of this paper is to describe the American Indian/Alaska Native (AI/AN) dentist workforce, the general practice patterns of these providers, and their contributions to oral health care for AI/AN and underserved patients. Methods A national sample survey of underrepresented minority dentists was conducted in 2012 and received a 34.0% response rate for self-reported AI/AN dentists. Data were weighted for selection and response bias to be nationally representative. Descriptive and multivariable statistics were computed to provide a workforce profile. Comparisons to Census data and published information on dental students and dentists were used to examine practice patterns. Results The AI/AN dentist workforce (weighted n=442) is very diverse with 55 reported individual tribal affiliations. Tribal heritage was provided by 96.4% of AI/AN dentists (n=426), and of these, 93.9% (n=400) reported an affiliation with only one tribe. The largest share of AI/AN dentists were born in the U.S. (98.2%, n=434), married (75.6%, n=333), and had dependent children under age 18 (52.0%, n=222). Only 0.9% (n=4) of AI/AN dentists spoke a traditional AI/AN language in patient care, while 10.6% (n=46) were raised on tribal land or reservation. Initial practice in the Indian Health Service was reported by 15.8% of AI/AN dentists while 16.2% report currently practicing in a safety-net setting, and 42.0% report working in a practice that primarily serves underserved patients. Conclusions AI/AN dentists provide a disproportionate share of care for AI/AN populations, yet the number of AI/AN dentists would need to increase 7.4 fold in order to meet population parity. PMID:27922723

  6. Integrating motivational interviewing and traditional practices to address alcohol and drug use among urban American Indian/Alaska Native youth

    PubMed Central

    Dickerson, Daniel L.; Brown, Ryan A.; Johnson, Carrie L.; Schweigman, Kurt; D’Amico, Elizabeth J.

    2015-01-01

    American Indians/Alaska Natives (AI/AN) exhibit high levels of alcohol and drug (AOD) use and problems. Although approximately 70% of AI/ANs reside in urban areas, few culturally relevant AOD use programs targeting urban AI/AN youth exist. Furthermore, federally-funded studies focused on the integration of evidence-based treatments with AI/AN traditional practices are limited. The current study addresses a critical gap in the delivery of culturally appropriate AOD use programs for urban AI/AN youth, and outlines the development of a culturally tailored AOD program for urban AI/AN youth called Motivational Interviewing and Culture for Urban Native American Youth (MICUNAY). We conducted focus groups among urban AI/AN youth, providers, parents, and elders in two urban communities in northern and southern California aimed at 1) identifying challenges confronting urban AI/AN youth and 2) obtaining feedback on MICUNAY program content. Qualitative data were analyzed using Dedoose, a team-based qualitative and mixed methods analysis software platform. Findings highlight various challenges, including community stressors (e.g., gangs, violence), shortage of resources, cultural identity issues, and a high prevalence of AOD use within these urban communities. Regarding MICUNAY, urban AI/AN youth liked the collaborative nature of the motivational interviewing (MI) approach, especially with regard to eliciting their opinions and expressing their thoughts. Based on feedback from the youth, three AI/AN traditional practices (beading, AI/AN cooking, and prayer/sage ceremony) were chosen for the workshops. MICUNAY is the first AOD use prevention intervention program for urban AI/AN youth that integrates evidence-based treatment with traditional practices. This program addresses an important gap in services for this underserved population. PMID:26306776

  7. Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A-I in healthy men

    PubMed Central

    Lamarche, Benoît; Uffelman, Kristine D.; Carpentier, André; Cohn, Jeffrey S.; Steiner, George; Barrett, P. Hugh; Lewis, Gary F.

    1999-01-01

    Triglyceride (TG) enrichment of HDL resulting from cholesteryl ester transfer protein–mediated exchange with TG-rich lipoproteins may enhance the lipolytic transformation and subsequent metabolic clearance of HDL particles in hypertriglyceridemic states. The present study investigates the effect of TG enrichment of HDL on the clearance of HDL-associated apo A-I in humans. HDL was isolated from plasma of six normolipidemic men (mean age: 29.7 ± 2.7 years) in the fasting state and after a five-hour intravenous infusion with a synthetic TG emulsion, Intralipid. Intralipid infusion resulted in a 2.1-fold increase in the TG content of HDL. Each tracer was then whole-labeled with 125I or 131I and injected intravenously into the subject. Apo A-I in TG-enriched HDL was cleared 26% more rapidly than apo A-I in fasting HDL. A strong correlation between the Intralipid-induced increase in the TG content of HDL and the increase in HDL apo A-I fractional catabolic rate reinforced the importance of TG enrichment of HDL in enhancing its metabolic clearance. HDL was separated further into lipoproteins containing apo A-II (LpAI:AII) and those without apo A-II (LpAI). Results revealed that the enhanced clearance of apo A-I from TG-enriched HDL could be largely attributed to differences in the clearance of LpAI but not LpAI:AII. This is, to our knowledge, the first direct demonstration in humans that TG enrichment of HDL enhances the clearance of HDL apo A-I from the circulation. This phenomenon could provide an important mechanism explaining how HDL apo A-I and HDL cholesterol are lowered in hypertriglyceridemic states. PMID:10207171

  8. A Case Series of the Probability Density and Cumulative Distribution of Laryngeal Disease in a Tertiary Care Voice Center.

    PubMed

    de la Fuente, Jaime; Garrett, C Gaelyn; Ossoff, Robert; Vinson, Kim; Francis, David O; Gelbard, Alexander

    2017-11-01

    To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

  9. Rhodamine Inhibitors of P-glycoprotein: An Amide/Thioamide “Switch” for ATPase Activity

    PubMed Central

    Gannon, Michael K.; Holt, Jason J.; Bennett, Stephanie M.; Wetzel, Bryan R.; Loo, Tip W.; Bartlett, M. Claire; Clarke, David M.; Sawada, Geri A.; Higgins, J. William; Tombline, Gregory; Raub, Thomas J.; Detty, Michael R.

    2012-01-01

    We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His10, for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave KM of 0.087 μM in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC50’s of ~2 μM in MDCKII-MDR1 cells. PMID:19402665

  10. Yemen: Background and U.S. Relations

    DTIC Science & Technology

    2014-11-19

    been fighting t he central government, other northern Yemeni tribes, and militants associated with AI Qaeda in the Arabian Peninsula. The opponents...in self-defense. The AI Ahmar Family (pictured: Sheikh Sadiq AI Ahmar) The AI Ahmar family is t he leading clan in t he one of the largest tribal...family. Another prominent political figure in the clan is Hamid AI Ahmar, who sided with Yemeni protestors and against former president Saleh back in

  11. Impacts of drought and crayfish invasion on stream ecosystem structure and function

    USGS Publications Warehouse

    Magoulick, Daniel D.

    2014-01-01

    Drought and seasonal drying can be important disturbance events in many small streams, leading to intermittent or isolated habitats. Many small streams contain crayfish populations that are often keystone or dominant species in these systems. I conducted an experiment in stream mesocosms to examine the effects of drought and potential ecological redundancy of a native and invasive crayfish species. I examined the effects of drought (drought or control) and crayfish presence (none, native crayfish Orconectes eupunctus or invasive crayfish Orconectes neglectus) on stream mesocosm structure and function (leaf breakdown, community metabolism, periphyton, sediment and chironomid densities) in a fully factorial design. Each mesocosm contained a deep and shallow section, and drought treatments had surface water present (5-cm depth) in deep sections where tiles and leaf packs were placed. Drought and crayfish presence did not interact for any response variable. Drought significantly reduced leaf breakdown, and crayfish presence significantly increased leaf breakdown. However, the native and invasive crayfish species did not differ significantly in their effects on leaf breakdown. Drought significantly reduced primary production and community respiration overall, whereas crayfish presence did not significantly affect primary production and community respiration. Neither drought nor crayfish presence significantly affected periphyton overall. However, drought significantly reduced autotrophic index (AI), and crayfish presence increased AI. Inorganic sediment and chironomid density were not affected by drought, but both were significantly reduced by crayfish presence. O. eupunctus reduced AI and sediment more than O. neglectus did. Neither drought nor crayfish species significantly affected crayfish growth or survival. Drought can have strong effects on ecosystem function, but weaker effects on benthic structure. Crayfish can have strong effects on ecosystem structure and function regardless of drought. In stream mesocosms, native and invasive crayfish species appeared largely ecologically redundant, although subtle differences in crayfish effects could cascade throughout the food web, and further research is needed to address this question. 

  12. The effects of health education on knowledge and attitudes to emergency contraception by female students of a tertiary educational institution in Enugu, South East Nigeria.

    PubMed

    Arinze-Onyia, S U; Onwasigwe, C N; Uzochukwu, B S C; Nwobi, E A; Ndu, A C; Nwobodo, Ed

    2010-11-28

    This was an intervention study to assess the effects of health education on the knowledge and attitudes to emergency contraception (EC) by female students of University of Nigeria in southeast Nigeria. A structured questionnaire was used to collect data from 337 female students of a tertiary educational institution (150 in the study group and 187 from the control group) who were selected by multistage sampling. Subsequently, health education was conducted only among students in the study institution. Three months after this intervention, its effects were assessed through a survey using the same structured questionnaire employed in the baseline survey. Unlike the pre-intervention results, knowledge of EC was significantly higher among the study group than the controls. Attitudes to EC were also more favourable at the post- intervention survey among the study group. Health education can effectively improve knowledge and attitudes to EC among female students of tertiary institutions and this should be encouraged.

  13. Tertiary tilting and dismemberment of the laramide arc and related hydrothermal systems, Sierrita Mountain, Arizona

    USGS Publications Warehouse

    Stavast, W.J.A.; Butler, R.P.; Seedorff, E.; Barton, M.D.; Ferguson, C.A.

    2008-01-01

    Multiple lines of evidence, including new and published geologic mapping and paleomagnetic and geobarometric determinations, demonstrate that the rocks and large porphyry copper systems of the Sierrita Mountains in southern Arizona were dismembered and tilted 50?? to 60?? to the south by Tertiary normal faulting. Repetition of geologic features and geobarometry indicate that the area is segmented into at least three major structural blocks, and the present surface corresponds to oblique sections through the Laramide plutonic-hydrothermal complex, ranging in paleodepth from ???1 to ???12 km. These results add to an evolving view of a north-south extensional domain at high angles to much extension in the southern Basin and Range, contrast with earlier interpretations that the Laramide systems are largely upright and dismembered by thrust faults, highlight the necessity of restoring Tertiary rotations before interpreting Laramide structural and hydrothermal features, and add to the broader understanding of pluton emplacement and evolution of porphyry copper systems. ?? 2008 Society of Economic Geologists, Inc.

  14. Evaluation of criteria for optimal time AI postulated by estrous signs in lactating dairy cows kept in tie-stalls

    PubMed Central

    SUMIYOSHI, Toshiaki; ENDO, Natsumi; TANAKA, Tomomi; KAMOMAE, Hideo

    2017-01-01

    Relaxation of the intravaginal part of the uterus is obvious around 6 to 18 h before ovulation, and this is considered the optimal time for artificial insemination (AI), as demonstrated in recent studies. Estrous signs have been suggested as useful criteria for determining the optimal time for AI. Therefore, this study evaluated the usefulness of estrous signs, particularly the relaxation of the intravaginal part of the uterus, as criteria for determining the optimal time for AI. A Total of 100 lactating Holstein-Friesian cows kept in tie-stall barns were investigated. AI was carried out based on the criterion for the optimal time for AI (optimal group), and earlier (early group) and later (late group) than the optimal time for AI, determined on the basis of estrous signs. After AI, ovulation was assessed by rectal palpation and ultrasonographic observation at 6-h intervals. For 87.5% (35/40) of cows in the optimal group, AI was carried out 24-6 h before ovulation, which was previously accepted as the optimal time for AI. AI was carried out earlier (early group) and later (late group) than optimal time for AI in 62.1% (18/29) and 71.0% (22/31) of cows, respectively. The conception rate for the optimal group was 60.0%, and this conception rate was higher than that for the early group (44.8%) and late group (32.2%), without significance. Further, the conception rate of the optimal group was significantly higher than the sum of the conception rates of the early and late groups (38.3%; 23/60) (P < 0.05). These results indicate that the criteria postulated, relaxation of the intravaginal part of the uterus and other estrous signs are useful in determining the optimal time for AI. Furthermore, these estrous signs enable the estimations of stages in the periovulatory period. PMID:29081451

  15. Avian Influenza Risk Perception and Preventive Behavior among Traditional Market Workers and Shoppers in Taiwan: Practical Implications for Prevention

    PubMed Central

    Liu, Ming-Der

    2011-01-01

    Background Avian influenza (AI) can be highly pathogenic and fatal. Preventive behavior such as handwashing and wearing face masks has been recommended. However, little is known about what psychosocial factors might influence people's decision to adopt such preventive behavior. This study aims to explore risk perception and other factors associated with handwashing and wearing face masks to prevent AI. Methodology/Principal Findings An interviewer-administered survey was conducted among 352 traditional market workers and shoppers in Taiwan between December 2009 and January 2010. Factors associated with the recommended AI preventive behavior (i.e., when in a traditional market, wearing a face mask and also washing hands after any contact with poultry) included: having correct knowledge about the fatality rate of AI (adjusted odds ratio [AOR] = 4.18), knowing of severe cases of AI (AOR = 2.13), being informed of local AI outbreaks (AOR = 2.24), living in northeastern Taiwan (AOR = 6.01), having a senior high-school education (AOR = 3.33), and having a university or higher education (AOR = 6.86). Gender interactive effect was also found among participants with a senior high-school education, with males being less likely to engage in the recommended AI preventive behavior than their female counterparts (AOR = 0.34). Conclusions/Significance Specific information concerning AI risk perception was associated with the recommended AI preventive behavior. In particular, having correct knowledge about the fatality rate of AI and being informed of severe cases and local outbreaks of AI were linked to increased AI preventive behavior. These findings underscore the importance of transparency in dealing with epidemic information. These results also have practical implications for prevention and policy-making to more effectively promote the recommended AI preventive behavior in the public. PMID:21912667

  16. Açai (Euterpe oleracea Mart.) dietary intake affects plasma lipids, apolipoproteins, cholesteryl ester transfer to high-density lipoprotein and redox metabolism: A prospective study in women.

    PubMed

    Pala, Daniela; Barbosa, Priscila Oliveira; Silva, Carla Teixeira; de Souza, Melina Oliveira; Freitas, Fatima Rodrigues; Volp, Ana Carolina Pinheiro; Maranhão, Raul Cavalcante; Freitas, Renata Nascimento de

    2018-04-01

    The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  17. Time-Lapse Acoustic Impedance Inversion in CO2 Sequestration Study (Weyburn Field, Canada)

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Morozov, I. B.

    2016-12-01

    Acoustic-impedance (AI) pseudo-logs are useful for characterising subtle variations of fluid content during seismic monitoring of reservoirs undergoing enhanced oil recovery and/or geologic CO2 sequestration. However, highly accurate AI images are required for time-lapse analysis, which may be difficult to achieve with conventional inversion approaches. In this study, two enhancements of time-lapse AI analysis are proposed. First, a well-known uncertainty of AI inversion is caused by the lack of low-frequency signal in reflection seismic data. To resolve this difficulty, we utilize an integrated AI inversion approach combining seismic data, acoustic well logs and seismic-processing velocities. The use of well logs helps stabilizing the recursive AI inverse, and seismic-processing velocities are used to complement the low-frequency information in seismic records. To derive the low-frequency AI from seismic-processing velocity data, an empirical relation is determined by using the available acoustic logs. This method is simple and does not require subjective choices of parameters and regularization schemes as in the more sophisticated joint inversion methods. The second improvement to accurate time-lapse AI imaging consists in time-variant calibration of reflectivity. Calibration corrections consist of time shifts, amplitude corrections, spectral shaping and phase rotations. Following the calibration, average and differential reflection amplitudes are calculated, from which the average and differential AI are obtained. The approaches are applied to a time-lapse 3-D 3-C dataset from Weyburn CO2 sequestration project in southern Saskatchewan, Canada. High quality time-lapse AI volumes are obtained. Comparisons with traditional recursive and colored AI inversions (obtained without using seismic-processing velocities) show that the new method gives a better representation of spatial AI variations. Although only early stages of monitoring seismic data are available, time-lapse AI variations mapped within and near the reservoir zone suggest correlations with CO2 injection. By extending this procedure to elastic impedances, additional constraints on the variations of physical properties within the reservoir can be obtained.

  18. 77 FR 23462 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ... this law allocates the Aleutian Islands (AI) directed pollock fishery to the Aleut Corporation for... agents for activities necessary for conducting the AI directed pollock fishery. Management provisions for the AI directed pollock fishery include: restrictions on the harvest specifications for the AI...

  19. Effects of Climate Change on Aquatic Invasive Species and ...

    EPA Pesticide Factsheets

    This draft report reviews available literature on climate change effects on aquatic invasive species (AIS) and examines state level AIS management activities. This draft report assesses the state of the science of climate change effects on AIS and examines state level AIS management activities.

  20. A Starter's Guide to Artificial Intelligence.

    ERIC Educational Resources Information Center

    McConnell, Barry A.; McConnell, Nancy J.

    1988-01-01

    Discussion of the history and development of artificial intelligence (AI) highlights a bibliography of introductory books on various aspects of AI, including AI programing; problem solving; automated reasoning; game playing; natural language; expert systems; machine learning; robotics and vision; critics of AI; and representative software. (LRW)

  1. Adventures in supercomputing: An innovative program for high school teachers

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

    Oliver, C.E.; Hicks, H.R.; Summers, B.G.

    1994-12-31

    Within the realm of education, seldom does an innovative program become available with the potential to change an educator`s teaching methodology. Adventures in Supercomputing (AiS), sponsored by the U.S. Department of Energy (DOE), is such a program. It is a program for high school teachers that changes the teacher paradigm from a teacher-directed approach of teaching to a student-centered approach. {open_quotes}A student-centered classroom offers better opportunities for development of internal motivation, planning skills, goal setting and perseverance than does the traditional teacher-directed mode{close_quotes}. Not only is the process of teaching changed, but the cross-curricula integration within the AiS materials ismore » remarkable. Written from a teacher`s perspective, this paper will describe the AiS program and its effects on teachers and students, primarily at Wartburg Central High School, in Wartburg, Tennessee. The AiS program in Tennessee is sponsored by Oak Ridge National Laboratory (ORNL).« less

  2. Terpecurcumins A-I from the rhizomes of Curcuma longa: absolute configuration and cytotoxic activity.

    PubMed

    Lin, Xionghao; Ji, Shuai; Li, Rui; Dong, Yinhui; Qiao, Xue; Hu, Hongbo; Yang, Wenzhi; Guo, Dean; Tu, Pengfei; Ye, Min

    2012-12-28

    Terpecurcumins A-I (1-9), together with three known analogues (10-12), were isolated from the rhizomes of Curcuma longa (turmeric). They were derived from the hybridization of curcuminoids and bisabolanes. The structures and absolute configurations of 1-9 were elucidated on the basis of extensive spectroscopic data analysis, including NMR and electronic circular dichroism spectra. The configuration of 10 was further confirmed by X-ray crystallography. A plausible biogenetic relationship for 1-12 is proposed. Compounds 4, 6, 7, 10, and 11 showed higher cytotoxic activities (IC(50), 10.3-19.4 μM) than curcumin (IC(50), 31.3-49.2 μM) against human cancer cell lines (A549, HepG2, and MDA-MB-231).

  3. Potentially Missed Diagnosis of Ischemic Stroke in the Emergency Department in the Greater Cincinnati/Northern Kentucky Stroke Study.

    PubMed

    Madsen, Tracy E; Khoury, Jane; Cadena, Rhonda; Adeoye, Opeolu; Alwell, Kathleen A; Moomaw, Charles J; McDonough, Erin; Flaherty, Matthew L; Ferioli, Simona; Woo, Daniel; Khatri, Pooja; Broderick, Joseph P; Kissela, Brett M; Kleindorfer, Dawn

    2016-10-01

    Missed diagnoses of acute ischemic stroke (AIS) in the ED may result in lost opportunities to treat AIS. Our objectives were to describe the rate and clinical characteristics of missed AIS in the ED, to determine clinical predictors of missed AIS, and to report tissue plasminogen (tPA) eligibility among those with missed strokes. Among a population of 1.3 million in a five-county region of southwest Ohio and northern Kentucky, cases of AIS that presented to 16 EDs during 2010 were identified using ICD-9 codes followed by physician verification of cases. Missed ED diagnoses were physician-verified strokes that did not receive a diagnosis indicative of stroke in the ED. Bivariate analyses were used to compare clinical characteristics between patients with and without an ED diagnosis of AIS. Logistic regression was used to evaluate predictors of missed AIS diagnoses. Alternative diagnoses given to those with missed AIS were codified. Eligibility for tPA was reported between those with and without a missed stroke diagnosis. Of 2,027 AIS cases, 14.0% (n = 283) were missed in the ED. Race, sex, and stroke subtypes were similar between those with missed AIS diagnoses and those identified in the ED. Hospital length of stay was longer in those with a missed diagnosis (5 days vs. 3 days, p < 0.0001). Younger age (adjusted odds ratio [aOR] = 0.94, 95% confidence interval [CI] = 0.89 to 0.98) and decreased level of consciousness (LOC) (aOR = 3.58, 95% CI = 2.63 to 4.87) were associated with higher odds of missed AIS. Altered mental status was the most common diagnosis among those with missed AIS. Only 1.1% of those with a missed stroke diagnosis were eligible for tPA. In a large population-based sample of AIS cases, one in seven cases were not diagnosed as AIS in the ED, but the impact on acute treatment rates is likely small. Missed diagnosis was more common among those with decreased LOC, suggesting the need for improved diagnostic approaches in these patients. © 2016 by the Society for Academic Emergency Medicine.

  4. Optical spectroscopic methods for probing the conformational stability of immobilised enzymes.

    PubMed

    Ganesan, Ashok; Moore, Barry D; Kelly, Sharon M; Price, Nicholas C; Rolinski, Olaf J; Birch, David J S; Dunkin, Ian R; Halling, Peter J

    2009-07-13

    We report the development of biophysical techniques based on circular dichroism (CD), diffuse reflectance infrared Fourier transform (DRIFT) and tryptophan (Trp) fluorescence to investigate in situ the structure of enzymes immobilised on solid particles. Their applicability is demonstrated using subtilisin Carlsberg (SC) immobilised on silica gel and Candida antartica lipase B immobilised on Lewatit VP.OC 1600 (Novozyme 435). SC shows nearly identical secondary structure in solution and in the immobilised state as evident from far UV CD spectra and amide I vibration bands. Increased near UV CD intensity and reduced Trp fluorescence suggest a more rigid tertiary structure on the silica surface. After immobilised SC is inactivated, these techniques reveal: a) almost complete loss of near UV CD signal, suggesting loss of tertiary structure; b) a shift in the amide I vibrational band from 1658 cm(-1) to 1632 cm(-1), indicating a shift from alpha-helical structure to beta-sheet; c) a substantial blue shift and reduced dichroism in the far UV CD, supporting a shift to beta-sheet structure; d) strong increase in Trp fluorescence intensity, which reflects reduced intramolecular quenching with loss of tertiary structure; and e) major change in fluorescence lifetime distribution, confirming a substantial change in Trp environment. DRIFT measurements suggest that pressing KBr discs may perturb protein structure. With the enzyme on organic polymer it was possible to obtain near UV CD spectra free of interference by the carrier material. However, far UV CD, DRIFT and fluorescence measurements showed strong signals from the organic support. In conclusion, the spectroscopic methods described here provide structural information hitherto inaccessible, with their applicability limited by interference from, rather than the particulate nature of, the support material.

  5. 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

  6. Geologic Map of the Gold Creek Gold District, Elko County, Nevada

    USGS Publications Warehouse

    Ketner, Keith B.

    2007-01-01

    The Gold Creek, Nev. area displays important stratigraphic and structural relationships between Paleozoic and early Tertiary sedimentary strata in an area dominated by large intrusive bodies of Mesozoic age and extensive volcanic fields of middle to late Tertiary age. An autochthonous sequence includes the Cambrian and Proterozoic(?) Prospect Mountain Quartzite and the overlying Cambrian and Ordovician Tennessee Mountain Formation. This autochthon is overlain by three allochthonous plates each composed of a distinctive sequence of strata and having a distinctive internal structure. The structurally lowest plate is composed of the Havallah sequence, locally of Mississippian and Pennsylvanian age, which is folded on north-south trending axes. The next higher plate is composed of somewhat younger Pennsylvanian and Permian strata cut by east-west trending low-angle faults. The highest plate is composed of early Tertiary non-marine sedimentary and igneous rocks folded on varied but mainly north-south trending axes. The question of whether the allochthonous plates were emplaced by contractional or extensional forces is indeterminate from the local evidence. Mineral deposits include gold placers of moderate size and small pockets of base metals, none of which is currently being exploited.

  7. Final acceptance testing of the LSST monolithic primary/tertiary mirror

    NASA Astrophysics Data System (ADS)

    Tuell, Michael T.; Burge, James H.; Cuerden, Brian; Gressler, William; Martin, Hubert M.; West, Steven C.; Zhao, Chunyu

    2014-07-01

    The Large Synoptic Survey Telescope (LSST) is a three-mirror wide-field survey telescope with the primary and tertiary mirrors on one monolithic substrate1. This substrate is made of Ohara E6 borosilicate glass in a honeycomb sandwich, spin cast at the Steward Observatory Mirror Lab at The University of Arizona2. Each surface is aspheric, with the specification in terms of conic constant error, maximum active bending forces and finally a structure function specification on the residual errors3. There are high-order deformation terms, but with no tolerance, any error is considered as a surface error and is included in the structure function. The radii of curvature are very different, requiring two independent test stations, each with instantaneous phase-shifting interferometers with null correctors. The primary null corrector is a standard two-element Offner null lens. The tertiary null corrector is a phase-etched computer-generated hologram (CGH). This paper details the two optical systems and their tolerances, showing that the uncertainty in measuring the figure is a small fraction of the structure function specification. Additional metrology includes the radii of curvature, optical axis locations, and relative surface tilts. The methods for measuring these will also be described along with their tolerances.

  8. The LuxS/AI-2 Quorum-Sensing System of Streptococcus pneumoniae Is Required to Cause Disease, and to Regulate Virulence- and Metabolism-Related Genes in a Rat Model of Middle Ear Infection.

    PubMed

    Yadav, Mukesh K; Vidal, Jorge E; Go, Yoon Y; Kim, Shin H; Chae, Sung-Won; Song, Jae-Jun

    2018-01-01

    Objective: Streptococcus pneumoniae colonizes the nasopharynx of children, and from nasopharynx it could migrate to the middle ear and causes acute otitis media (AOM). During colonization and AOM, the pneumococcus forms biofilms. In vitro biofilm formation requires a functional LuxS/AI-2 quorum-sensing system. We investigated the role of LuxS/AI-2 signaling in pneumococcal middle ear infection, and identified the genes that are regulated by LuxS/AI-2 during pneumococcal biofilm formation. Methods: Streptococcus pneumoniae D39 wild-type and an isogenic D39Δ luxS strain were utilized to evaluate in vitro biofilm formation, and in vivo colonization and epithelial damage using a microtiter plate assay and a rat model of pneumococcal middle ear infection, respectively. Biofilm structures and colonization and epithelial damage were evaluated at the ultrastructural level by scanning electron microscopy and confocal microscopy. Microarrays were used to investigate the global genes that were regulated by LuxS/AI-2 during biofilm formation. Results: The biofilm biomass and density of D39Δ luxS were significantly ( p < 0.05) lower than those of D39 wild-type. SEM and confocal microscopy revealed that D39Δ luxS formed thin biofilms in vitro compared with D39 wild-type. The in vivo model of middle ear infection showed that D39Δ luxS resulted in ~60% less ( p < 0.05) bacterial colonization than the wild-type. SEM analysis of the rat middle ears revealed dense biofilm-like cell debris deposited on the cilia in wild-type D39-infected rats. However, little cell debris was deposited in the middle ears of the D39Δ luxS -inoculated rats, and the cilia were visible. cDNA-microarray analysis revealed 117 differentially expressed genes in D39Δ luxS compared with D39 wild-type. Among the 66 genes encoding putative proteins and previously characterized proteins, 60 were significantly downregulated, whereas 6 were upregulated. Functional annotation revealed that genes involved in DNA replication and repair, ATP synthesis, capsule biosynthesis, cell division, the cell cycle, signal transduction, transcription regulation, competence, virulence, and carbohydrate metabolism were downregulated in the absence of LuxS/AI-2. Conclusion: The S. pneumoniae LuxS/AI-2 quorum-sensing system is necessary for biofilm formation and the colonization of the ear epithelium, and caused middle ear infection in the rat model. LuxS/AI-2 regulates the expression of the genes involved in virulence and bacterial fitness during pneumococcal biofilm formation.

  9. FuncPatch: a web server for the fast Bayesian inference of conserved functional patches in protein 3D structures.

    PubMed

    Huang, Yi-Fei; Golding, G Brian

    2015-02-15

    A number of statistical phylogenetic methods have been developed to infer conserved functional sites or regions in proteins. Many methods, e.g. Rate4Site, apply the standard phylogenetic models to infer site-specific substitution rates and totally ignore the spatial correlation of substitution rates in protein tertiary structures, which may reduce their power to identify conserved functional patches in protein tertiary structures when the sequences used in the analysis are highly similar. The 3D sliding window method has been proposed to infer conserved functional patches in protein tertiary structures, but the window size, which reflects the strength of the spatial correlation, must be predefined and is not inferred from data. We recently developed GP4Rate to solve these problems under the Bayesian framework. Unfortunately, GP4Rate is computationally slow. Here, we present an intuitive web server, FuncPatch, to perform a fast approximate Bayesian inference of conserved functional patches in protein tertiary structures. Both simulations and four case studies based on empirical data suggest that FuncPatch is a good approximation to GP4Rate. However, FuncPatch is orders of magnitudes faster than GP4Rate. In addition, simulations suggest that FuncPatch is potentially a useful tool complementary to Rate4Site, but the 3D sliding window method is less powerful than FuncPatch and Rate4Site. The functional patches predicted by FuncPatch in the four case studies are supported by experimental evidence, which corroborates the usefulness of FuncPatch. The software FuncPatch is freely available at the web site, http://info.mcmaster.ca/yifei/FuncPatch golding@mcmaster.ca Supplementary data are available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. 77 FR 20531 - Correction of Authority Citations for Commercial Space Transportation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-05

    ...-AI50, 2120-AI57, 2120-AI56, 2120-AI88] Correction of Authority Citations for Commercial Space..., Congress transferred the statute authorizing the FAA's commercial space transportation regulations. This...: Laura Montgomery, Senior Attorney for Commercial Space Transportation, Office of the Chief Counsel...

  11. The AI Interdisciplinary Context: Single or Multiple Research Bases?

    ERIC Educational Resources Information Center

    Khawam, Yves J.

    1992-01-01

    This study used citation analysis to determine whether the disciplines contributing to the journal literature of artificial intelligence (AI)--philosophy, psychology, linguistics, computer science, and engineering--share a common AI research base. The idea that AI consists of a completely interdisciplinary endeavor was refuted. (MES)

  12. AI in space: Past, present, and possible futures

    NASA Technical Reports Server (NTRS)

    Rose, Donald D.; Post, Jonathan V.

    1992-01-01

    While artificial intelligence (AI) has become increasingly present in recent space applications, new missions being planned will require even more incorporation of AI techniques. In this paper, we survey some of the progress made to date in implementing such programs, some current directions and issues, and speculate about the future of AI in space scenarios. We also provide examples of how thinkers from the realm of science fiction have envisioned AI's role in various aspects of space exploration.

  13. Behavioral and Biological Effects of Prenatal Stress and Social Enrichment: Relevance to Heart Disease

    DTIC Science & Technology

    2009-08-17

    Weight: Repeated Measures (Between-Subjects Effects ) Body Weight: Analysis of Variance (ANOVA) - Males Only Body Weight: Last Measurement Corticosterone ...also decreased the effects of stress on freezing behavior and corticosterone levels in mice (Benaroya-Milshtein et aI., 2004). Summary of Social...rats (e.g., Faradayet aI., 2005; Kalinichev et aI., 2002; Kant et aI., 1987; Hayley et aI., 2001). 22 Corticosterone responses to stressors are

  14. Expression and purification of recombinant apolipoprotein A-I Zaragoza (L144R) and formation of reconstituted HDL particles.

    PubMed

    Fiddyment, Sarah; Barceló-Batllori, Sílvia; Pocoví, Miguel; García-Otín, Angel-Luis

    2011-11-01

    Apolipoprotein A-I Zaragoza (L144R) (apo A-I Z), has been associated with severe hypoalphalipoproteinemia and an enhanced effect of high density lipoprotein (HDL) reverse cholesterol transport. In order to perform further studies with this protein we have optimized an expression and purification method of recombinant wild-type apo A-I and apo A-I Z and produced mimetic HDL particles with each protein. An pET-45 expression system was used to produce N-terminal His-tagged apo A-I, wild-type or mutant, in Escherichia coli BL21 (DE3) which was subsequently purified by affinity chromatography in non-denaturing conditions. HDL particles were generated via a modified sodium cholate method. Expression and purification of both proteins was verified by SDS-PAGE, MALDI-TOF MS and immunochemical procedures. Yield was 30mg of purified protein (94% purity) per liter of culture. The reconstituted HDL particles checked via non-denaturing PAGE showed high homogeneity in their size when reconstituted both with wild-type apo A-I and apo A-I Z. An optimized system for the expression and purification of wild-type apo A-I and apo A-I Z with high yield and purity grade has been achieved, in addition to their use in reconstituted HDL particles, as a basis for further studies. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. A method to identify the areas at risk for the introduction of avian influenza virus into poultry flocks through direct contact with wild ducks.

    PubMed

    Galletti, G; Santi, A; Guberti, V; Paternoster, G; Licata, E; Loli Piccolomini, L; Procopio, A; Tamba, M

    2018-02-22

    Wild dabbling ducks are the main reservoir for avian influenza (AI) viruses and pose an ongoing threat to commercial poultry flocks. Combining the (i) size of that population, (ii) their flight distances and (iii) their AI prevalence, the density of AI-infected dabbling ducks (DID) was calculated as a risk factor for the introduction of AI viruses into poultry holdings of Emilia-Romagna region, Northern Italy. Data on 747 poultry holdings and on 39 AI primary outbreaks notified in Emilia-Romagna between 2000 and 2017 were used to validate that risk factor. A multivariable Bayesian logistic regression was performed to assess whether DID could be associated with the occurrence of AI primary outbreaks. DID value, being an outdoor flock, hobby poultry trading, species reared, length of cycle and flock size were used as explanatory variables. Being an outdoor poultry flock was significantly associated with a higher risk of AI outbreak occurrence. The probability of DID to be a risk factor for AI virus introduction was estimated to be 90%. A DID cut-off of 0.23 was identified to define high-risk areas for AI virus introduction. Using this value, the high-risk area covers 43% of the region. Seventy-four per cent of the primary AI outbreaks have occurred in that area, containing 39% of the regional poultry holdings. Poultry holdings located in areas with a high DID value should be included in a risk-based surveillance programme aimed at AI early detection. © 2018 Blackwell Verlag GmbH.

  16. Symptoms of autism and schizophrenia spectrum disorders in clinically referred youth with oppositional defiant disorder.

    PubMed

    Gadow, Kenneth D; Drabick, Deborah A G

    2012-01-01

    Examined autism spectrum disorder (ASD) and schizophrenia spectrum disorder (SSD) symptoms in a clinically referred, non-ASD sample (N=1160; ages 6-18) with and without oppositional defiant disorder (ODD). Mothers and teachers completed DSM-IV-referenced symptom checklists. Youth with ODD were subdivided into angry/irritable symptom (AIS) or noncompliant symptom (NS) subtypes. Two different classification strategies were used: within-informant (source-specific) and between-informant (source-exclusive). For the source-specific strategy, youth were classified AIS, NS, or Control (C) according to mothers' and teachers' ratings separately. A second set of analyses focused on youth classified AIS according to mother or teacher report but not both (source-exclusive) versus both mother and teacher (cross-informant) AIS. Results indicated the mother-defined source-specific AIS groups generally evidenced the most severe ASD and SSD symptoms (AIS>NS>C), but this was more pronounced among younger youth. Teacher-defined source-specific ODD groups exhibited comparable levels of symptom severity (AIS, NS>C) with the exception of SSD (AIS>NS>C; younger youth). Source-exclusive AIS groups were clearly differentiated from each other, but there was little evidence of differential symptom severity in cross-informant versus source-exclusive AIS. These findings were largely dependent on the informant used to define the source-exclusive groups. AIS and NS groups differed in their associations with ASD and SSD symptoms. Informant discrepancy provides valuable information that can inform nosological and clinical concerns and has important implications for studies that use different strategies to configure clinical phenotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. De novo aortic insufficiency during long-term support on a left ventricular assist device: a systematic review and meta-analysis.

    PubMed

    Deo, Salil V; Sharma, Vikas; Cho, Yang Hyun; Shah, Ishan K; Park, Soon J

    2014-01-01

    Aortic insufficiency (AI) may occur while supported on a left ventricular assist device (LVAD). We conducted a systematic review to determine the incidence, predictors, and consequences of AI during LVAD support. MEDLINE was searched for original studies presenting clinical data regarding patients who developed AI during LVAD implant. Seven observational studies (657 patients) were selected for review; 65% of patients underwent implantation with a continuous-flow device (Cf-LVAD). The incidence of AI was 25% (11-42%) (Support period: 412 ± 281 days). AI increased by 4% (1-6%) per month of support (p < 0.01). AI-positive patients were older at implant (weighted mean difference, 7.7 [4.3; 11.1]; p < 0.01). Female sex (0.002 ± 0.001; p = 0.01) and smaller body surface area (-0.003 ± 0.001 per m; p < 0.01) correlated with progressive AI. Destination therapy patients (odds ratio [OR], 5.3 [1.2, 24]; p = 0.02) and those with Cf-LVAD pumps were likely to develop AI (hazard ratio [HR], 2.2 [1.2, 3.8]; p < 0.01). A closed aortic valve was associated with AI (OR, 4.7 [1.9, 11.8]; p < 0.01). Survival was comparable in both cohorts (HR, 1.5 [0.81, 2.8]; p = 0.2). A significant number of patients develop de novo AI during LVAD support. Advanced age, longer support duration, continuous-flow pumps, and a closed aortic valve are associated with AI. Large cohort studies would improve our understanding of this condition.

  18. A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

    PubMed

    Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

    2017-03-01

    Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

  19. Protein Structure

    ERIC Educational Resources Information Center

    Asmus, Elaine Garbarino

    2007-01-01

    Individual students model specific amino acids and then, through dehydration synthesis, a class of students models a protein. The students clearly learn amino acid structure, primary, secondary, tertiary, and quaternary structure in proteins and the nature of the bonds maintaining a protein's shape. This activity is fun, concrete, inexpensive and…

  20. Laser Hybrid Fabrication of Nanoporous Structures on Metallic Material Surface

    DTIC Science & Technology

    2009-06-01

    Research Center, Department of Mechanical Engineering,Beijing, 100084&# 65292 ;China, 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING...rials, 2005, 15: 989-994. [9]Jia F, Yu C, Ai Z, et al. Fabrication of nanoporous gold film electrodes with ultrahigh surface area and electro

  1. Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein.

    PubMed

    Lazim, Raudah; Mei, Ye; Zhang, Dawei

    2012-03-01

    Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.

  2. Structure of an E. coli integral membrane sulfurtransferase and its structural transition upon SCN- binding defined by EPR-based hybrid method

    NASA Astrophysics Data System (ADS)

    Ling, Shenglong; Wang, Wei; Yu, Lu; Peng, Junhui; Cai, Xiaoying; Xiong, Ying; Hayati, Zahra; Zhang, Longhua; Zhang, Zhiyong; Song, Likai; Tian, Changlin

    2016-01-01

    Electron paramagnetic resonance (EPR)-based hybrid experimental and computational approaches were applied to determine the structure of a full-length E. coli integral membrane sulfurtransferase, dimeric YgaP, and its structural and dynamic changes upon ligand binding. The solution NMR structures of the YgaP transmembrane domain (TMD) and cytosolic catalytic rhodanese domain were reported recently, but the tertiary fold of full-length YgaP was not yet available. Here, systematic site-specific EPR analysis defined a helix-loop-helix secondary structure of the YagP-TMD monomers using mobility, accessibility and membrane immersion measurements. The tertiary folds of dimeric YgaP-TMD and full-length YgaP in detergent micelles were determined through inter- and intra-monomer distance mapping and rigid-body computation. Further EPR analysis demonstrated the tight packing of the two YgaP second transmembrane helices upon binding of the catalytic product SCN-, which provides insight into the thiocyanate exportation mechanism of YgaP in the E. coli membrane.

  3. RaptorX server: a resource for template-based protein structure modeling.

    PubMed

    Källberg, Morten; Margaryan, Gohar; Wang, Sheng; Ma, Jianzhu; Xu, Jinbo

    2014-01-01

    Assigning functional properties to a newly discovered protein is a key challenge in modern biology. To this end, computational modeling of the three-dimensional atomic arrangement of the amino acid chain is often crucial in determining the role of the protein in biological processes. We present a community-wide web-based protocol, RaptorX server ( http://raptorx.uchicago.edu ), for automated protein secondary structure prediction, template-based tertiary structure modeling, and probabilistic alignment sampling.Given a target sequence, RaptorX server is able to detect even remotely related template sequences by means of a novel nonlinear context-specific alignment potential and probabilistic consistency algorithm. Using the protocol presented here it is thus possible to obtain high-quality structural models for many target protein sequences when only distantly related protein domains have experimentally solved structures. At present, RaptorX server can perform secondary and tertiary structure prediction of a 200 amino acid target sequence in approximately 30 min.

  4. 76 FR 2084 - North Pacific Fishery Management Council; Public Meetings

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... Amendment(T). 6. Aleutian Island (AI) Pacific Cod Issues: Discussion paper on BS&AI Pacific cod Split take action as necessary; Initial review AI Pacific cod processing Sideboards; (postponed). 7. BSAI Crab.... AI Pacific Cod. 4. BSAI Crab Management. 5. Miscellaneous Groundfish. 6. Economic SAFE review. 7...

  5. CENTRAL PLAINS CENTER FOR AMERICAN INDIAN HEALTH DISPARITIES (CPC-AIHD) REVISION

    EPA Science Inventory

    American Indians (AI) suffer some of the greatest health disparities in the US. Many conditions, including asthma, obesity, and diabetes, are prevalent among AI and are influenced by the places AI live. In addition, AI have high rates of severe physical housing problems and...

  6. 47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

  7. 47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

  8. 33 CFR 164.46 - Automatic Identification System (AIS).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

  9. 47 CFR 80.231 - Technical Requirements for Class B Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Identification System (AIS) equipment. 80.231 Section 80.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION... § 80.231 Technical Requirements for Class B Automatic Identification System (AIS) equipment. (a) Class B Automatic Identification System (AIS) equipment must meet the technical requirements of IEC 62287...

  10. 33 CFR 164.46 - Automatic Identification System (AIS).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

  11. 47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  12. 33 CFR 164.46 - Automatic Identification System (AIS).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

  13. 47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  14. 33 CFR 164.46 - Automatic Identification System (AIS).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

  15. 47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  16. 33 CFR 164.46 - Automatic Identification System (AIS).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... (AIS). 164.46 Section 164.46 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND... Identification System (AIS). (a) The following vessels must have a properly installed, operational, type approved AIS as of the date specified: (1) Self-propelled vessels of 65 feet or more in length, other than...

  17. 47 CFR 80.275 - Technical Requirements for Class A Automatic Identification System (AIS) equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Compulsory Ships § 80.275 Technical Requirements for Class A Automatic Identification System (AIS) equipment. (a) Prior to submitting a certification application for a Class A AIS device, the following... Identification System (AIS) equipment. 80.275 Section 80.275 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  18. 76 FR 68161 - Proposed Information Collection; Comment Request; Aleutian Islands Pollock Fishery Requirements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-03

    ... Aleutian Islands (AI) directed pollock fishery to the Aleut Corporation for economic development of Adak... necessary for conducting the AI directed pollock fishery. Management provisions for the AI directed pollock fishery include: restrictions on the harvest specifications for the AI directed pollock fishery...

  19. Geologic framework of lower Cook Inlet, Alaska

    USGS Publications Warehouse

    Fisher, M.A.; Magoon, L.B.

    1978-01-01

    Three seismic reflectors are present throughout the lower Cook Inlet basin and can be correlated with onshore geologic features. The reflections come from unconformities at the base of the Tertiary sequence, at the base of Upper Cretaceous rocks, and near the base of Upper Jurassic strata. A contour map of the deepest horizon shows that Mesozoic rocks are formed into a northeast-trending syncline. Along the southeast flank of the basin, the northwest-dipping Mesozoic rocks are truncated at the base of Tertiary rocks. The Augustine-Seldovia arch trends across the basin axis between Augustine Island and Seldovia. Tertiary rocks thin onto the arch from the north and south. Numerous anticlines, smaller in structural relief and breadth than the Augustine-Seldovia arch, trend northeast parallel with the basin, and intersect the arch at oblique angles. The stratigraphic record shows four cycles of sedimentation and tectonism that are bounded by three regional unconformities in lower Cook Inlet and by four thrust faults and the modern Benioff zone in flysch rocks of the Kenai Peninsula and the Gulf of Alaska. The four cycles of sedimentation are, from oldest to youngest, the early Mesozoic, late Mesozoic, early Cenozoic, and late Cenozoic. Data on organic geochemistry of the rocks from one well suggest that Middle Jurassic strata may be a source of hydrocarbons. Seismic data show that structural traps are formed by northeast-trending anticlines and by structures formed at the intersections of these anticlines with the transbasin arch. Stratigraphic traps may be formed beneath the unconformity at the base of Tertiary strata and beneath unconformities within Mesozoic strata.

  20. Long-range tertiary interactions in single hammerhead ribozymes bias motional sampling toward catalytically active conformations

    PubMed Central

    McDowell, S. Elizabeth; Jun, Jesse M.; Walter, Nils G.

    2010-01-01

    Enzymes generally are thought to derive their functional activity from conformational motions. The limited chemical variation in RNA suggests that such structural dynamics may play a particularly important role in RNA function. Minimal hammerhead ribozymes are known to cleave efficiently only in ∼10-fold higher than physiologic concentrations of Mg2+ ions. Extended versions containing native loop–loop interactions, however, show greatly enhanced catalytic activity at physiologically relevant Mg2+ concentrations, for reasons that are still ill-understood. Here, we use Mg2+ titrations, activity assays, ensemble, and single molecule fluorescence resonance energy transfer (FRET) approaches, combined with molecular dynamics (MD) simulations, to ask what influence the spatially distant tertiary loop–loop interactions of an extended hammerhead ribozyme have on its structural dynamics. By comparing hammerhead variants with wild-type, partially disrupted, and fully disrupted loop–loop interaction sequences we find that the tertiary interactions lead to a dynamic motional sampling that increasingly populates catalytically active conformations. At the global level the wild-type tertiary interactions lead to more frequent, if transient, encounters of the loop-carrying stems, whereas at the local level they lead to an enrichment in favorable in-line attack angles at the cleavage site. These results invoke a linkage between RNA structural dynamics and function and suggest that loop–loop interactions in extended hammerhead ribozymes—and Mg2+ ions that bind to minimal ribozymes—may generally allow more frequent access to a catalytically relevant conformation(s), rather than simply locking the ribozyme into a single active state. PMID:20921269

  1. Exploration of Novel Chemical Space: Synthesis and in vitro Evaluation of N-Functionalized Tertiary Sulfonimidamides.

    PubMed

    Izzo, Flavia; Schäfer, Martina; Lienau, Philip; Ganzer, Ursula; Stockman, Robert; Lücking, Ulrich

    2018-05-04

    An unprecedented set of structurally diverse sulfonimidamides (47 compounds) has been prepared by various N-functionalization reactions of tertiary =NH sulfonimidamide 2 aa. These N-functionalization reactions of model compound 2 aa include arylation, alkylation, trifluoromethylation, cyanation, sulfonylation, alkoxycarbonylation (carbamate formation) and aminocarbonylation (urea formation). Small molecule X-ray analyses of selected N-functionalized products are reported. To gain further insight into the properties of sulfonimidamides relevant to medicinal chemistry, a variety of structurally diverse reaction products were tested in selected in vitro assays. The described N-functionalization reactions provide a short and efficient approach to structurally diverse sulfonimidamides which have been the subject of recent, growing interest in the life sciences. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Artificial intelligence, expert systems, computer vision, and natural language processing

    NASA Technical Reports Server (NTRS)

    Gevarter, W. B.

    1984-01-01

    An overview of artificial intelligence (AI), its core ingredients, and its applications is presented. The knowledge representation, logic, problem solving approaches, languages, and computers pertaining to AI are examined, and the state of the art in AI is reviewed. The use of AI in expert systems, computer vision, natural language processing, speech recognition and understanding, speech synthesis, problem solving, and planning is examined. Basic AI topics, including automation, search-oriented problem solving, knowledge representation, and computational logic, are discussed.

  3. AIS training manual

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

    Kramer, C.F.; Barancik, J.I.

    1989-05-01

    This Training Manual was developed by the Injury Prevention and Analysis Group (IPAG) as part of a training program in AIS 85 and AIS-EM (Epidemiological Modifications) coding. The IPAG Program is designed primarily to train medical record and other health professionals from diverse backgrounds and experience levels in the use of AIS 85 and AIS 85-EM. The Manual is designed to be used as a reference text after completion of the Program and includes copies of visual projection materials used during the training sessions.

  4. Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

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

    Fauber, Benjamin P.; René, Olivier; de Leon Boenig, Gladys

    2014-08-01

    Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma–protein unbound fraction and improvements in cellular permeability and aqueous solubility.

  5. ProTSAV: A protein tertiary structure analysis and validation server.

    PubMed

    Singh, Ankita; Kaushik, Rahul; Mishra, Avinash; Shanker, Asheesh; Jayaram, B

    2016-01-01

    Quality assessment of predicted model structures of proteins is as important as the protein tertiary structure prediction. A highly efficient quality assessment of predicted model structures directs further research on function. Here we present a new server ProTSAV, capable of evaluating predicted model structures based on some popular online servers and standalone tools. ProTSAV furnishes the user with a single quality score in case of individual protein structure along with a graphical representation and ranking in case of multiple protein structure assessment. The server is validated on ~64,446 protein structures including experimental structures from RCSB and predicted model structures for CASP targets and from public decoy sets. ProTSAV succeeds in predicting quality of protein structures with a specificity of 100% and a sensitivity of 98% on experimentally solved structures and achieves a specificity of 88%and a sensitivity of 91% on predicted protein structures of CASP11 targets under 2Å.The server overcomes the limitations of any single server/method and is seen to be robust in helping in quality assessment. ProTSAV is freely available at http://www.scfbio-iitd.res.in/software/proteomics/protsav.jsp. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. The Development of AI in Medicine and the Research Environment of the SPHINX Project at the Start of the 1980s.

    PubMed

    Fieschi, M

    2012-01-01

    To review the history of AI in Medicine in the 1980's, placing the SPHINX system in the context of other research in this field. Summarize the main systems for AI in medicine developed in the 1970-1980 decade and their relationship to the development of clinical decision-making and consultation systems The approaches taken by AI in medicine research groups is compared and contrasted to those of others using statistical and logical methods for representing clinical inferences, and the different AI approaches are summarized, and related to the architecture and systems implementation of SPHINX CONCLUSION: The SPHINX system combined a number of advanced representational and inference choices from AI in designing a decision- support system for clinical consultation in the 1980s. The context within which the system was developed is outlined and related to the historical evolution of AI in medicine during that decade.

  7. 10 CFR 1017.28 - Processing on Automated Information Systems (AIS).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Processing on Automated Information Systems (AIS). 1017.28... UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Physical Protection Requirements § 1017.28 Processing on Automated Information Systems (AIS). UCNI may be processed or produced on any AIS that complies with the guidance in OMB...

  8. 76 FR 44045 - Establishment of the SANE/SART AI/AN Initiative Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... SANE/SART AI/AN Initiative Committee AGENCY: Office for Victims of Crime, Justice. ACTION: Notice of...) Initiative (``SANE/SART AI/AN Initiative Committee'' or ``Committee'') is being established in accordance... SANE/SART AI/AN Initiative Committee will provide the Office for Victims of Crime, a component of the U...

  9. 75 FR 21307 - Injury Prevention Program; Announcement Type: Cooperative Agreement

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... effective will be considered. Motor vehicle related injuries and deaths impact AI/AN communities in... leading cause of death and disability for AI/AN communities. Injuries cause more deaths among AI/AN ages 1... AI/AN communities. Unintentional falls reduce independence and quality of life for adults ages 65 and...

  10. Why Don't Accounting Students like AIS?

    ERIC Educational Resources Information Center

    Vatanasakdakul, Savanid; Aoun, Chadi

    2011-01-01

    Purpose: The demand for Accounting Information Systems (AIS) knowledge has increased exponentially over the past two decades, but studying AIS has not proved easy for many accounting students. The aim of the study is to understand the challenges accounting students face in studying AIS through investigation of the factors which may be contributing…

  11. Methods for Processing and Interpretation of AIS Signals Corrupted by Noise and Packet Collisions

    NASA Astrophysics Data System (ADS)

    Poļevskis, J.; Krastiņš, M.; Korāts, G.; Skorodumovs, A.; Trokšs, J.

    2012-01-01

    The authors deal with the operation of Automatic Identification System (AIS) used in the marine traffic monitoring to broadcast messages containing information about the vessel: id, payload, size, speed, destination etc., meant primarily for avoidance of ship collisions. To extend the radius of AIS operation, it is envisaged to dispose its receivers on satellites. However, in space, due to a large coverage area, interfering factors are especially pronounced - such as packet collision, Doppler's shift and noise impact on AIS message receiving, pre-processing and decoding. To assess the quality of an AIS receiver's operation, a test was carried out in which, varying automatically frequency, amplitude, noise, and other parameters, the data on the ability of the receiver's ability to decode AIS signals are collected. In the work, both hardware- and software-based AIS decoders were tested. As a result, quite satisfactory statistics has been gathered - both on the common and the differing features of such decoders when operating in space. To obtain reliable data on the software-defined radio AIS receivers, further research is envisaged.

  12. Discrimination of Avian Influenza Virus using Host-cell Infection Fingerprinting by Sulfinate-based Fluorescence Superoxide Probe.

    PubMed

    Hong, Seong Cheol; Murale, Dhiraj P; Jang, Se-Young; Haque, Md Mamunul; Seo, Minah; Lee, Seok; Woo, Deok Ha; Kwon, Junghoon; Song, Chang-Seon; Kim, Yun Kyung; Lee, Jun-Seok

    2018-06-22

    Avian Influenza (AI) caused an annual epidemic outbreak that led to destroying tens of millions of poultry worldwide. Current gold standard AI diagnosis method is an embryonic egg-based hemagglutination assay followed by immunoblotting or PCR sequencing to confirm subtypes. It requires, however, specialized facilities to handle egg inoculation and incubation, and the subtyping methods relied on costly reagents. Here, we demonstrated the first differential sensing approach to distinguish AI subtypes using series of cell lines and fluorescent sensor. Susceptibility of AI virus differs depending on genetic backgrounds of host cells. Thus, we examined cells from different organ origin, and the infection patterns against a panel of cells were utilized for AI virus subtyping. To quantify AI infection, we designed a highly cell-permeable fluorescent superoxide sensor to visualize infection. Though many AI monitoring strategies relied on sophisticated antibody have been extensively studied, our differential sensing strategy successfully proved discriminations of AI subtypes and demonstrated as a useful primary screening platform to monitor a large number of samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Advancing differential atom interferometry for space applications

    NASA Astrophysics Data System (ADS)

    Chiow, Sheng-Wey; Williams, Jason; Yu, Nan

    2016-05-01

    Atom interferometer (AI) based sensors exhibit precision and accuracy unattainable with classical sensors, thanks to the inherent stability of atomic properties. Dual atomic sensors operating in a differential mode further extend AI applicability beyond environmental disturbances. Extraction of the phase difference between dual AIs, however, typically introduces uncertainty and systematic in excess of that warranted by each AI's intrinsic noise characteristics, especially in practical applications and real time measurements. In this presentation, we report our efforts in developing practical schemes for reducing noises and enhancing sensitivities in the differential AI measurement implementations. We will describe an active phase extraction method that eliminates the noise overhead and demonstrates a performance boost of a gravity gradiometer by a factor of 3. We will also describe a new long-baseline approach for differential AI measurements in a laser ranging assisted AI configuration. The approach uses well-developed AIs for local measurements but leverage the mature schemes of space laser interferometry for LISA and GRACE. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a Contract with NASA.

  14. Comparison of AIS Versus TMS Data Collected over the Virginia Piedmont

    NASA Technical Reports Server (NTRS)

    Bell, R.; Evans, C. S.

    1985-01-01

    The Airborne Imaging Spectrometer (AIS, NS001 Thematic Mapper Simlulator (TMS), and Zeiss camera collected remotely sensed data simultaneously on October 27, 1983, at an altitude of 6860 meters (22,500 feet). AIS data were collected in 32 channels covering 1200 to 1500 nm. A simple atmospheric correction was applied to the AIS data, after which spectra for four cover types were plotted. Spectra for these ground cover classes showed a telescoping effect for the wavelength endpoints. Principal components were extracted from the shortwave region of the AIS (1200 to 1280 nm), full spectrum AIS (1200 to 1500 nm) and TMS (450 to 12,500 nm) to create three separate three-component color image composites. A comparison of the TMS band 5 (1000 to 1300 nm) to the six principal components from the shortwave AIS region (1200 to 1280 nm) showed improved visual discrimination of ground cover types. Contrast of color image composites created from principal components showed the AIS composites to exhibit a clearer demarcation between certain ground cover types but subtle differences within other regions of the imagery were not as readily seen.

  15. Prediction of protein tertiary structure to low resolution: performance for a large and structurally diverse test set.

    PubMed

    Eyrich, V A; Standley, D M; Friesner, R A

    1999-05-14

    We report the tertiary structure predictions for 95 proteins ranging in size from 17 to 160 residues starting from known secondary structure. Predictions are obtained from global minimization of an empirical potential function followed by the application of a refined atomic overlap potential. The minimization strategy employed represents a variant of the Monte Carlo plus minimization scheme of Li and Scheraga applied to a reduced model of the protein chain. For all of the cases except beta-proteins larger than 75 residues, a native-like structure, usually 4-6 A root-mean-square deviation from the native, is located. For beta-proteins larger than 75 residues, the energy gap between native-like structures and the lowest energy structures produced in the simulation is large, so that low RMSD structures are not generated starting from an unfolded state. This is attributed to the lack of an explicit hydrogen bond term in the potential function, which we hypothesize is necessary to stabilize large assemblies of beta-strands. Copyright 1999 Academic Press.

  16. Interaction between research and diagnosis and surveillance of avian influenza within the Caribbean animal health network (CaribVET).

    PubMed

    Lefrançois, T; Hendrikx, P; Vachiéry, N; Ehrhardt, N; Millien, M; Gomez, L; Gouyet, L; Gerbier, G; Gongora, V; Shaw, J; Trotman, M

    2010-04-01

    The Caribbean region is considered to be at risk for avian influenza (AI) because of predominance of the backyard poultry system, important commercial poultry production, migratory birds and disparities in the surveillance systems. The Caribbean animal health network (CaribVET) has developed tools to implement AI surveillance in the region: (i) a regionally harmonized surveillance protocol, (ii) specific web pages for AI surveillance on http://www.caribvet.net, and (iii) a diagnostic network for the Caribbean including AI virus molecular diagnostic capability in Guadeloupe and technology transfer. Altogether 303 samples from four Caribbean countries were tested between June 2006 and March 2009 by real time PCR either for importation purposes or following clinical suspicion. Following AI H5N2 outbreaks in the Dominican Republic in 2007, a questionnaire was developed to collect data for risk analysis of AI spread in the region through fighting cocks. The infection pathway of Martinique commercial poultry sector by AI through introduction of infected cocks was designed and recommendations were provided to the Caribbean veterinary services to improve fighting cock movement controls and biosecurity measures. Altogether, these CaribVET activities contribute to strengthen surveillance of AI in the Caribbean region and may allow the development of research studies on AI risk analysis.

  17. Leading causes of death and all-cause mortality in American Indians and Alaska Natives.

    PubMed

    Espey, David K; Jim, Melissa A; Cobb, Nathaniel; Bartholomew, Michael; Becker, Tom; Haverkamp, Don; Plescia, Marcus

    2014-06-01

    We present regional patterns and trends in all-cause mortality and leading causes of death in American Indians and Alaska Natives (AI/ANs). US National Death Index records were linked with Indian Health Service (IHS) registration records to identify AI/AN deaths misclassified as non-AI/AN. We analyzed temporal trends for 1990 to 2009 and comparisons between non-Hispanic AI/AN and non-Hispanic White persons by geographic region for 1999 to 2009. Results focus on IHS Contract Health Service Delivery Area counties in which less race misclassification occurs. From 1990 to 2009 AI/AN persons did not experience the significant decreases in all-cause mortality seen for Whites. For 1999 to 2009 the all-cause death rate in CHSDA counties for AI/AN persons was 46% more than that for Whites. Death rates for AI/AN persons varied as much as 50% among regions. Except for heart disease and cancer, subsequent ranking of specific causes of death differed considerably between AI/AN and White persons. AI/AN populations continue to experience much higher death rates than Whites. Patterns of mortality are strongly influenced by the high incidence of diabetes, smoking prevalence, problem drinking, and social determinants. Much of the observed excess mortality can be addressed through known public health interventions.

  18. MANAGEMENT OF ENDOCRINE DISEASE: Fertility, pregnancy and lactation in women with adrenal insufficiency.

    PubMed

    Anand, Gurpreet; Beuschlein, Felix

    2018-02-01

    With the introduction of hormonal substitution therapy in the 1950s, adrenal insufficiency (AI) has been turned into a manageable disease in pregnant women. In fact, in the light of glucocorticoid replacement therapy and improved obstetric care, it is realistic to expect good maternal and fetal outcomes in patients with AI. However, there are still a number of challenges such as establishing the diagnosis of AI in pregnant women and optimizing the treatment of AI and related comorbidities prior to as well as during pregnancy. Clinical and biochemical diagnoses of a new-onset AI may be challenging because of overlapping symptoms of normal pregnancy as well as pregnancy-induced changes in cortisol values. Physiological changes occurring during pregnancy should be taken into account while adjusting the substitution therapy. The high proportion of reported adrenal crisis in pregnant women with AI highlights persistent problems in this particular clinical situation. Due to the rarity of the disease, there is no prospective data-guiding management of pregnancy in patients with known AI. The aim of this review is to summarize the maternal and fetal outcomes based on recently published case reports in patients with AI and to suggest a practical approach to diagnose and manage AI in pregnancy. © 2018 European Society of Endocrinology.

  19. Bayesian Model Averaging of Artificial Intelligence Models for Hydraulic Conductivity Estimation

    NASA Astrophysics Data System (ADS)

    Nadiri, A.; Chitsazan, N.; Tsai, F. T.; Asghari Moghaddam, A.

    2012-12-01

    This research presents a Bayesian artificial intelligence model averaging (BAIMA) method that incorporates multiple artificial intelligence (AI) models to estimate hydraulic conductivity and evaluate estimation uncertainties. Uncertainty in the AI model outputs stems from error in model input as well as non-uniqueness in selecting different AI methods. Using one single AI model tends to bias the estimation and underestimate uncertainty. BAIMA employs Bayesian model averaging (BMA) technique to address the issue of using one single AI model for estimation. BAIMA estimates hydraulic conductivity by averaging the outputs of AI models according to their model weights. In this study, the model weights were determined using the Bayesian information criterion (BIC) that follows the parsimony principle. BAIMA calculates the within-model variances to account for uncertainty propagation from input data to AI model output. Between-model variances are evaluated to account for uncertainty due to model non-uniqueness. We employed Takagi-Sugeno fuzzy logic (TS-FL), artificial neural network (ANN) and neurofuzzy (NF) to estimate hydraulic conductivity for the Tasuj plain aquifer, Iran. BAIMA combined three AI models and produced better fitting than individual models. While NF was expected to be the best AI model owing to its utilization of both TS-FL and ANN models, the NF model is nearly discarded by the parsimony principle. The TS-FL model and the ANN model showed equal importance although their hydraulic conductivity estimates were quite different. This resulted in significant between-model variances that are normally ignored by using one AI model.

  20. Climate factors affecting fertility after cervical insemination during the first months of the breeding season in Rasa Aragonesa ewes

    NASA Astrophysics Data System (ADS)

    Santolaria, P.; Yániz, J.; Fantova, E.; Vicente-Fiel, S.; Palacín, I.

    2014-09-01

    This study was carried out to examine the impact of several climate variables on the pregnancy rate after cervical artificial insemination (AI) of Rasa Aragonesa ewes. Data were derived from 8,977 inseminations in 76 well-managed flocks performed during the first month of the breeding season (July to October). The following data were recorded for each animal: farm, year, month of AI, parity, lambing-treatment interval, inseminating ram, AI technician, and climatic variables such as mean, maximum and minimum temperature, mean and maximum relative humidity, rainfall, and mean and maximum temperature-humidity index (THI) for each day from day 12 before AI to day 14 post-AI. Means were furthermore calculated for the following periods around AI (day 0): -12 to 0, -2 to 0, AI day, 0 to 2, and 0 to 14. Logistic regression analysis indicated that the likelihood of pregnancy decreased when maximum temperature in the 2 days prior to AI was higher than 30 °C (by a factor of 0.81). Fertility was also lower for primiparous ewes and in multiparous ewes with more than five previous parturitions. Other factors with significant impact on fertility were flock, technician, inseminating ram, and a lambing-AI interval longer than 240 days. It was concluded that the 2 days prior to AI seems to be the period when heat stress had the greatest impact on pregnancy rate in Rasa Aragonesa ewes.

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