Sample records for positive selection candidate

  1. Optimization of Candidate Selection Using Naive Bayes: Case Study in Company X

    NASA Astrophysics Data System (ADS)

    Kadar, JA; Agustono, D.; Napitupulu, D.

    2018-01-01

    This research was conducted as a decision-making system, and an alternative solution to complete the candidate assessment for a particular position. The human resources (HR) section on company X is responsible and initiative in selecting candidates in accordance with the assessment of their superiors. Selection by using the method of filling out the manager’s assessment questionnaire on the candidate’s subordinate. Three (3) managers have been determined to assess the 11 candidates for subordinates. By using questionnaire of quality classification of human resources and formula naive bayes it will get result which finally grouped using criteria scale as final grouping. The HR department has also determined that what is received is that which meets criteria 5. The result is three (3) candidates who can be proposed as candidates for certain positions in company X, and have met all required calculations. Furthermore the candidate will be given to management as an alternative input data in the selection of candidates.

  2. Effects of organizational citizenship behaviors on selection decisions in employment interviews.

    PubMed

    Podsakoff, Nathan P; Whiting, Steven W; Podsakoff, Philip M; Mishra, Paresh

    2011-03-01

    This article reports on an experiment examining the effects of job candidates' propensity to exhibit organizational citizenship behaviors (OCBs) on selection decisions made in the context of a job interview. We developed videos that manipulated candidate responses to interview questions tapping task performance and citizenship behavior content in 2 administrative positions. Results obtained from 480 undergraduates provided support for our hypotheses that job candidates who exhibited higher levels of helping, voice, and loyalty behaviors were generally rated as more competent, received higher overall evaluations, and received higher salary recommendations than job candidates who exhibited lower levels of these behaviors. These effects held even after taking into account candidate responses regarding task performance. We also found that candidate responses to OCB-related questions tended to have a greater effect on selection decisions for the higher level position (supervisor of administrative personnel) than for the lower level one (administrative assistant). Finally, content analyses of open-ended responses indicated that participants' selection decisions were particularly sensitive to candidates who exhibited low levels of voice and helping behaviors. Implications and future research are discussed. PsycINFO Database Record (c) 2011 APA, all rights reserved.

  3. Path Diversity Improved Opportunistic Routing for Underwater Sensor Networks.

    PubMed

    Bai, Weigang; Wang, Haiyan; He, Ke; Zhao, Ruiqin

    2018-04-23

    The packets carried along a pre-defined route in underwater sensor networks are very vulnerble. Node mobility or intermittent channel availability easily leads to unreachable routing. Opportunistic routing has been proven to be a promising paradigm to design routing protocols for underwater sensor networks. It takes advantage of the broadcast nature of the wireless medium to combat packet losses and selects potential paths on the fly. Finding an appropriate forwarding candidate set is a key issue in opportunistic routing. Many existing solutions ignore the impact of candidates location distribution on packet forwarding. In this paper, a path diversity improved candidate selection strategy is applied in opportunistic routing to improve packet forwarding efficiency. It not only maximizes the packet forwarding advancements but also takes the candidate’s location distribution into account. Based on this strategy, we propose two effective routing protocols: position improved candidates selection (PICS) and position random candidates selection (PRCS). PICS employs two-hop neighbor information to make routing decisions. PRCS only uses one-hop neighbor information. Simulation results show that both PICS and PRCS can significantly improve network performance when compared with the previous solutions, in terms of packet delivery ratio, average energy consumption and end-to-end delay.

  4. The NASA competitive placement plan for positions GS-15 and below (including trades and labor positions)

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This plan provides the framework for selection based on merit from among the best qualified candidates available. Selections will be made without regard to political, religious, or labor organization affiliation or nonaffiliation, marital status, race, color, sex, national origin, nondisqualifying disability, or age. This plan does not guarantee promotion but rather ensures that all qualified available candidates receive fair and equitable consideration for positions filled under these competitive procedures. Announcing a vacancy under this plan is only one method of locating applicants for a position and can be used in conjunction with other methods. Subject to applicable law and regulation, selection of an individual to fill a position is the decision of management, as is the decision as to the method(s) to be used in identifying candidates. This plan is applicable to all NASA Installations. It covers all positions in the competitive service at (and below) the GS/GM-15 level (including all trades and labor positions), except positions in the Office of the Inspector General. The requirements herein are not intended to, nor should they be construed to limit in any way, the independent personnel authority of the Inspector General under the Inspector General Act, as Amended.

  5. Genome-wide detection and characterization of positive selection in human populations.

    PubMed

    Sabeti, Pardis C; Varilly, Patrick; Fry, Ben; Lohmueller, Jason; Hostetter, Elizabeth; Cotsapas, Chris; Xie, Xiaohui; Byrne, Elizabeth H; McCarroll, Steven A; Gaudet, Rachelle; Schaffner, Stephen F; Lander, Eric S; Frazer, Kelly A; Ballinger, Dennis G; Cox, David R; Hinds, David A; Stuve, Laura L; Gibbs, Richard A; Belmont, John W; Boudreau, Andrew; Hardenbol, Paul; Leal, Suzanne M; Pasternak, Shiran; Wheeler, David A; Willis, Thomas D; Yu, Fuli; Yang, Huanming; Zeng, Changqing; Gao, Yang; Hu, Haoran; Hu, Weitao; Li, Chaohua; Lin, Wei; Liu, Siqi; Pan, Hao; Tang, Xiaoli; Wang, Jian; Wang, Wei; Yu, Jun; Zhang, Bo; Zhang, Qingrun; Zhao, Hongbin; Zhao, Hui; Zhou, Jun; Gabriel, Stacey B; Barry, Rachel; Blumenstiel, Brendan; Camargo, Amy; Defelice, Matthew; Faggart, Maura; Goyette, Mary; Gupta, Supriya; Moore, Jamie; Nguyen, Huy; Onofrio, Robert C; Parkin, Melissa; Roy, Jessica; Stahl, Erich; Winchester, Ellen; Ziaugra, Liuda; Altshuler, David; Shen, Yan; Yao, Zhijian; Huang, Wei; Chu, Xun; He, Yungang; Jin, Li; Liu, Yangfan; Shen, Yayun; Sun, Weiwei; Wang, Haifeng; Wang, Yi; Wang, Ying; Xiong, Xiaoyan; Xu, Liang; Waye, Mary M Y; Tsui, Stephen K W; Xue, Hong; Wong, J Tze-Fei; Galver, Luana M; Fan, Jian-Bing; Gunderson, Kevin; Murray, Sarah S; Oliphant, Arnold R; Chee, Mark S; Montpetit, Alexandre; Chagnon, Fanny; Ferretti, Vincent; Leboeuf, Martin; Olivier, Jean-François; Phillips, Michael S; Roumy, Stéphanie; Sallée, Clémentine; Verner, Andrei; Hudson, Thomas J; Kwok, Pui-Yan; Cai, Dongmei; Koboldt, Daniel C; Miller, Raymond D; Pawlikowska, Ludmila; Taillon-Miller, Patricia; Xiao, Ming; Tsui, Lap-Chee; Mak, William; Song, You Qiang; Tam, Paul K H; Nakamura, Yusuke; Kawaguchi, Takahisa; Kitamoto, Takuya; Morizono, Takashi; Nagashima, Atsushi; Ohnishi, Yozo; Sekine, Akihiro; Tanaka, Toshihiro; Tsunoda, Tatsuhiko; Deloukas, Panos; Bird, Christine P; Delgado, Marcos; Dermitzakis, Emmanouil T; Gwilliam, Rhian; Hunt, Sarah; Morrison, Jonathan; Powell, Don; Stranger, Barbara E; Whittaker, Pamela; Bentley, David R; Daly, Mark J; de Bakker, Paul I W; Barrett, Jeff; Chretien, Yves R; Maller, Julian; McCarroll, Steve; Patterson, Nick; Pe'er, Itsik; Price, Alkes; Purcell, Shaun; Richter, Daniel J; Sabeti, Pardis; Saxena, Richa; Schaffner, Stephen F; Sham, Pak C; Varilly, Patrick; Altshuler, David; Stein, Lincoln D; Krishnan, Lalitha; Smith, Albert Vernon; Tello-Ruiz, Marcela K; Thorisson, Gudmundur A; Chakravarti, Aravinda; Chen, Peter E; Cutler, David J; Kashuk, Carl S; Lin, Shin; Abecasis, Gonçalo R; Guan, Weihua; Li, Yun; Munro, Heather M; Qin, Zhaohui Steve; Thomas, Daryl J; McVean, Gilean; Auton, Adam; Bottolo, Leonardo; Cardin, Niall; Eyheramendy, Susana; Freeman, Colin; Marchini, Jonathan; Myers, Simon; Spencer, Chris; Stephens, Matthew; Donnelly, Peter; Cardon, Lon R; Clarke, Geraldine; Evans, David M; Morris, Andrew P; Weir, Bruce S; Tsunoda, Tatsuhiko; Johnson, Todd A; Mullikin, James C; Sherry, Stephen T; Feolo, Michael; Skol, Andrew; Zhang, Houcan; Zeng, Changqing; Zhao, Hui; Matsuda, Ichiro; Fukushima, Yoshimitsu; Macer, Darryl R; Suda, Eiko; Rotimi, Charles N; Adebamowo, Clement A; Ajayi, Ike; Aniagwu, Toyin; Marshall, Patricia A; Nkwodimmah, Chibuzor; Royal, Charmaine D M; Leppert, Mark F; Dixon, Missy; Peiffer, Andy; Qiu, Renzong; Kent, Alastair; Kato, Kazuto; Niikawa, Norio; Adewole, Isaac F; Knoppers, Bartha M; Foster, Morris W; Clayton, Ellen Wright; Watkin, Jessica; Gibbs, Richard A; Belmont, John W; Muzny, Donna; Nazareth, Lynne; Sodergren, Erica; Weinstock, George M; Wheeler, David A; Yakub, Imtaz; Gabriel, Stacey B; Onofrio, Robert C; Richter, Daniel J; Ziaugra, Liuda; Birren, Bruce W; Daly, Mark J; Altshuler, David; Wilson, Richard K; Fulton, Lucinda L; Rogers, Jane; Burton, John; Carter, Nigel P; Clee, Christopher M; Griffiths, Mark; Jones, Matthew C; McLay, Kirsten; Plumb, Robert W; Ross, Mark T; Sims, Sarah K; Willey, David L; Chen, Zhu; Han, Hua; Kang, Le; Godbout, Martin; Wallenburg, John C; L'Archevêque, Paul; Bellemare, Guy; Saeki, Koji; Wang, Hongguang; An, Daochang; Fu, Hongbo; Li, Qing; Wang, Zhen; Wang, Renwu; Holden, Arthur L; Brooks, Lisa D; McEwen, Jean E; Guyer, Mark S; Wang, Vivian Ota; Peterson, Jane L; Shi, Michael; Spiegel, Jack; Sung, Lawrence M; Zacharia, Lynn F; Collins, Francis S; Kennedy, Karen; Jamieson, Ruth; Stewart, John

    2007-10-18

    With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population:LARGE and DMD, both related to infection by the Lassa virus, in West Africa;SLC24A5 and SLC45A2, both involved in skin pigmentation, in Europe; and EDAR and EDA2R, both involved in development of hair follicles, in Asia.

  6. Path Diversity Improved Opportunistic Routing for Underwater Sensor Networks

    PubMed Central

    Wang, Haiyan; He, Ke

    2018-01-01

    The packets carried along a pre-defined route in underwater sensor networks are very vulnerble. Node mobility or intermittent channel availability easily leads to unreachable routing. Opportunistic routing has been proven to be a promising paradigm to design routing protocols for underwater sensor networks. It takes advantage of the broadcast nature of the wireless medium to combat packet losses and selects potential paths on the fly. Finding an appropriate forwarding candidate set is a key issue in opportunistic routing. Many existing solutions ignore the impact of candidates location distribution on packet forwarding. In this paper, a path diversity improved candidate selection strategy is applied in opportunistic routing to improve packet forwarding efficiency. It not only maximizes the packet forwarding advancements but also takes the candidate’s location distribution into account. Based on this strategy, we propose two effective routing protocols: position improved candidates selection (PICS) and position random candidates selection (PRCS). PICS employs two-hop neighbor information to make routing decisions. PRCS only uses one-hop neighbor information. Simulation results show that both PICS and PRCS can significantly improve network performance when compared with the previous solutions, in terms of packet delivery ratio, average energy consumption and end-to-end delay. PMID:29690621

  7. Positive selection on human gamete-recognition genes

    PubMed Central

    Stover, Daryn A.; Guerra, Vanessa; Mozaffari, Sahar V.; Ober, Carole; Mugal, Carina F.; Kaj, Ingemar

    2018-01-01

    Coevolution of genes that encode interacting proteins expressed on the surfaces of sperm and eggs can lead to variation in reproductive compatibility between mates and reproductive isolation between members of different species. Previous studies in mice and other mammals have focused in particular on evidence for positive or diversifying selection that shapes the evolution of genes that encode sperm-binding proteins expressed in the egg coat or zona pellucida (ZP). By fitting phylogenetic models of codon evolution to data from the 1000 Genomes Project, we identified candidate sites evolving under diversifying selection in the human genes ZP3 and ZP2. We also identified one candidate site under positive selection in C4BPA, which encodes a repetitive protein similar to the mouse protein ZP3R that is expressed in the sperm head and binds to the ZP at fertilization. Results from several additional analyses that applied population genetic models to the same data were consistent with the hypothesis of selection on those candidate sites leading to coevolution of sperm- and egg-expressed genes. By contrast, we found no candidate sites under selection in a fourth gene (ZP1) that encodes an egg coat structural protein not directly involved in sperm binding. Finally, we found that two of the candidate sites (in C4BPA and ZP2) were correlated with variation in family size and birth rate among Hutterite couples, and those two candidate sites were also in linkage disequilibrium in the same Hutterite study population. All of these lines of evidence are consistent with predictions from a previously proposed hypothesis of balancing selection on epistatic interactions between C4BPA and ZP3 at fertilization that lead to the evolution of co-adapted allele pairs. Such patterns also suggest specific molecular traits that may be associated with both natural reproductive variation and clinical infertility. PMID:29340252

  8. Genomic signatures of positive selection in humans and the limits of outlier approaches.

    PubMed

    Kelley, Joanna L; Madeoy, Jennifer; Calhoun, John C; Swanson, Willie; Akey, Joshua M

    2006-08-01

    Identifying regions of the human genome that have been targets of positive selection will provide important insights into recent human evolutionary history and may facilitate the search for complex disease genes. However, the confounding effects of population demographic history and selection on patterns of genetic variation complicate inferences of selection when a small number of loci are studied. To this end, identifying outlier loci from empirical genome-wide distributions of genetic variation is a promising strategy to detect targets of selection. Here, we evaluate the power and efficiency of a simple outlier approach and describe a genome-wide scan for positive selection using a dense catalog of 1.58 million SNPs that were genotyped in three human populations. In total, we analyzed 14,589 genes, 385 of which possess patterns of genetic variation consistent with the hypothesis of positive selection. Furthermore, several extended genomic regions were found, spanning >500 kb, that contained multiple contiguous candidate selection genes. More generally, these data provide important practical insights into the limits of outlier approaches in genome-wide scans for selection, provide strong candidate selection genes to study in greater detail, and may have important implications for disease related research.

  9. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy.

    PubMed

    Byars, Sean G; Huang, Qin Qin; Gray, Lesley-Ann; Bakshi, Andrew; Ripatti, Samuli; Abraham, Gad; Stearns, Stephen C; Inouye, Michael

    2017-06-01

    Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD.

  10. Genome-wide signals of positive selection in human evolution

    PubMed Central

    Enard, David; Messer, Philipp W.; Petrov, Dmitri A.

    2014-01-01

    The role of positive selection in human evolution remains controversial. On the one hand, scans for positive selection have identified hundreds of candidate loci, and the genome-wide patterns of polymorphism show signatures consistent with frequent positive selection. On the other hand, recent studies have argued that many of the candidate loci are false positives and that most genome-wide signatures of adaptation are in fact due to reduction of neutral diversity by linked deleterious mutations, known as background selection. Here we analyze human polymorphism data from the 1000 Genomes Project and detect signatures of positive selection once we correct for the effects of background selection. We show that levels of neutral polymorphism are lower near amino acid substitutions, with the strongest reduction observed specifically near functionally consequential amino acid substitutions. Furthermore, amino acid substitutions are associated with signatures of recent adaptation that should not be generated by background selection, such as unusually long and frequent haplotypes and specific distortions in the site frequency spectrum. We use forward simulations to argue that the observed signatures require a high rate of strongly adaptive substitutions near amino acid changes. We further demonstrate that the observed signatures of positive selection correlate better with the presence of regulatory sequences, as predicted by the ENCODE Project Consortium, than with the positions of amino acid substitutions. Our results suggest that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson that adaptive divergence is primarily driven by regulatory changes. PMID:24619126

  11. Genetic Variation and Recent Positive Selection in Worldwide Human Populations: Evidence from Nearly 1 Million SNPs

    PubMed Central

    Theunert, Christoph; Pugach, Irina; Li, Jing; Nandineni, Madhusudan R.; Gross, Arnd; Scholz, Markus; Stoneking, Mark

    2009-01-01

    Background Genome-wide scans of hundreds of thousands of single-nucleotide polymorphisms (SNPs) have resulted in the identification of new susceptibility variants to common diseases and are providing new insights into the genetic structure and relationships of human populations. Moreover, genome-wide data can be used to search for signals of recent positive selection, thereby providing new insights into the genetic adaptations that occurred as modern humans spread out of Africa and around the world. Methodology We genotyped approximately 500,000 SNPs in 255 individuals (5 individuals from each of 51 worldwide populations) from the Human Genome Diversity Panel (HGDP-CEPH). When merged with non-overlapping SNPs typed previously in 250 of these same individuals, the resulting data consist of over 950,000 SNPs. We then analyzed the genetic relationships and ancestry of individuals without assigning them to populations, and we also identified candidate regions of recent positive selection at both the population and regional (continental) level. Conclusions Our analyses both confirm and extend previous studies; in particular, we highlight the impact of various dispersals, and the role of substructure in Africa, on human genetic diversity. We also identified several novel candidate regions for recent positive selection, and a gene ontology (GO) analysis identified several GO groups that were significantly enriched for such candidate genes, including immunity and defense related genes, sensory perception genes, membrane proteins, signal receptors, lipid binding/metabolism genes, and genes involved in the nervous system. Among the novel candidate genes identified are two genes involved in the thyroid hormone pathway that show signals of selection in African Pygmies that may be related to their short stature. PMID:19924308

  12. Signatures of positive selection in East African Shorthorn Zebu: A genome-wide single nucleotide polymorphism analysis

    PubMed Central

    Bahbahani, Hussain; Clifford, Harry; Wragg, David; Mbole-Kariuki, Mary N; Van Tassell, Curtis; Sonstegard, Tad; Woolhouse, Mark; Hanotte, Olivier

    2015-01-01

    The small East African Shorthorn Zebu (EASZ) is the main indigenous cattle across East Africa. A recent genome wide SNP analysis revealed an ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signatures of positive selection in their genome, with the aim to provide qualitative insights about the corresponding selective pressures. Four hundred and twenty-five EASZ and four reference populations (Holstein-Friesian, Jersey, N’Dama and Nellore) were analysed using 46,171 SNPs covering all autosomes and the X chromosome. Following FST and two extended haplotype homozygosity-based (iHS and Rsb) analyses 24 candidate genome regions within 14 autosomes and the X chromosome were revealed, in which 18 and 4 were previously identified in tropical-adapted and commercial breeds, respectively. These regions overlap with 340 bovine QTL. They include 409 annotated genes, in which 37 were considered as candidates. These genes are involved in various biological pathways (e.g. immunity, reproduction, development and heat tolerance). Our results support that different selection pressures (e.g. environmental constraints, human selection, genome admixture constrains) have shaped the genome of EASZ. We argue that these candidate regions represent genome landmarks to be maintained in breeding programs aiming to improve sustainable livestock productivity in the tropics. PMID:26130263

  13. Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs

    PubMed Central

    Freedman, Adam H.; Schweizer, Rena M.; Ortega-Del Vecchyo, Diego; Han, Eunjung; Davis, Brian W.; Gronau, Ilan; Silva, Pedro M.; Galaverni, Marco; Fan, Zhenxin; Marx, Peter; Lorente-Galdos, Belen; Ramirez, Oscar; Hormozdiari, Farhad; Alkan, Can; Vilà, Carles; Squire, Kevin; Geffen, Eli; Kusak, Josip; Boyko, Adam R.; Parker, Heidi G.; Lee, Clarence; Tadigotla, Vasisht; Siepel, Adam; Bustamante, Carlos D.; Harkins, Timothy T.; Nelson, Stanley F.; Marques-Bonet, Tomas; Ostrander, Elaine A.; Wayne, Robert K.; Novembre, John

    2016-01-01

    Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers. PMID:26943675

  14. A novel adjuvant to the resident selection process: the hartman value profile.

    PubMed

    Cone, Jeffrey D; Byrum, C Stephen; Payne, Wyatt G; Smith, David J

    2012-01-01

    The goal of resident selection is twofold: (1) select candidates who will be successful residents and eventually successful practitioners and (2) avoid selecting candidates who will be unsuccessful residents and/or eventually unsuccessful practitioners. Traditional tools used to select residents have well-known limitations. The Hartman Value Profile (HVP) is a proven adjuvant tool to predicting future performance in candidates for advanced positions in the corporate setting. No literature exists to indicate use of the HVP for resident selection. The HVP evaluates the structure and the dynamics of an individual value system. Given the potential impact, we implemented its use beginning in 2007 as an adjuvant tool to the traditional selection process. Experience gained from incorporating the HVP into the residency selection process suggests that it may add objectivity and refinement in predicting resident performance. Further evaluation is warranted with longer follow-up times.

  15. A Novel Adjuvant to the Resident Selection Process: the Hartman Value Profile

    PubMed Central

    Cone, Jeffrey D.; Byrum, C. Stephen; Payne, Wyatt G.; Smith, David J.

    2012-01-01

    Objectives: The goal of resident selection is twofold: (1) select candidates who will be successful residents and eventually successful practitioners and (2) avoid selecting candidates who will be unsuccessful residents and/or eventually unsuccessful practitioners. Traditional tools used to select residents have well-known limitations. The Hartman Value Profile (HVP) is a proven adjuvant tool to predicting future performance in candidates for advanced positions in the corporate setting. Methods: No literature exists to indicate use of the HVP for resident selection. Results: The HVP evaluates the structure and the dynamics of an individual value system. Given the potential impact, we implemented its use beginning in 2007 as an adjuvant tool to the traditional selection process. Conclusions: Experience gained from incorporating the HVP into the residency selection process suggests that it may add objectivity and refinement in predicting resident performance. Further evaluation is warranted with longer follow-up times. PMID:22720114

  16. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy

    PubMed Central

    Byars, Sean G.; Gray, Lesley-Ann; Ripatti, Samuli; Stearns, Stephen C.; Inouye, Michael

    2017-01-01

    Traditional genome-wide scans for positive selection have mainly uncovered selective sweeps associated with monogenic traits. While selection on quantitative traits is much more common, very few signals have been detected because of their polygenic nature. We searched for positive selection signals underlying coronary artery disease (CAD) in worldwide populations, using novel approaches to quantify relationships between polygenic selection signals and CAD genetic risk. We identified new candidate adaptive loci that appear to have been directly modified by disease pressures given their significant associations with CAD genetic risk. These candidates were all uniquely and consistently associated with many different male and female reproductive traits suggesting selection may have also targeted these because of their direct effects on fitness. We found that CAD loci are significantly enriched for lifetime reproductive success relative to the rest of the human genome, with evidence that the relationship between CAD and lifetime reproductive success is antagonistic. This supports the presence of antagonistic-pleiotropic tradeoffs on CAD loci and provides a novel explanation for the maintenance and high prevalence of CAD in modern humans. Lastly, we found that positive selection more often targeted CAD gene regulatory variants using HapMap3 lymphoblastoid cell lines, which further highlights the unique biological significance of candidate adaptive loci underlying CAD. Our study provides a novel approach for detecting selection on polygenic traits and evidence that modern human genomes have evolved in response to CAD-induced selection pressures and other early-life traits sharing pleiotropic links with CAD. PMID:28640878

  17. Selecting Candidates for Key Leadership Positions in Program Executive Offices Ground Combat Systems and Combat Service and Combat Service Support

    DTIC Science & Technology

    2016-10-14

    the quantitative and qualitative data for this study . This study focuses on determining how well the current process for selecting candidates... Research Design This study is structured as a mixed methods survey, incorporating qualitative and quantitative questions. Mixed method was selected to...Management Command (LCMC) on the Detroit Arsenal in Warren, MI. At the time of the study , PEO GCS and PEO CS&CSS did not have a specific policy for

  18. Genomic selection in plant breeding

    USDA-ARS?s Scientific Manuscript database

    Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor ...

  19. Signatures of positive selection in East African Shorthorn Zebu: a genome-wide SNP analysis

    USDA-ARS?s Scientific Manuscript database

    The small East African Shorthorn Zebu is the main indigenous cattle across East Africa. A recent genome wide SNPs analysis has revealed their ancient stable African taurine x Asian zebu admixture. Here, we assess the presence of candidate signature of positive selection in their genome, with the aim...

  20. Oriented regions grouping based candidate proposal for infrared pedestrian detection

    NASA Astrophysics Data System (ADS)

    Wang, Jiangtao; Zhang, Jingai; Li, Huaijiang

    2018-04-01

    Effectively and accurately locating the positions of pedestrian candidates in image is a key task for the infrared pedestrian detection system. In this work, a novel similarity measuring metric is designed. Based on the selective search scheme, the developed similarity measuring metric is utilized to yield the possible locations for pedestrian candidate. Besides this, corresponding diversification strategies are also provided according to the characteristics of the infrared thermal imaging system. Experimental results indicate that the presented scheme can achieve more efficient outputs than the traditional selective search methodology for the infrared pedestrian detection task.

  1. The popularity of neurology in Spain: An analysis of specialty selection.

    PubMed

    Curbelo, J; Romeo, J M; Galván-Román, J M; Vega-Villar, J; Martinez-Lapiscina, E H; Jiménez-Fonseca, P; Villacampa, T; Sánchez-Lasheras, F; Fernández-Somoano, A; Baladrón, J

    2017-12-23

    Neurology is one of the medical specialties offered each year to residency training candidates. This project analyses the data associated with candidates choosing neurology residency programmes in recent years. Data related to specialty selection were obtained from official reports by the Spanish Ministry of Health, Social Services, and Equality. Information was collected on several characteristics of teaching centres: availability of stroke units, endovascular intervention, national reference clinics for neurology, specific on-call shifts for neurology residents, and links with medical schools or national research networks. The median selection list position of candidates selecting neurology training has been higher year on year; neurology was among the 4 most popular residency programmes in 2016. Potential residents were mainly female, Spanish, and had good academic results. The median number of hospitals with higher numbers of beds, endovascular intervention, stroke units, and national reference clinics for neurology is significantly lower. This is also true when centers are analysed by presence of specific on-call shifts for neurology residents and association with medical schools or national research networks. The centres selected by candidates with the highest median selection list position in 2012-2016 were the Clínico San Carlos, 12 de Octubre, and Vall d'Hebron university hospitals. Neurology has gradually improved in residency selection choices and is now one of the 4 most popular options. Potential residents prefer larger centres which are more demanding in terms of patient care and which perform more research activity. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Identification of downy mildew resistance gene candidates by positional cloning in maize (Zea mays subsp. mays; Poaceae)1

    PubMed Central

    Kim, Jae Yoon; Moon, Jun-Cheol; Kim, Hyo Chul; Shin, Seungho; Song, Kitae; Kim, Kyung-Hee; Lee, Byung-Moo

    2017-01-01

    Premise of the study: Positional cloning in combination with phenotyping is a general approach to identify disease-resistance gene candidates in plants; however, it requires several time-consuming steps including population or fine mapping. Therefore, in the present study, we suggest a new combined strategy to improve the identification of disease-resistance gene candidates. Methods and Results: Downy mildew (DM)–resistant maize was selected from five cultivars using a spreader row technique. Positional cloning and bioinformatics tools were used to identify the DM-resistance quantitative trait locus marker (bnlg1702) and 47 protein-coding gene annotations. Eventually, five DM-resistance gene candidates, including bZIP34, Bak1, and Ppr, were identified by quantitative reverse-transcription PCR (RT-PCR) without fine mapping of the bnlg1702 locus. Conclusions: The combined protocol with the spreader row technique, quantitative trait locus positional cloning, and quantitative RT-PCR was effective for identifying DM-resistance candidate genes. This cloning approach may be applied to other whole-genome-sequenced crops or resistance to other diseases. PMID:28224059

  3. Ten Years of Experience with a Performance-Based Promotional Selection and Career Development System within State Government.

    ERIC Educational Resources Information Center

    Baugher, Dan; And Others

    1994-01-01

    The New York State Division of Budget uses a decentralized system to assess promotion candidates by comparing their training, experience, and recent performance to the proposed position. Managers and candidates find the system more effective than traditional written/oral exams. (SK)

  4. Genomic signatures reveal geographic adaption and human selection in cattle

    USDA-ARS?s Scientific Manuscript database

    We investigated geographic adaptation and human selection using high-density SNP data of five diverse cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-k...

  5. Perceived entitlement causes discrimination against attractive job candidates in the domain of relatively less desirable jobs.

    PubMed

    Lee, Margaret; Pitesa, Marko; Pillutla, Madan M; Thau, Stefan

    2018-03-01

    People generally hold positive stereotypes of physically attractive people and because of those stereotypes often treat them more favorably. However, we propose that some beliefs about attractive people, specifically, the perception that attractive individuals have a greater sense of entitlement than less attractive individuals, can result in negative treatment of attractive people. We examine this in the context of job selection and propose that for relatively less desirable jobs, attractive candidates will be discriminated against. We argue that the ascribed sense of entitlement to good outcomes leads to perceptions that attractive individuals are more likely to be dissatisfied working in relatively less desirable jobs. When selecting candidates for relatively less desirable jobs, decision makers try to ascertain whether a candidate would be satisfied in those jobs, and the stereotype of attractive individuals feeling entitled to good outcomes makes decision makers judge attractive candidates as more likely to be dissatisfied in relatively less (but not more) desirable jobs. Consequently, attractive candidates are discriminated against in the selection for relatively less desirable jobs. Four experiments found support for this theory. Our results suggest that different discriminatory processes operate when decision makers select among candidates for relatively less desirable jobs and that attractive people might be systematically discriminated against in a segment of the workforce. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  6. Superintendents' Perceptions about Social Distance, Succession, and "Sunset" Provisions for Asian, Latino, and Native American Candidates Seeking Building-Level Administrator Positions

    ERIC Educational Resources Information Center

    Young, I. Phillip; De La Torre, Guadalupe Xavier

    2006-01-01

    Research addressing the attraction and selection of individuals for administrator positions is encapsulated in a structural model that depicts different phases of the employee procurement process. Within the present study, attention is devoted to the prescreening stage of the selection process, and screening decisions of superintendents are…

  7. Legal Implications for Teacher Selection as Defined by the ADA and the ADEA.

    ERIC Educational Resources Information Center

    Young, I. Phillip; Prince, Arthur L.

    1999-01-01

    Hypothetical teacher candidates were created, some of whom were depicted as having an acknowledged disability, others having no acknowledged disability and all varied with respect to chronological age. A national random sample of public school principals evaluated the teacher candidates as if screening for a vacant position within their school…

  8. Principal Efficacy: Implications for Rural "Grow Your Own" Leadership Programs

    ERIC Educational Resources Information Center

    Versland, Tena M.

    2013-01-01

    Although "grow your own" principal preparation programs have become a popular method for recruiting and selecting administrator candidates for hard to fill positions in both urban and rural schools, "grow your own" principal candidates in rural contexts may be more vulnerable to the phenomenon of loss of self-efficacy. This…

  9. SEARCHING FOR NEW YELLOW SYMBIOTIC STARS: POSITIVE IDENTIFICATION OF StHα63

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

    Baella, N. O.; Pereira, C. B.; Alvarez-Candal, A.

    2016-04-15

    Yellow symbiotic stars are useful targets for probing whether mass transfer has happened in their binary systems. However, the number of known yellow symbiotic stars is very scarce. We report spectroscopic observations of five candidate yellow symbiotic stars that were selected by their positions in the 2MASS (J − H) versus (H − K{sub s}) diagram and which were included in some emission-line catalogs. Among the five candidates, only StHα63 is identified as a new yellow symbiotic star because of its spectrum and its position in the [TiO]{sub 1}–[TiO]{sub 2} diagram, which indicates a K4–K6 spectral type. In addition, themore » derived electron density (∼10{sup 8.4} cm{sup −3}) and several emission-line intensity ratios provide further support for that classification. The other four candidates are rejected as symbiotic stars because three of them actually do not show emission lines and the fourth one only Balmer emission lines. We also found that the WISE W3–W4 index clearly separates normal K-giants from yellow symbiotic stars and therefore can be used as an additional tool for selecting candidate yellow symbiotic stars.« less

  10. ‘Obesity’ is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism

    PubMed Central

    Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

    2015-01-01

    Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that ‘obesity’ might be an indicator of good health for cetaceans. PMID:26381091

  11. 'Obesity' is healthy for cetaceans? Evidence from pervasive positive selection in genes related to triacylglycerol metabolism.

    PubMed

    Wang, Zhengfei; Chen, Zhuo; Xu, Shixia; Ren, Wenhua; Zhou, Kaiya; Yang, Guang

    2015-09-18

    Cetaceans are a group of secondarily adapted marine mammals with an enigmatic history of transition from terrestrial to fully aquatic habitat and subsequent adaptive radiation in waters around the world. Numerous physiological and morphological cetacean characteristics have been acquired in response to this drastic habitat transition; for example, the thickened blubber is one of the most striking changes that increases their buoyancy, supports locomotion, and provides thermal insulation. However, the genetic basis underlying the blubber thickening in cetaceans remains poorly explored. Here, 88 candidate genes associated with triacylglycerol metabolism were investigated in representative cetaceans and other mammals to test whether the thickened blubber matched adaptive evolution of triacylglycerol metabolism-related genes. Positive selection was detected in 41 of the 88 candidate genes, and functional characterization of these genes indicated that these are involved mainly in triacylglycerol synthesis and lipolysis processes. In addition, some essential regulatory genes underwent significant positive selection in cetacean-specific lineages, whereas no selection signal was detected in the counterpart terrestrial mammals. The extensive occurrence of positive selection in triacylglycerol metabolism-related genes is suggestive of their essential role in secondary adaptation to an aquatic life, and further implying that 'obesity' might be an indicator of good health for cetaceans.

  12. Genomic selection in plant breeding.

    PubMed

    Newell, Mark A; Jannink, Jean-Luc

    2014-01-01

    Genomic selection (GS) is a method to predict the genetic value of selection candidates based on the genomic estimated breeding value (GEBV) predicted from high-density markers positioned throughout the genome. Unlike marker-assisted selection, the GEBV is based on all markers including both minor and major marker effects. Thus, the GEBV may capture more of the genetic variation for the particular trait under selection.

  13. Selection of Malaysia School Youth Cadet Corps leader by using analytical hierarchy process: A case study at SMK Ahmad Boestamam

    NASA Astrophysics Data System (ADS)

    Mohamed, Nurul Huda; Ahmat, Norhayati; Mohamed, Nurul Akmal; Razmi, Syazwani Che; Mohamed, Nurul Farihan

    2017-05-01

    This research is a case study to identify the best criteria that a person should have as the leader of Malaysia School Youth Cadet Corps (Kadet Remaja Sekolah (KRS)) at SMK Ahmad Boestamam, Sitiawan in order to select the most appropriate person to hold the position. The approach used in this study is Analytical Hierarchy Process (AHP) which include pairwise comparison to compare the criteria and also the candidates. There are four criteria namely charisma, interpersonal communication, personality and physical. Four candidates (1, 2, 3 and 4) are being considered in this study. Purposive sampling and questionnaires are used as instruments to obtain the data which are then analyzed by using the AHP method. The final output indicates that Candidate 1 has the highest score, followed by Candidate 2, Candidate 4 and Candidate 3. It shows that this method is very helpful in the multi-criteria decision making when there are several options available.

  14. Performance of combined fragmentation and retention prediction for the identification of organic micropollutants by LC-HRMS.

    PubMed

    Hu, Meng; Müller, Erik; Schymanski, Emma L; Ruttkies, Christoph; Schulze, Tobias; Brack, Werner; Krauss, Martin

    2018-03-01

    In nontarget screening, structure elucidation of small molecules from high resolution mass spectrometry (HRMS) data is challenging, particularly the selection of the most likely candidate structure among the many retrieved from compound databases. Several fragmentation and retention prediction methods have been developed to improve this candidate selection. In order to evaluate their performance, we compared two in silico fragmenters (MetFrag and CFM-ID) and two retention time prediction models (based on the chromatographic hydrophobicity index (CHI) and on log D). A set of 78 known organic micropollutants was analyzed by liquid chromatography coupled to a LTQ Orbitrap HRMS with electrospray ionization (ESI) in positive and negative mode using two fragmentation techniques with different collision energies. Both fragmenters (MetFrag and CFM-ID) performed well for most compounds, with average ranking the correct candidate structure within the top 25% and 22 to 37% for ESI+ and ESI- mode, respectively. The rank of the correct candidate structure slightly improved when MetFrag and CFM-ID were combined. For unknown compounds detected in both ESI+ and ESI-, generally positive mode mass spectra were better for further structure elucidation. Both retention prediction models performed reasonably well for more hydrophobic compounds but not for early eluting hydrophilic substances. The log D prediction showed a better accuracy than the CHI model. Although the two fragmentation prediction methods are more diagnostic and sensitive for candidate selection, the inclusion of retention prediction by calculating a consensus score with optimized weighting can improve the ranking of correct candidates as compared to the individual methods. Graphical abstract Consensus workflow for combining fragmentation and retention prediction in LC-HRMS-based micropollutant identification.

  15. Determination of hepatocellular carcinoma grade by needle biopsy is unreliable for liver transplant candidate selection.

    PubMed

    Court, Colin M; Harlander-Locke, Michael P; Markovic, Daniela; French, Samuel W; Naini, Bita V; Lu, David S; Raman, Steven S; Kaldas, Fady M; Zarrinpar, Ali; Farmer, Douglas G; Finn, Richard S; Sadeghi, Saeed; Tomlinson, James S; Busuttil, Ronald W; Agopian, Vatche G

    2017-09-01

    The objective of this article is to evaluate the utility of preoperative needle biopsy (PNB) grading of hepatocellular carcinoma (HCC) as a biomarker for liver transplantation (LT) candidate selection. Given the prognostic significance of HCC tumor grade, PNB grading has been proposed as a biomarker for LT candidate selection. Clinicopathologic characteristics of HCC LT recipients (1989-2014) with a PNB were analyzed, and the concordance of PNB grade to explant grade and vascular invasion was assessed to determine whether incorporation of PNB grade to accepted transplant criteria improved candidate selection. Of 965 patients undergoing LT for HCC, 234 (24%) underwent PNB at a median of 280 days prior to transplant. Grade by PNB had poor concordance to final explant pathology (κ = 0.22; P = 0.003), and low sensitivity (29%) and positive predictive value (35%) in identifying poorly differentiated tumors. Vascular invasion was predicted by explant pathologic grade (r s = 0.24; P < 0.001) but not PNB grade (r s = -0.05; P = 0.50). Increasing explant pathology grade (P = 0.02), but not PNB grade (P = 0.65), discriminated post-LT HCC recurrence risk. The incorporation of PNB grade to the established radiologic Milan criteria (MC) did not result in improved prognostication of post-LT recurrence (net reclassification index [NRI] = 0%), whereas grade by explant pathology resulted in significantly improved reclassification of risk (NRI = 19%). Preoperative determination of HCC grade by PNB has low concordance with explant pathologic grade and low sensitivity and positive predictive value in identifying poorly differentiated tumors. PNB grade did not accurately discriminate post-LT HCC recurrence and had no utility in improving prognostication compared with the MC alone. Incorporation of PNB to guide transplant candidate selection appears unjustified. Liver Transplantation 23 1123-1132 2017 AASLD. © 2017 by the American Association for the Study of Liver Diseases.

  16. Finding strong lenses in CFHTLS using convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Jacobs, C.; Glazebrook, K.; Collett, T.; More, A.; McCarthy, C.

    2017-10-01

    We train and apply convolutional neural networks, a machine learning technique developed to learn from and classify image data, to Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) imaging for the identification of potential strong lensing systems. An ensemble of four convolutional neural networks was trained on images of simulated galaxy-galaxy lenses. The training sets consisted of a total of 62 406 simulated lenses and 64 673 non-lens negative examples generated with two different methodologies. An ensemble of trained networks was applied to all of the 171 deg2 of the CFHTLS wide field image data, identifying 18 861 candidates including 63 known and 139 other potential lens candidates. A second search of 1.4 million early-type galaxies selected from the survey catalogue as potential deflectors, identified 2465 candidates including 117 previously known lens candidates, 29 confirmed lenses/high-quality lens candidates, 266 novel probable or potential lenses and 2097 candidates we classify as false positives. For the catalogue-based search we estimate a completeness of 21-28 per cent with respect to detectable lenses and a purity of 15 per cent, with a false-positive rate of 1 in 671 images tested. We predict a human astronomer reviewing candidates produced by the system would identify 20 probable lenses and 100 possible lenses per hour in a sample selected by the robot. Convolutional neural networks are therefore a promising tool for use in the search for lenses in current and forthcoming surveys such as the Dark Energy Survey and the Large Synoptic Survey Telescope.

  17. Systematic search for UV-excess quasar candidates in 40 square degrees at the North Galactic Pole.

    NASA Astrophysics Data System (ADS)

    Moreau, O.; Reboul, H.

    1995-05-01

    We have developed a procedure (so called PAPA) for measurement of magnitudes (about 0.1mag accurate) and positions (with accuracy better than 0.5arcsec) of all the objects present on photographic plates digitised with the MAMA machine. This homogeneous procedure was applied to four Schmidt plates - in U, B and twice V - covering the Palomar-Sky-Survey field PS +30deg 13h00m, a 40-square-degree zone at the North Galactic Pole. A general-interest exhaustive tricolour catalogue of 19542 star-like objects down to V=20.0 has been produced and we selected 1681 quasar candidates on the basis of ultraviolet excess and, when possible, absence of any measurable proper motion. The astrometric and photometric catalogue of the candidates is given in electronic form. A first multi-object spectroscopy of a few candidates confirms validity of the selection.

  18. Searching for New Yellow Symbiotic Stars: Positive Identification of StHα63

    NASA Astrophysics Data System (ADS)

    Baella, N. O.; Pereira, C. B.; Miranda, L. F.; Alvarez-Candal, A.

    2016-04-01

    Yellow symbiotic stars are useful targets for probing whether mass transfer has happened in their binary systems. However, the number of known yellow symbiotic stars is very scarce. We report spectroscopic observations of five candidate yellow symbiotic stars that were selected by their positions in the 2MASS (J - H) versus (H - Ks) diagram and which were included in some emission-line catalogs. Among the five candidates, only StHα63 is identified as a new yellow symbiotic star because of its spectrum and its position in the [TiO]1-[TiO]2 diagram, which indicates a K4-K6 spectral type. In addition, the derived electron density (˜108.4 cm-3) and several emission-line intensity ratios provide further support for that classification. The other four candidates are rejected as symbiotic stars because three of them actually do not show emission lines and the fourth one only Balmer emission lines. We also found that the WISE W3-W4 index clearly separates normal K-giants from yellow symbiotic stars and therefore can be used as an additional tool for selecting candidate yellow symbiotic stars. Based on observations collected at the Centro Astronómico Hispano-Alemán, Calar Alto, jointly operated by the Max-Planck-Institut für Astronomie (Heidelberg) and the Instituto de Astrofísica de Andalucía (CSIC), and at the 4.1 m telescope at Cerro Pachón Observatory, Chile.

  19. Properties OF M31. V. 298 eclipsing binaries from PAndromeda

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

    Lee, C.-H.; Koppenhoefer, J.; Seitz, S.

    2014-12-10

    The goal of this work is to conduct a photometric study of eclipsing binaries in M31. We apply a modified box-fitting algorithm to search for eclipsing binary candidates and determine their period. We classify these candidates into detached, semi-detached, and contact systems using the Fourier decomposition method. We cross-match the position of our detached candidates with the photometry from Local Group Survey and select 13 candidates brighter than 20.5 mag in V. The relative physical parameters of these detached candidates are further characterized with the Detached Eclipsing Binary Light curve fitter (DEBiL) by Devor. We will follow up the detachedmore » eclipsing binaries spectroscopically and determine the distance to M31.« less

  20. Identification of positive selection in disease response genes within members of the Poaceae.

    PubMed

    Rech, Gabriel E; Vargas, Walter A; Sukno, Serenella A; Thon, Michael R

    2012-12-01

    Millions of years of coevolution between plants and pathogens can leave footprints on their genomes and genes involved on this interaction are expected to show patterns of positive selection in which novel, beneficial alleles are rapidly fixed within the population. Using information about upregulated genes in maize during Colletotrichum graminicola infection and resources available in the Phytozome database, we looked for evidence of positive selection in the Poaceae lineage, acting on protein coding sequences related with plant defense. We found six genes with evidence of positive selection and another eight with sites showing episodic selection. Some of them have already been described as evolving under positive selection, but others are reported here for the first time including genes encoding isocitrate lyase, dehydrogenases, a multidrug transporter, a protein containing a putative leucine-rich repeat and other proteins with unknown functions. Mapping positively selected residues onto the predicted 3-D structure of proteins showed that most of them are located on the surface, where proteins are in contact with other molecules. We present here a set of Poaceae genes that are likely to be involved in plant defense mechanisms and have evidence of positive selection. These genes are excellent candidates for future functional validation.

  1. Could situational judgement tests be used for selection into dental foundation training?

    PubMed

    Patterson, F; Ashworth, V; Mehra, S; Falcon, H

    2012-07-13

    To pilot and evaluate a machine-markable situational judgement test (SJT) designed to select candidates into UK dental foundation training. Single centre pilot study. UK postgraduate deanery in 2010. Seventy-four candidates attending interview for dental foundation training in Oxford and Wessex Deaneries volunteered to complete the situational judgement test. The situational judgement test was developed to assess relevant professional attributes for dentistry (for example, empathy and integrity) in a machine-markable format. Test content was developed by subject matter experts working with experienced psychometricians. Evaluation of psychometric properties of the pilot situational judgement test (for example, reliability, validity and fairness). Scores in the dental foundation training selection process (short-listing and interviews) were used to examine criterion-related validity. Candidates completed an evaluation questionnaire to examine candidate reactions and face validity of the new test. Forty-six candidates were female and 28 male; mean age was 23.5-years-old (range 22-32). Situational judgement test scores were normally distributed and the test showed good internal reliability when corrected for test length (α = 0.74). Situational judgement test scores positively correlated with the management, leadership and professionalism interview (N = 50; r = 0.43, p <0.01) but not with the clinical skills interview, providing initial evidence of criterion-related validity as the situational judgement test is designed to test non-cognitive professional attributes beyond clinical knowledge. Most candidates perceived the situational judgement test as relevant to dentistry, appropriate for their training level, and fair. This initial pilot study suggests that a situational judgement test is an appropriate and innovative method to measure professional attributes (eg empathy and integrity) for selection into foundation training. Further research will explore the long-term predictive validity of the situational judgement test once candidates have entered training.

  2. Spitzer Photometry of WISE-Selected Brown Dwarf and Hyper-Lumninous Infrared Galaxy Candidates

    NASA Technical Reports Server (NTRS)

    Griffith, Roger L.; Kirkpatrick, J. Davy; Eisenhardt, Peter R. M.; Gelino, Christopher R.; Cushing, Michael C.; Benford, Dominic; Blain, Andrew; Bridge, Carrie R.; Cohen, Martin; Cutri, Roc M.; hide

    2012-01-01

    We present Spitzer 3.6 and 4.5 micrometer photometry and positions for a sample of 1510 brown dwarf candidates identified by the Wide-field Infrared Survey Explorer (WISE) all-sky survey. Of these, 166 have been spectroscopically classified as objects with spectral types M(1), L(7), T(146), and Y(12). Sixteen other objects are non-(sub)stellar in nature. The remainder are most likely distant L and T dwarfs lacking spectroscopic verification, other Y dwarf candidates still awaiting follow-up, and assorted other objects whose Spitzer photometry reveals them to be background sources. We present a catalog of Spitzer photometry for all astrophysical sources identified in these fields and use this catalog to identify seven fainter (4.5 m to approximately 17.0 mag) brown dwarf candidates, which are possibly wide-field companions to the original WISE sources. To test this hypothesis, we use a sample of 919 Spitzer observations around WISE-selected high-redshift hyper-luminous infrared galaxy candidates. For this control sample, we find another six brown dwarf candidates, suggesting that the seven companion candidates are not physically associated. In fact, only one of these seven Spitzer brown dwarf candidates has a photometric distance estimate consistent with being a companion to the WISE brown dwarf candidate. Other than this, there is no evidence for any widely separated (greater than 20 AU) ultra-cool binaries. As an adjunct to this paper, we make available a source catalog of 7.33 x 10(exp 5) objects detected in all of these Spitzer follow-up fields for use by the astronomical community. The complete catalog includes the Spitzer 3.6 and 4.5 m photometry, along with positionally matched B and R photometry from USNO-B; J, H, and Ks photometry from Two Micron All-Sky Survey; and W1, W2, W3, and W4 photometry from the WISE all-sky catalog.

  3. A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments.

    PubMed

    Yudin, Nikolay S; Larkin, Denis M; Ignatieva, Elena V

    2017-12-28

    Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals. After a search for publications containing keywords: "whole genome", "transcriptome or exome sequencing data", and "genome-wide genotyping array data" authors looked for information related to genetic signatures ascribable to positive selection in Arctic or Antarctic mammalian species. Publications related to Human, Arctic fox, Yakut horse, Mammoth, Polar bear, and Minke whale were chosen. The compendium of genes that potentially underwent positive selection in >1 of these six species consisted of 416 genes. Twelve of them showed traces of positive selection in three species. Gene ontology term enrichment analysis of 416 genes from the compendium has revealed 13 terms relevant to the scope of this study. We found that enriched terms were relevant to three major groups: terms associated with collagen proteins and the extracellular matrix; terms associated with the anatomy and physiology of cilium; terms associated with docking. We further revealed that genes from compendium were over-represented in the lists of genes expressed in the lung and liver. A compendium combining mammalian genes involved in adaptation to cold environment was designed, based on the intersection of positively selected genes from six Arctic and Antarctic species. The compendium contained 416 genes that have been positively selected in at least two species. However, we did not reveal any positively selected genes that would be related to cold adaptation in all species from our list. But, our work points to several strong candidate genes involved in mechanisms and biochemical pathways related to cold adaptation response in different species.

  4. Identifying positive selection candidate loci for high-altitude adaptation in Andean populations

    PubMed Central

    2009-01-01

    High-altitude environments (>2,500 m) provide scientists with a natural laboratory to study the physiological and genetic effects of low ambient oxygen tension on human populations. One approach to understanding how life at high altitude has affected human metabolism is to survey genome-wide datasets for signatures of natural selection. In this work, we report on a study to identify selection-nominated candidate genes involved in adaptation to hypoxia in one highland group, Andeans from the South American Altiplano. We analysed dense microarray genotype data using four test statistics that detect departures from neutrality. Using a candidate gene, single nucleotide polymorphism-based approach, we identified genes exhibiting preliminary evidence of recent genetic adaptation in this population. These included genes that are part of the hypoxia-inducible transcription factor (HIF) pathway, a biochemical pathway involved in oxygen homeostasis, as well as three other genomic regions previously not known to be associated with high-altitude phenotypes. In addition to identifying selection-nominated candidate genes, we also tested whether the HIF pathway shows evidence of natural selection. Our results indicate that the genes of this biochemical pathway as a group show no evidence of having evolved in response to hypoxia in Andeans. Results from particular HIF-targeted genes, however, suggest that genes in this pathway could play a role in Andean adaptation to high altitude, even if the pathway as a whole does not show higher relative rates of evolution. These data suggest a genetic role in high-altitude adaptation and provide a basis for genotype/phenotype association studies that are necessary to confirm the role of putative natural selection candidate genes and gene regions in adaptation to altitude. PMID:20038496

  5. Survival in HIV-positive transplant recipients compared with transplant candidates and with HIV-negative controls

    PubMed Central

    Roland, Michelle E.; Barin, Burc; Huprikar, Shirish; Murphy, Barbara; Hanto, Douglas W.; Blumberg, Emily; Olthoff, Kim; Simon, David; Hardy, William D.; Beatty, George; Stock, Peter G.

    2016-01-01

    Objectives To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. Design Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. Methods We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. Results There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P <0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P =0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P =0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P =0.07) and HR 1.4 (P =0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. Conclusion Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. Trial Registration ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/. PMID:26765937

  6. Mapping of quantitative trait loci controlling adaptive traits in coastal Douglas-fir

    Treesearch

    Nicholas C. Wheeler; Kathleen D. Jermstad; Konstantin V. Krutovsky; Sally N. Aitken; Glenn T. Howe; Jodie Krakowski; David B. Neale

    2005-01-01

    Quantitative trait locus (QTL) analyses are used by geneticists to characterize the genetic architecture of quantitative traits, provide a foundation for marker-aided-selection (MAS), and provide a framework for positional selection of candidate genes. The most useful QTL for breeding applications are those that have been verified in time, space, and/or genetic...

  7. Legal Aspects of Employee Assessment and Selection in Public Schools. 1985 Monograph Series.

    ERIC Educational Resources Information Center

    Beckham, Joseph C.

    Legally sound assessment and selection processes in public schools must relate criteria to job requirements and must adopt procedures that are clearly articulated and uniformly applied to all candidates for a position. Legal challenges to school districts related to employment decisions can be grouped as allegations of (1) discriminatory practice,…

  8. Signatures of positive selection in African Butana and Kenana dairy zebu cattle.

    PubMed

    Bahbahani, Hussain; Salim, Bashir; Almathen, Faisal; Al Enezi, Fahad; Mwacharo, Joram M; Hanotte, Olivier

    2018-01-01

    Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds.

  9. A Gene-Oriented Haplotype Comparison Reveals Recently Selected Genomic Regions in Temperate and Tropical Maize Germplasm

    PubMed Central

    Zhang, Jie; Li, Yongxiang; Zheng, Jun; Zhang, Hongwei; Yang, Xiaohong; Wang, Jianhua; Wang, Guoying

    2017-01-01

    The extensive genetic variation present in maize (Zea mays) germplasm makes it possible to detect signatures of positive artificial selection that occurred during temperate and tropical maize improvement. Here we report an analysis of 532,815 polymorphisms from a maize association panel consisting of 368 diverse temperate and tropical inbred lines. We developed a gene-oriented approach adapting exonic polymorphisms to identify recently selected alleles by comparing haplotypes across the maize genome. This analysis revealed evidence of selection for more than 1100 genomic regions during recent improvement, and included regulatory genes and key genes with visible mutant phenotypes. We find that selected candidate target genes in temperate maize are enriched in biosynthetic processes, and further examination of these candidates highlights two cases, sucrose flux and oil storage, in which multiple genes in a common pathway can be cooperatively selected. Finally, based on available parallel gene expression data, we hypothesize that some genes were selected for regulatory variations, resulting in altered gene expression. PMID:28099470

  10. How immunogenetically different are domestic pigs from wild boars: a perspective from single-nucleotide polymorphisms of 19 immunity-related candidate genes.

    PubMed

    Chen, Shanyuan; Gomes, Rui; Costa, Vânia; Santos, Pedro; Charneca, Rui; Zhang, Ya-ping; Liu, Xue-hong; Wang, Shao-qing; Bento, Pedro; Nunes, Jose-Luis; Buzgó, József; Varga, Gyula; Anton, István; Zsolnai, Attila; Beja-Pereira, Albano

    2013-10-01

    The coexistence of wild boars and domestic pigs across Eurasia makes it feasible to conduct comparative genetic or genomic analyses for addressing how genetically different a domestic species is from its wild ancestor. To test whether there are differences in patterns of genetic variability between wild and domestic pigs at immunity-related genes and to detect outlier loci putatively under selection that may underlie differences in immune responses, here we analyzed 54 single-nucleotide polymorphisms (SNPs) of 19 immunity-related candidate genes on 11 autosomes in three pairs of wild boar and domestic pig populations from China, Iberian Peninsula, and Hungary. Our results showed no statistically significant differences in allele frequency and heterozygosity across SNPs between three pairs of wild and domestic populations. This observation was more likely due to the widespread and long-lasting gene flow between wild boars and domestic pigs across Eurasia. In addition, we detected eight coding SNPs from six genes as outliers being under selection consistently by three outlier tests (BayeScan2.1, FDIST2, and Arlequin3.5). Among four non-synonymous outlier SNPs, one from TLR4 gene was identified as being subject to positive (diversifying) selection and three each from CD36, IFNW1, and IL1B genes were suggested as under balancing selection. All of these four non-synonymous variants were predicted as being benign by PolyPhen-2. Our results were supported by other independent lines of evidence for positive selection or balancing selection acting on these four immune genes (CD36, IFNW1, IL1B, and TLR4). Our study showed an example applying a candidate gene approach to identify functionally important mutations (i.e., outlier loci) in wild and domestic pigs for subsequent functional experiments.

  11. Genome-wide detection of selection signatures in Chinese indigenous Laiwu pigs revealed candidate genes regulating fat deposition in muscle.

    PubMed

    Chen, Minhui; Wang, Jiying; Wang, Yanping; Wu, Ying; Fu, Jinluan; Liu, Jian-Feng

    2018-05-18

    Currently, genome-wide scans for positive selection signatures in commercial breed have been investigated. However, few studies have focused on selection footprints of indigenous breeds. Laiwu pig is an invaluable Chinese indigenous pig breed with extremely high proportion of intramuscular fat (IMF), and an excellent model to detect footprint as the result of natural and artificial selection for fat deposition in muscle. In this study, based on GeneSeek Genomic profiler Porcine HD data, three complementary methods, F ST , iHS (integrated haplotype homozygosity score) and CLR (composite likelihood ratio), were implemented to detect selection signatures in the whole genome of Laiwu pigs. Totally, 175 candidate selected regions were obtained by at least two of the three methods, which covered 43.75 Mb genomic regions and corresponded to 1.79% of the genome sequence. Gene annotation of the selected regions revealed a list of functionally important genes for feed intake and fat deposition, reproduction, and immune response. Especially, in accordance to the phenotypic features of Laiwu pigs, among the candidate genes, we identified several genes, NPY1R, NPY5R, PIK3R1 and JAKMIP1, involved in the actions of two sets of neurons, which are central regulators in maintaining the balance between food intake and energy expenditure. Our results identified a number of regions showing signatures of selection, as well as a list of functionally candidate genes with potential effect on phenotypic traits, especially fat deposition in muscle. Our findings provide insights into the mechanisms of artificial selection of fat deposition and further facilitate follow-up functional studies.

  12. A Feature Selection Method Based on Fisher's Discriminant Ratio for Text Sentiment Classification

    NASA Astrophysics Data System (ADS)

    Wang, Suge; Li, Deyu; Wei, Yingjie; Li, Hongxia

    With the rapid growth of e-commerce, product reviews on the Web have become an important information source for customers' decision making when they intend to buy some product. As the reviews are often too many for customers to go through, how to automatically classify them into different sentiment orientation categories (i.e. positive/negative) has become a research problem. In this paper, based on Fisher's discriminant ratio, an effective feature selection method is proposed for product review text sentiment classification. In order to validate the validity of the proposed method, we compared it with other methods respectively based on information gain and mutual information while support vector machine is adopted as the classifier. In this paper, 6 subexperiments are conducted by combining different feature selection methods with 2 kinds of candidate feature sets. Under 1006 review documents of cars, the experimental results indicate that the Fisher's discriminant ratio based on word frequency estimation has the best performance with F value 83.3% while the candidate features are the words which appear in both positive and negative texts.

  13. Improving the quality of the NHS workforce through values and competency-based selection.

    PubMed

    McGuire, Clare; Rankin, Jean; Matthews, Lynsay; Cerinus, Marie; Zaveri, Swati

    2016-07-01

    Robust selection processes are essential to ensure the best and most appropriate candidates for nursing, midwifery and allied health professional (NMAHP) positions are appointed, and subsequently enhance patient care. This article reports on a study that explored interviewers' and interviewees' experiences of using values and competency-based interview (VCBI) methods for NMAHPs. Results suggest that this resource could have a positive effect on the quality of the NMAHP workforce, and therefore on patient care. This method of selection could be used in other practice areas in health care, and refinement of the resource should focus on supporting interview panels to develop their VCBI skills and experience.

  14. Remote controlled capsules in human drug absorption (HDA) studies.

    PubMed

    Wilding, Ian R; Prior, David V

    2003-01-01

    The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery.

  15. A Model-Based Approach for Identifying Signatures of Ancient Balancing Selection in Genetic Data

    PubMed Central

    DeGiorgio, Michael; Lohmueller, Kirk E.; Nielsen, Rasmus

    2014-01-01

    While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates. PMID:25144706

  16. A model-based approach for identifying signatures of ancient balancing selection in genetic data.

    PubMed

    DeGiorgio, Michael; Lohmueller, Kirk E; Nielsen, Rasmus

    2014-08-01

    While much effort has focused on detecting positive and negative directional selection in the human genome, relatively little work has been devoted to balancing selection. This lack of attention is likely due to the paucity of sophisticated methods for identifying sites under balancing selection. Here we develop two composite likelihood ratio tests for detecting balancing selection. Using simulations, we show that these methods outperform competing methods under a variety of assumptions and demographic models. We apply the new methods to whole-genome human data, and find a number of previously-identified loci with strong evidence of balancing selection, including several HLA genes. Additionally, we find evidence for many novel candidates, the strongest of which is FANK1, an imprinted gene that suppresses apoptosis, is expressed during meiosis in males, and displays marginal signs of segregation distortion. We hypothesize that balancing selection acts on this locus to stabilize the segregation distortion and negative fitness effects of the distorter allele. Thus, our methods are able to reproduce many previously-hypothesized signals of balancing selection, as well as discover novel interesting candidates.

  17. Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection

    PubMed Central

    Hsieh, PingHsun; Veeramah, Krishna R.; Lachance, Joseph; Tishkoff, Sarah A.; Wall, Jeffrey D.; Hammer, Michael F.; Gutenkunst, Ryan N.

    2016-01-01

    African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors. PMID:26888263

  18. In silico identification of novel and selective monoamine oxidase B inhibitors.

    PubMed

    Yelekçi, Kemal; Büyüktürk, Bora; Kayrak, Nurdan

    2013-06-01

    Monoamine oxidases (MAO) A and B are flavin adenine dinucleotides containing enzymes bound to the mitochondrial outer membranes of the cells of the brain, liver, intestine, and placenta, as well as platelets. Recently, selective MAO-B inhibitors have received increasing attention due to their neuroprotective properties and the multiple roles they can play in the therapy of neurodegenerative disorders. This study was based on 10 scaffolds that were selected from more than a million lead compounds in the ZINCv12 lead library for their structural and physicochemical properties which inhibit MAO-B. Utilizing ZINC and Accelrys 3.1 fragment-based libraries, which contain about 400 thousand fragments, we generated 200 potential candidates. GOLD, LibDock, and AutoDock 4.02 were used to identify the inhibition constants and their position in the active sites of both MAO isozymes. The dispositions of the candidate molecules within the organism were checked with ADMET PSA 2D (polar surface area) against ADMET AlogP98 (the logarithm of the partition coefficient between n-octanol and water). The MAO-B inhibition activities of the candidates were compared with the properties of rasagiline which is known to be a selective inhibitor of MAO-B.

  19. An Energy Balanced and Lifetime Extended Routing Protocol for Underwater Sensor Networks.

    PubMed

    Wang, Hao; Wang, Shilian; Zhang, Eryang; Lu, Luxi

    2018-05-17

    Energy limitation is an adverse problem in designing routing protocols for underwater sensor networks (UWSNs). To prolong the network lifetime with limited battery power, an energy balanced and efficient routing protocol, called energy balanced and lifetime extended routing protocol (EBLE), is proposed in this paper. The proposed EBLE not only balances traffic loads according to the residual energy, but also optimizes data transmissions by selecting low-cost paths. Two phases are operated in the EBLE data transmission process: (1) candidate forwarding set selection phase and (2) data transmission phase. In candidate forwarding set selection phase, nodes update candidate forwarding nodes by broadcasting the position and residual energy level information. The cost value of available nodes is calculated and stored in each sensor node. Then in data transmission phase, high residual energy and relatively low-cost paths are selected based on the cost function and residual energy level information. We also introduce detailed analysis of optimal energy consumption in UWSNs. Numerical simulation results on a variety of node distributions and data load distributions prove that EBLE outperforms other routing protocols (BTM, BEAR and direct transmission) in terms of network lifetime and energy efficiency.

  20. Transit shapes and self-organizing maps as a tool for ranking planetary candidates: application to Kepler and K2

    NASA Astrophysics Data System (ADS)

    Armstrong, D. J.; Pollacco, D.; Santerne, A.

    2017-03-01

    A crucial step in planet hunting surveys is to select the best candidates for follow-up observations, given limited telescope resources. This is often performed by human 'eyeballing', a time consuming and statistically awkward process. Here, we present a new, fast machine learning technique to separate true planet signals from astrophysical false positives. We use self-organizing maps (SOMs) to study the transit shapes of Kepler and K2 known and candidate planets. We find that SOMs are capable of distinguishing known planets from known false positives with a success rate of 87.0 per cent, using the transit shape alone. Furthermore, they do not require any candidate to be dispositioned prior to use, meaning that they can be used early in a mission's lifetime. A method for classifying candidates using a SOM is developed, and applied to previously unclassified members of the Kepler Objects of Interest (KOI) list as well as candidates from the K2 mission. The method is extremely fast, taking minutes to run the entire KOI list on a typical laptop. We make PYTHON code for performing classifications publicly available, using either new SOMs or those created in this work. The SOM technique represents a novel method for ranking planetary candidate lists, and can be used both alone or as part of a larger autovetting code.

  1. Signatures of positive selection in African Butana and Kenana dairy zebu cattle

    PubMed Central

    Salim, Bashir; Almathen, Faisal; Al Enezi, Fahad; Mwacharo, Joram M.; Hanotte, Olivier

    2018-01-01

    Butana and Kenana are two types of zebu cattle found in Sudan. They are unique amongst African indigenous zebu cattle because of their high milk production. Aiming to understand their genome structure, we genotyped 25 individuals from each breed using the Illumina BovineHD Genotyping BeadChip. Genetic structure analysis shows that both breeds have an admixed genome composed of an even proportion of indicine (0.75 ± 0.03 in Butana, 0.76 ± 0.006 in Kenana) and taurine (0.23 ± 0.009 in Butana, 0.24 ± 0.006 in Kenana) ancestries. We also observe a proportion of 0.02 to 0.12 of European taurine ancestry in ten individuals of Butana that were sampled from cattle herds in Tamboul area suggesting local crossbreeding with exotic breeds. Signatures of selection analyses (iHS and Rsb) reveal 87 and 61 candidate positive selection regions in Butana and Kenana, respectively. These regions span genes and quantitative trait loci (QTL) associated with biological pathways that are important for adaptation to marginal environments (e.g., immunity, reproduction and heat tolerance). Trypanotolerance QTL are intersecting candidate regions in Kenana cattle indicating selection pressure acting on them, which might be associated with an unexplored level of trypanotolerance in this cattle breed. Several dairy traits QTL are overlapping the identified candidate regions in these two zebu cattle breeds. Our findings underline the potential to improve dairy production in the semi-arid pastoral areas of Africa through breeding improvement strategy of indigenous local breeds. PMID:29300786

  2. No recent adaptive selection on the apyrase of Mediterranean Phlebotomus: implications for using salivary peptides to vaccinate against canine leishmaniasis.

    PubMed

    Mahamdallie, Shazia S; Ready, Paul D

    2012-04-01

    Vaccine development is informed by a knowledge of genetic variation among antigen alleles, especially the distribution of positive and balancing selection in populations and species. A combined approach using population genetic and phylogenetic methods to detect selective signatures can therefore be informative for identifying vaccine candidates. Parasitic Leishmania species cause the disease leishmaniasis in humans and mammalian reservoir hosts after inoculation by female phlebotomine sandflies. Like other arthropod vectors of disease agents, sandflies use salivary peptides to counteract host haemostatic and immunomodulatory responses during bloodfeeding, and these peptides are vaccine candidates because they can protect against Leishmania infection. We detected no contemporary adaptive selection on one salivary peptide, apyrase, in 20 populations of Phlebotomus ariasi, a European vector of Leishmania infantum. Maximum likelihood branch models on a gene phylogeny showed apyrase to be a single copy in P. ariasi but an ancient duplication event associated with temporary positive selection was observed in its sister group, which contains most Mediterranean vectors of L. infantum. The absence of contemporary adaptive selection on the apyrase of P. ariasi may result from this sandfly's opportunistic feeding behaviour. Our study illustrates how the molecular population genetics of arthropods can help investigate the potential of salivary peptides for disease control and for understanding geographical variation in vector competence.

  3. Spectroscopic confirmation of a galaxy cluster associated with 7C 1756+6520 at z = 1.416

    NASA Astrophysics Data System (ADS)

    Galametz, A.; Stern, D.; Stanford, S. A.; De Breuck, C.; Vernet, J.; Griffith, R. L.; Harrison, F. A.

    2010-06-01

    We present spectroscopic follow-up of an overdensity of galaxies photometrically selected to be at 1.4 < z < 2.5 found in the vicinity of the radio galaxy 7C 1756+6520 at z = 1.4156. Using the DEIMOS optical multi-object spectrograph on the Keck 2 telescope, we observed a total of 129 BzK-selected sources, comprising 82 blue, star-forming galaxy candidates (sBzK) and 47 red, passively-evolving galaxy candidates (pBzK*), as well as 11 mid-infrared selected AGN candidates. We obtain robust spectroscopic redshifts for 36 blue galaxies, 7 red galaxies and 9 AGN candidates. Assuming all foreground interlopers were identified, we find that only 16% (9%) of the sBzK (pBzK*) galaxies are at z < 1.4. Therefore, the BzK criteria are shown to be relatively robust at identifying galaxies at moderate redshifts. Twenty-one galaxies, including the radio galaxy, four additional AGN candidates and three red galaxy candidates are found with 1.4156 ± 0.025, forming a large scale structure at the redshift of the radio galaxy. Of these, eight have projected offsets <2 Mpc relative to the radio galaxy position and have velocity offsets <1000 km s-1 relative to the radio galaxy redshift. This confirms that 7C 1756+6520 is associated with a high-redshift galaxy cluster. A second compact group of four galaxies is found at z ~ 1.437, forming a sub-group offset by Δv ~ 3000 km s-1 and approximately 1.'5 east of the radio galaxy.

  4. Genomic Signatures Reveal New Evidences for Selection of Important Traits in Domestic Cattle

    PubMed Central

    Xu, Lingyang; Bickhart, Derek M.; Cole, John B.; Schroeder, Steven G.; Song, Jiuzhou; Tassell, Curtis P. Van; Sonstegard, Tad S.; Liu, George E.

    2015-01-01

    We investigated diverse genomic selections using high-density single nucleotide polymorphism data of five distinct cattle breeds. Based on allele frequency differences, we detected hundreds of candidate regions under positive selection across Holstein, Angus, Charolais, Brahman, and N'Dama. In addition to well-known genes such as KIT, MC1R, ASIP, GHR, LCORL, NCAPG, WIF1, and ABCA12, we found evidence for a variety of novel and less-known genes under selection in cattle, such as LAP3, SAR1B, LRIG3, FGF5, and NUDCD3. Selective sweeps near LAP3 were then validated by next-generation sequencing. Genome-wide association analysis involving 26,362 Holsteins confirmed that LAP3 and SAR1B were related to milk production traits, suggesting that our candidate regions were likely functional. In addition, haplotype network analyses further revealed distinct selective pressures and evolution patterns across these five cattle breeds. Our results provided a glimpse into diverse genomic selection during cattle domestication, breed formation, and recent genetic improvement. These findings will facilitate genome-assisted breeding to improve animal production and health. PMID:25431480

  5. Triton stellar occultation candidates - 1992-1994

    NASA Technical Reports Server (NTRS)

    Mcdonald, S. W.; Elliot, J. T.

    1992-01-01

    A search for Triton stellar occultation candidates for the period 1992-1994 has been completed with CCD strip-scanning observations. The search reached an R magnitude of about 17.4 and found 129 candidates within 1.5 arcsec of Triton's ephemeris during this period. Of these events, around 30 occultations are expected to be visible from the earth, indicating that a number of Triton occultation events should be visible from major observatories. Even the faintest of the present candidate events could produce useful occultation data if observed with a large enough telescope. The present astrometric accuracy is inadequate to identify which of these appulse events will produce occultations on the earth; further astrometry is needed to refine the predictions for positive occultation identification. To aid in selecting candidates for additional astrometric and photometric studies, finder charts and earth-based visibility charts for each event are included.

  6. Finding the rarest objects in the universe: A new, efficient method for discovering BL Lacertae objects

    NASA Technical Reports Server (NTRS)

    Stocke, John; Perlman, Eric; Granados, Arno; Schachter, Jonathan; Elvis, Martin; Urry, Meg; Impey, Chris; Smith, Paul

    1993-01-01

    We present a new, efficient method for discovering new BL Lac Objects based upon the results of the Einstein Extended Medium Sensitivity Survey (EMSS). We have found that all x-ray selected BL Lacs are radio emitters, and further, that in a 'color-color' diagram (radio/optical and optical/x-ray) the BL Lac Objects occupy an area distinct from both radio loud quasars and the radio quiet QSOs and Seyferts which dominate x-ray selected samples. After obtaining radio counterparts via VLA 'snapshot' observations of a large sample of unidentified x-ray sources, the list of candidates is reduced. These candidates then can be confirmed with optical spectroscopy and/or polarimetry. Since greater than 70 percent of these sources are expected to be BL Lacs, the optical observations are very efficient. We have tested this method using unidentified sources found in the Einstein Slew Survey. The 162 Slew Survey x-ray source positions were observed with the VLA in a mixed B/C configuration at 6 cm resulting in 60 detections within 1.5 position error circle radii. These x-ray/optical/radio sources were then plotted, and 40 BL Lac candidates were identified. To date, 10 candidates have been spectroscopically observed resulting in 10 new BL Lac objects! Radio flux, optical magnitude, and polarization statistics (obtained in white light with the Steward Observatory 2.3 m CCD polarimeter) for each are given.

  7. Reducing 4D CT artifacts using optimized sorting based on anatomic similarity.

    PubMed

    Johnston, Eric; Diehn, Maximilian; Murphy, James D; Loo, Billy W; Maxim, Peter G

    2011-05-01

    Four-dimensional (4D) computed tomography (CT) has been widely used as a tool to characterize respiratory motion in radiotherapy. The two most commonly used 4D CT algorithms sort images by the associated respiratory phase or displacement into a predefined number of bins, and are prone to image artifacts at transitions between bed positions. The purpose of this work is to demonstrate a method of reducing motion artifacts in 4D CT by incorporating anatomic similarity into phase or displacement based sorting protocols. Ten patient datasets were retrospectively sorted using both the displacement and phase based sorting algorithms. Conventional sorting methods allow selection of only the nearest-neighbor image in time or displacement within each bin. In our method, for each bed position either the displacement or the phase defines the center of a bin range about which several candidate images are selected. The two dimensional correlation coefficients between slices bordering the interface between adjacent couch positions are then calculated for all candidate pairings. Two slices have a high correlation if they are anatomically similar. Candidates from each bin are then selected to maximize the slice correlation over the entire data set using the Dijkstra's shortest path algorithm. To assess the reduction of artifacts, two thoracic radiation oncologists independently compared the resorted 4D datasets pairwise with conventionally sorted datasets, blinded to the sorting method, to choose which had the least motion artifacts. Agreement between reviewers was evaluated using the weighted kappa score. Anatomically based image selection resulted in 4D CT datasets with significantly reduced motion artifacts with both displacement (P = 0.0063) and phase sorting (P = 0.00022). There was good agreement between the two reviewers, with complete agreement 34 times and complete disagreement 6 times. Optimized sorting using anatomic similarity significantly reduces 4D CT motion artifacts compared to conventional phase or displacement based sorting. This improved sorting algorithm is a straightforward extension of the two most common 4D CT sorting algorithms.

  8. Transcriptome Sequencing of Lima Bean (Phaseolus lunatus) to Identify Putative Positive Selection in Phaseolus and Legumes

    PubMed Central

    Li, Fengqi; Cao, Depan; Liu, Yang; Yang, Ting; Wang, Guirong

    2015-01-01

    The identification of genes under positive selection is a central goal of evolutionary biology. Many legume species, including Phaseolus vulgaris (common bean) and Phaseolus lunatus (lima bean), have important ecological and economic value. In this study, we sequenced and assembled the transcriptome of one Phaseolus species, lima bean. A comparison with the genomes of six other legume species, including the common bean, Medicago, lotus, soybean, chickpea, and pigeonpea, revealed 15 and 4 orthologous groups with signatures of positive selection among the two Phaseolus species and among the seven legume species, respectively. Characterization of these positively selected genes using Non redundant (nr) annotation, gene ontology (GO) classification, GO term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that these genes are mostly involved in thylakoids, photosynthesis and metabolism. This study identified genes that may be related to the divergence of the Phaseolus and legume species. These detected genes are particularly good candidates for subsequent functional studies. PMID:26151849

  9. A Novel Image Recuperation Approach for Diagnosing and Ranking Retinopathy Disease Level Using Diabetic Fundus Image

    PubMed Central

    2015-01-01

    Retinal fundus images are widely used in diagnosing and providing treatment for several eye diseases. Prior works using retinal fundus images detected the presence of exudation with the aid of publicly available dataset using extensive segmentation process. Though it was proved to be computationally efficient, it failed to create a diabetic retinopathy feature selection system for transparently diagnosing the disease state. Also the diagnosis of diseases did not employ machine learning methods to categorize candidate fundus images into true positive and true negative ratio. Several candidate fundus images did not include more detailed feature selection technique for diabetic retinopathy. To apply machine learning methods and classify the candidate fundus images on the basis of sliding window a method called, Diabetic Fundus Image Recuperation (DFIR) is designed in this paper. The initial phase of DFIR method select the feature of optic cup in digital retinal fundus images based on Sliding Window Approach. With this, the disease state for diabetic retinopathy is assessed. The feature selection in DFIR method uses collection of sliding windows to obtain the features based on the histogram value. The histogram based feature selection with the aid of Group Sparsity Non-overlapping function provides more detailed information of features. Using Support Vector Model in the second phase, the DFIR method based on Spiral Basis Function effectively ranks the diabetic retinopathy diseases. The ranking of disease level for each candidate set provides a much promising result for developing practically automated diabetic retinopathy diagnosis system. Experimental work on digital fundus images using the DFIR method performs research on the factors such as sensitivity, specificity rate, ranking efficiency and feature selection time. PMID:25974230

  10. Kepler False Positive Rate & Occurrence of Earth-size and Larger Planets

    NASA Astrophysics Data System (ADS)

    Fressin, Francois; Torres, G.; Charbonneau, D.; Kepler Team

    2013-01-01

    We model the Kepler exoplanet survey targets and their background stars to estimate the occurrence of astrophysical configurations which could mimic an exoplanetary transit. Using real noise level estimates, we compute the number and the characteristics of detectable eclipsing pairs involving stars or planets. We select the fraction of those that would pass the Kepler candidate vetting procedure, including the modeling of the centroid shift of their position on the Kepler camera. By comparing their distribution with that of the Kepler Object Interests from the first 6 quarters of Kepler data, we quantify the false positive rate of Kepler, as a function of candidate planet size and period. Most importantly, this approach allows quantifying and characterizing the distribution of planets, with no assumption of any prior, as the remaining population of the Kepler candidate list minus the simulated population of alternate astrophysical causes. We study the actual detection recovery rate for Kepler that allows reproducing both the KOI size and period distribution as well as their SNR distribution. We estimate the occurrence of planets down to Earth-size, and study if their frequency is correlated with their host star spectral type. This work is supported by the Spitzer General Observer Proposal #80117 - Validating the First Habitable-Zone Planet Candidates Identified by the NASA Kepler Mission, and by the Kepler Participating Scientist Contract led by David Charbonneau, to confirm the planetary nature of candidates identified by the Kepler mission

  11. A long-term target detection approach in infrared image sequence

    NASA Astrophysics Data System (ADS)

    Li, Hang; Zhang, Qi; Wang, Xin; Hu, Chao

    2016-10-01

    An automatic target detection method used in long term infrared (IR) image sequence from a moving platform is proposed. Firstly, based on POME(the principle of maximum entropy), target candidates are iteratively segmented. Then the real target is captured via two different selection approaches. At the beginning of image sequence, the genuine target with litter texture is discriminated from other candidates by using contrast-based confidence measure. On the other hand, when the target becomes larger, we apply online EM method to estimate and update the distributions of target's size and position based on the prior detection results, and then recognize the genuine one which satisfies both the constraints of size and position. Experimental results demonstrate that the presented method is accurate, robust and efficient.

  12. Development of a Procedure for the Selection of Candidate Vessels of Opportunity in Support of the Submarine Rescue Diving and Recompression System

    DTIC Science & Technology

    2005-06-01

    ACRONYMS AHT Anchor Handling Tug AP After Perpendicular ASRV Australian Submarine Rescue Vehicle ASSET Advanced Surface Ship Evaluation Tool AUWS...Five hours after the Squalus sank, its sister ship, USS Sculpin began searching at the Squalus’ reported position prior to diving. Due to an error...ashore in recording that position, Sculpin was searching five miles from Squalus’ actual position. Finally, Ensign Ned Denby on 21 the bridge of Sculpin

  13. Relationship between amino acid changes in mitochondrial ATP6 and life-history variation in anguillid eels.

    PubMed

    Jacobsen, Magnus W; Pujolar, José Martin; Hansen, Michael M

    2015-03-01

    Mitochondrial genes are part of the oxidative phosphorylation pathway and important for energy production. Although evidence for positive selection at the mitochondrial level exists, few studies have investigated the link between amino acid changes and phenotype. Here we test the hypothesis that differences in two life-history related traits, migratory distance between spawning and foraging areas and larval phase duration, are associated with divergent selection within the mitochondrial ATP6 gene in anguillid eels. We compare amino acid changes among 18 species with the sequence of the putative ancestral species, believed to have shown short migratory distance and larval phase duration. We find positive correlations between both life-history related traits and (i) the number of amino acid changes and (ii) the strength of the combined physico-chemical and structural changes at positions previously identified as candidates for positive selection. This supports a link between genotype and phenotype driven by positive selection at ATP6. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  14. Thematic mapper studies band correlation analysis

    NASA Technical Reports Server (NTRS)

    Ungar, S. G.; Kiang, R.

    1976-01-01

    Spectral data representative of thematic mapper candidate bands 1 and 3 to 7 were obtained by selecting appropriate combinations of bands from the JSC 24 channel multispectral scanner. Of all the bands assigned, only candidate bands 4 (.74 mu to .80 mu) and 5 (.80 mu to .91 mu) showed consistently high intercorrelation from region to region and time to time. This extremely high correlation persisted when looking at the composite data set in a multitemporal, multilocation domain. The GISS investigations lend positive confirmation to the hypothesis, that TM bands 4 and 5 are redundant.

  15. First Searches for Optical Counterparts to Gravitational-wave Candidate Events

    NASA Astrophysics Data System (ADS)

    Aasi, J.; Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Accadia, T.; Acernese, F.; Adams, C.; Adams, T.; Adhikari, R. X.; Affeldt, C.; Agathos, M.; Aggarwal, N.; Aguiar, O. D.; Ajith, P.; Allen, B.; Allocca, A.; Amador Ceron, E.; Amariutei, D.; Anderson, R. A.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C.; Areeda, J.; Ast, S.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Austin, L.; Aylott, B. E.; Babak, S.; Baker, P. T.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barker, D.; Barnum, S. H.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barton, M. A.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J.; Bauchrowitz, J.; Bauer, Th. S.; Bebronne, M.; Behnke, B.; Bejger, M.; Beker, M. G.; Bell, A. S.; Bell, C.; Belopolski, I.; Bergmann, G.; Berliner, J. M.; Bertolini, A.; Bessis, D.; Betzwieser, J.; Beyersdorf, P. T.; Bhadbhade, T.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Bitossi, M.; Bizouard, M. A.; Black, E.; Blackburn, J. K.; Blackburn, L.; Blair, D.; Blom, M.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogan, C.; Bond, C.; Bondu, F.; Bonelli, L.; Bonnand, R.; Bork, R.; Born, M.; Bose, S.; Bosi, L.; Bowers, J.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brannen, C. A.; Brau, J. E.; Breyer, J.; Briant, T.; Bridges, D. O.; Brillet, A.; Brinkmann, M.; Brisson, V.; Britzger, M.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brückner, F.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Calderón Bustillo, J.; Calloni, E.; Camp, J. B.; Campsie, P.; Cannon, K. C.; Canuel, B.; Cao, J.; Capano, C. D.; Carbognani, F.; Carbone, L.; Caride, S.; Castiglia, A.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, X.; Chen, Y.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Chow, J.; Christensen, N.; Chu, Q.; Chua, S. S. Y.; Chung, S.; Ciani, G.; Clara, F.; Clark, D. E.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Colombini, M.; Constancio, M., Jr.; Conte, A.; Conte, R.; Cook, D.; Corbitt, T. R.; Cordier, M.; Cornish, N.; Corsi, A.; Costa, C. A.; Coughlin, M. W.; Coulon, J.-P.; Countryman, S.; Couvares, P.; Coward, D. M.; Cowart, M.; Coyne, D. C.; Craig, K.; Creighton, J. D. E.; Creighton, T. D.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dahl, K.; Dal Canton, T.; Damjanic, M.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Dattilo, V.; Daudert, B.; Daveloza, H.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; Dayanga, T.; De Rosa, R.; Debreczeni, G.; Degallaix, J.; Del Pozzo, W.; Deleeuw, E.; Deléglise, S.; Denker, T.; Dereli, H.; Dergachev, V.; DeRosa, R.; DeSalvo, R.; Dhurandhar, S.; Di Fiore, L.; Di Lieto, A.; Di Palma, I.; Di Virgilio, A.; Díaz, M.; Dietz, A.; Dmitry, K.; Donovan, F.; Dooley, K. L.; Doravari, S.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Dumas, J.-C.; Dwyer, S.; Eberle, T.; Edwards, M.; Effler, A.; Ehrens, P.; Eichholz, J.; Eikenberry, S. S.; Endrőczi, G.; Essick, R.; Etzel, T.; Evans, K.; Evans, M.; Evans, T.; Factourovich, M.; Fafone, V.; Fairhurst, S.; Fang, Q.; Farr, B.; Farr, W.; Favata, M.; Fazi, D.; Fehrmann, H.; Feldbaum, D.; Ferrante, I.; Ferrini, F.; Fidecaro, F.; Finn, L. S.; Fiori, I.; Fisher, R.; Flaminio, R.; Foley, E.; Foley, S.; Forsi, E.; Forte, L. A.; Fotopoulos, N.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frede, M.; Frei, M.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fujimoto, M.-K.; Fulda, P.; Fyffe, M.; Gair, J.; Gammaitoni, L.; Garcia, J.; Garufi, F.; Gehrels, N.; Gemme, G.; Genin, E.; Gennai, A.; Gergely, L.; Ghosh, S.; Giaime, J. A.; Giampanis, S.; Giardina, K. D.; Giazotto, A.; Gil-Casanova, S.; Gill, C.; Gleason, J.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gordon, N.; Gorodetsky, M. L.; Gossan, S.; Goßler, S.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greenhalgh, R. J. S.; Gretarsson, A. M.; Griffo, C.; Grote, H.; Grover, K.; Grunewald, S.; Guidi, G. M.; Guido, C.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hall, B.; Hall, E.; Hammer, D.; Hammond, G.; Hanke, M.; Hanks, J.; Hanna, C.; Hanson, J.; Harms, J.; Harry, G. M.; Harry, I. W.; Harstad, E. D.; Hartman, M. T.; Haughian, K.; Hayama, K.; Heefner, J.; Heidmann, A.; Heintze, M.; Heitmann, H.; Hello, P.; Hemming, G.; Hendry, M.; Heng, I. S.; Heptonstall, A. W.; Heurs, M.; Hild, S.; Hoak, D.; Hodge, K. A.; Holt, K.; Holtrop, M.; Hong, T.; Hooper, S.; Horrom, T.; Hosken, D. J.; Hough, J.; Howell, E. J.; Hu, Y.; Hua, Z.; Huang, V.; Huerta, E. A.; Hughey, B.; Husa, S.; Huttner, S. H.; Huynh, M.; Huynh-Dinh, T.; Iafrate, J.; Ingram, D. R.; Inta, R.; Isogai, T.; Ivanov, A.; Iyer, B. R.; Izumi, K.; Jacobson, M.; James, E.; Jang, H.; Jang, Y. J.; Jaranowski, P.; Jiménez-Forteza, F.; Johnson, W. W.; Jones, D.; Jones, D. I.; Jones, R.; Jonker, R. J. G.; Ju, L.; K, Haris; Kalmus, P.; Kalogera, V.; Kandhasamy, S.; Kang, G.; Kanner, J. B.; Kasprzack, M.; Kasturi, R.; Katsavounidis, E.; Katzman, W.; Kaufer, H.; Kaufman, K.; Kawabe, K.; Kawamura, S.; Kawazoe, F.; Kéfélian, F.; Keitel, D.; Kelley, D. B.; Kells, W.; Keppel, D. G.; Khalaidovski, A.; Khalili, F. Y.; Khazanov, E. A.; Kim, B. K.; Kim, C.; Kim, K.; Kim, N.; Kim, W.; Kim, Y.-M.; King, E. J.; King, P. J.; Kinzel, D. L.; Kissel, J. S.; Klimenko, S.; Kline, J.; Koehlenbeck, S.; Kokeyama, K.; Kondrashov, V.; Koranda, S.; Korth, W. Z.; Kowalska, I.; Kozak, D.; Kremin, A.; Kringel, V.; Krishnan, B.; Królak, A.; Kucharczyk, C.; Kudla, S.; Kuehn, G.; Kumar, A.; Kumar, P.; Kumar, R.; Kurdyumov, R.; Kwee, P.; Landry, M.; Lantz, B.; Larson, S.; Lasky, P. D.; Lawrie, C.; Lazzarini, A.; Le Roux, A.; Leaci, P.; Lebigot, E. O.; Lee, C.-H.; Lee, H. K.; Lee, H. M.; Lee, J.; Lee, J.; Leonardi, M.; Leong, J. R.; Leroy, N.; Letendre, N.; Levine, B.; Lewis, J. B.; Lhuillier, V.; Li, T. G. F.; Lin, A. C.; Littenberg, T. B.; Litvine, V.; Liu, F.; Liu, H.; Liu, Y.; Liu, Z.; Lloyd, D.; Lockerbie, N. A.; Lockett, V.; Lodhia, D.; Loew, K.; Logue, J.; Lombardi, A. L.; Lorenzini, M.; Loriette, V.; Lormand, M.; Losurdo, G.; Lough, J.; Luan, J.; Lubinski, M. J.; Lück, H.; Lundgren, A. P.; Macarthur, J.; Macdonald, E.; Machenschalk, B.; MacInnis, M.; Macleod, D. M.; Magana-Sandoval, F.; Mageswaran, M.; Mailand, K.; Majorana, E.; Maksimovic, I.; Malvezzi, V.; Man, N.; Manca, G. M.; Mandel, I.; Mandic, V.; Mangano, V.; Mantovani, M.; Marchesoni, F.; Marion, F.; Márka, S.; Márka, Z.; Markosyan, A.; Maros, E.; Marque, J.; Martelli, F.; Martin, I. W.; Martin, R. M.; Martinelli, L.; Martynov, D.; Marx, J. N.; Mason, K.; Masserot, A.; Massinger, T. J.; Matichard, F.; Matone, L.; Matzner, R. A.; Mavalvala, N.; May, G.; Mazumder, N.; Mazzolo, G.; McCarthy, R.; McClelland, D. E.; McGuire, S. C.; McIntyre, G.; McIver, J.; Meacher, D.; Meadors, G. D.; Mehmet, M.; Meidam, J.; Meier, T.; Melatos, A.; Mendell, G.; Mercer, R. A.; Meshkov, S.; Messenger, C.; Meyer, M. S.; Miao, H.; Michel, C.; Mikhailov, E. E.; Milano, L.; Miller, J.; Minenkov, Y.; Mingarelli, C. M. F.; Mitra, S.; Mitrofanov, V. P.; Mitselmakher, G.; Mittleman, R.; Moe, B.; Mohan, M.; Mohapatra, S. R. P.; Mokler, F.; Moraru, D.; Moreno, G.; Morgado, N.; Mori, T.; Morriss, S. R.; Mossavi, K.; Mours, B.; Mow-Lowry, C. M.; Mueller, C. L.; Mueller, G.; Mukherjee, S.; Mullavey, A.; Munch, J.; Murphy, D.; Murray, P. G.; Mytidis, A.; Nagy, M. F.; Nanda Kumar, D.; Nardecchia, I.; Nash, T.; Naticchioni, L.; Nayak, R.; Necula, V.; Neri, I.; Newton, G.; Nguyen, T.; Nishida, E.; Nishizawa, A.; Nitz, A.; Nocera, F.; Nolting, D.; Normandin, M. E.; Nuttall, L. K.; Ochsner, E.; O'Dell, J.; Oelker, E.; Ogin, G. H.; Oh, J. J.; Oh, S. H.; Ohme, F.; Oppermann, P.; O'Reilly, B.; Ortega Larcher, W.; O'Shaughnessy, R.; Osthelder, C.; Ottaway, D. J.; Ottens, R. S.; Ou, J.; Overmier, H.; Owen, B. J.; Padilla, C.; Pai, A.; Palomba, C.; Pan, Y.; Pankow, C.; Paoletti, F.; Paoletti, R.; Papa, M. A.; Paris, H.; Pasqualetti, A.; Passaquieti, R.; Passuello, D.; Pedraza, M.; Peiris, P.; Penn, S.; Perreca, A.; Phelps, M.; Pichot, M.; Pickenpack, M.; Piergiovanni, F.; Pierro, V.; Pinard, L.; Pindor, B.; Pinto, I. M.; Pitkin, M.; Poeld, J.; Poggiani, R.; Poole, V.; Poux, C.; Predoi, V.; Prestegard, T.; Price, L. R.; Prijatelj, M.; Principe, M.; Privitera, S.; Prix, R.; Prodi, G. A.; Prokhorov, L.; Puncken, O.; Punturo, M.; Puppo, P.; Quetschke, V.; Quintero, E.; Quitzow-James, R.; Raab, F. J.; Rabeling, D. S.; Rácz, I.; Radkins, H.; Raffai, P.; Raja, S.; Rajalakshmi, G.; Rakhmanov, M.; Ramet, C.; Rapagnani, P.; Raymond, V.; Re, V.; Reed, C. M.; Reed, T.; Regimbau, T.; Reid, S.; Reitze, D. H.; Ricci, F.; Riesen, R.; Riles, K.; Robertson, N. A.; Robinet, F.; Rocchi, A.; Roddy, S.; Rodriguez, C.; Rodruck, M.; Roever, C.; Rolland, L.; Rollins, J. G.; Romano, J. D.; Romano, R.; Romanov, G.; Romie, J. H.; Rosińska, D.; Rowan, S.; Rüdiger, A.; Ruggi, P.; Ryan, K.; Salemi, F.; Sammut, L.; Sandberg, V.; Sanders, J.; Sannibale, V.; Santiago-Prieto, I.; Saracco, E.; Sassolas, B.; Sathyaprakash, B. S.; Saulson, P. R.; Savage, R.; Schilling, R.; Schnabel, R.; Schofield, R. M. S.; Schreiber, E.; Schuette, D.; Schulz, B.; Schutz, B. F.; Schwinberg, P.; Scott, J.; Scott, S. M.; Seifert, F.; Sellers, D.; Sengupta, A. S.; Sentenac, D.; Sergeev, A.; Shaddock, D.; Shah, S.; Shahriar, M. S.; Shaltev, M.; Shapiro, B.; Shawhan, P.; Shoemaker, D. H.; Sidery, T. L.; Siellez, K.; Siemens, X.; Sigg, D.; Simakov, D.; Singer, A.; Singer, L.; Sintes, A. M.; Skelton, G. R.; Slagmolen, B. J. J.; Slutsky, J.; Smith, J. R.; Smith, M. R.; Smith, R. J. E.; Smith-Lefebvre, N. D.; Soden, K.; Son, E. J.; Sorazu, B.; Souradeep, T.; Sperandio, L.; Staley, A.; Steinert, E.; Steinlechner, J.; Steinlechner, S.; Steplewski, S.; Stevens, D.; Stochino, A.; Stone, R.; Strain, K. A.; Strigin, S.; Stroeer, A. S.; Sturani, R.; Stuver, A. L.; Summerscales, T. Z.; Susmithan, S.; Sutton, P. J.; Swinkels, B.; Szeifert, G.; Tacca, M.; Talukder, D.; Tang, L.; Tanner, D. B.; Tarabrin, S. P.; Taylor, R.; ter Braack, A. P. M.; Thirugnanasambandam, M. P.; Thomas, M.; Thomas, P.; Thorne, K. A.; Thorne, K. S.; Thrane, E.; Tiwari, V.; Tokmakov, K. V.; Tomlinson, C.; Toncelli, A.; Tonelli, M.; Torre, O.; Torres, C. V.; Torrie, C. I.; Travasso, F.; Traylor, G.; Tse, M.; Ugolini, D.; Unnikrishnan, C. S.; Vahlbruch, H.; Vajente, G.; Vallisneri, M.; van den Brand, J. F. J.; Van Den Broeck, C.; van der Putten, S.; van der Sluys, M. V.; van Heijningen, J.; van Veggel, A. A.; Vass, S.; Vasúth, M.; Vaulin, R.; Vecchio, A.; Vedovato, G.; Veitch, J.; Veitch, P. J.; Venkateswara, K.; Verkindt, D.; Verma, S.; Vetrano, F.; Viceré, A.; Vincent-Finley, R.; Vinet, J.-Y.; Vitale, S.; Vlcek, B.; Vo, T.; Vocca, H.; Vorvick, C.; Vousden, W. D.; Vrinceanu, D.; Vyachanin, S. P.; Wade, A.; Wade, L.; Wade, M.; Waldman, S. J.; Walker, M.; Wallace, L.; Wan, Y.; Wang, J.; Wang, M.; Wang, X.; Wanner, A.; Ward, R. L.; Was, M.; Weaver, B.; Wei, L.-W.; Weinert, M.; Weinstein, A. J.; Weiss, R.; Welborn, T.; Wen, L.; Wessels, P.; West, M.; Westphal, T.; Wette, K.; Whelan, J. T.; Whitcomb, S. E.; White, D. J.; Whiting, B. F.; Wibowo, S.; Wiesner, K.; Wilkinson, C.; Williams, L.; Williams, R.; Williams, T.; Willis, J. L.; Willke, B.; Wimmer, M.; Winkelmann, L.; Winkler, W.; Wipf, C. C.; Wittel, H.; Woan, G.; Worden, J.; Yablon, J.; Yakushin, I.; Yamamoto, H.; Yancey, C. C.; Yang, H.; Yeaton-Massey, D.; Yoshida, S.; Yum, H.; Yvert, M.; Zadrożny, A.; Zanolin, M.; Zendri, J.-P.; Zhang, F.; Zhang, L.; Zhao, C.; Zhu, H.; Zhu, X. J.; Zotov, N.; Zucker, M. E.; Zweizig, J.; LIGO Scientific Collaboration; Virgo Collaboration; Akerlof, C.; Baltay, C.; Bloom, J. S.; Cao, Y.; Cenko, S. B.; Ćwiek, A.; Ćwiok, M.; Dhillon, V.; Fox, D. B.; Gal-Yam, A.; Kasliwal, M. M.; Klotz, A.; Laas-Bourez, M.; Laher, R. R.; Law, N. M.; Majcher, A.; Małek, K.; Mankiewicz, L.; Nawrocki, K.; Nissanke, S.; Nugent, P. E.; Ofek, E. O.; Opiela, R.; Piotrowski, L.; Poznanski, D.; Rabinowitz, D.; Rapoport, S.; Richards, J. W.; Schmidt, B.; Siudek, M.; Sokołowski, M.; Steele, I. A.; Sullivan, M.; Żarnecki, A. F.; Zheng, W.

    2014-03-01

    During the Laser Interferometer Gravitational-wave Observatory and Virgo joint science runs in 2009-2010, gravitational wave (GW) data from three interferometer detectors were analyzed within minutes to select GW candidate events and infer their apparent sky positions. Target coordinates were transmitted to several telescopes for follow-up observations aimed at the detection of an associated optical transient. Images were obtained for eight such GW candidates. We present the methods used to analyze the image data as well as the transient search results. No optical transient was identified with a convincing association with any of these candidates, and none of the GW triggers showed strong evidence for being astrophysical in nature. We compare the sensitivities of these observations to several model light curves from possible sources of interest, and discuss prospects for future joint GW-optical observations of this type.

  16. First Searches for Optical Counterparts to Gravitational-Wave Candidate Events

    NASA Technical Reports Server (NTRS)

    Aasi, J.; Abadie, J.; Abbott, B. P.; Abbott, R.; Abbott, T.; Abernathy, M. R.; Accadia, T.; Acernese, F.; Adams, C.; Adams, T.; hide

    2014-01-01

    During the Laser Interferometer Gravitational-wave Observatory and Virgo joint science runs in 2009-2010, gravitational wave (GW) data from three interferometer detectors were analyzed within minutes to select GW candidate events and infer their apparent sky positions. Target coordinates were transmitted to several telescopes for follow-up observations aimed at the detection of an associated optical transient. Images were obtained for eight such GW candidates. We present the methods used to analyze the image data as well as the transient search results. No optical transient was identified with a convincing association with any of these candidates, and none of the GW triggers showed strong evidence for being astrophysical in nature. We compare the sensitivities of these observations to several model light curves from possible sources of interest, and discuss prospects for future joint GW-optical observations of this type.

  17. VizieR Online Data Catalog: New gamma-ray blazar candidates in the 3PBC (Maselli+, 2013)

    NASA Astrophysics Data System (ADS)

    Maselli, A.; Massaro, F.; Cusumano, G.; D'Abrusco, R.; La Parola, V.; Paggi, A.; Segreto, A.; Smith, H. A.; Tosti, G.

    2013-06-01

    We searched for γ-ray blazar candidates among the 382 unidentified hard X-ray sources of the third Palermo BAT Catalog (3PBC) obtained from the analysis of 66 months of Swift Burst Alert Telescope (BAT) survey data and listing 1586 sources. We adopted a recently developed association method based on the peculiar infrared colors that characterize the γ-ray blazars included in the second catalog of active galactic nuclei detected by the Fermi Large Area Telescope. We used this method exploiting the data of the all-sky survey performed by the Wide-field Infrared Survey Explorer (WISE) to establish correspondences between unidentified 3PBC sources and WISE γ-ray blazar candidates located within the BAT positional uncertainty region at a 99% confidence level. We obtained a preliminary list of candidates for which we analyzed all the available data in the Swift archive to complement the information in the literature and in the radio, infrared, and optical catalogs with the information on their optical-UV and soft X-ray emission. Requiring the presence of radio and soft X-ray counterparts consistent with the infrared positions of the selected WISE sources, as well as a blazar-like radio morphology, we finally obtained a list of 24 γ-ray blazar candidates. (2 data files).

  18. Searching for New γ-Ray Blazar Candidates in the Third Palermo BAT Hard X-Ray Catalog with WISE

    NASA Astrophysics Data System (ADS)

    Maselli, A.; Massaro, F.; Cusumano, G.; D'Abrusco, R.; La Parola, V.; Paggi, A.; Segreto, A.; Smith, Howard A.; Tosti, G.

    2013-06-01

    We searched for γ-ray blazar candidates among the 382 unidentified hard X-ray sources of the third Palermo BAT Catalog (3PBC) obtained from the analysis of 66 months of Swift Burst Alert Telescope (BAT) survey data and listing 1586 sources. We adopted a recently developed association method based on the peculiar infrared colors that characterize the γ-ray blazars included in the second catalog of active galactic nuclei detected by the Fermi Large Area Telescope. We used this method exploiting the data of the all-sky survey performed by the Wide-field Infrared Survey Explorer (WISE) to establish correspondences between unidentified 3PBC sources and WISE γ-ray blazar candidates located within the BAT positional uncertainty region at a 99% confidence level. We obtained a preliminary list of candidates for which we analyzed all the available data in the Swift archive to complement the information in the literature and in the radio, infrared, and optical catalogs with the information on their optical-UV and soft X-ray emission. Requiring the presence of radio and soft X-ray counterparts consistent with the infrared positions of the selected WISE sources, as well as a blazar-like radio morphology, we finally obtained a list of 24 γ-ray blazar candidates.

  19. Selection for population-specific adaptation shaped patterns of variation in the photoperiod pathway genes in Arabidopsis lyrata during post-glacial colonization.

    PubMed

    Mattila, Tiina M; Aalto, Esa A; Toivainen, Tuomas; Niittyvuopio, Anne; Piltonen, Susanna; Kuittinen, Helmi; Savolainen, Outi

    2016-01-01

    Spatially varying selection can lead to population-specific adaptation, which is often recognized at the phenotypic level; however, the genetic evidence is weaker in many groups of organisms. In plants, environmental shifts that occur due to colonization of a novel environment may require adaptive changes in the timing of growth and flowering, which are often governed by location-specific environmental cues such as day length. We studied locally varying selection in 19 flowering time loci in nine populations of the perennial herb Arabidopsis lyrata, which has a wide but patchy distribution in temperate and boreal regions of the northern hemisphere. The populations differ in their recent population demographic and colonization histories and current environmental conditions, especially in the growing season length. We searched for population-specific molecular signatures of directional selection by comparing a set of candidate flowering time loci with a genomic reference set within each population using multiple approaches and contrasted the patterns of different populations. The candidate loci possessed approximately 20% of the diversity of the reference loci. On average the flowering time loci had more rare alleles (a smaller Tajima's D) and an excess of highly differentiated sites relative to the reference, suggesting positive selection. The strongest signal of selection was detected in photoperiodic pathway loci in the colonizing populations of Northwestern Europe, whereas no evidence of positive selection was detected in the Central European populations. These findings emphasized the population-specific nature of selection and suggested that photoperiodic adaptation was important during postglacial colonization of the species. © 2015 John Wiley & Sons Ltd.

  20. Use of the Interview in Resident Candidate Selection: A Review of the Literature.

    PubMed

    Stephenson-Famy, Alyssa; Houmard, Brenda S; Oberoi, Sidharth; Manyak, Anton; Chiang, Seine; Kim, Sara

    2015-12-01

    Although the resident candidate interview is costly and time-consuming for both applicants and programs, it is considered critically important for resident selection. Noncognitive attributes, including communication skills and professionalism, can be assessed by the personal interview. We conducted a review of the literature on the residency interview to identify the interview characteristics used for resident selection and to ascertain to what extent the interview yields information that predicts future performance. We searched PubMed and Scopus using the following search terms: residency, internship, interview, selection, and performance. We extracted information on characteristics of the interview process, including type of interview format, measures taken to minimize bias by interviewers, and testing of other clinical/surgical skills. We identified 104 studies that pertained to the resident selection interview, with highly varied interview formats and assessment tools. A positive correlation was demonstrated between a medical school academic record and the interview, especially for unblinded interview formats. A total of 34 studies attempted to correlate interview score with performance in residency, with mixed results. We also identified a number of studies that included personality testing, clinical skills testing, or surgical skills testing. Our review identified a wide variety of approaches to the selection interview and a range of factors that have been studied to assess its effectiveness. More research needs to be done not only to address and ascertain appropriate interview formats that predict positive performance in residency, but also to determine interview factors that can predict both residents' "success" and program attrition.

  1. Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

    PubMed

    Eckert, Andrew J; Wegrzyn, Jill L; Pande, Barnaly; Jermstad, Kathleen D; Lee, Jennifer M; Liechty, John D; Tearse, Brandon R; Krutovsky, Konstantin V; Neale, David B

    2009-09-01

    Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular diversity in forest tree genomes. Here, we report an analysis of diversity and divergence for a set of 121 cold-hardiness candidate genes in coastal Douglas fir (Pseudotsuga menziesii var. menziesii). Application of several different tests for neutrality, including those that incorporated demographic models, revealed signatures of selection consistent with selective sweeps at three to eight loci, depending upon the severity of a bottleneck event and the method used to detect selection. Given the high levels of recombination, these candidate genes are likely to be closely linked to the target of selection if not the genes themselves. Putative homologs in Arabidopsis act primarily to stabilize the plasma membrane and protect against denaturation of proteins at freezing temperatures. These results indicate that surveys of nucleotide diversity and divergence, when framed within the context of further association mapping experiments, will come full circle with respect to their utility in the dissection of complex phenotypic traits into their genetic components.

  2. Revealing phenotype-associated functional differences by genome-wide scan of ancient haplotype blocks

    PubMed Central

    Onuki, Ritsuko; Yamaguchi, Rui; Shibuya, Tetsuo; Kanehisa, Minoru; Goto, Susumu

    2017-01-01

    Genome-wide scans for positive selection have become important for genomic medicine, and many studies aim to find genomic regions affected by positive selection that are associated with risk allele variations among populations. Most such studies are designed to detect recent positive selection. However, we hypothesize that ancient positive selection is also important for adaptation to pathogens, and has affected current immune-mediated common diseases. Based on this hypothesis, we developed a novel linkage disequilibrium-based pipeline, which aims to detect regions associated with ancient positive selection across populations from single nucleotide polymorphism (SNP) data. By applying this pipeline to the genotypes in the International HapMap project database, we show that genes in the detected regions are enriched in pathways related to the immune system and infectious diseases. The detected regions also contain SNPs reported to be associated with cancers and metabolic diseases, obesity-related traits, type 2 diabetes, and allergic sensitization. These SNPs were further mapped to biological pathways to determine the associations between phenotypes and molecular functions. Assessments of candidate regions to identify functions associated with variations in incidence rates of these diseases are needed in the future. PMID:28445522

  3. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

  4. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

  5. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 3 2011-01-01 2011-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

  6. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

  7. 15 CFR 922.21 - Selection of active candidates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Selection of active candidates. 922.21... Selection of active candidates. (a) The Secretary shall, from time to time, select a limited number of sites from the SEL for Active Candidate consideration based on a preliminary assessment of the designation...

  8. Thermal Characterization of Adhesive

    NASA Technical Reports Server (NTRS)

    Spomer, Ken A.

    1999-01-01

    The current Space Shuttle Reusable Solid Rocket Motor (RSRM) nozzle adhesive bond system is being replaced due to obsolescence. Down-selection and performance testing of the structural adhesives resulted in the selection of two candidate replacement adhesives, Resin Technology Group's Tiga 321 and 3M's EC2615XLW. This paper describes rocket motor testing of these two adhesives. Four forty-pound charge motors were fabricated in configurations that would allow side by side comparison testing of the candidate replacement adhesives and the current RSRM adhesives. The motors provided an environment where the thermal performance of adhesives in flame surface bondlines was compared. Results of the FPC testing show that: 1) The phenolic char depths on radial bond lines is approximately the same and vary depending on the position in the blast tube regardless of which adhesive was used; 2) The adhesive char depth of the candidate replacement adhesives is less than the char depth of the current adhesives; 3) The heat-affected depth of the candidate replacement adhesives is less than the heat-affected depth of the current adhesives; and 4) The ablation rates for both replacement adhesives are slower than that of the current adhesives.

  9. Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

    PubMed

    Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

    2012-01-01

    The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

  10. confFuse: High-Confidence Fusion Gene Detection across Tumor Entities.

    PubMed

    Huang, Zhiqin; Jones, David T W; Wu, Yonghe; Lichter, Peter; Zapatka, Marc

    2017-01-01

    Background: Fusion genes play an important role in the tumorigenesis of many cancers. Next-generation sequencing (NGS) technologies have been successfully applied in fusion gene detection for the last several years, and a number of NGS-based tools have been developed for identifying fusion genes during this period. Most fusion gene detection tools based on RNA-seq data report a large number of candidates (mostly false positives), making it hard to prioritize candidates for experimental validation and further analysis. Selection of reliable fusion genes for downstream analysis becomes very important in cancer research. We therefore developed confFuse, a scoring algorithm to reliably select high-confidence fusion genes which are likely to be biologically relevant. Results: confFuse takes multiple parameters into account in order to assign each fusion candidate a confidence score, of which score ≥8 indicates high-confidence fusion gene predictions. These parameters were manually curated based on our experience and on certain structural motifs of fusion genes. Compared with alternative tools, based on 96 published RNA-seq samples from different tumor entities, our method can significantly reduce the number of fusion candidates (301 high-confidence from 8,083 total predicted fusion genes) and keep high detection accuracy (recovery rate 85.7%). Validation of 18 novel, high-confidence fusions detected in three breast tumor samples resulted in a 100% validation rate. Conclusions: confFuse is a novel downstream filtering method that allows selection of highly reliable fusion gene candidates for further downstream analysis and experimental validations. confFuse is available at https://github.com/Zhiqin-HUANG/confFuse.

  11. Physical Characteristics and Performance of Japanese Top-Level American Football Players.

    PubMed

    Yamashita, Daichi; Asakura, Masaki; Ito, Yoshihiko; Yamada, Shinzo; Yamada, Yosuke

    2017-09-01

    Yamashita, D, Asakura, M, Ito, Y, Yamada, S, and Yamada, Y. Physical characteristics and performance of Japanese top-level American football players. J Strength Cond Res 31(9): 2455-2461, 2017-This study aimed to compare the physical characteristics and performance between top-level nonprofessional football players in Japan and National Football League (NFL) Combine invited players and between top-level and middle-level players in Japan to determine the factors that enhance performance in international and national competitions. A total of 168 American football players (>20 years) in Japan participated in an anthropometric (height and weight) and physical (vertical jump, long jump, 40-yard dash, pro-agility shuttle, 3-cone drill, and bench press repetition test) measurement program based on the NFL Combine program to compete in the selection of candidates for the Senior World Championship. All players were categorized into 1 of the 3 position groups based on playing position: skill players, big skill players, and linemen. Japanese players were additionally categorized into selected and nonselected players for the second tryout. The NFL Combine candidates had significantly better performance than selected Japanese players on all variables except on performance related to quickness among the 3 position groups. Compared with nonselected players, selected Japanese skill players had better performance in the 40-yard dash and bench press test and big skill players had better performance in the vertical jump, broad jump, and 40-yard dash. Selected and nonselected Japanese linemen were not different in any measurements. These results showed the challenges in American football in Japan, which include not only improving physical performance of top-level players, but also increasing the number of football players with good physical performance.

  12. Physical Characteristics and Performance of Japanese Top-Level American Football Players

    PubMed Central

    Asakura, Masaki; Ito, Yoshihiko; Yamada, Shinzo; Yamada, Yosuke

    2017-01-01

    Abstract Yamashita, D, Asakura, M, Ito, Y, Yamada, S, and Yamada, Y. Physical characteristics and performance of Japanese top-level American football players. J Strength Cond Res 31(9): 2455–2461, 2017—This study aimed to compare the physical characteristics and performance between top-level nonprofessional football players in Japan and National Football League (NFL) Combine invited players and between top-level and middle-level players in Japan to determine the factors that enhance performance in international and national competitions. A total of 168 American football players (>20 years) in Japan participated in an anthropometric (height and weight) and physical (vertical jump, long jump, 40-yard dash, pro-agility shuttle, 3-cone drill, and bench press repetition test) measurement program based on the NFL Combine program to compete in the selection of candidates for the Senior World Championship. All players were categorized into 1 of the 3 position groups based on playing position: skill players, big skill players, and linemen. Japanese players were additionally categorized into selected and nonselected players for the second tryout. The NFL Combine candidates had significantly better performance than selected Japanese players on all variables except on performance related to quickness among the 3 position groups. Compared with nonselected players, selected Japanese skill players had better performance in the 40-yard dash and bench press test and big skill players had better performance in the vertical jump, broad jump, and 40-yard dash. Selected and nonselected Japanese linemen were not different in any measurements. These results showed the challenges in American football in Japan, which include not only improving physical performance of top-level players, but also increasing the number of football players with good physical performance. PMID:28052052

  13. The ethno-racial segmentation jobs: The impacts of the occupational stereotypes on hiring decisions.

    PubMed

    Ndobo, André; Faure, Alice; Boisselier, Jeanne; Giannaki, Stella

    2017-10-12

    This paper considers both the division of the labor market and the occupational stereotyping as explanatory mechanisms of discrimination in hiring decisions. It hypothesized that recruiters would favor candidates applying for a position that is stereotypically identified with their ethnic category. We solicited 146 recruiters in order to evaluate the hireability of either a native-born or an immigrant candidate, either competent or not competent, for either a prestigious or a low-skill occupation, and to justify their decision in writing. As predicted, both the hireability ratings and the narrative comments produced by recruiters showed that native-born applicants were preferred for prestigious jobs while immigrants tended to be selected more often for low-skill positions.The discussion addresses various issues related to decision-making in recruitment settings.

  14. Automated corresponding point candidate selection for image registration using wavelet transformation neurla network with rotation invariant inputs and context information about neighboring candidates

    NASA Astrophysics Data System (ADS)

    Okumura, Hiroshi; Suezaki, Masashi; Sueyasu, Hideki; Arai, Kohei

    2003-03-01

    An automated method that can select corresponding point candidates is developed. This method has the following three features: 1) employment of the RIN-net for corresponding point candidate selection; 2) employment of multi resolution analysis with Haar wavelet transformation for improvement of selection accuracy and noise tolerance; 3) employment of context information about corresponding point candidates for screening of selected candidates. Here, the 'RIN-net' means the back-propagation trained feed-forward 3-layer artificial neural network that feeds rotation invariants as input data. In our system, pseudo Zernike moments are employed as the rotation invariants. The RIN-net has N x N pixels field of view (FOV). Some experiments are conducted to evaluate corresponding point candidate selection capability of the proposed method by using various kinds of remotely sensed images. The experimental results show the proposed method achieves fewer training patterns, less training time, and higher selection accuracy than conventional method.

  15. SS 383: A NEW S-TYPE YELLOW SYMBIOTIC STAR?

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

    Baella, N. O.; Pereira, C. B.; Miranda, L. F.

    Symbiotic stars are key objects in understanding the formation and evolution of interacting binary systems, and are probably the progenitors of Type Ia supernovae. However, the number of known symbiotic stars is much lower than predicted. We aim to search for new symbiotic stars, with particular emphasis on the S-type yellow symbiotic stars, in order to determine their total population, evolutionary timescales, and physical properties. The Two Micron All Sky Survey (2MASS) (J – H) versus (H – K {sub s}) color-color diagram has been previously used to identify new symbiotic star candidates and show that yellow symbiotics are locatedmore » in a particular region of that diagram. Candidate symbiotic stars are selected on the basis of their locus in the 2MASS (J – H) versus (H – K {sub s}) diagram and the presence of Hα line emission in the Stephenson and Sanduleak Hα survey. This diagram separates S-type yellow symbiotic stars from the rest of the S-type symbiotic stars, allowing us to select candidate yellow symbiotics. To establish the true nature of the candidates, intermediate-resolution spectroscopy is obtained. We have identified the Hα emission line source SS 383 as an S-type yellow symbiotic candidate by its position in the 2MASS color-color diagram. The optical spectrum of SS 383 shows Balmer, He I, He II, and [O III] emission lines, in combination with TiO absorption bands that confirm its symbiotic nature. The derived electron density (≅10{sup 8-9} cm{sup –3}), He I emission line intensity ratios, and position in the [O III] λ5007/Hβ versus [O III] λ4363/Hγ diagram indicate that SS 383 is an S-type symbiotic star, with a probable spectral type of K7-M0 deduced for its cool component based on TiO indices. The spectral type and the position of SS 383 (corrected for reddening) in the 2MASS color-color diagram strongly suggest that SS 383 is an S-type yellow symbiotic. Our result points out that the 2MASS color-color diagram is a powerful tool in identifying new S-type yellow symbiotics.« less

  16. Detection of Fundus Lesions Using Classifier Selection

    NASA Astrophysics Data System (ADS)

    Nagayoshi, Hiroto; Hiramatsu, Yoshitaka; Sako, Hiroshi; Himaga, Mitsutoshi; Kato, Satoshi

    A system for detecting fundus lesions caused by diabetic retinopathy from fundus images is being developed. The system can screen the images in advance in order to reduce the inspection workload on doctors. One of the difficulties that must be addressed in completing this system is how to remove false positives (which tend to arise near blood vessels) without decreasing the detection rate of lesions in other areas. To overcome this difficulty, we developed classifier selection according to the position of a candidate lesion, and we introduced new features that can distinguish true lesions from false positives. A system incorporating classifier selection and these new features was tested in experiments using 55 fundus images with some lesions and 223 images without lesions. The results of the experiments confirm the effectiveness of the proposed system, namely, degrees of sensitivity and specificity of 98% and 81%, respectively.

  17. LOW FALSE POSITIVE RATE OF KEPLER CANDIDATES ESTIMATED FROM A COMBINATION OF SPITZER AND FOLLOW-UP OBSERVATIONS

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

    Désert, Jean-Michel; Brown, Timothy M.; Charbonneau, David

    NASA’s Kepler mission has provided several thousand transiting planet candidates during the 4 yr of its nominal mission, yet only a small subset of these candidates have been confirmed as true planets. Therefore, the most fundamental question about these candidates is the fraction of bona fide planets. Estimating the rate of false positives of the overall Kepler sample is necessary to derive the planet occurrence rate. We present the results from two large observational campaigns that were conducted with the Spitzer Space Telescope during the the Kepler mission. These observations are dedicated to estimating the false positive rate (FPR) amongmore » the Kepler candidates. We select a sub-sample of 51 candidates, spanning wide ranges in stellar, orbital, and planetary parameter space, and we observe their transits with Spitzer at 4.5 μm. We use these observations to measures the candidate’s transit depths and infrared magnitudes. An authentic planet produces an achromatic transit depth (neglecting the modest effect of limb darkening). Conversely a bandpass-dependent depth alerts us to the potential presence of a blending star that could be the source of the observed eclipse: a false positive scenario. For most of the candidates (85%), the transit depths measured with Kepler are consistent with the transit depths measured with Spitzer as expected for planetary objects, while we find that the most discrepant measurements are due to the presence of unresolved stars that dilute the photometry. The Spitzer constraints on their own yield FPRs between 5% and depending on the Kepler Objects of Interest. By considering the population of the Kepler field stars, and by combining follow-up observations (imaging) when available, we find that the overall FPR of our sample is low. The measured upper limit on the FPR of our sample is 8.8% at a confidence level of 3σ. This observational result, which uses the achromatic property of planetary transit signals that is not investigated by the Kepler observations, provides an independent indication that Kepler’s FPR is low.« less

  18. Pilot selection and training

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Personality and situational factors relevant to individual and group performance in highly demanding environments, such as those faced by astronauts or by jet transport crew, are discussed. It is emphasized that although technical competence and proficiency in pilot selection are prerequisites for safety, operating a modern jet transport is a group endeavor that requires the effective coordination of the entire crew. A self-report test battery for measuring positive and negative personality traits of pilot candidates, termed the Personal Characteristics Inventory, is described.

  19. Automatic detection of regions of interest in mammographic images

    NASA Astrophysics Data System (ADS)

    Cheng, Erkang; Ling, Haibin; Bakic, Predrag R.; Maidment, Andrew D. A.; Megalooikonomou, Vasileios

    2011-03-01

    This work is a part of our ongoing study aimed at comparing the topology of anatomical branching structures with the underlying image texture. Detection of regions of interest (ROIs) in clinical breast images serves as the first step in development of an automated system for image analysis and breast cancer diagnosis. In this paper, we have investigated machine learning approaches for the task of identifying ROIs with visible breast ductal trees in a given galactographic image. Specifically, we have developed boosting based framework using the AdaBoost algorithm in combination with Haar wavelet features for the ROI detection. Twenty-eight clinical galactograms with expert annotated ROIs were used for training. Positive samples were generated by resampling near the annotated ROIs, and negative samples were generated randomly by image decomposition. Each detected ROI candidate was given a confidences core. Candidate ROIs with spatial overlap were merged and their confidence scores combined. We have compared three strategies for elimination of false positives. The strategies differed in their approach to combining confidence scores by summation, averaging, or selecting the maximum score.. The strategies were compared based upon the spatial overlap with annotated ROIs. Using a 4-fold cross-validation with the annotated clinical galactographic images, the summation strategy showed the best performance with 75% detection rate. When combining the top two candidates, the selection of maximum score showed the best performance with 96% detection rate.

  20. Looking into flowering time in almond (Prunus dulcis (Mill) D. A. Webb): the candidate gene approach.

    PubMed

    Silva, C; Garcia-Mas, J; Sánchez, A M; Arús, P; Oliveira, M M

    2005-03-01

    Blooming time is one of the most important agronomic traits in almond. Biochemical and molecular events underlying flowering regulation must be understood before methods to stimulate late flowering can be developed. Attempts to elucidate the genetic control of this process have led to the identification of a major gene (Lb) and quantitative trait loci (QTLs) linked to observed phenotypic differences, but although this gene and these QTLs have been placed on the Prunus reference genetic map, their sequences and specific functions remain unknown. The aim of our investigation was to associate these loci with known genes using a candidate gene approach. Two almond cDNAs and eight Prunus expressed sequence tags were selected as candidate genes (CGs) since their sequences were highly identical to those of flowering regulatory genes characterized in other species. The CGs were amplified from both parental lines of the mapping population using specific primers. Sequence comparison revealed DNA polymorphisms between the parental lines, mainly of the single nucleotide type. Polymorphisms were used to develop co-dominant cleaved amplified polymorphic sequence markers or length polymorphisms based on insertion/deletion events for mapping the candidate genes on the Prunus reference map. Ten candidate genes were assigned to six linkage groups in the Prunus genome. The positions of two of these were compatible with the regions where two QTLs for blooming time were detected. One additional candidate was localized close to the position of the Evergrowing gene, which determines a non-deciduous behaviour in peach.

  1. Detecting Signatures of Positive Selection along Defined Branches of a Population Tree Using LSD.

    PubMed

    Librado, Pablo; Orlando, Ludovic

    2018-06-01

    Identifying the genomic basis underlying local adaptation is paramount to evolutionary biology, and bears many applications in the fields of conservation biology, crop, and animal breeding, as well as personalized medicine. Although many approaches have been developed to detect signatures of positive selection within single populations and population pairs, the increasing wealth of high-throughput sequencing data requires improved methods capable of handling multiple, and ideally large number of, populations in a single analysis. In this study, we introduce LSD (levels of exclusively shared differences), a fast and flexible framework to perform genome-wide selection scans, along the internal and external branches of a given population tree. We use forward simulations to demonstrate that LSD can identify branches targeted by positive selection with remarkable sensitivity and specificity. We illustrate a range of potential applications by analyzing data from the 1000 Genomes Project and uncover a list of adaptive candidates accompanying the expansion of anatomically modern humans out of Africa and their spread to Europe.

  2. Women in Community College Leadership Roles. ERIC Digest.

    ERIC Educational Resources Information Center

    Getskow, Veronica

    At community colleges, women currently comprise approximately 20% of all chief executive officer (CEO) positions. The single most important source from which new community college CEO candidates are selected, however, is the pool of deans of instruction and since 21% of current deans are women, it is likely that these numbers will rise. Moreover,…

  3. Rural and Small School Principal Candidates: Perspectives of Hiring Superintendents

    ERIC Educational Resources Information Center

    Cruzeiro, Patricia A.; Boone, Mike

    2009-01-01

    This article reports the results of an inquiry into the dynamics of principal selection in rural school districts in two mid-American states with high numbers of rural schools. The study focuses on two questions: (1) are rural school districts experiencing a shortage of qualified applicants for vacant principal's positions; and (2) what…

  4. Integrating evolutionary and functional approaches to infer adaptation at specific loci.

    PubMed

    Storz, Jay F; Wheat, Christopher W

    2010-09-01

    Inferences about adaptation at specific loci are often exclusively based on the static analysis of DNA sequence variation. Ideally,population-genetic evidence for positive selection serves as a stepping-off point for experimental studies to elucidate the functional significance of the putatively adaptive variation. We argue that inferences about adaptation at specific loci are best achieved by integrating the indirect, retrospective insights provided by population-genetic analyses with the more direct, mechanistic insights provided by functional experiments. Integrative studies of adaptive genetic variation may sometimes be motivated by experimental insights into molecular function, which then provide the impetus to perform population genetic tests to evaluate whether the functional variation is of adaptive significance. In other cases, studies may be initiated by genome scans of DNA variation to identify candidate loci for recent adaptation. Results of such analyses can then motivate experimental efforts to test whether the identified candidate loci do in fact contribute to functional variation in some fitness-related phenotype. Functional studies can provide corroborative evidence for positive selection at particular loci, and can potentially reveal specific molecular mechanisms of adaptation.

  5. Tracing evolutionary relicts of positive selection on eight malaria-related immune genes in mammals.

    PubMed

    Huang, Bing-Hong; Liao, Pei-Chun

    2015-07-01

    Plasmodium-induced malaria widely infects primates and other mammals. Multiple past studies have revealed that positive selection could be the main evolutionary force triggering the genetic diversity of anti-malaria resistance-associated genes in human or primates. However, researchers focused most of their attention on the infra-generic and intra-specific genome evolution rather than analyzing the complete evolutionary history of mammals. Here we extend previous research by testing the evolutionary link of natural selection on eight candidate genes associated with malaria resistance in mammals. Three of the eight genes were detected to be affected by recombination, including TNF-α, iNOS and DARC. Positive selection was detected in the rest five immunogenes multiple times in different ancestral lineages of extant species throughout the mammalian evolution. Signals of positive selection were exposed in four malaria-related immunogenes in primates: CCL2, IL-10, HO1 and CD36. However, selection signals of G6PD have only been detected in non-primate eutherians. Significantly higher evolutionary rates and more radical amino acid replacement were also detected in primate CD36, suggesting its functional divergence from other eutherians. Prevalent positive selection throughout the evolutionary trajectory of mammalian malaria-related genes supports the arms race evolutionary hypothesis of host genetic response of mammalian immunogenes to infectious pathogens. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  6. Immune-Related Functions of the Hivep Gene Family in East African Cichlid Fishes

    PubMed Central

    Diepeveen, Eveline T.; Roth, Olivia; Salzburger, Walter

    2013-01-01

    Immune-related genes are often characterized by adaptive protein evolution. Selection on immune genes can be particularly strong when hosts encounter novel parasites, for instance, after the colonization of a new habitat or upon the exploitation of vacant ecological niches in an adaptive radiation. We examined a set of new candidate immune genes in East African cichlid fishes. More specifically, we studied the signatures of selection in five paralogs of the human immunodeficiency virus type I enhancer-binding protein (Hivep) gene family, tested their involvement in the immune defense, and related our results to explosive speciation and adaptive radiation events in cichlids. We found signatures of long-term positive selection in four Hivep paralogs and lineage-specific positive selection in Hivep3b in two radiating cichlid lineages. Exposure of the cichlid Astatotilapia burtoni to a vaccination with Vibrio anguillarum bacteria resulted in a positive correlation between immune response parameters and expression levels of three Hivep loci. This work provides the first evidence for a role of Hivep paralogs in teleost immune defense and links the signatures of positive selection to host–pathogen interactions within an adaptive radiation. PMID:24142922

  7. 14 CFR 1214.1106 - Selection of astronaut candidates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Selection of astronaut candidates. 1214.1106 Section 1214.1106 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate Recruitment and Selection Program § 1214.1106 Selection of astronaut...

  8. SEARCHING FOR NEW {gamma}-RAY BLAZAR CANDIDATES IN THE THIRD PALERMO BAT HARD X-RAY CATALOG WITH WISE

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

    Maselli, A.; Cusumano, G.; La Parola, V.

    We searched for {gamma}-ray blazar candidates among the 382 unidentified hard X-ray sources of the third Palermo BAT Catalog (3PBC) obtained from the analysis of 66 months of Swift Burst Alert Telescope (BAT) survey data and listing 1586 sources. We adopted a recently developed association method based on the peculiar infrared colors that characterize the {gamma}-ray blazars included in the second catalog of active galactic nuclei detected by the Fermi Large Area Telescope. We used this method exploiting the data of the all-sky survey performed by the Wide-field Infrared Survey Explorer (WISE) to establish correspondences between unidentified 3PBC sources andmore » WISE {gamma}-ray blazar candidates located within the BAT positional uncertainty region at a 99% confidence level. We obtained a preliminary list of candidates for which we analyzed all the available data in the Swift archive to complement the information in the literature and in the radio, infrared, and optical catalogs with the information on their optical-UV and soft X-ray emission. Requiring the presence of radio and soft X-ray counterparts consistent with the infrared positions of the selected WISE sources, as well as a blazar-like radio morphology, we finally obtained a list of 24 {gamma}-ray blazar candidates.« less

  9. Use of the Interview in Resident Candidate Selection: A Review of the Literature

    PubMed Central

    Stephenson-Famy, Alyssa; Houmard, Brenda S.; Oberoi, Sidharth; Manyak, Anton; Chiang, Seine; Kim, Sara

    2015-01-01

    Background Although the resident candidate interview is costly and time-consuming for both applicants and programs, it is considered critically important for resident selection. Noncognitive attributes, including communication skills and professionalism, can be assessed by the personal interview. Objective We conducted a review of the literature on the residency interview to identify the interview characteristics used for resident selection and to ascertain to what extent the interview yields information that predicts future performance. Methods We searched PubMed and Scopus using the following search terms: residency, internship, interview, selection, and performance. We extracted information on characteristics of the interview process, including type of interview format, measures taken to minimize bias by interviewers, and testing of other clinical/surgical skills. Results We identified 104 studies that pertained to the resident selection interview, with highly varied interview formats and assessment tools. A positive correlation was demonstrated between a medical school academic record and the interview, especially for unblinded interview formats. A total of 34 studies attempted to correlate interview score with performance in residency, with mixed results. We also identified a number of studies that included personality testing, clinical skills testing, or surgical skills testing. Conclusions Our review identified a wide variety of approaches to the selection interview and a range of factors that have been studied to assess its effectiveness. More research needs to be done not only to address and ascertain appropriate interview formats that predict positive performance in residency, but also to determine interview factors that can predict both residents' “success” and program attrition. PMID:26692964

  10. Signatures of positive selection and local adaptation to urbanization in white-footed mice (Peromyscus leucopus).

    PubMed

    Harris, Stephen E; Munshi-South, Jason

    2017-11-01

    Urbanization significantly alters natural ecosystems and has accelerated globally. Urban wildlife populations are often highly fragmented by human infrastructure, and isolated populations may adapt in response to local urban pressures. However, relatively few studies have identified genomic signatures of adaptation in urban animals. We used a landscape genomic approach to examine signatures of selection in urban populations of white-footed mice (Peromyscus leucopus) in New York City. We analysed 154,770 SNPs identified from transcriptome data from 48 P. leucopus individuals from three urban and three rural populations and used outlier tests to identify evidence of urban adaptation. We accounted for demography by simulating a neutral SNP data set under an inferred demographic history as a null model for outlier analysis. We also tested whether candidate genes were associated with environmental variables related to urbanization. In total, we detected 381 outlier loci and after stringent filtering, identified and annotated 19 candidate loci. Many of the candidate genes were involved in metabolic processes and have well-established roles in metabolizing lipids and carbohydrates. Our results indicate that white-footed mice in New York City are adapting at the biomolecular level to local selective pressures in urban habitats. Annotation of outlier loci suggests selection is acting on metabolic pathways in urban populations, likely related to novel diets in cities that differ from diets in less disturbed areas. © 2017 John Wiley & Sons Ltd.

  11. Molecular evolution of candidate male reproductive genes in the brown algal model Ectocarpus.

    PubMed

    Lipinska, Agnieszka P; Van Damme, Els J M; De Clerck, Olivier

    2016-01-05

    Evolutionary studies of genes that mediate recognition between sperm and egg contribute to our understanding of reproductive isolation and speciation. Surface receptors involved in fertilization are targets of sexual selection, reinforcement, and other evolutionary forces including positive selection. This observation was made across different lineages of the eukaryotic tree from land plants to mammals, and is particularly evident in free-spawning animals. Here we use the brown algal model species Ectocarpus (Phaeophyceae) to investigate the evolution of candidate gamete recognition proteins in a distant major phylogenetic group of eukaryotes. Male gamete specific genes were identified by comparing transcriptome data covering different stages of the Ectocarpus life cycle and screened for characteristics expected from gamete recognition receptors. Selected genes were sequenced in a representative number of strains from distant geographical locations and varying stages of reproductive isolation, to search for signatures of adaptive evolution. One of the genes (Esi0130_0068) showed evidence of selective pressure. Interestingly, that gene displayed domain similarities to the receptor for egg jelly (REJ) protein involved in sperm-egg recognition in sea urchins. We have identified a male gamete specific gene with similarity to known gamete recognition receptors and signatures of adaptation. Altogether, this gene could contribute to gamete interaction during reproduction as well as reproductive isolation in Ectocarpus and is therefore a good candidate for further functional evaluation.

  12. Innovation in values based public health nursing student selection: A qualitative evaluation of candidate and selection panel member perspectives.

    PubMed

    McGraw, Caroline; Abbott, Stephen; Brook, Judy

    2018-02-19

    Values based recruitment emerges from the premise that a high degree of value congruence, or the extent to which an individual's values are similar to those of the health organization in which they work, leads to organizational effectiveness. The aim of this evaluation was to explore how candidates and selection panel members experienced and perceived innovative methods of values based public health nursing student selection. The evaluation was framed by a qualitative exploratory design involving semi-structured interviews and a group exercise. Data were thematically analyzed. Eight semi-structured interviews were conducted with selection panel members. Twenty-two successful candidates took part in a group exercise. The use of photo elicitation interviews and situational judgment questions in the context of selection to a university-run public health nursing educational program was explored. While candidates were ambivalent about the use of photo elicitation interviews, with some misunderstanding the task, selection panel members saw the benefits for improving candidate expression and reducing gaming and deception. Situational interview questions were endorsed by candidates and selection panel members due to their fidelity to real-life problems and the ability of panel members to discern value congruence from candidates' responses. Both techniques offered innovative solutions to candidate selection for entry to the public health nursing education program. © 2018 Wiley Periodicals, Inc.

  13. Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences.

    PubMed

    Colonna, Vincenza; Ayub, Qasim; Chen, Yuan; Pagani, Luca; Luisi, Pierre; Pybus, Marc; Garrison, Erik; Xue, Yali; Tyler-Smith, Chris; Abecasis, Goncalo R; Auton, Adam; Brooks, Lisa D; DePristo, Mark A; Durbin, Richard M; Handsaker, Robert E; Kang, Hyun Min; Marth, Gabor T; McVean, Gil A

    2014-06-30

    Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.

  14. Artepillin C induces selective oxidative stress and inhibits migration and invasion in a comprehensive panel of human cervical cancer cell lines.

    PubMed

    Souza, Raquel Pantarotto; de Souza Bonfim-Mendonca, Patricia; Damke, Gabrielle Marconi Zago Ferreira; De Assis Carvalho, Analine Rosa Barquez; Ratti, Bianca Altrao; de Oliveira Dembogurski, Djaceli Sampaio; da Silva, Vania Ramos Sela; Silva, Sueli Oliveira; da Silva, Denise Brentan; Bruschi, Marcos Luciano; Maria-Engler, Silvya Stuchi; Consolaro, Marcia Edilaine Lopes

    2018-06-03

    Artepillin C (3,5-diprenyl-4-hydroxycinnamic acid) is the main bioactive component of Brazilian green propolis, and possesses, among other things, anticancer properties. However, to the best of our knowledge, there are no studies of artepillin C in cervical cancer. To explore a new therapeutic candidate for cervical cancer, we have evaluated the effects of artepillin C on cellular viability in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16- and 18-positive) and C33A (HPV-negative) cells compared to a spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that artepillin C had a selective effect on cellular viability and could induce apoptosis possibly by intrinsic pathway, likely a result of oxidative stress, in all cancer-derived cell lines but not in HaCaT. Additionally, artepillin C was able to inhibit the migration and invasion of cancer cells. Thus, artepillin C appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV types. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Psychometric Personality Differences Between Candidates in Astronaut Selection.

    PubMed

    Mittelstädt, Justin M; Pecena, Yvonne; Oubaid, Viktor; Maschke, Peter

    This paper investigates personality traits as potential factors for success in an astronaut selection by comparing personality profiles of unsuccessful and successful astronaut candidates in different phases of the ESA selection procedure. It is further addressed whether personality traits could predict an overall assessment rating at the end of the selection. In 2008/2009, ESA performed an astronaut selection with 902 candidates who were either psychologically recommended for mission training (N = 46) or failed in basic aptitude (N = 710) or Assessment Center and interview testing (N = 146). Candidates completed the Temperament Structure Scales (TSS) and the NEO Personality Inventory Revised (NEO-PI-R). Those candidates who failed in basic aptitude testing showed higher levels of Neuroticism (M = 49.8) than the candidates who passed that phase (M = 45.4 and M = 41.6). Additionally, candidates who failed in basic testing had lower levels of Agreeableness (M = 132.9) than recommended candidates (M = 138.1). TSS scales for Achievement (r = 0.19) and Vitality (r = 0.18) showed a significant correlation with the overall assessment rating given by a panel board after a final interview. Results indicate that a personality profile similar to Helmreich's "Right Stuff" is beneficial in astronaut selection. Influences of test anxiety on performance are discussed. Mittelstädt JM, Pecena Y, Oubaid V, Maschke P. Psychometric personality differences between candidates in astronaut selection. Aerosp Med Hum Perform. 2016; 87(11):933-939.

  16. A long-term target detection approach in infrared image sequence

    NASA Astrophysics Data System (ADS)

    Li, Hang; Zhang, Qi; Li, Yuanyuan; Wang, Liqiang

    2015-12-01

    An automatic target detection method used in long term infrared (IR) image sequence from a moving platform is proposed. Firstly, based on non-linear histogram equalization, target candidates are coarse-to-fine segmented by using two self-adapt thresholds generated in the intensity space. Then the real target is captured via two different selection approaches. At the beginning of image sequence, the genuine target with litter texture is discriminated from other candidates by using contrast-based confidence measure. On the other hand, when the target becomes larger, we apply online EM method to iteratively estimate and update the distributions of target's size and position based on the prior detection results, and then recognize the genuine one which satisfies both the constraints of size and position. Experimental results demonstrate that the presented method is accurate, robust and efficient.

  17. Thermal Characterization of Epoxy Adhesive by Hotfire Testing

    NASA Technical Reports Server (NTRS)

    Spomer, Ken A.; Haddock, M. Reed; McCool, Alex (Technical Monitor)

    2001-01-01

    This paper describes subscale solid-rocket motor hot-fire testing of epoxy adhesives in flame surface bondlines to evaluate heat-affected depth, char depth and ablation rate. Hot-fire testing is part of an adhesive down-selection program on the Space Shuttle Solid Rocket Motor Nozzle to provide additional confidence in the down-selected adhesives. The current nozzle structural adhesive bond system is being replaced due to obsolescence. Prior to hot-fire testing, adhesives were tested for chemical, physical and mechanical properties, which resulted in the selection of two potential replacement adhesives, Resin Technology Group's TIGA 321 and 3M's EC2615XLW. Hot-fire testing consisted of four forty-pound charge (FPC) motors fabricated in configurations that would allow side-by-side comparison testing of the candidate replacement adhesives with the current RSRM adhesives. Results of the FPC motor testing show that: 1) the phenolic char depths on radial bondlines is approximately the same and vary depending on the position in the blast tube regardless of which adhesive was used, 2) the replacement candidate adhesive char depths are equivalent to the char depths of the current adhesives, 3) the heat-affected depths of the candidate and current adhesives are equivalent, and 4) the ablation rates for both replacement adhesives were equivalent to the current adhesives.

  18. Lung nodule detection from CT scans using 3D convolutional neural networks without candidate selection

    NASA Astrophysics Data System (ADS)

    Jenuwine, Natalia M.; Mahesh, Sunny N.; Furst, Jacob D.; Raicu, Daniela S.

    2018-02-01

    Early detection of lung nodules from CT scans is key to improving lung cancer treatment, but poses a significant challenge for radiologists due to the high throughput required of them. Computer-Aided Detection (CADe) systems aim to automatically detect these nodules with computer algorithms, thus improving diagnosis. These systems typically use a candidate selection step, which identifies all objects that resemble nodules, followed by a machine learning classifier which separates true nodules from false positives. We create a CADe system that uses a 3D convolutional neural network (CNN) to detect nodules in CT scans without a candidate selection step. Using data from the LIDC database, we train a 3D CNN to analyze subvolumes from anywhere within a CT scan and output the probability that each subvolume contains a nodule. Once trained, we apply our CNN to detect nodules from entire scans, by systematically dividing the scan into overlapping subvolumes which we input into the CNN to obtain the corresponding probabilities. By enabling our network to process an entire scan, we expect to streamline the detection process while maintaining its effectiveness. Our results imply that with continued training using an iterative training scheme, the one-step approach has the potential to be highly effective.

  19. Sustainable diversity. This year's Top 25 minority Executives in Healthcare highlights leadership diversity, but some question the true level of inclusion.

    PubMed

    Kirchheimer, Barbara

    2008-04-07

    While more minority candidates are moving into top healthcare positions, many challenges remain. One is to address true inclusion, an expert says. And Andrea Price, left, selected as one of Modem Healthcare's Top 25 Minority Executives in Healthcare, says minorities can have a hard time rising to top positions. "The industry needs to understand that everyone doesn't start off on the same playing field," she says.

  20. Ambiguity resolution in systems using Omega for position location

    NASA Technical Reports Server (NTRS)

    Frenkel, G.; Gan, D. G.

    1974-01-01

    The lane ambiguity problem prevents the utilization of the Omega system for many applications such as locating buoys and balloons. The method of multiple lines of position introduced herein uses signals from four or more Omega stations for ambiguity resolution. The coordinates of the candidate points are determined first through the use of the Newton iterative procedure. Subsequently, a likelihood function is generated for each point, and the ambiguity is resolved by selecting the most likely point. The method was tested through simulation.

  1. Lessons learned from selecting and testing spaceflight potentiometers

    NASA Technical Reports Server (NTRS)

    Iskenderian, T.

    1994-01-01

    A solar array drive (SAD) was designed for operation on the TOPEX/POSEIDON spacecraft that was launched in August, 1992. The experience gained in selecting, specifying, testing to failure, and redesigning its position sensor produced valuable lessons for future component selection and qualification. Issues of spaceflight heritage, cost/benefit/risk assessment, and component specification are addressed. It was found that costly schedule and budget overruns may have been avoided if the capability of the candidate sensors to meet requirements had been more critically examined prior to freezing the design. The use of engineering models and early qualification tests is also recommended.

  2. Pursuing Excellence: The Power of Selection Science to Provide Meaningful Data and Enhance Efficiency in Selecting Surgical Trainees.

    PubMed

    Gardner, Aimee K; Dunkin, Brian J

    2018-05-01

    As current screening methods for selecting surgical trainees are receiving increasing scrutiny, development of a more efficient and effective selection system is needed. We describe the process of creating an evidence-based selection system and examine its impact on screening efficiency, faculty perceptions, and improving representation of underrepresented minorities. The program partnered with an expert in organizational science to identify fellowship position requirements and associated competencies. Situational judgment tests, personality profiles, structured interviews, and technical skills assessments were used to measure these competencies. The situational judgment test and personality profiles were administered online and used to identify candidates to invite for on-site structured interviews and skills testing. A final rank list was created based on all data points and their respective importance. All faculty completed follow-up surveys regarding their perceptions of the process. Candidate demographic and experience data were pulled from the application website. Fifty-five of 72 applicants met eligibility requirements and were invited to take the online assessment, with 50 (91%) completing it. Average time to complete was 42 ± 12 minutes. Eighteen applicants (35%) were invited for on-site structured interviews and skills testing-a greater than 50% reduction in number of invites compared to prior years. Time estimates reveal that the process will result in a time savings of 68% for future iterations, compared to traditional methodologies. Fellowship faculty (N = 5) agreed on the value and efficiency of the process. Underrepresented minority candidates increased from an initial 70% to 92% being invited for an interview and ranked using the new screening tools. Applying selection science to the process of choosing surgical trainees is feasible, efficient, and well-received by faculty for making selection decisions.

  3. Recent Coselection in Human Populations Revealed by Protein–Protein Interaction Network

    PubMed Central

    Qian, Wei; Zhou, Hang; Tang, Kun

    2015-01-01

    Genome-wide scans for signals of natural selection in human populations have identified a large number of candidate loci that underlie local adaptations. This is surprising given the relatively short evolutionary time since the divergence of the human population. One hypothesis that has not been formally examined is whether and how the recent human evolution may have been shaped by coselection in the context of complex molecular interactome. In this study, genome-wide signals of selection were scanned in East Asians, Europeans, and Africans using 1000 Genome data, and subsequently mapped onto the protein–protein interaction (PPI) network. We found that the candidate genes of recent positive selection localized significantly closer to each other on the PPI network than expected, revealing substantial clustering of selected genes. Furthermore, gene pairs of shorter PPI network distances showed higher similarities of their recent evolutionary paths than those further apart. Last, subnetworks enriched with recent coselection signals were identified, which are substantially overrepresented in biological pathways related to signal transduction, neurogenesis, and immune function. These results provide the first genome-wide evidence for association of recent selection signals with the PPI network, shedding light on the potential mechanisms of recent coselection in the human genome. PMID:25532814

  4. Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.

    PubMed

    Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

    2007-01-01

    T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.

  5. Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling

    PubMed Central

    Liston, Adrian; Hardy, Kristine; Pittelkow, Yvonne; Wilson, Susan R; Makaroff, Lydia E; Fahrer, Aude M; Goodnow, Christopher C

    2007-01-01

    Background T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non-obese diabetic (NOD) mouse strain Results Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data, we identify differentially expressed candidate genes, including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusion The data provide a molecular map of the negative selection response in vivo and, by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death. PMID:17239257

  6. Evaluating candidate reactions to selection practices using organisational justice theory.

    PubMed

    Patterson, Fiona; Zibarras, Lara; Carr, Victoria; Irish, Bill; Gregory, Simon

    2011-03-01

    This study aimed to examine candidate reactions to selection practices in postgraduate medical training using organisational justice theory. We carried out three independent cross-sectional studies using samples from three consecutive annual recruitment rounds. Data were gathered from candidates applying for entry into UK general practice (GP) training during 2007, 2008 and 2009. Participants completed an evaluation questionnaire immediately after the short-listing stage and after the selection centre (interview) stage. Participants were doctors applying for GP training in the UK. Main outcome measures were participants' evaluations of the selection methods and perceptions of the overall fairness of each selection stage (short-listing and selection centre). A total of 23,855 evaluation questionnaires were completed (6893 in 2007, 10,497 in 2008 and 6465 in 2009). Absolute levels of perceptions of fairness of all the selection methods at both the short-listing and selection centre stages were consistently high over the 3years. Similarly, all selection methods were considered to be job-related by candidates. However, in general, candidates considered the selection centre stage to be significantly fairer than the short-listing stage. Of all the selection methods, the simulated patient consultation completed at the selection centre stage was rated as the most job-relevant. This is the first study to use a model of organisational justice theory to evaluate candidate reactions during selection into postgraduate specialty training. The high-fidelity selection methods are consistently viewed as more job-relevant and fairer by candidates. This has important implications for the design of recruitment systems for all specialties and, potentially, for medical school admissions. Using this approach, recruiters can systematically compare perceptions of the fairness and job relevance of various selection methods. © Blackwell Publishing Ltd 2011.

  7. Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians

    PubMed Central

    Chen, Yuan; Xue, Yali; Luiselli, Donata; Tyler-Smith, Chris; Pagani, Luca; Ayub, Qasim

    2015-01-01

    Vitamin D and folate are activated and degraded by sunlight, respectively, and the physiological processes they control are likely to have been targets of selection as humans expanded from Africa into Eurasia. We investigated signals of positive selection in gene sets involved in the metabolism, regulation and action of these two vitamins in worldwide populations sequenced by Phase I of the 1000 Genomes Project. Comparing allele frequency-spectrum-based summary statistics between these gene sets and matched control genes, we observed a selection signal specific to East Asians for a gene set associated with vitamin D action in bones. The selection signal was mainly driven by three genes CXXC finger protein 1 (CXXC1), low density lipoprotein receptor-related protein 5 (LRP5) and runt-related transcription factor 2 (RUNX2). Examination of population differentiation and haplotypes allowed us to identify several candidate causal regulatory variants in each gene. Four of these candidate variants (one each in CXXC1 and RUNX2 and two in LRP5) had a >70% derived allele frequency in East Asians, but were present at lower (20–60%) frequency in Europeans as well, suggesting that the adaptation might have been part of a common response to climatic and dietary changes as humans expanded out of Africa, with implications for their role in vitamin D-dependent bone mineralization and osteoporosis insurgence. We also observed haplotype sharing between East Asians, Finns and an extinct archaic human (Denisovan) sample at the CXXC1 locus, which is best explained by incomplete lineage sorting. PMID:26719974

  8. Do surgeon interviewers have human factor-related issues during the long day UK National Trauma and Orthopaedic specialty recruitment process?

    PubMed

    Scrimgeour, D S G; Higgins, J; Bucknall, V; Arnett, R; Featherstone, C R; Cleland, J; Lee, A J; Brennan, P A

    2018-03-05

    The role that human factors (HF) play in contributing to medical error is increasingly being recognised by healthcare professionals. Surprisingly, much less is known about the possible effects of HF including boredom, fatigue and organisational influences, on performance outside of the clinical environment such as examining or assessing candidates in other high stakes situations. The authors used a validated 38 response questionnaire based around the HF analysis and classification system (HFACS) to assess factors including stress and pressure, care and support and working within the rules for surgeon interviewers at the UK national trainee selection process in Trauma and Orthopaedic surgery. 121 completed questionnaires were analysed (86% response rate). No statistically significant differences were found between interviewer experience, grade or role at the interview and the mean scores obtained for all four factor items. Overall interviewers had a positive experience during national selection with mean factor scores ranging from 3.80 to 3.98 (out of a maximum satisfaction score of 5). Careful planning by organisations and recognising the importance of the human element are essential to ensure assessors are looked after properly during high stakes assessment processes. Our data suggests that a positive experience for examiners is likely to benefit candidate performance and contribute to a fair and reliable recruitment process. The relationship between examiner experience and candidate performance merits further investigation. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  9. Touching the base: heart-warming ads from the 2016 U.S. election moved viewers to partisan tears.

    PubMed

    Seibt, Beate; Schubert, Thomas W; Zickfeld, Janis H; Fiske, Alan P

    2018-03-07

    Some political ads used in the 2016 U.S. election evoked feelings colloquially known as being moved to tears. We conceptualise this phenomenon as a positive social emotion that appraises and motivates communal relations, is accompanied by physical sensations (including lachrymation, piloerection, chest warmth), and often labelled metaphorically. We surveyed U.S. voters in the fortnight before the 2016 U.S. election. Selected ads evoked the emotion completely and reliably, but in a partisan fashion: Clinton voters were moved to tears by three selected Clinton ads, and Trump voters were moved to tears by two Trump ads. Viewers were much less moved by ads of the candidate they did not support. Being moved to tears predicted intention to vote for the candidate depicted. We conclude that some contemporary political advertising is able to move its audience to tears, and thereby motivates support.

  10. VizieR Online Data Catalog: UV-excess quasar candidates (Moreau+, 1995)

    NASA Astrophysics Data System (ADS)

    Moreau, O.; Reboul, H.

    1995-01-01

    We have developed a procedure (so called PAPA) for measurement of magnitudes (about 0.1mag accurate) and positions (with accuracy better than 0.5arcsec) of all the objects present on photographic plates digitised with the MAMA machine. This homogeneous procedure was applied to four Schmidt plates - in U, B and twice V - covering the Palomar-Sky-Survey field PS +30deg 13h00m, a 40-square-degree zone at the North Galactic Pole. A general-interest exhaustive tricolour catalogue of 19542 star-like objects down to V=20.0 has been produced and we selected 1681 quasar candidates on the basis of ultraviolet excess and, when possible, absence of any measurable proper motion. The astrometric and photometric catalogue of the candidates is given in electronic form. (4 data files).

  11. Hunting the most distant stars in the Milky Way: methods and initial results

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

    Bochanski, John J.; Willman, Beth; West, Andrew A.

    2014-04-01

    We present a new catalog of 404 M giant candidates found in the UKIRT Infrared Deep Sky Survey (UKIDSS). The 2400 deg{sup 2} available in the UKIDSS Large Area Survey Data Release 8 resolve M giants through a volume four times larger than that of the entire Two Micron All Sky Survey. Combining near-infrared photometry with optical photometry and proper motions from the Sloan Digital Sky Survey yields an M giant candidate catalog with less M dwarf and quasar contamination than previous searches for similarly distant M giants. Extensive follow-up spectroscopy of this sample will yield the first map ofmore » our Galaxy's outermost reaches over a large area of sky. Our initial spectroscopic follow-up of ∼30 bright candidates yielded the positive identification of five M giants at distances ∼20-90 kpc. Each of these confirmed M giants have positions and velocities consistent with the Sagittarius stream. The fainter M giant candidates in our sample have estimated photometric distances ∼200 kpc (assuming [Fe/H] = 0.0), but require further spectroscopic verification. The photometric distance estimates extend beyond the Milky Way's virial radius, and increase by ∼50% for each 0.5 dex decrease in assumed [Fe/H]. Given the number of M giant candidates, initial selection efficiency, and volume surveyed, we loosely estimate that at least one additional Sagittarius-like accretion event could have contributed to the hierarchical build-up of the Milky Way's outer halo.« less

  12. Relative extended haplotype homozygosity signals across breeds reveal dairy and beef specific signatures of selection.

    PubMed

    Bomba, Lorenzo; Nicolazzi, Ezequiel L; Milanesi, Marco; Negrini, Riccardo; Mancini, Giordano; Biscarini, Filippo; Stella, Alessandra; Valentini, Alessio; Ajmone-Marsan, Paolo

    2015-04-02

    A number of methods are available to scan a genome for selection signatures by evaluating patterns of diversity within and between breeds. Among these, "extended haplotype homozygosity" (EHH) is a reliable approach to detect genome regions under recent selective pressure. The objective of this study was to use this approach to identify regions that are under recent positive selection and shared by the most representative Italian dairy and beef cattle breeds. A total of 3220 animals from Italian Holstein (2179), Italian Brown (775), Simmental (493), Marchigiana (485) and Piedmontese (379) breeds were genotyped with the Illumina BovineSNP50 BeadChip v.1. After standard quality control procedures, genotypes were phased and core haplotypes were identified. The decay of linkage disequilibrium (LD) for each core haplotype was assessed by measuring the EHH. Since accurate estimates of local recombination rates were not available, relative EHH (rEHH) was calculated for each core haplotype. Genomic regions that carry frequent core haplotypes and with significant rEHH values were considered as candidates for recent positive selection. Candidate regions were aligned across to identify signals shared by dairy or beef cattle breeds. Overall, 82 and 87 common regions were detected among dairy and beef cattle breeds, respectively. Bioinformatic analysis identified 244 and 232 genes in these common genomic regions. Gene annotation and pathway analysis showed that these genes are involved in molecular functions that are biologically related to milk or meat production. Our results suggest that a multi-breed approach can lead to the identification of genomic signatures in breeds of cattle that are selected for the same production goal and thus to the localisation of genomic regions of interest in dairy and beef production.

  13. Presidential Search: Selecting the Top Candidates.

    ERIC Educational Resources Information Center

    Stead, Ronald S.

    1988-01-01

    The winnowing of a large number of presidential candidates to a smaller, more manageable group is discussed. Initial screening, candidate information, evaluation form, reference checking, and selecting interviewees are described. (MLW)

  14. What Do Job Candidates Consider Important When Assessing an Academic Position?

    ERIC Educational Resources Information Center

    Honeycutt, Earl D., Jr.; Thelen, Shawn T.

    2016-01-01

    Surveyed job candidates and academic mavens differ in regard to what the candidates should consider most important (e.g., quality-of-life issues, characteristics of the position, and school/department dynamics) when interviewing for an academic position. A principal finding is that candidates weigh quality of life as the most important issue,…

  15. Effects of Student Achievement on Satisfaction of Newly Appointed Teachers: A Cognitive Dissonance Perspective

    ERIC Educational Resources Information Center

    Young, I. Phillip; Chounet, F. Paul; Buster, Amy; Sailor, Scott

    2005-01-01

    Research addressing attraction and selection of employees within the public school setting seems to indicate that the higher a school's student achievement the more likely a potential job candidate is to assess a position at that school favorably. However, the validity of this finding has failed to be assessed with "real teachers" accepting actual…

  16. Old and Unemployable? How Age-Based Stereotypes Affect Willingness to Hire Job Candidates.

    PubMed

    Abrams, Dominic; Swift, Hannah J; Drury, Lisbeth

    2016-03-01

    Across the world, people are required, or want, to work until an increasingly old age. But how might prospective employers view job applicants who have skills and qualities that they associate with older adults? This article draws on social role theory, age stereotypes and research on hiring biases, and reports three studies using age-diverse North American participants. These studies reveal that: (1) positive older age stereotype characteristics are viewed less favorably as criteria for job hire, (2) even when the job role is low-status, a younger stereotype profile tends to be preferred, and (3) an older stereotype profile is only considered hirable when the role is explicitly cast as subordinate to that of a candidate with a younger age profile. Implications for age-positive selection procedures and ways to reduce the impact of implicit age biases are discussed.

  17. Old and Unemployable? How Age‐Based Stereotypes Affect Willingness to Hire Job Candidates

    PubMed Central

    Swift, Hannah J.; Drury, Lisbeth

    2016-01-01

    Across the world, people are required, or want, to work until an increasingly old age. But how might prospective employers view job applicants who have skills and qualities that they associate with older adults? This article draws on social role theory, age stereotypes and research on hiring biases, and reports three studies using age‐diverse North American participants. These studies reveal that: (1) positive older age stereotype characteristics are viewed less favorably as criteria for job hire, (2) even when the job role is low‐status, a younger stereotype profile tends to be preferred, and (3) an older stereotype profile is only considered hirable when the role is explicitly cast as subordinate to that of a candidate with a younger age profile. Implications for age‐positive selection procedures and ways to reduce the impact of implicit age biases are discussed. PMID:27635102

  18. Limited Evidence for Classic Selective Sweeps in African Populations

    PubMed Central

    Granka, Julie M.; Henn, Brenna M.; Gignoux, Christopher R.; Kidd, Jeffrey M.; Bustamante, Carlos D.; Feldman, Marcus W.

    2012-01-01

    While hundreds of loci have been identified as reflecting strong-positive selection in human populations, connections between candidate loci and specific selective pressures often remain obscure. This study investigates broader patterns of selection in African populations, which are underrepresented despite their potential to offer key insights into human adaptation. We scan for hard selective sweeps using several haplotype and allele-frequency statistics with a data set of nearly 500,000 genome-wide single-nucleotide polymorphisms in 12 highly diverged African populations that span a range of environments and subsistence strategies. We find that positive selection does not appear to be a strong determinant of allele-frequency differentiation among these African populations. Haplotype statistics do identify putatively selected regions that are shared across African populations. However, as assessed by extensive simulations, patterns of haplotype sharing between African populations follow neutral expectations and suggest that tails of the empirical distributions contain false-positive signals. After highlighting several genomic regions where positive selection can be inferred with higher confidence, we use a novel method to identify biological functions enriched among populations’ empirical tail genomic windows, such as immune response in agricultural groups. In general, however, it seems that current methods for selection scans are poorly suited to populations that, like the African populations in this study, are affected by ascertainment bias and have low levels of linkage disequilibrium, possibly old selective sweeps, and potentially reduced phasing accuracy. Additionally, population history can confound the interpretation of selection statistics, suggesting that greater care is needed in attributing broad genetic patterns to human adaptation. PMID:22960214

  19. Principal Selection Decisions Made by Teachers: The Influence of Principal Candidate Experience

    ERIC Educational Resources Information Center

    Winter, Paul A.; Jaeger, Mary Grace

    2004-01-01

    Public school teachers (N = 189) role-played as members of school councils making principal selection decisions by rating simulated candidates for principal vacancies. The independent variables were principal candidate job experience, candidate person characteristics, and teacher school level. The dependent variable was teacher rating of the job…

  20. Political Candidate Campaign Advertising: A Selected Review of the Literature.

    ERIC Educational Resources Information Center

    Hellweg, Susan A.

    This paper provides a selected review of political candidate campaign advertising studies from the political science, mass communication, advertising, and political communication literature. The paper examines the literature in terms of research pertaining to (1) candidate advertising content (commercials for male versus female candidates and for…

  1. Planning for success: desired characteristics of special operations surgeons, a pilot study.

    PubMed

    Campbell, Barrett H; Alderman, Shawn M

    2012-01-01

    Selection criteria for Special Operations Forces (SOF) physicians are often unclear to potential candidates without prior SOF experience. To date, no published career resource exists to guide the careers of physicians interested in becoming a SOF surgeon. Using a survey tool, desirable characteristics and personal attributes were identified that can be used to inform candidate career decisions and better prepare them for a future position in Special Operations. A descriptive, cross-sectional survey instrument was developed and distributed to current Army SOF Command Surgeons for further distribution to subordinate surgeons. RESULTS were analyzed as a cohort and by subordinate command. Respondents consisted of current SOF Surgeons. Uniformly, the individual characteristics most strongly desired are professionalism, being a team player, and leadership. Possessing or obtaining Airborne and Flight Surgeon qualifications prior to consideration for a surgeon position was highly desired. Residency training within Family Medicine or Emergency Medicine constituted the vast majority of specialty preference. Understanding which characteristics and attributes are desirable to current surgeons and commanders can aid physicians interested in SOF surgeon positions. Using this study and future studies can guide career planning and foster the selection of ideally trained physicians who will operate at the tip of the spear. The views expressed are those of the author(s) and do not reflect the official policy of the Department of the Army, the Department of Defense or the U.S. Government. 2012.

  2. A Corpus-Based Approach for Automatic Thai Unknown Word Recognition Using Boosting Techniques

    NASA Astrophysics Data System (ADS)

    Techo, Jakkrit; Nattee, Cholwich; Theeramunkong, Thanaruk

    While classification techniques can be applied for automatic unknown word recognition in a language without word boundary, it faces with the problem of unbalanced datasets where the number of positive unknown word candidates is dominantly smaller than that of negative candidates. To solve this problem, this paper presents a corpus-based approach that introduces a so-called group-based ranking evaluation technique into ensemble learning in order to generate a sequence of classification models that later collaborate to select the most probable unknown word from multiple candidates. Given a classification model, the group-based ranking evaluation (GRE) is applied to construct a training dataset for learning the succeeding model, by weighing each of its candidates according to their ranks and correctness when the candidates of an unknown word are considered as one group. A number of experiments have been conducted on a large Thai medical text to evaluate performance of the proposed group-based ranking evaluation approach, namely V-GRE, compared to the conventional naïve Bayes classifier and our vanilla version without ensemble learning. As the result, the proposed method achieves an accuracy of 90.93±0.50% when the first rank is selected while it gains 97.26±0.26% when the top-ten candidates are considered, that is 8.45% and 6.79% improvement over the conventional record-based naïve Bayes classifier and the vanilla version. Another result on applying only best features show 93.93±0.22% and up to 98.85±0.15% accuracy for top-1 and top-10, respectively. They are 3.97% and 9.78% improvement over naive Bayes and the vanilla version. Finally, an error analysis is given.

  3. Validation of candidate gene markers for marker-assisted selection of potato cultivars with improved tuber quality.

    PubMed

    Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane

    2013-04-01

    Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were identified that significantly improved average chip quality after cold storage and tuber starch content. In F1 progeny of a single-cross combination, MAS with six markers did not give the expected result. Reasons and implications for MAS in potato are discussed.

  4. Composite selection signals can localize the trait specific genomic regions in multi-breed populations of cattle and sheep

    PubMed Central

    2014-01-01

    Background Discerning the traits evolving under neutral conditions from those traits evolving rapidly because of various selection pressures is a great challenge. We propose a new method, composite selection signals (CSS), which unifies the multiple pieces of selection evidence from the rank distribution of its diverse constituent tests. The extreme CSS scores capture highly differentiated loci and underlying common variants hauling excess haplotype homozygosity in the samples of a target population. Results The data on high-density genotypes were analyzed for evidence of an association with either polledness or double muscling in various cohorts of cattle and sheep. In cattle, extreme CSS scores were found in the candidate regions on autosome BTA-1 and BTA-2, flanking the POLL locus and MSTN gene, for polledness and double muscling, respectively. In sheep, the regions with extreme scores were localized on autosome OAR-2 harbouring the MSTN gene for double muscling and on OAR-10 harbouring the RXFP2 gene for polledness. In comparison to the constituent tests, there was a partial agreement between the signals at the four candidate loci; however, they consistently identified additional genomic regions harbouring no known genes. Persuasively, our list of all the additional significant CSS regions contains genes that have been successfully implicated to secondary phenotypic diversity among several subpopulations in our data. For example, the method identified a strong selection signature for stature in cattle capturing selective sweeps harbouring UQCC-GDF5 and PLAG1-CHCHD7 gene regions on BTA-13 and BTA-14, respectively. Both gene pairs have been previously associated with height in humans, while PLAG1-CHCHD7 has also been reported for stature in cattle. In the additional analysis, CSS identified significant regions harbouring multiple genes for various traits under selection in European cattle including polledness, adaptation, metabolism, growth rate, stature, immunity, reproduction traits and some other candidate genes for dairy and beef production. Conclusions CSS successfully localized the candidate regions in validation datasets as well as identified previously known and novel regions for various traits experiencing selection pressure. Together, the results demonstrate the utility of CSS by its improved power, reduced false positives and high-resolution of selection signals as compared to individual constituent tests. PMID:24636660

  5. Cardiac transplantation: candidate identification, evaluation, and management.

    PubMed

    McCalmont, Vicki; Ohler, Linda

    2008-01-01

    For more than 40 years, cardiac transplantation has been a treatment option for patients with severe heart failure in whom optimal medical management is no longer effective. Critical care nurses are integrally involved in the care of patients with severe heart failure who may benefit from cardiac transplantation and are in a special position to recognize potential candidates for transplantation. Understanding patient selection criteria, the evaluation process, and how patients are managed while awaiting transplantation is key to the knowledge and skills required. It is also important to understand the allocation of donor hearts as part of this process. The waiting period for a suitable donor heart can be long and a patient's condition may deteriorate, requiring an increase in pharmacologic bridges with intravenous inotropic agents or mechanical bridges with circulatory assist devices. Critical care nurses become important as a personal bridge to transplantation through their education of patients and families and helping them cope with their fears during the waiting period. Critical care nurses who possess knowledge of patient selection and organ allocation processes along with the skills of caring for this complex patient population can contribute to better outcomes for patients with heart failure who may be candidates for cardiac transplantation.

  6. Signatures of Rapid Evolution in Urban and Rural Transcriptomes of White-Footed Mice (Peromyscus leucopus) in the New York Metropolitan Area

    PubMed Central

    Harris, Stephen E.; Munshi-South, Jason; Obergfell, Craig; O’Neill, Rachel

    2013-01-01

    Urbanization is a major cause of ecological degradation around the world, and human settlement in large cities is accelerating. New York City (NYC) is one of the oldest and most urbanized cities in North America, but still maintains 20% vegetation cover and substantial populations of some native wildlife. The white-footed mouse, Peromyscus leucopus , is a common resident of NYC’s forest fragments and an emerging model system for examining the evolutionary consequences of urbanization. In this study, we developed transcriptomic resources for urban P . leucopus to examine evolutionary changes in protein-coding regions for an exemplar “urban adapter.” We used Roche 454 GS FLX+ high throughput sequencing to derive transcriptomes from multiple tissues from individuals across both urban and rural populations. From these data, we identified 31,015 SNPs and several candidate genes potentially experiencing positive selection in urban populations of P . leucopus . These candidate genes are involved in xenobiotic metabolism, innate immune response, demethylation activity, and other important biological phenomena in novel urban environments. This study is one of the first to report candidate genes exhibiting signatures of directional selection in divergent urban ecosystems. PMID:24015321

  7. Effect of segmentation algorithms on the performance of computerized detection of lung nodules in CT

    PubMed Central

    Guo, Wei; Li, Qiang

    2014-01-01

    Purpose: The purpose of this study is to reveal how the performance of lung nodule segmentation algorithm impacts the performance of lung nodule detection, and to provide guidelines for choosing an appropriate segmentation algorithm with appropriate parameters in a computer-aided detection (CAD) scheme. Methods: The database consisted of 85 CT scans with 111 nodules of 3 mm or larger in diameter from the standard CT lung nodule database created by the Lung Image Database Consortium. The initial nodule candidates were identified as those with strong response to a selective nodule enhancement filter. A uniform viewpoint reformation technique was applied to a three-dimensional nodule candidate to generate 24 two-dimensional (2D) reformatted images, which would be used to effectively distinguish between true nodules and false positives. Six different algorithms were employed to segment the initial nodule candidates in the 2D reformatted images. Finally, 2D features from the segmented areas in the 24 reformatted images were determined, selected, and classified for removal of false positives. Therefore, there were six similar CAD schemes, in which only the segmentation algorithms were different. The six segmentation algorithms included the fixed thresholding (FT), Otsu thresholding (OTSU), fuzzy C-means (FCM), Gaussian mixture model (GMM), Chan and Vese model (CV), and local binary fitting (LBF). The mean Jaccard index and the mean absolute distance (Dmean) were employed to evaluate the performance of segmentation algorithms, and the number of false positives at a fixed sensitivity was employed to evaluate the performance of the CAD schemes. Results: For the segmentation algorithms of FT, OTSU, FCM, GMM, CV, and LBF, the highest mean Jaccard index between the segmented nodule and the ground truth were 0.601, 0.586, 0.588, 0.563, 0.543, and 0.553, respectively, and the corresponding Dmean were 1.74, 1.80, 2.32, 2.80, 3.48, and 3.18 pixels, respectively. With these segmentation results of the six segmentation algorithms, the six CAD schemes reported 4.4, 8.8, 3.4, 9.2, 13.6, and 10.4 false positives per CT scan at a sensitivity of 80%. Conclusions: When multiple algorithms are available for segmenting nodule candidates in a CAD scheme, the “optimal” segmentation algorithm did not necessarily lead to the “optimal” CAD detection performance. PMID:25186393

  8. Convergent evolution of marine mammals is associated with distinct substitutions in common genes

    PubMed Central

    Zhou, Xuming; Seim, Inge; Gladyshev, Vadim N.

    2015-01-01

    Phenotypic convergence is thought to be driven by parallel substitutions coupled with natural selection at the sequence level. Multiple independent evolutionary transitions of mammals to an aquatic environment offer an opportunity to test this thesis. Here, whole genome alignment of coding sequences identified widespread parallel amino acid substitutions in marine mammals; however, the majority of these changes were not unique to these animals. Conversely, we report that candidate aquatic adaptation genes, identified by signatures of likelihood convergence and/or elevated ratio of nonsynonymous to synonymous nucleotide substitution rate, are characterized by very few parallel substitutions and exhibit distinct sequence changes in each group. Moreover, no significant positive correlation was found between likelihood convergence and positive selection in all three marine lineages. These results suggest that convergence in protein coding genes associated with aquatic lifestyle is mainly characterized by independent substitutions and relaxed negative selection. PMID:26549748

  9. A region on BTA14 that includes the positional candidate genes LYPLA1, XKR4 and TMEM68 is associated with feed intake and growth phenotypes in cattle

    USDA-ARS?s Scientific Manuscript database

    The cost of feed for beef cattle is the largest expense incurred by cattle producers. Development of genetic markers to enhance selection of more efficient animals that require less feed while still achieving acceptable levels of production has the potential to substantially reduce production costs....

  10. Comparison of the sensitivity of the UKCAT and A Levels to sociodemographic characteristics: a national study

    PubMed Central

    2014-01-01

    Background The UK Clinical Aptitude Test (UKCAT) was introduced to facilitate widening participation in medical and dental education in the UK by providing universities with a continuous variable to aid selection; one that might be less sensitive to the sociodemographic background of candidates compared to traditional measures of educational attainment. Initial research suggested that males, candidates from more advantaged socioeconomic backgrounds and those who attended independent or grammar schools performed better on the test. The introduction of the A* grade at A level permits more detailed analysis of the relationship between UKCAT scores, secondary educational attainment and sociodemographic variables. Thus, our aim was to further assess whether the UKCAT is likely to add incremental value over A level (predicted or actual) attainment in the selection process. Methods Data relating to UKCAT and A level performance from 8,180 candidates applying to medicine in 2009 who had complete information relating to six key sociodemographic variables were analysed. A series of regression analyses were conducted in order to evaluate the ability of sociodemographic status to predict performance on two outcome measures: A level ‘best of three’ tariff score; and the UKCAT scores. Results In this sample A level attainment was independently and positively predicted by four sociodemographic variables (independent/grammar schooling, White ethnicity, age and professional social class background). These variables also independently and positively predicted UKCAT scores. There was a suggestion that UKCAT scores were less sensitive to educational background compared to A level attainment. In contrast to A level attainment, UKCAT score was independently and positively predicted by having English as a first language and male sex. Conclusions Our findings are consistent with a previous report; most of the sociodemographic factors that predict A level attainment also predict UKCAT performance. However, compared to A levels, males and those speaking English as a first language perform better on UKCAT. Our findings suggest that UKCAT scores may be more influenced by sex and less sensitive to school type compared to A levels. These factors must be considered by institutions utilising the UKCAT as a component of the medical and dental school selection process. PMID:24400861

  11. Simulation Testing for Selection of Critical Care Medicine Trainees. A Pilot Feasibility Study.

    PubMed

    Cocciante, Adriano G; Nguyen, Martin N; Marane, Candida F; Panayiotou, Anita E; Karahalios, Amalia; Beer, Janet A; Johal, Navroop; Morris, John; Turner, Stacy; Hessian, Elizabeth C

    2016-04-01

    Selection of physicians into anesthesiology, intensive care, and emergency medicine training has traditionally relied on evaluation of curriculum vitae, letters of recommendation, and interviews, despite these methods being poor predictors of subsequent workplace performance. In this study, we evaluated the feasibility and face validity of incorporating assessment of nontechnical skills in simulation and personality traits into an existing junior doctor selection framework. Candidates short-listed for a critical care residency position were invited to participate in the study. On the interview day, consenting candidates participated in a simulation scenario and debriefing and completed a personality test (16 Personality Factor Questionnaire) and a survey. Timing of participants' progression through the stations and faculty staff numbers were evaluated. Nontechnical skills were evaluated and candidates ranked using the Ottawa Crisis Resource Management Global Rating Scale (Ottawa GRS). Nontechnical skills ranking and traditional selection method ranking were compared using the concordance correlation coefficient. Interrater reliability was assessed using the concordance correlation coefficient. Thirteen of 20 eligible participants consented to study inclusion. All participants completed the necessary stations without significant time delays. Eighteen staff members were required to conduct interviews, simulation, debriefing, and personality testing. Participants rated the simulation station to be acceptable, fair, and relevant and as providing an opportunity to demonstrate abilities. Personality testing was rated less fair, less relevant, and less acceptable, and as giving less opportunity to demonstrate abilities. Participants reported that simulation was equally as stressful as the interview, whereas personality testing was rated less stressful. Assessors rated both personality testing and simulation as acceptable and able to provide additional information about candidates. The Ottawa GRS showed moderate interrater concordance. There was moderate concordance between rankings based on traditional selection methods and Ottawa GRS rankings (ρ = 0.52; 95% confidence interval, -0.02 to 0.82; P = 0.06). A multistation selection process involving interviews, simulation, and personality testing is feasible and has face validity. A potential barrier to adoption is the high number of faculty required to conduct the process.

  12. Genetic diversity of transmission-blocking vaccine candidate Pvs48/45 in Plasmodium vivax populations in China.

    PubMed

    Feng, Hui; Gupta, Bhavna; Wang, Meilian; Zheng, Wenqi; Zheng, Li; Zhu, Xiaotong; Yang, Yimei; Fang, Qiang; Luo, Enjie; Fan, Qi; Tsuboi, Takafumi; Cao, Yaming; Cui, Liwang

    2015-12-01

    The male gamete fertilization factor P48/45 in malaria parasites is a prime transmission-blocking vaccine (TBV) candidate. Efforts to develop antimalarial vaccines are often thwarted by genetic diversity of the target antigens. Here we evaluated the genetic diversity of Pvs48/45 gene in global Plasmodium vivax populations. We determined 200 Pvs48/45 sequences collected from temperate and subtropical parasite populations in China. Population genetic and evolutionary analyses were performed to determine the levels of genetic diversity, potential signature of selection, and population differentiation. Analysis of the Pvs48/45 sequences from 200 P. vivax parasites collected in a temperate and a tropical region revealed a low level of genetic diversity (π = 0.0012) with 14 single nucleotide polymorphisms, of which 11 were nonsynonymous. Analysis of 344 Pvs48/45 sequences from nine worldwide P. vivax populations detected a total of 38 haplotypes, of which 13 haplotypes were present only once. Multiple tests for selection confirmed a signature of positive selection on Pvs48/45 with selection skewed to the second cysteine domain. Haplotype network analysis and Wright's fixation index showed large geographical differentiation with the presence of continent-or region-specific mutations in this gene. Pvs48/45 displays low levels of genetic diversity with the presence of region-specific mutations. Some of the mutations may be potential epitope targets based on their positions in the predicted structure, highlighting the need for future evaluation of these mutations in designing Pvs48/45-based TBV.

  13. DISSECTING THE GENETICS OF HUMAN HIGH MYOPIA: A MOLECULAR BIOLOGIC APPROACH

    PubMed Central

    Young, Terri L

    2004-01-01

    ABSTRACT Purpose Despite the plethora of experimental myopia animal studies that demonstrate biochemical factor changes in various eye tissues, and limited human studies utilizing pharmacologic agents to thwart axial elongation, we have little knowledge of the basic physiology that drives myopic development. Identifying the implicated genes for myopia susceptibility will provide a fundamental molecular understanding of how myopia occurs and may lead to directed physiologic (ie, pharmacologic, gene therapy) interventions. The purpose of this proposal is to describe the results of positional candidate gene screening of selected genes within the autosomal dominant high-grade myopia-2 locus (MYP2) on chromosome 18p11.31. Methods A physical map of a contracted MYP2 interval was compiled, and gene expression studies in ocular tissues using complementary DNA library screens, microarray matches, and reverse-transcription techniques aided in prioritizing gene selection for screening. The TGIF, EMLIN-2, MLCB, and CLUL1 genes were screened in DNA samples from unrelated controls and in high-myopia affected and unaffected family members from the original seven MYP2 pedigrees. All candidate genes were screened by direct base pair sequence analysis. Results Consistent segregation of a gene sequence alteration (polymorphism) with myopia was not demonstrated in any of the seven families. Novel single nucleotide polymorphisms were found. Conclusion The positional candidate genes TGIF, EMLIN-2, MLCB, and CLUL1 are not associated with MYP2-linked high-grade myopia. Base change polymorphisms discovered with base sequence screening of these genes were submitted to an Internet database. Other genes that also map within the interval are currently undergoing mutation screening. PMID:15747770

  14. Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

    PubMed

    Aagaard, Jan E; George, Renee D; Fishman, Lila; Maccoss, Michael J; Swanson, Willie J

    2013-01-01

    Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation), we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp.) resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube) proteins within maternal reproductive structures (styles) of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens towards the goal of identifying the molecular basis of genetically complex traits.

  15. Genetic mechanisms involved in the evolution of the cephalopod camera eye revealed by transcriptomic and developmental studies

    PubMed Central

    2011-01-01

    Background Coleoid cephalopods (squids and octopuses) have evolved a camera eye, the structure of which is very similar to that found in vertebrates and which is considered a classic example of convergent evolution. Other molluscs, however, possess mirror, pin-hole, or compound eyes, all of which differ from the camera eye in the degree of complexity of the eye structures and neurons participating in the visual circuit. Therefore, genes expressed in the cephalopod eye after divergence from the common molluscan ancestor could be involved in eye evolution through association with the acquisition of new structural components. To clarify the genetic mechanisms that contributed to the evolution of the cephalopod camera eye, we applied comprehensive transcriptomic analysis and conducted developmental validation of candidate genes involved in coleoid cephalopod eye evolution. Results We compared gene expression in the eyes of 6 molluscan (3 cephalopod and 3 non-cephalopod) species and selected 5,707 genes as cephalopod camera eye-specific candidate genes on the basis of homology searches against 3 molluscan species without camera eyes. First, we confirmed the expression of these 5,707 genes in the cephalopod camera eye formation processes by developmental array analysis. Second, using molecular evolutionary (dN/dS) analysis to detect positive selection in the cephalopod lineage, we identified 156 of these genes in which functions appeared to have changed after the divergence of cephalopods from the molluscan ancestor and which contributed to structural and functional diversification. Third, we selected 1,571 genes, expressed in the camera eyes of both cephalopods and vertebrates, which could have independently acquired a function related to eye development at the expression level. Finally, as experimental validation, we identified three functionally novel cephalopod camera eye genes related to optic lobe formation in cephalopods by in situ hybridization analysis of embryonic pygmy squid. Conclusion We identified 156 genes positively selected in the cephalopod lineage and 1,571 genes commonly found in the cephalopod and vertebrate camera eyes from the analysis of cephalopod camera eye specificity at the expression level. Experimental validation showed that the cephalopod camera eye-specific candidate genes include those expressed in the outer part of the optic lobes, which unique to coleoid cephalopods. The results of this study suggest that changes in gene expression and in the primary structure of proteins (through positive selection) from those in the common molluscan ancestor could have contributed, at least in part, to cephalopod camera eye acquisition. PMID:21702923

  16. Evolution of the Transmission-Blocking Vaccine Candidates Pvs28 and Pvs25 in Plasmodium vivax: Geographic Differentiation and Evidence of Positive Selection

    PubMed Central

    Cornejo, Omar E.; Durrego, Ester; Stanley, Craig E.; Castillo, Andreína I.; Herrera, Sócrates; Escalante, Ananias A.

    2016-01-01

    Transmission-blocking (TB) vaccines are considered an important tool for malaria control and elimination. Among all the antigens characterized as TB vaccines against Plasmodium vivax, the ookinete surface proteins Pvs28 and Pvs25 are leading candidates. These proteins likely originated by a gene duplication event that took place before the radiation of the known Plasmodium species to primates. We report an evolutionary genetic analysis of a worldwide sample of pvs28 and pvs25 alleles. Our results show that both genes display low levels of genetic polymorphism when compared to the merozoite surface antigens AMA-1 and MSP-1; however, both ookinete antigens can be as polymorphic as other merozoite antigens such as MSP-8 and MSP-10. We found that parasite populations in Asia and the Americas are geographically differentiated with comparable levels of genetic diversity and specific amino acid replacements found only in the Americas. Furthermore, the observed variation was mainly accumulated in the EGF2- and EGF3-like domains for P. vivax in both proteins. This pattern was shared by other closely related non-human primate parasites such as Plasmodium cynomolgi, suggesting that it could be functionally important. In addition, examination with a suite of evolutionary genetic analyses indicated that the observed patterns are consistent with positive natural selection acting on Pvs28 and Pvs25 polymorphisms. The geographic pattern of genetic differentiation and the evidence for positive selection strongly suggest that the functional consequences of the observed polymorphism should be evaluated during development of TBVs that include Pvs25 and Pvs28. PMID:27347876

  17. Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data.

    PubMed

    Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M; Mei, Rui; Scherer, Stephen W; Julian, Colleen G; Wilson, Megan J; López Herráez, David; Brutsaert, Tom; Parra, Esteban J; Moore, Lorna G; Shriver, Mark D

    2010-09-09

    High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude.

  18. Identifying Signatures of Natural Selection in Tibetan and Andean Populations Using Dense Genome Scan Data

    PubMed Central

    Bigham, Abigail; Bauchet, Marc; Pinto, Dalila; Mao, Xianyun; Akey, Joshua M.; Mei, Rui; Scherer, Stephen W.; Julian, Colleen G.; Wilson, Megan J.; López Herráez, David; Brutsaert, Tom; Parra, Esteban J.; Moore, Lorna G.; Shriver, Mark D.

    2010-01-01

    High-altitude hypoxia (reduced inspired oxygen tension due to decreased barometric pressure) exerts severe physiological stress on the human body. Two high-altitude regions where humans have lived for millennia are the Andean Altiplano and the Tibetan Plateau. Populations living in these regions exhibit unique circulatory, respiratory, and hematological adaptations to life at high altitude. Although these responses have been well characterized physiologically, their underlying genetic basis remains unknown. We performed a genome scan to identify genes showing evidence of adaptation to hypoxia. We looked across each chromosome to identify genomic regions with previously unknown function with respect to altitude phenotypes. In addition, groups of genes functioning in oxygen metabolism and sensing were examined to test the hypothesis that particular pathways have been involved in genetic adaptation to altitude. Applying four population genetic statistics commonly used for detecting signatures of natural selection, we identified selection-nominated candidate genes and gene regions in these two populations (Andeans and Tibetans) separately. The Tibetan and Andean patterns of genetic adaptation are largely distinct from one another, with both populations showing evidence of positive natural selection in different genes or gene regions. Interestingly, one gene previously known to be important in cellular oxygen sensing, EGLN1 (also known as PHD2), shows evidence of positive selection in both Tibetans and Andeans. However, the pattern of variation for this gene differs between the two populations. Our results indicate that several key HIF-regulatory and targeted genes are responsible for adaptation to high altitude in Andeans and Tibetans, and several different chromosomal regions are implicated in the putative response to selection. These data suggest a genetic role in high-altitude adaption and provide a basis for future genotype/phenotype association studies necessary to confirm the role of selection-nominated candidate genes and gene regions in adaptation to altitude. PMID:20838600

  19. Establishment of a Comprehensive List of Candidate Antiaging Medicinal Herb Used in Korean Medicine by Text Mining of the Classical Korean Medical Literature, “Dongeuibogam,” and Preliminary Evaluation of the Antiaging Effects of These Herbs

    PubMed Central

    Choi, Moo Jin; Choi, Byung Tae; Shin, Hwa Kyoung; Shin, Byung Cheul; Han, Yoo Kyoung; Baek, Jin Ung

    2015-01-01

    The major objectives of this study were to provide a list of candidate antiaging medicinal herbs that have been widely utilized in Korean medicine and to organize preliminary data for the benefit of experimental and clinical researchers to develop new drug therapies by analyzing previous studies. “Dongeuibogam,” a representative source of the Korean medicine literature, was selected to investigate candidate antiaging medicinal herbs and to identify appropriate terms that describe the specific antiaging effects that these herbs are predicted to elicit. In addition, we aimed to review previous studies that referenced the selected candidate antiaging medicinal herbs. From our chosen source, “Dongeuibogam,” we were able to screen 102 terms describing antiaging effects, which were further classified into 11 subtypes. Ninety-seven candidate antiaging medicinal herbs were selected using the criterion that their antiaging effects were described using the same terms as those employed in “Dongeuibogam.” These candidates were classified into 11 subtypes. Of the 97 candidate antiaging medicinal herbs selected, 47 are widely used by Korean medical doctors in Korea and were selected for further analysis of their antiaging effects. Overall, we found an average of 7.7 previous studies per candidate herb that described their antiaging effects. PMID:25861371

  20. A Novel Candidate Region for Genetic Adaptation to High Altitude in Andean Populations

    PubMed Central

    Lippold, Sebastian; de Filippo, Cesare; Tang, Kun; López Herráez, David; Li, Jing; Stoneking, Mark

    2015-01-01

    Humans living at high altitude (≥2,500 meters above sea level) have acquired unique abilities to survive the associated extreme environmental conditions, including hypoxia, cold temperature, limited food availability and high levels of free radicals and oxidants. Long-term inhabitants of the most elevated regions of the world have undergone extensive physiological and/or genetic changes, particularly in the regulation of respiration and circulation, when compared to lowland populations. Genome scans have identified candidate genes involved in altitude adaption in the Tibetan Plateau and the Ethiopian highlands, in contrast to populations from the Andes, which have not been as intensively investigated. In the present study, we focused on three indigenous populations from Bolivia: two groups of Andean natives, Aymara and Quechua, and the low-altitude control group of Guarani from the Gran Chaco lowlands. Using pooled samples, we identified a number of SNPs exhibiting large allele frequency differences over 900,000 genotyped SNPs. A region in chromosome 10 (within the cytogenetic bands q22.3 and q23.1) was significantly differentiated between highland and lowland groups. We resequenced ~1.5 Mb surrounding the candidate region and identified strong signals of positive selection in the highland populations. A composite of multiple signals like test localized the signal to FAM213A and a related enhancer; the product of this gene acts as an antioxidant to lower oxidative stress and may help to maintain bone mass. The results suggest that positive selection on the enhancer might increase the expression of this antioxidant, and thereby prevent oxidative damage. In addition, the most significant signal in a relative extended haplotype homozygosity analysis was localized to the SFTPD gene, which encodes a surfactant pulmonary-associated protein involved in normal respiration and innate host defense. Our study thus identifies two novel candidate genes and associated pathways that may be involved in high-altitude adaptation in Andean populations. PMID:25961286

  1. Choice of the specialty of diagnostic radiology by results of the competitive examination to assign residency positions from 2006 to 2015.

    PubMed

    Murias Quintana, E; Sánchez Lasheras, F; Fernández-Somoano, A; Romeo Ladrero, J M; Costilla García, S M; Cadenas Rodríguez, M; Baladrón Romero, J B

    To analyze the profile of residency candidates choosing the specialty of diagnostic radiology in function of variables related to the positions available in different years. We compiled the data published on the Spanish Ministry of Health's website during the acts celebrated to allow residency candidates to choose positions based on the results of the competitive examinations held from 2006 to 2015, comparing the specialty of diagnostic radiology with the other specialties available in terms of positions available, net questions, sex, nationality, and order of choice of the position. The specialty of diagnostic radiology occupied the 16 th position in the ranking of specialties according to the median number of order in the choice for each of the positions offered in the years studied. The first diagnostic radiology residency position was usually assigned after 75 candidates had chosen other specialties, and the last position was usually assigned after 3700 to 4100 candidates had chosen their positions. During the period studied, of those who chose diagnostic radiology 58% were women and 76% were Spanish nationality. Candidates preferred hospitals in the Autonomous Community of Madrid, and the hospital chosen with the lowest median position (highest score on the competitive examination) was the Hospital Clínic de Barcelona. Diagnostic radiology is chosen by candidates with good positioning in the ranking according to official examination results, is less likely than other specialties to be chosen by women, and is chosen mostly by Spanish physicians. Candidates prefer large hospitals in provincial capitals. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Automated microaneurysm detection in diabetic retinopathy using curvelet transform

    NASA Astrophysics Data System (ADS)

    Ali Shah, Syed Ayaz; Laude, Augustinus; Faye, Ibrahima; Tang, Tong Boon

    2016-10-01

    Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies.

  3. Automated microaneurysm detection in diabetic retinopathy using curvelet transform.

    PubMed

    Ali Shah, Syed Ayaz; Laude, Augustinus; Faye, Ibrahima; Tang, Tong Boon

    2016-10-01

    Microaneurysms (MAs) are known to be the early signs of diabetic retinopathy (DR). An automated MA detection system based on curvelet transform is proposed for color fundus image analysis. Candidates of MA were extracted in two parallel steps. In step one, blood vessels were removed from preprocessed green band image and preliminary MA candidates were selected by local thresholding technique. In step two, based on statistical features, the image background was estimated. The results from the two steps allowed us to identify preliminary MA candidates which were also present in the image foreground. A collection set of features was fed to a rule-based classifier to divide the candidates into MAs and non-MAs. The proposed system was tested with Retinopathy Online Challenge database. The automated system detected 162 MAs out of 336, thus achieved a sensitivity of 48.21% with 65 false positives per image. Counting MA is a means to measure the progression of DR. Hence, the proposed system may be deployed to monitor the progression of DR at early stage in population studies.

  4. Voters' Fickleness:. a Mathematical Model

    NASA Astrophysics Data System (ADS)

    Boccara, Nino

    This paper presents a spatial agent-based model in order to study the evolution of voters' choice during the campaign of a two-candidate election. Each agent, represented by a point inside a two-dimensional square, is under the influence of its neighboring agents, located at a Euclidean distance less than or equal to d, and under the equal influence of both candidates seeking to win its support. Moreover, each agent located at time t at a given point moves at the next timestep to a randomly selected neighboring location distributed normally around its position at time t. Besides their location in space, agents are characterized by their level of awareness, a real a ∈ [0, 1], and their opinion ω ∈ {-1, 0, +1}, where -1 and +1 represent the respective intentions to cast a ballot in favor of one of the two candidates while 0 indicates either disinterest or refusal to vote. The essential purpose of the paper is qualitative; its aim is to show that voters' fickleness is strongly correlated to the level of voters' awareness and the efficiency of candidates' propaganda.

  5. No evidence for positive selection at two potential targets for malaria transmission-blocking vaccines in Anopheles gambiae s.s.

    PubMed

    Crawford, Jacob E; Rottschaefer, Susan M; Coulibaly, Boubacar; Sacko, Madjou; Niaré, Oumou; Riehle, Michelle M; Traore, Sékou F; Vernick, Kenneth D; Lazzaro, Brian P

    2013-06-01

    Human malaria causes nearly a million deaths in sub-Saharan Africa each year. The evolution of drug-resistance in the parasite and insecticide resistance in the mosquito vector has complicated control measures and made the need for new control strategies more urgent. Anopheles gambiae s.s. is one of the primary vectors of human malaria in Africa, and parasite-transmission-blocking vaccines targeting Anopheles proteins have been proposed as a possible strategy to control the spread of the disease. However, the success of these hypothetical technologies would depend on the successful ability to broadly target mosquito populations that may be genetically heterogeneous. Understanding the evolutionary pressures shaping genetic variation among candidate target molecules offers a first step towards evaluating the prospects of successfully deploying such technologies. We studied the population genetics of genes encoding two candidate target proteins, the salivary gland protein saglin and the basal lamina structural protein laminin, in wild populations of the M and S molecular forms of A. gambiae in Mali. Through analysis of intraspecific genetic variation and interspecific comparisons, we found no evidence of positive natural selection at the genes encoding these proteins. On the contrary, we found evidence for particularly strong purifying selection at the laminin gene. These results provide insight into the patterns of genetic diversity of saglin and laminin, and we discuss these findings in relation to the potential development of these molecules as vaccine targets. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Multilocus patterns of nucleotide diversity and divergence reveal positive selection at candidate genes related to cold hardiness in coastal Douglas Fir (Pseudotsuga menziesii var. menziesii).

    Treesearch

    A. Eckert; J. Wegrzyn; B. Pande; K. Jermstad; J. Lee; J. Liechty; B. Tearse; K. Krutovsky; D. Neale

    2009-01-01

    Forest trees exhibit remarkable adaptations to their environments. The genetic basis for phenotypic adaptation to climatic gradients has been established through a long history of common garden, provenance, and genecological studies. The identities of genes underlying these traits, however, have remained elusive and thus so have the patterns of adaptive molecular...

  7. Informative Top-k Retrieval for Advanced Skill Management

    NASA Astrophysics Data System (ADS)

    Colucci, Simona; di Noia, Tommaso; Ragone, Azzurra; Ruta, Michele; Straccia, Umberto; Tinelli, Eufemia

    The paper presents a knowledge-based framework for skills and talent management based on an advanced matchmaking between profiles of candidates and available job positions. Interestingly, informative content of top-k retrieval is enriched through semantic capabilities. The proposed approach allows to: (1) express a requested profile in terms of both hard constraints and soft ones; (2) provide a ranking function based also on qualitative attributes of a profile; (3) explain the resulting outcomes (given a job request, a motivation for the obtained score of each selected profile is provided). Top-k retrieval allows to select most promising candidates according to an ontology formalizing the domain knowledge. Such a knowledge is further exploited to provide a semantic-based explanation of missing or conflicting features in retrieved profiles. They also indicate additional profile characteristics emerging by the retrieval procedure for a further request refinement. A concrete case study followed by an exhaustive experimental campaign is reported to prove the approach effectiveness.

  8. Remembering and Voting: Theory and Evidence from Amnesic Patients

    PubMed Central

    Coronel, Jason C.; Duff, Melissa C.; Warren, David E.; Federmeier, Kara D.; Gonsalves, Brian D.; Tranel, Daniel; Cohen, Neal J.

    2013-01-01

    One of the most prominent claims to emerge from the field of public opinion is that citizens can vote for candidates whose issue positions best reflect their own beliefs even when they cannot remember previously learned stances associated with the candidates. The current experiment provides a unique and powerful examination of this claim by determining whether individuals with profound amnesia, whose severe memory impairments prevent them from remembering specific issue information associated with any particular candidate, can vote for candidates whose issue positions come closest to their own political views. We report here that amnesic patients, despite not being able to remember any issue information, consistently voted for candidates with favored political positions. Thus, sound voting decisions do not require recall or recognition of previously learned associations between candidates and their issue positions. This result supports a multiple memory systems model of political decision making. PMID:24511170

  9. Anion permselective membrane

    NASA Technical Reports Server (NTRS)

    Alexander, S.; Hodgdon, R. B.

    1977-01-01

    The objective of NAS 3-20108 was the development and evaluation of improved anion selective membranes useful as efficient separators in a redox power storage cell system being constructed. The program was divided into three parts, (a) optimization of the selected candidate membrane systems, (b) investigation of alternative membrane/polymer systems, and (c) characterization of candidate membranes. The major synthesis effort was aimed at improving and optimizing as far as possible each candidate system with respect to three critical membrane properties essential for good redox cell performance. Substantial improvements were made in 5 candidate membrane systems. The critical synthesis variables of cross-link density, monomer ratio, and solvent composition were examined over a wide range. In addition, eight alternative polymer systems were investigated, two of which attained candidate status. Three other alternatives showed potential but required further research and development. Each candidate system was optimized for selectivity.

  10. Parallel Selection Revealed by Population Sequencing in Chicken.

    PubMed

    Qanbari, Saber; Seidel, Michael; Strom, Tim-Mathias; Mayer, Klaus F X; Preisinger, Ruedi; Simianer, Henner

    2015-11-13

    Human-driven selection during domestication and subsequent breed formation has likely left detectable signatures within the genome of modern chicken. The elucidation of these signatures of selection is of interest from the perspective of evolutionary biology, and for identifying genes relevant to domestication and improvement that ultimately may help to further genetically improve this economically important animal. We used whole genome sequence data from 50 hens of commercial white (WL) and brown (BL) egg-laying chicken along with pool sequences of three meat-type chicken to perform a systematic screening of past selection in modern chicken. Evidence of positive selection was investigated in two steps. First, we explored evidence of parallel fixation in regions with overlapping elevated allele frequencies in replicated populations of layers and broilers, suggestive of selection during domestication or preimprovement ages. We confirmed parallel fixation in BCDO2 and TSHR genes and found four candidates including AGTR2, a gene heavily involved in "Ascites" in commercial birds. Next, we explored differentiated loci between layers and broilers suggestive of selection during improvement in chicken. This analysis revealed evidence of parallel differentiation in genes relevant to appearance and production traits exemplified with the candidate gene OPG, implicated in Osteoporosis, a disorder related to overconsumption of calcium in egg-laying hens. Our results illustrate the potential for population genetic techniques to identify genomic regions relevant to the phenotypes of importance to breeders. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Selecting the Administrative Computing Executive.

    ERIC Educational Resources Information Center

    Bielec, John A.

    1985-01-01

    Important steps in the computing administrator selection process are outlined, including: reviewing the administrative computing organization, determining a search methodology, selecting a search or screening committee, narrowing the candidate pool, scheduling interviews and evaluating candidates, and conducting negotiations. (MSE)

  12. A genome-wide scan for signatures of selection in Chinese indigenous and commercial pig breeds.

    PubMed

    Yang, Songbai; Li, Xiuling; Li, Kui; Fan, Bin; Tang, Zhonglin

    2014-01-15

    Modern breeding and artificial selection play critical roles in pig domestication and shape the genetic variation of different breeds. China has many indigenous pig breeds with various characteristics in morphology and production performance that differ from those of foreign commercial pig breeds. However, the signatures of selection on genes implying for economic traits between Chinese indigenous and commercial pigs have been poorly understood. We identified footprints of positive selection at the whole genome level, comprising 44,652 SNPs genotyped in six Chinese indigenous pig breeds, one developed breed and two commercial breeds. An empirical genome-wide distribution of Fst (F-statistics) was constructed based on estimations of Fst for each SNP across these nine breeds. We detected selection at the genome level using the High-Fst outlier method and found that 81 candidate genes show high evidence of positive selection. Furthermore, the results of network analyses showed that the genes that displayed evidence of positive selection were mainly involved in the development of tissues and organs, and the immune response. In addition, we calculated the pairwise Fst between Chinese indigenous and commercial breeds (CHN VS EURO) and between Northern and Southern Chinese indigenous breeds (Northern VS Southern). The IGF1R and ESR1 genes showed evidence of positive selection in the CHN VS EURO and Northern VS Southern groups, respectively. In this study, we first identified the genomic regions that showed evidences of selection between Chinese indigenous and commercial pig breeds using the High-Fst outlier method. These regions were found to be involved in the development of tissues and organs, the immune response, growth and litter size. The results of this study provide new insights into understanding the genetic variation and domestication in pigs.

  13. A genome-wide scan for signatures of selection in Chinese indigenous and commercial pig breeds

    PubMed Central

    2014-01-01

    Background Modern breeding and artificial selection play critical roles in pig domestication and shape the genetic variation of different breeds. China has many indigenous pig breeds with various characteristics in morphology and production performance that differ from those of foreign commercial pig breeds. However, the signatures of selection on genes implying for economic traits between Chinese indigenous and commercial pigs have been poorly understood. Results We identified footprints of positive selection at the whole genome level, comprising 44,652 SNPs genotyped in six Chinese indigenous pig breeds, one developed breed and two commercial breeds. An empirical genome-wide distribution of Fst (F-statistics) was constructed based on estimations of Fst for each SNP across these nine breeds. We detected selection at the genome level using the High-Fst outlier method and found that 81 candidate genes show high evidence of positive selection. Furthermore, the results of network analyses showed that the genes that displayed evidence of positive selection were mainly involved in the development of tissues and organs, and the immune response. In addition, we calculated the pairwise Fst between Chinese indigenous and commercial breeds (CHN VS EURO) and between Northern and Southern Chinese indigenous breeds (Northern VS Southern). The IGF1R and ESR1 genes showed evidence of positive selection in the CHN VS EURO and Northern VS Southern groups, respectively. Conclusions In this study, we first identified the genomic regions that showed evidences of selection between Chinese indigenous and commercial pig breeds using the High-Fst outlier method. These regions were found to be involved in the development of tissues and organs, the immune response, growth and litter size. The results of this study provide new insights into understanding the genetic variation and domestication in pigs. PMID:24422716

  14. 42 CFR 482.90 - Condition of participation: Patient and living donor selection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... principles of medical ethics. Transplant centers must: (1) Ensure that a prospective living donor receives a... candidate on its waiting list, the candidate's medical record must contain documentation that the candidate... selected to receive a transplant, the center must document in the patient's medical record the patient...

  15. News video story segmentation method using fusion of audio-visual features

    NASA Astrophysics Data System (ADS)

    Wen, Jun; Wu, Ling-da; Zeng, Pu; Luan, Xi-dao; Xie, Yu-xiang

    2007-11-01

    News story segmentation is an important aspect for news video analysis. This paper presents a method for news video story segmentation. Different form prior works, which base on visual features transform, the proposed technique uses audio features as baseline and fuses visual features with it to refine the results. At first, it selects silence clips as audio features candidate points, and selects shot boundaries and anchor shots as two kinds of visual features candidate points. Then this paper selects audio feature candidates as cues and develops different fusion method, which effectively using diverse type visual candidates to refine audio candidates, to get story boundaries. Experiment results show that this method has high efficiency and adaptability to different kinds of news video.

  16. 1,2,3,4-tetrahydroquinoline-based selective human neuronal nitric oxide synthase (nNOS) inhibitors: lead optimization studies resulting in the identification of N-(1-(2-(methylamino)ethyl)-1,2,3,4-tetrahydroquinolin-6-yl)thiophene-2-carboximidamide as a preclinical development candidate.

    PubMed

    Ramnauth, Jailall; Renton, Paul; Dove, Peter; Annedi, Subhash C; Speed, Joanne; Silverman, Sarah; Mladenova, Gabriela; Maddaford, Shawn P; Zinghini, Salvatore; Rakhit, Suman; Andrews, John; Lee, David K H; Zhang, Dongqin; Porreca, Frank

    2012-03-22

    Numerous studies have shown that selective nNOS inhibitors could be therapeutic in many neurological disorders. Previously, we reported a series of 1,2,3,4-tetrahydroquinoline-based potent and selective nNOS inhibitors, highlighted by 1 ( J. Med. Chem. 2011 , 54 , 5562 - 5575 ). Despite showing activity in two rodent pain models, 1 suffered from low oral bioavailability (18%) and moderate hERG channel inhibition (IC(50) = 4.7 μM). To optimize the properties of 1, we synthesized a small focused library containing various alkylamino groups on the 1-position of the 1,2,3,4-tetrahydroquinoline scaffold. The compounds were triaged based on their activity in the NOS and hERG manual patch clamp assays and their calculated physicochemical parameters. From these studies, we identified 47 as a potent and selective nNOS inhibitor with improved oral bioavailability (60%) and no hERG channel inhibition (IC(50) > 30 μM). Furthermore, 47 was efficacious in the Chung model of neuropathic pain and has an excellent safety profile, making it a promising preclinical development candidate.

  17. Preformulation considerations for controlled release dosage forms. Part III. Candidate form selection using numerical weighting and scoring.

    PubMed

    Chrzanowski, Frank

    2008-01-01

    Two numerical methods, Decision Analysis (DA) and Potential Problem Analysis (PPA) are presented as alternative selection methods to the logical method presented in Part I. In DA properties are weighted and outcomes are scored. The weighted scores for each candidate are totaled and final selection is based on the totals. Higher scores indicate better candidates. In PPA potential problems are assigned a seriousness factor and test outcomes are used to define the probability of occurrence. The seriousness-probability products are totaled and forms with minimal scores are preferred. DA and PPA have never been compared to the logical-elimination method. Additional data were available for two forms of McN-5707 to provide complete preformulation data for five candidate forms. Weight and seriousness factors (independent variables) were obtained from a survey of experienced formulators. Scores and probabilities (dependent variables) were provided independently by Preformulation. The rankings of the five candidate forms, best to worst, were similar for all three methods. These results validate the applicability of DA and PPA for candidate form selection. DA and PPA are particularly applicable in cases where there are many candidate forms and where each form has some degree of unfavorable properties.

  18. 2012 NCME Election of Board of Directors Candidate Biographies (in Alphabetical Order According to Position)

    ERIC Educational Resources Information Center

    Educational Measurement: Issues and Practice, 2012

    2012-01-01

    This article profiles the candidates for the 2012 NCME election of board of directors. This includes the candidates for the office of the vice president and positions representing testing organizations and members at-large.

  19. New Constraints on the False Positive Rate for Short-Period Kepler Planet Candidates

    NASA Astrophysics Data System (ADS)

    Colón, Knicole D.; Morehead, Robert C.; Ford, Eric B.

    2015-01-01

    The Kepler space mission has discovered thousands of potential planets orbiting other stars, thereby setting the stage for in-depth studies of different populations of planets. We present new multi-wavelength transit photometry of small (Rp < 6 Earth radii), short-period (P < 6 days) Kepler planet candidates acquired with the Gran Telescopio Canarias. Multi-wavelength transit photometry allows us to search for wavelength-dependent transit depths and subsequently identify eclipsing binary false positives (which are especially prevalent at the shortest orbital periods). We combine these new observations of three candidates with previous results for five other candidates (Colón & Ford 2011 and Colón, Ford, & Morehead 2012) to provide new constraints on the false positive rate for small, close-in candidates. In our full sample, we identify four candidates as viable planets and four as eclipsing binary false positives. We therefore find a higher false positive rate for small, close-in candidates compared to the lower false positive rate of ~10% determined by other studies for the full sample of Kepler planet candidates (e.g. Fressin et al. 2013). We also discuss the dearth of known planets with periods less than ~2.5 days and radii between ~3 and 11 Earth radii (the so-called 'sub-Jovian desert'), since the majority of the candidates in our study are located in or around this 'desert.' The lack of planets with these orbital and physical properties is not expected to be due to observational bias, as short-period planets are generally easier to detect (especially if they are larger or more massive than Earth). We consider the implications of our results for the other ~20 Kepler planet candidates located in this desert. Characterizing these candidates will allow us to better understand the formation processes of this apparently rare class of planets.

  20. A New HIV Prevention Network Approach: Sociometric Peer Change Agent Selection

    PubMed Central

    Schneider, John A.; Zhou, A. Ning; Laumann, Edward O.

    2014-01-01

    Internationally, the Peer Change Agent (PCA) model is the most frequently used conceptual framework for HIV prevention. Change agents themselves can be more important than the messages they convey. PCA selection is operationalized via heterogeneous methods based upon individual-level attributes. A sociometric position selection strategy, however, could increase peer influence potency and halt transmission at key network locations. In this study, we selected candidate PCAs based upon relative sociometric bridging and centrality scores and assessed their attributes in comparison to one another and to existing peer educators. We focused upon an emerging HIV epidemic among men who have sex with men in Southern India in 2011. PCAs selected based on their bridging score were more likely to be innovators when compared to other centrally-located PCAs, to PCAs located on the periphery, and to existing peer educators. We also found that sociodemographic attributes and risk behaviors were similar across all candidate PCAs, but risk behaviors of existing peer educators differed. Existing peer educators were more likely to engage in higher risk behavior such as receiving money for sex when compared to sociometrically selected peer changes agents. These existing peer educators were also more likely to exhibit leadership qualities within the overall network; they were, however, just as likely as other non-trained candidate peer change agents to report important HIV intravention behavior (encouraging condoms within their network). The importance of identifying bridges who may be able to diffuse innovation more effectively within high risk HIV networks is especially critical given recent efficacy data from novel HIV prevention interventions such as pre-exposure prophylaxis. Moreover, while existing peer educators were more likely to be leaders in our analysis, using peer educators with high risk behavior may have limited utility in enacting behavior change among sex worker peers or male clients in the network. PMID:24518188

  1. Recent coselection in human populations revealed by protein-protein interaction network.

    PubMed

    Qian, Wei; Zhou, Hang; Tang, Kun

    2014-12-21

    Genome-wide scans for signals of natural selection in human populations have identified a large number of candidate loci that underlie local adaptations. This is surprising given the relatively short evolutionary time since the divergence of the human population. One hypothesis that has not been formally examined is whether and how the recent human evolution may have been shaped by coselection in the context of complex molecular interactome. In this study, genome-wide signals of selection were scanned in East Asians, Europeans, and Africans using 1000 Genome data, and subsequently mapped onto the protein-protein interaction (PPI) network. We found that the candidate genes of recent positive selection localized significantly closer to each other on the PPI network than expected, revealing substantial clustering of selected genes. Furthermore, gene pairs of shorter PPI network distances showed higher similarities of their recent evolutionary paths than those further apart. Last, subnetworks enriched with recent coselection signals were identified, which are substantially overrepresented in biological pathways related to signal transduction, neurogenesis, and immune function. These results provide the first genome-wide evidence for association of recent selection signals with the PPI network, shedding light on the potential mechanisms of recent coselection in the human genome. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Targeted Feature Detection for Data-Dependent Shotgun Proteomics

    PubMed Central

    2017-01-01

    Label-free quantification of shotgun LC–MS/MS data is the prevailing approach in quantitative proteomics but remains computationally nontrivial. The central data analysis step is the detection of peptide-specific signal patterns, called features. Peptide quantification is facilitated by associating signal intensities in features with peptide sequences derived from MS2 spectra; however, missing values due to imperfect feature detection are a common problem. A feature detection approach that directly targets identified peptides (minimizing missing values) but also offers robustness against false-positive features (by assigning meaningful confidence scores) would thus be highly desirable. We developed a new feature detection algorithm within the OpenMS software framework, leveraging ideas and algorithms from the OpenSWATH toolset for DIA/SRM data analysis. Our software, FeatureFinderIdentification (“FFId”), implements a targeted approach to feature detection based on information from identified peptides. This information is encoded in an MS1 assay library, based on which ion chromatogram extraction and detection of feature candidates are carried out. Significantly, when analyzing data from experiments comprising multiple samples, our approach distinguishes between “internal” and “external” (inferred) peptide identifications (IDs) for each sample. On the basis of internal IDs, two sets of positive (true) and negative (decoy) feature candidates are defined. A support vector machine (SVM) classifier is then trained to discriminate between the sets and is subsequently applied to the “uncertain” feature candidates from external IDs, facilitating selection and confidence scoring of the best feature candidate for each peptide. This approach also enables our algorithm to estimate the false discovery rate (FDR) of the feature selection step. We validated FFId based on a public benchmark data set, comprising a yeast cell lysate spiked with protein standards that provide a known ground-truth. The algorithm reached almost complete (>99%) quantification coverage for the full set of peptides identified at 1% FDR (PSM level). Compared with other software solutions for label-free quantification, this is an outstanding result, which was achieved at competitive quantification accuracy and reproducibility across replicates. The FDR for the feature selection was estimated at a low 1.5% on average per sample (3% for features inferred from external peptide IDs). The FFId software is open-source and freely available as part of OpenMS (www.openms.org). PMID:28673088

  3. Targeted Feature Detection for Data-Dependent Shotgun Proteomics.

    PubMed

    Weisser, Hendrik; Choudhary, Jyoti S

    2017-08-04

    Label-free quantification of shotgun LC-MS/MS data is the prevailing approach in quantitative proteomics but remains computationally nontrivial. The central data analysis step is the detection of peptide-specific signal patterns, called features. Peptide quantification is facilitated by associating signal intensities in features with peptide sequences derived from MS2 spectra; however, missing values due to imperfect feature detection are a common problem. A feature detection approach that directly targets identified peptides (minimizing missing values) but also offers robustness against false-positive features (by assigning meaningful confidence scores) would thus be highly desirable. We developed a new feature detection algorithm within the OpenMS software framework, leveraging ideas and algorithms from the OpenSWATH toolset for DIA/SRM data analysis. Our software, FeatureFinderIdentification ("FFId"), implements a targeted approach to feature detection based on information from identified peptides. This information is encoded in an MS1 assay library, based on which ion chromatogram extraction and detection of feature candidates are carried out. Significantly, when analyzing data from experiments comprising multiple samples, our approach distinguishes between "internal" and "external" (inferred) peptide identifications (IDs) for each sample. On the basis of internal IDs, two sets of positive (true) and negative (decoy) feature candidates are defined. A support vector machine (SVM) classifier is then trained to discriminate between the sets and is subsequently applied to the "uncertain" feature candidates from external IDs, facilitating selection and confidence scoring of the best feature candidate for each peptide. This approach also enables our algorithm to estimate the false discovery rate (FDR) of the feature selection step. We validated FFId based on a public benchmark data set, comprising a yeast cell lysate spiked with protein standards that provide a known ground-truth. The algorithm reached almost complete (>99%) quantification coverage for the full set of peptides identified at 1% FDR (PSM level). Compared with other software solutions for label-free quantification, this is an outstanding result, which was achieved at competitive quantification accuracy and reproducibility across replicates. The FDR for the feature selection was estimated at a low 1.5% on average per sample (3% for features inferred from external peptide IDs). The FFId software is open-source and freely available as part of OpenMS ( www.openms.org ).

  4. Detecting signatures of positive selection associated with musical aptitude in the human genome

    PubMed Central

    Liu, Xuanyao; Kanduri, Chakravarthi; Oikkonen, Jaana; Karma, Kai; Raijas, Pirre; Ukkola-Vuoti, Liisa; Teo, Yik-Ying; Järvelä, Irma

    2016-01-01

    Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and FST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude. PMID:26879527

  5. Detecting signatures of positive selection associated with musical aptitude in the human genome.

    PubMed

    Liu, Xuanyao; Kanduri, Chakravarthi; Oikkonen, Jaana; Karma, Kai; Raijas, Pirre; Ukkola-Vuoti, Liisa; Teo, Yik-Ying; Järvelä, Irma

    2016-02-16

    Abilities related to musical aptitude appear to have a long history in human evolution. To elucidate the molecular and evolutionary background of musical aptitude, we compared genome-wide genotyping data (641 K SNPs) of 148 Finnish individuals characterized for musical aptitude. We assigned signatures of positive selection in a case-control setting using three selection methods: haploPS, XP-EHH and FST. Gene ontology classification revealed that the positive selection regions contained genes affecting inner-ear development. Additionally, literature survey has shown that several of the identified genes were known to be involved in auditory perception (e.g. GPR98, USH2A), cognition and memory (e.g. GRIN2B, IL1A, IL1B, RAPGEF5), reward mechanisms (RGS9), and song perception and production of songbirds (e.g. FOXP1, RGS9, GPR98, GRIN2B). Interestingly, genes related to inner-ear development and cognition were also detected in a previous genome-wide association study of musical aptitude. However, the candidate genes detected in this study were not reported earlier in studies of musical abilities. Identification of genes related to language development (FOXP1 and VLDLR) support the popular hypothesis that music and language share a common genetic and evolutionary background. The findings are consistent with the evolutionary conservation of genes related to auditory processes in other species and provide first empirical evidence for signatures of positive selection for abilities that contribute to musical aptitude.

  6. Surgical evaluation of candidates for cochlear implants

    NASA Technical Reports Server (NTRS)

    Black, F. O.; Lilly, D. J.; Fowler, L. P.; Stypulkowski, P. H.

    1987-01-01

    The customary presentation of surgical procedures to patients in the United States consists of discussions on alternative treatment methods, risks of the procedure(s) under consideration, and potential benefits for the patient. Because the contents of the normal speech signal have not been defined in a way that permits a surgeon systematically to provide alternative auditory signals to a deaf patient, the burden is placed on the surgeon to make an arbitrary selection of candidates and available devices for cochlear prosthetic implantation. In an attempt to obtain some information regarding the ability of a deaf patient to use electrical signals to detect and understand speech, the Good Samaritan Hospital and Neurological Sciences Institute cochlear implant team has routinely performed tympanotomies using local anesthesia and has positioned temporary electrodes onto the round windows of implant candidates. The purpose of this paper is to review our experience with this procedure and to provide some observations that may be useful in a comprehensive preoperative evaluation for totally deaf patients who are being considered for cochlear implantation.

  7. GWA Mapping of Anthocyanin Accumulation Reveals Balancing Selection of MYB90 in Arabidopsis thaliana

    PubMed Central

    Bac-Molenaar, Johanna A.; Fradin, Emilie F.; Rienstra, Juriaan A.; Vreugdenhil, Dick; Keurentjes, Joost J. B.

    2015-01-01

    Induction of anthocyanin accumulation by osmotic stress was assessed in 360 accessions of Arabidopsis thaliana. A wide range of natural variation, with phenotypes ranging from green to completely red/purple rosettes, was observed. A genome wide association (GWA) mapping approach revealed that sequence diversity in a small 15 kb region on chromosome 1 explained 40% of the variation observed. Sequence and expression analyses of alleles of the candidate gene MYB90 identified a causal polymorphism at amino acid (AA) position 210 of this transcription factor of the anthocyanin biosynthesis pathway. This amino acid discriminates the two most frequent alleles of MYB90. Both alleles are present in a substantial part of the population, suggesting balancing selection between these two alleles. Analysis of the geographical origin of the studied accessions suggests that the macro climate is not the driving force behind positive or negative selection for anthocyanin accumulation. An important role for local climatic conditions is, therefore, suggested. This study emphasizes that GWA mapping is a powerful approach to identify alleles that are under balancing selection pressure in nature. PMID:26588092

  8. Systems genetics: a paradigm to improve discovery of candidate genes and mechanisms underlying complex traits.

    PubMed

    Feltus, F Alex

    2014-06-01

    Understanding the control of any trait optimally requires the detection of causal genes, gene interaction, and mechanism of action to discover and model the biochemical pathways underlying the expressed phenotype. Functional genomics techniques, including RNA expression profiling via microarray and high-throughput DNA sequencing, allow for the precise genome localization of biological information. Powerful genetic approaches, including quantitative trait locus (QTL) and genome-wide association study mapping, link phenotype with genome positions, yet genetics is less precise in localizing the relevant mechanistic information encoded in DNA. The coupling of salient functional genomic signals with genetically mapped positions is an appealing approach to discover meaningful gene-phenotype relationships. Techniques used to define this genetic-genomic convergence comprise the field of systems genetics. This short review will address an application of systems genetics where RNA profiles are associated with genetically mapped genome positions of individual genes (eQTL mapping) or as gene sets (co-expression network modules). Both approaches can be applied for knowledge independent selection of candidate genes (and possible control mechanisms) underlying complex traits where multiple, likely unlinked, genomic regions might control specific complex traits. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Machine-learning approaches to select Wolf-Rayet candidates

    NASA Astrophysics Data System (ADS)

    Marston, A. P.; Morello, G.; Morris, P.; van Dyk, S.; Mauerhan, J.

    2017-11-01

    The WR stellar population can be distinguished, at least partially, from other stellar populations by broad-band IR colour selection. We present the use of a machine learning classifier to quantitatively improve the selection of Galactic Wolf-Rayet (WR) candidates. These methods are used to separate the other stellar populations which have similar IR colours. We show the results of the classifications obtained by using the 2MASS J, H and K photometric bands, and the Spitzer/IRAC bands at 3.6, 4.5, 5.8 and 8.0μm. The k-Nearest Neighbour method has been used to select Galactic WR candidates for observational follow-up. A few candidates have been spectroscopically observed. Preliminary observations suggest that a detection rate of 50% can easily be achieved.

  10. Improving the efficiency of selection to Core Medical Training: a study of the use of multiple assessment stations.

    PubMed

    Atkinson, J M; Tullo, E; Mitchison, H; Pearce, M S; Kumar, N

    2012-06-01

    To compare three separate assessment stations used for selection to Core Medical Training (CMT) and to determine the effect of reducing the number from three to two. Quantitative analysis of candidates' assessment station scores, financial analysis of costs of the selection process and quantitative and qualitative surveys of candidates and assessors. The assessment stations used for selection to CMT were reliable and valid for assessing suitability for employment as a CMT trainee. There was no significant difference in candidate ranking if only two assessment stations were used rather than three, i.e. there was no change in the likelihood of receiving a job offer. All of the assessment stations were perceived to have face validity by candidates and assessors. The efficiency of the selection process could be improved without loss of quality if two stations were used rather than three. Using two assessment stations rather than three would appear to improve the efficiency and maintain the quality of the CMT selection process while reducing costs.

  11. BallotMaps: detecting name bias in alphabetically ordered ballot papers.

    PubMed

    Wood, Jo; Badawood, Donia; Dykes, Jason; Slingsby, Aidan

    2011-12-01

    The relationship between candidates' position on a ballot paper and vote rank is explored in the case of 5000 candidates for the UK 2010 local government elections in the Greater London area. This design study uses hierarchical spatially arranged graphics to represent two locations that affect candidates at very different scales: the geographical areas for which they seek election and the spatial location of their names on the ballot paper. This approach allows the effect of position bias to be assessed; that is, the degree to which the position of a candidate's name on the ballot paper influences the number of votes received by the candidate, and whether this varies geographically. Results show that position bias was significant enough to influence rank order of candidates, and in the case of many marginal electoral wards, to influence who was elected to government. Position bias was observed most strongly for Liberal Democrat candidates but present for all major political parties. Visual analysis of classification of candidate names by ethnicity suggests that this too had an effect on votes received by candidates, in some cases overcoming alphabetic name bias. The results found contradict some earlier research suggesting that alphabetic name bias was not sufficiently significant to affect electoral outcome and add new evidence for the geographic and ethnicity influences on voting behaviour. The visual approach proposed here can be applied to a wider range of electoral data and the patterns identified and hypotheses derived from them could have significant implications for the design of ballot papers and the conduct of fair elections. © 2010 IEEE

  12. Fine mapping and candidate gene analysis of qFL-chr1, a fiber length QTL in cotton.

    PubMed

    Xu, Peng; Gao, Jin; Cao, Zhibin; Chee, Peng W; Guo, Qi; Xu, Zhenzhen; Paterson, Andrew H; Zhang, Xianggui; Shen, Xinlian

    2017-06-01

    A fiber length QTL, qFL-chr1, was fine mapped to a 0.9 cM interval of cotton chromosome 1. Two positional candidate genes showed positive correlation between gene expression level and fiber length. Prior analysis of a backcross-self mapping population derived from a cross between Gossypium hirsutum L. and G. barbadense L. revealed a QTL on chromosome 1 associated with increased fiber length (qFL-chr1), which was confirmed in three independent populations of near-isogenic introgression lines (NIILs). Here, a single NIIL, R01-40-08, was used to develop a large population segregating for the target region. Twenty-two PCR-based polymorphic markers used to genotype 1672 BC 4 F 2 plants identified 432 recombinants containing breakpoints in the target region. Substitution mapping using 141 informative recombinants narrowed the position of qFL-chr1 to a 1.0-cM interval between SSR markers MUSS084 and CIR018. To exclude possible effects of non-target introgressions on fiber length, different heterozygous BC 4 F 3 plants introgressed between SSR markers NAU3384 and CGR5144 were selected to develop sub-NILs. The qFL-chr1 was further mapped at 0.9-cM interval between MUSS422 and CIR018 by comparisons of sub-NIL phenotype, and increased fiber length by ~1 mm. The 2.38-Mb region between MUSS422 and CIR018 in G. barbadense contained 19 annotated genes. Expression levels of two of these genes, GOBAR07705 (encoding 1-aminocyclopropane-1-carboxylate synthase) and GOBAR25992 (encoding amino acid permease), were positively correlated with fiber length in a small F 2 population, supporting these genes as candidates for qFL-chr1.

  13. Identification of contemporary selection signatures using composite log likelihood and their associations with marbling score in Korean cattle.

    PubMed

    Ryu, Jihye; Lee, Chaeyoung

    2014-12-01

    Positive selection not only increases beneficial allele frequency but also causes augmentation of allele frequencies of sequence variants in close proximity. Signals for positive selection were detected by the statistical differences in subsequent allele frequencies. To identify selection signatures in Korean cattle, we applied a composite log-likelihood (CLL)-based method, which calculates a composite likelihood of the allelic frequencies observed across sliding windows of five adjacent loci and compares the value with the critical statistic estimated by 50,000 permutations. Data for a total of 11,799 nucleotide polymorphisms were used with 71 Korean cattle and 209 foreign beef cattle. As a result, 147 signals were identified for Korean cattle based on CLL estimates (P < 0.01). The signals might be candidate genetic factors for meat quality by which the Korean cattle have been selected. Further genetic association analysis with 41 intragenic variants in the selection signatures with the greatest CLL for each chromosome revealed that marbling score was associated with five variants. Intensive association studies with all the selection signatures identified in this study are required to exclude signals associated with other phenotypes or signals falsely detected and thus to identify genetic markers for meat quality. © 2014 Stichting International Foundation for Animal Genetics.

  14. Discovery of a novel class of potent coumarin monoamine oxidase B inhibitors: development and biopharmacological profiling of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate (NW-1772) as a highly potent, selective, reversible, and orally active monoamine oxidase B inhibitor.

    PubMed

    Pisani, Leonardo; Muncipinto, Giovanni; Miscioscia, Teresa Fabiola; Nicolotti, Orazio; Leonetti, Francesco; Catto, Marco; Caccia, Carla; Salvati, Patricia; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passeleu, Celine; Carotti, Angelo

    2009-11-12

    In an effort to discover novel selective monoamine oxidase (MAO) B inhibitors with favorable physicochemical and pharmacokinetic profiles, 7-[(m-halogeno)benzyloxy]coumarins bearing properly selected polar substituents at position 4 were designed, synthesized, and evaluated as MAO inhibitors. Several compounds with MAO-B inhibitory activity in the nanomolar range and excellent MAO-B selectivity (selectivity index SI > 400) were identified. Structure-affinity relationships and docking simulations provided valuable insights into the enzyme-inhibitor binding interactions at position 4, which has been poorly explored. Furthermore, computational and experimental studies led to the identification and biopharmacological characterization of 7-[(3-chlorobenzyl)oxy]-4-[(methylamino)methyl]-2H-chromen-2-one methanesulfonate 22b (NW-1772) as an in vitro and in vivo potent and selective MAO-B inhibitor, with rapid blood-brain barrier penetration, short-acting and reversible inhibitory activity, slight inhibition of selected cytochrome P450s, and low in vitro toxicity. On the basis of this preliminary preclinical profile, inhibitor 22b might be viewed as a promising clinical candidate for the treatment of neurodegenerative diseases.

  15. A genomic scan for selection reveals candidates for genes involved in the evolution of cultivated sunflower (Helianthus annuus).

    PubMed

    Chapman, Mark A; Pashley, Catherine H; Wenzler, Jessica; Hvala, John; Tang, Shunxue; Knapp, Steven J; Burke, John M

    2008-11-01

    Genomic scans for selection are a useful tool for identifying genes underlying phenotypic transitions. In this article, we describe the results of a genome scan designed to identify candidates for genes targeted by selection during the evolution of cultivated sunflower. This work involved screening 492 loci derived from ESTs on a large panel of wild, primitive (i.e., landrace), and improved sunflower (Helianthus annuus) lines. This sampling strategy allowed us to identify candidates for selectively important genes and investigate the likely timing of selection. Thirty-six genes showed evidence of selection during either domestication or improvement based on multiple criteria, and a sequence-based test of selection on a subset of these loci confirmed this result. In view of what is known about the structure of linkage disequilibrium across the sunflower genome, these genes are themselves likely to have been targeted by selection, rather than being merely linked to the actual targets. While the selection candidates showed a broad range of putative functions, they were enriched for genes involved in amino acid synthesis and protein catabolism. Given that a similar pattern has been detected in maize (Zea mays), this finding suggests that selection on amino acid composition may be a general feature of the evolution of crop plants. In terms of genomic locations, the selection candidates were significantly clustered near quantitative trait loci (QTL) that contribute to phenotypic differences between wild and cultivated sunflower, and specific instances of QTL colocalization provide some clues as to the roles that these genes may have played during sunflower evolution.

  16. An examination of key experiences which contribute to a positive change in attitude toward science in two elementary education teacher candidates at the University of Wyoming

    NASA Astrophysics Data System (ADS)

    Cason, Maggie A.

    This investigation utilized life history methodology (Armstrong, 1987; Bogdan & Biklen, 1998; Lawrence-Lightfoot, 1977; Marshall & Rossman, 1995; Patton, 1987; Taylor & Bogdan; 1984) to examine lifelong science experiences of two elementary education teacher candidates at a land grant institution with a large, undergraduate teacher education program. Purposive sampling techniques (Bogdan & Biklen, 1998) led to the selection of two teacher candidates who reported high science anxiety when they began university coursework. The investigation focused on five broad questions: (a) What were key experiences in the elementary teacher education program which contributed to a positive change in attitude toward science? (b) What science experiences, in and out of school, did the teacher candidates encounter while they were in elementary school, junior high school, high school, and college? (c) How did the elementary education program's science course structure, professors, and field experiences contribute to the change in attitude toward science? (d) How much time was involved in the change in attitude toward science? and (e) What were the effects of the change in attitude on the teaching of science in the elementary classroom? Each candidate completed approximately twenty hours of interviews yielding rich descriptions of their lifelong science experiences. Data also included interviews with science and science education professors, journaling, and observations of student teaching experiences. Data analysis revealed four over-arching themes with implications for teacher educators. First, data showed the importance of relationship building between professors and teacher candidates. Professors must know and work with teacher candidates, and provide a structure that encourages question asking. Second, course structure including hands-on teaching strategies and students working in small groups over an extended period of time was vital. Third, integrating language arts with science proved important because the generally high comfort level experienced by elementary teacher candidates toward language arts may be extended to the teaching of science. Teacher candidates realize the benefits for both teaching and learning when the two subjects are integrated. Last, the study revealed the powerful effects of field experiences which include teaching science in the public schools and demonstrated the drawbacks of field experiences which do not include teaching science.

  17. Dual Career Faculty Appointments: A Successful Model from ADVANCE-Nebraska

    NASA Astrophysics Data System (ADS)

    Holmes, M.; Advance-Nebraska Evaluation Team

    2011-12-01

    At the University of Nebraska-Lincoln (UNL), 20% of short list candidates for faculty openings in science, engineering and mathematics (STEM) brought an academic partner into the hiring picture between 2008 and 2010, with a peak of 38% in 2010. Having a process in place to address dual career opportunities is a key component in an overall strategy to increase the number of women STEM faculty: 83% of academic scientist women's partners are also academics in STEM, according to a 2009 Stanford report, and 54% of academic scientist men's are. Offering two positions to qualified couples benefits the institution by increasing the chances of recruitment and retention of both candidates. UNL's ADVANCE program, ADVANCE-Nebraska, developed a process to take advantage of dual career opportunities. Nine dual career couples have been hired in the last three years; we expected to hire eight during the five-year life of the grant. We increased the proportion of women in the Engineering College by twenty percent (from n=10 to n=12). The success of the program arises from four key components: early notification to short-list candidates of the dual career program, a point person to coordinate dual career requests across the campus, flexible faculty appointments that provide a variety of opportunities for the partner, and a funding stream to support the partner hire. The point person, the ADVANCE Program Director, was created by the provost through the ADVANCE program. The Director communicates with every short list candidate for each open faculty position and with department and search committee chairs across STEM colleges as soon as the candidate is selected. When there is an eligible partner of the candidate who receives the job offer, if there is approval from the Office of Academic Affairs, the Dean of the target college, and the chair and faculty of the partner's target department, the partner is brought to UNL to interview, and the faculty of the partner's target department votes the candidate up or down. The third component provides a variety of faculty positions, including part-time tenure-track, post-doctoral, research professor, and professor of practice positions. Professors of practice are primarily teaching positions with three to five-year renewable contracts. The fourth component, funding, is aided by the NSF ADVANCE cooperative agreement providing one-fourth of the partner's salary for up to three years of the partner's appointment. This gives enough time for the administration to find permanent funding through faculty retirements, departures, or new funding streams. At UNL, department chairs have been exemplary in promoting the necessary cooperative spirit for the program to succeed. This model can be replicated at other institutions. Dual career couples are here to stay, and institutions that see them as great opportunities will win the lottery for the best talent available.

  18. LBNP as useful tool for pilot candidates selection to the Polish Air Force: a preliminary study.

    PubMed

    Romuald, M; Mariusz, Z; Artur, D; Krzysztof, R

    2001-07-01

    Candidates to the Polish Air Force are to fulfill strict medical conditions. Every candidate, wanting to become a fighter pilot or not, has to pass a rigorous centrifuge examination. This is a costly and especially stressful process for the candidates, as first-timers. This article explores possibility for different approach to candidates fitness to fly assessment. 14 candidates (21-22 yrs old) were subjected to a regular GOR centrifuge profile (0.1 G/s; up to +7.0 Gz; unprotected) and to lower body negative pressure (LBNP) examination (2 min. rest period followed by 3 min. at -40 mm Hg; supine position). Both, centrifuge and LBNP examinations were carried out the same day, with about 1 hour gap between them. ECG and impedance cardiography (ICG) were being recorded during both tests. The following parameters were calculated: HR and QZ (time between ventricular depolarization [beginning of the Q wave in ECG] and local maximum of the first derivative [dZ/dt] in ICG). QZ was considered to be an effective measure of dynamic heart function. +Gz tolerance for the group was +5.94 +/- 0.98 Gz. Correlation between +Gz tolerance and QZ values during LBNP test (-40 mm Hg) for all subjects was equal to r=0.6. Correlation between sets of parameters (canonical analysis) for LBNP and centrifuge was equal to r=0.78. Both results were statistically insignificant (p<0.09). Baseline HR values were 121 +/- 19 bpm and 75 +/- 12 bpm, and maximal HR values were 172 +/- 21 bpm and 81 +/- 13 bpm, respectively for centrifuge and LBNP. For both, baseline and maximal HR during LBNP and G exposure canonical correlation was equal to r=0.72. The results were statistically not significant, however. Centrifuge examination is much more stressful than LBNP test. This could have implication on the objective results of centrifuge test. The results may suggest that LBNP test could be a used in pilot candidates selection, especially those presenting high baseline HR values.

  19. Kepler Reliability and Occurrence Rates

    NASA Astrophysics Data System (ADS)

    Bryson, Steve

    2016-10-01

    The Kepler mission has produced tables of exoplanet candidates (``KOI table''), as well as tables of transit detections (``TCE table''), hosted at the Exoplanet Archive (http://exoplanetarchive.ipac.caltech.edu). Transit detections in the TCE table that are plausibly due to a transiting object are selected for inclusion in the KOI table. KOI table entries that have not been identified as false positives (FPs) or false alarms (FAs) are classified as planet candidates (PCs, Mullally et al. 2015). A subset of PCs have been confirmed as planetary transits with greater than 99% probability, but most PCs have <99% probability of being true planets. The fraction of PCs that are true transiting planets is the PC reliability rate. The overall PC population is believed to have a reliability rate >90% (Morton & Johnson 2011).

  20. Worlds Beyond: Follow-up Observations and Confirmation of K2 Exoplanet Candidates

    NASA Astrophysics Data System (ADS)

    O'Connor, Rachel; Lowenthal, James; Lowenthal, James D.; Cooper, Olivia; Helou, Elana; Papineau, Emily; Peck, Annie; Stephens, Loren; Walker, Kerry

    2018-06-01

    We present the results of an 8-month follow-up transit photometry campaign focused on exoplanet candidates produced by the K2 mission. Observations were conducted at the McConnell Rooftop Observatory at Smith College in Northampton, MA, with a 16” telescope and CCD. Targets were observed through a 400-700 nm broadband filter at a 1 minute cadence. We attempted to observe the complete duration of the transit plus a minimum one-hour baseline before and after the transit event whenever possible. Our observations typically reach an RMS of 2 millimags for an 11th-magnitude star. Candidates were selected based on a number of factors, including a transit depth of around 10 millimags, a host star magnitude between 10-13, a duration that is observable over the span of a night, and a period shorter than 30 days. There are currently around 700 unconfirmed exoplanets from K2, and these criteria shortened that list to around 20 ideal candidates, many of which were flagged as possible false positives. Our results showcase the capability of small observatories to conduct precise follow-up observations of exoplanet transits.

  1. 5 CFR 302.401 - Selection and appointment.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... reemployment, reemployment, or regular list on which candidates have not received numerical scores, an agency... candidates have received numerical scores, the agency must make its selection for each vacancy from not more...

  2. 5 CFR 302.401 - Selection and appointment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... reemployment, reemployment, or regular list on which candidates have not received numerical scores, an agency... candidates have received numerical scores, the agency must make its selection for each vacancy from not more...

  3. 5 CFR 302.401 - Selection and appointment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... reemployment, reemployment, or regular list on which candidates have not received numerical scores, an agency... candidates have received numerical scores, the agency must make its selection for each vacancy from not more...

  4. Sequence Evolution and Expression Regulation of Stress-Responsive Genes in Natural Populations of Wild Tomato

    PubMed Central

    Fischer, Iris; Steige, Kim A.; Stephan, Wolfgang; Mboup, Mamadou

    2013-01-01

    The wild tomato species Solanum chilense and S. peruvianum are a valuable non-model system for studying plant adaptation since they grow in diverse environments facing many abiotic constraints. Here we investigate the sequence evolution of regulatory regions of drought and cold responsive genes and their expression regulation. The coding regions of these genes were previously shown to exhibit signatures of positive selection. Expression profiles and sequence evolution of regulatory regions of members of the Asr (ABA/water stress/ripening induced) gene family and the dehydrin gene pLC30-15 were analyzed in wild tomato populations from contrasting environments. For S. chilense, we found that Asr4 and pLC30-15 appear to respond much faster to drought conditions in accessions from very dry environments than accessions from more mesic locations. Sequence analysis suggests that the promoter of Asr2 and the downstream region of pLC30-15 are under positive selection in some local populations of S. chilense. By investigating gene expression differences at the population level we provide further support of our previous conclusions that Asr2, Asr4, and pLC30-15 are promising candidates for functional studies of adaptation. Our analysis also demonstrates the power of the candidate gene approach in evolutionary biology research and highlights the importance of wild Solanum species as a genetic resource for their cultivated relatives. PMID:24205149

  5. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life.

    PubMed

    Wissler, Lothar; Codoñer, Francisco M; Gu, Jenny; Reusch, Thorsten B H; Olsen, Jeanine L; Procaccini, Gabriele; Bornberg-Bauer, Erich

    2011-01-12

    Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs) of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L.) Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica) and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  6. 28 CFR 42.303 - Evaluation of employment opportunities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...'s employment phases (e.g., recruitment, selection, and promotion) and the evaluation of employment... recruitment and selection of entrance candidates and selection of candidates for promotion. (c) In making the... requirements of this section should be cross classified by sex to ascertain the extent to which minority women...

  7. 28 CFR 42.303 - Evaluation of employment opportunities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...'s employment phases (e.g., recruitment, selection, and promotion) and the evaluation of employment... recruitment and selection of entrance candidates and selection of candidates for promotion. (c) In making the... requirements of this section should be cross classified by sex to ascertain the extent to which minority women...

  8. 28 CFR 42.303 - Evaluation of employment opportunities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...'s employment phases (e.g., recruitment, selection, and promotion) and the evaluation of employment... recruitment and selection of entrance candidates and selection of candidates for promotion. (c) In making the... requirements of this section should be cross classified by sex to ascertain the extent to which minority women...

  9. Constraints on the richness-mass relation and the optical-SZE positional offset distribution for SZE-selected clusters

    DOE PAGES

    Saro, A.

    2015-10-12

    In this study, we cross-match galaxy cluster candidates selected via their Sunyaev–Zel'dovich effect (SZE) signatures in 129.1 deg 2 of the South Pole Telescope 2500d SPT-SZ survey with optically identified clusters selected from the Dark Energy Survey science verification data. We identify 25 clusters between 0.1 ≲ z ≲ 0.8 in the union of the SPT-SZ and redMaPPer (RM) samples. RM is an optical cluster finding algorithm that also returns a richness estimate for each cluster. We model the richness λ-mass relation with the following function 500> ∝ B λlnM 500 + C λlnE(z) and use SPT-SZ cluster masses andmore » RM richnesses λ to constrain the parameters. We find B λ = 1.14 +0.21 –0.18 and C λ = 0.73 +0.77 –0.75. The associated scatter in mass at fixed richness is σ lnM|λ = 0.18 +0.08 –0.05 at a characteristic richness λ = 70. We demonstrate that our model provides an adequate description of the matched sample, showing that the fraction of SPT-SZ-selected clusters with RM counterparts is consistent with expectations and that the fraction of RM-selected clusters with SPT-SZ counterparts is in mild tension with expectation. We model the optical-SZE cluster positional offset distribution with the sum of two Gaussians, showing that it is consistent with a dominant, centrally peaked population and a subdominant population characterized by larger offsets. We also cross-match the RM catalogue with SPT-SZ candidates below the official catalogue threshold significance ξ = 4.5, using the RM catalogue to provide optical confirmation and redshifts for 15 additional clusters with ξ ϵ [4, 4.5].« less

  10. Inferring Planet Occurrence Rates With a Q1-Q17 Kepler Planet Candidate Catalog Produced by a Machine Learning Classifier

    NASA Astrophysics Data System (ADS)

    Catanzarite, Joseph; Jenkins, Jon Michael; McCauliff, Sean D.; Burke, Christopher; Bryson, Steve; Batalha, Natalie; Coughlin, Jeffrey; Rowe, Jason; mullally, fergal; thompson, susan; Seader, Shawn; Twicken, Joseph; Li, Jie; morris, robert; smith, jeffrey; haas, michael; christiansen, jessie; Clarke, Bruce

    2015-08-01

    NASA’s Kepler Space Telescope monitored the photometric variations of over 170,000 stars, at half-hour cadence, over its four-year prime mission. The Kepler pipeline calibrates the pixels of the target apertures for each star, produces light curves with simple aperture photometry, corrects for systematic error, and detects threshold-crossing events (TCEs) that may be due to transiting planets. The pipeline estimates planet parameters for all TCEs and computes diagnostics used by the Threshold Crossing Event Review Team (TCERT) to produce a catalog of objects that are deemed either likely transiting planet candidates or false positives.We created a training set from the Q1-Q12 and Q1-Q16 TCERT catalogs and an ensemble of synthetic transiting planets that were injected at the pixel level into all 17 quarters of data, and used it to train a random forest classifier. The classifier uniformly and consistently applies diagnostics developed by the Transiting Planet Search and Data Validation pipeline components and by TCERT to produce a robust catalog of planet candidates.The characteristics of the planet candidates detected by Kepler (planet radius and period) do not reflect the intrinsic planet population. Detection efficiency is a function of SNR, so the set of detected planet candidates is incomplete. Transit detection preferentially finds close-in planets with nearly edge-on orbits and misses planets whose orbital geometry precludes transits. Reliability of the planet candidates must also be considered, as they may be false positives. Errors in detected planet radius and in assumed star properties can also bias inference of intrinsic planet population characteristics.In this work we infer the intrinsic planet population, starting with the catalog of detected planet candidates produced by our random forest classifier, and accounting for detection biases and reliabilities as well as for radius errors in the detected population.Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  11. Inferring Planet Occurrence Rates With a Q1-Q16 Kepler Planet Candidate Catalog Produced by a Machine Learning Classifier

    NASA Astrophysics Data System (ADS)

    Catanzarite, Joseph; Jenkins, Jon Michael; Burke, Christopher J.; McCauliff, Sean D.; Kepler Science Operations Center

    2015-01-01

    NASA's Kepler Space Telescope monitored the photometric variations of over 170,000 stars within a ~100 square degree field in the constellation Cygnus, at half-hour cadence, over its four year prime mission. The Kepler SOC (Science Operations Center) pipeline calibrates the pixels of the target apertures for each star, corrects light curves for systematic error, and detects TCEs (threshold-crossing events) that may be due to transiting planets. Finally the pipeline estimates planet parameters for all TCEs and computes quantitative diagnostics that are used by the TCERT (Threshold Crossing Event Review Team) to produce a catalog containing KOIs (Kepler Objects of Interest). KOIs are TCEs that are determined to be either likely transiting planets or astrophysical false positives such as background eclipsing binary stars. Using examples from the Q1-Q16 TCERT KOI catalog as a training set, we created a machine-learning classifier that dispositions the TCEs into categories of PC (planet candidate), AFP (astrophysical false positive) and NTP (non-transiting phenomenon). The classifier uniformly and consistently applies heuristics developed by TCERT as well as other diagnostics to the Q1-Q16 TCEs to produce a more robust and reliable catalog of planet candidates than is possible with only human classification. In this work, we estimate planet occurrence rates, based on the machine-learning-produced catalog of Kepler planet candidates. Kepler was selected as the 10th mission of the Discovery Program. Funding for this mission is provided by NASA, Science Mission Directorate.

  12. Neighbouring-group composition and within-group relatedness drive extra-group paternity rate in the European badger (Meles meles)

    PubMed Central

    Annavi, G; Newman, C; Dugdale, H L; Buesching, C D; Sin, Y W; Burke, T; Macdonald, D W

    2014-01-01

    Extra-group paternity (EGP) occurs commonly among group-living mammals and plays an important role in mating systems and the dynamics of sexual selection; however, socio-ecological and genetic correlates of EGP have been underexplored. We use 23 years of demographic and genetic data from a high-density European badger (Meles meles) population, to investigate the relationship between the rate of EGP in litters and mate availability, mate incompatibility and mate quality (heterozygosity). Relatedness between within-group assigned mothers and candidate fathers had a negative quadratic effect on EGP, whereas the number of neighbouring-group candidate fathers had a linear positive effect. We detected no effect of mean or maximum heterozygosity of within-group candidate fathers on EGP. Consequently, EGP was associated primarily with mate availability, subject to within-group genetic effects, potentially to mitigate mate incompatibility and inbreeding. In badgers, cryptic female choice, facilitated by superfecundation, superfoetation and delayed implantation, prevents males from monopolizing within-group females. This resonates with a meta-analysis in group-living mammals, which proposed that higher rates of EGP occur when within-group males cannot monopolize within-group females. In contrast to the positive meta-analytic association, however, we found that EGP associated negatively with the number of within-group assigned mothers and the number of within-group candidate fathers; potentially a strategy to counter within-group males committing infanticide. The relationship between the rate of EGP and socio-ecological or genetic factors can therefore be intricate, and the potential for cryptic female choice must be accounted for in comparative studies. PMID:25234113

  13. HERSCHEL-ATLAS: TOWARD A SAMPLE OF {approx}1000 STRONGLY LENSED GALAXIES

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

    Gonzalez-Nuevo, J.; Lapi, A.; Bressan, S.

    2012-04-10

    While the selection of strongly lensed galaxies (SLGs) with 500 {mu}m flux density S{sub 500} > 100 mJy has proven to be rather straightforward, for many applications it is important to analyze samples larger than the ones obtained when confining ourselves to such a bright limit. Moreover, only by probing to fainter flux densities is it possible to exploit strong lensing to investigate the bulk of the high-z star-forming galaxy population. We describe HALOS (the Herschel-ATLAS Lensed Objects Selection), a method for efficiently selecting fainter candidate SLGs, reaching a surface density of {approx_equal} 1.5-2 deg{sup -2}, i.e., a factor ofmore » about 4-6 higher than that at the 100 mJy flux limit. HALOS will allow the selection of up to {approx}1000 candidate SLGs (with amplifications {mu} {approx}> 2) over the full H-ATLAS survey area. Applying HALOS to the H-ATLAS Science Demonstration Phase field ({approx_equal} 14.4 deg{sup 2}) we find 31 candidate SLGs, whose candidate lenses are identified in the VIKING near-infrared catalog. Using the available information on candidate sources and candidate lenses we tentatively estimate a {approx_equal} 72% purity of the sample. As expected, the purity decreases with decreasing flux density of the sources and with increasing angular separation between candidate sources and lenses. The redshift distribution of the candidate lensed sources is close to that reported for most previous surveys for lensed galaxies, while that of candidate lenses extends to redshifts substantially higher than found in the other surveys. The counts of candidate SLGs are also in good agreement with model predictions. Even though a key ingredient of the method is the deep near-infrared VIKING photometry, we show that H-ATLAS data alone allow the selection of a similarly deep sample of candidate SLGs with an efficiency close to 50%; a slightly lower surface density ({approx_equal} 1.45 deg{sup -2}) can be reached with a {approx}70% efficiency.« less

  14. Solar Radiation-Associated Adaptive SNP Genetic Differentiation in Wild Emmer Wheat, Triticum dicoccoides.

    PubMed

    Ren, Jing; Chen, Liang; Jin, Xiaoli; Zhang, Miaomiao; You, Frank M; Wang, Jirui; Frenkel, Vladimir; Yin, Xuegui; Nevo, Eviatar; Sun, Dongfa; Luo, Ming-Cheng; Peng, Junhua

    2017-01-01

    Whole-genome scans with large number of genetic markers provide the opportunity to investigate local adaptation in natural populations and identify candidate genes under positive selection. In the present study, adaptation genetic differentiation associated with solar radiation was investigated using 695 polymorphic SNP markers in wild emmer wheat originated in a micro-site at Yehudiyya, Israel. The test involved two solar radiation niches: (1) sun, in-between trees; and (2) shade, under tree canopy, separated apart by a distance of 2-4 m. Analysis of molecular variance showed a small (0.53%) but significant portion of overall variation between the sun and shade micro-niches, indicating a non-ignorable genetic differentiation between sun and shade habitats. Fifty SNP markers showed a medium (0.05 ≤ F ST ≤ 0.15) or high genetic differentiation ( F ST > 0.15). A total of 21 outlier loci under positive selection were identified by using four different F ST -outlier testing algorithms. The markers and genome locations under positive selection are consistent with the known patterns of selection. These results suggested that genetic differentiation between sun and shade habitats is substantial, radiation-associated, and therefore ecologically determined. Hence, the results of this study reflected effects of natural selection through solar radiation on EST-related SNP genetic diversity, resulting presumably in different adaptive complexes at a micro-scale divergence. The present work highlights the evolutionary theory and application significance of solar radiation-driven natural selection in wheat improvement.

  15. Automated vector selection of SIVQ and parallel computing integration MATLAB™: Innovations supporting large-scale and high-throughput image analysis studies.

    PubMed

    Cheng, Jerome; Hipp, Jason; Monaco, James; Lucas, David R; Madabhushi, Anant; Balis, Ulysses J

    2011-01-01

    Spatially invariant vector quantization (SIVQ) is a texture and color-based image matching algorithm that queries the image space through the use of ring vectors. In prior studies, the selection of one or more optimal vectors for a particular feature of interest required a manual process, with the user initially stochastically selecting candidate vectors and subsequently testing them upon other regions of the image to verify the vector's sensitivity and specificity properties (typically by reviewing a resultant heat map). In carrying out the prior efforts, the SIVQ algorithm was noted to exhibit highly scalable computational properties, where each region of analysis can take place independently of others, making a compelling case for the exploration of its deployment on high-throughput computing platforms, with the hypothesis that such an exercise will result in performance gains that scale linearly with increasing processor count. An automated process was developed for the selection of optimal ring vectors to serve as the predicate matching operator in defining histopathological features of interest. Briefly, candidate vectors were generated from every possible coordinate origin within a user-defined vector selection area (VSA) and subsequently compared against user-identified positive and negative "ground truth" regions on the same image. Each vector from the VSA was assessed for its goodness-of-fit to both the positive and negative areas via the use of the receiver operating characteristic (ROC) transfer function, with each assessment resulting in an associated area-under-the-curve (AUC) figure of merit. Use of the above-mentioned automated vector selection process was demonstrated in two cases of use: First, to identify malignant colonic epithelium, and second, to identify soft tissue sarcoma. For both examples, a very satisfactory optimized vector was identified, as defined by the AUC metric. Finally, as an additional effort directed towards attaining high-throughput capability for the SIVQ algorithm, we demonstrated the successful incorporation of it with the MATrix LABoratory (MATLAB™) application interface. The SIVQ algorithm is suitable for automated vector selection settings and high throughput computation.

  16. Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing, Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase.

    PubMed

    Huang, Wei-Sheng; Liu, Shuangying; Zou, Dong; Thomas, Mathew; Wang, Yihan; Zhou, Tianjun; Romero, Jan; Kohlmann, Anna; Li, Feng; Qi, Jiwei; Cai, Lisi; Dwight, Timothy A; Xu, Yongjin; Xu, Rongsong; Dodd, Rory; Toms, Angela; Parillon, Lois; Lu, Xiaohui; Anjum, Rana; Zhang, Sen; Wang, Frank; Keats, Jeffrey; Wardwell, Scott D; Ning, Yaoyu; Xu, Qihong; Moran, Lauren E; Mohemmad, Qurish K; Jang, Hyun Gyung; Clackson, Tim; Narasimhan, Narayana I; Rivera, Victor M; Zhu, Xiaotian; Dalgarno, David; Shakespeare, William C

    2016-05-26

    In the treatment of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase positive (ALK+) non-small-cell lung cancer (NSCLC), secondary mutations within the ALK kinase domain have emerged as a major resistance mechanism to both first- and second-generation ALK inhibitors. This report describes the design and synthesis of a series of 2,4-diarylaminopyrimidine-based potent and selective ALK inhibitors culminating in identification of the investigational clinical candidate brigatinib. A unique structural feature of brigatinib is a phosphine oxide, an overlooked but novel hydrogen-bond acceptor that drives potency and selectivity in addition to favorable ADME properties. Brigatinib displayed low nanomolar IC50s against native ALK and all tested clinically relevant ALK mutants in both enzyme-based biochemical and cell-based viability assays and demonstrated efficacy in multiple ALK+ xenografts in mice, including Karpas-299 (anaplastic large-cell lymphomas [ALCL]) and H3122 (NSCLC). Brigatinib represents the most clinically advanced phosphine oxide-containing drug candidate to date and is currently being evaluated in a global phase 2 registration trial.

  17. Genome-Wide Association Study of Piglet Uniformity and Farrowing Interval

    PubMed Central

    Wang, Yuan; Ding, Xiangdong; Tan, Zhen; Ning, Chao; Xing, Kai; Yang, Ting; Pan, Yongjie; Sun, Dongxiao; Wang, Chuduan

    2017-01-01

    Piglet uniformity (PU) and farrowing interval (FI) are important reproductive traits related to production and economic profits in the pig industry. However, the genetic architecture of the longitudinal trends of reproductive traits still remains elusive. Herein, we performed a genome-wide association study (GWAS) to detect potential genetic variation and candidate genes underlying the phenotypic records at different parities for PU and FI in a population of 884 Large White pigs. In total, 12 significant SNPs were detected on SSC1, 3, 4, 9, and 14, which collectively explained 1–1.79% of the phenotypic variance for PU from parity 1 to 4, and 2.58–4.11% for FI at different stages. Of these, seven SNPs were located within 16 QTL regions related to swine reproductive traits. One QTL region was associated with birth body weight (related to PU) and contained the peak SNP MARC0040730, and another was associated with plasma FSH concentration (related to FI) and contained the SNP MARC0031325. Finally, some positional candidate genes for PU and FI were identified because of their roles in prenatal skeletal muscle development, fetal energy substrate, pre-implantation, and the expression of mammary gland epithelium. Identification of novel variants and candidate genes will greatly advance our understanding of the genetic mechanisms of PU and FI, and suggest a specific opportunity for improving marker assisted selection or genomic selection in pigs. PMID:29234349

  18. Pulmonary nodule detection using a cascaded SVM classifier

    NASA Astrophysics Data System (ADS)

    Bergtholdt, Martin; Wiemker, Rafael; Klinder, Tobias

    2016-03-01

    Automatic detection of lung nodules from chest CT has been researched intensively over the last decades resulting also in several commercial products. However, solutions are adopted only slowly into daily clinical routine as many current CAD systems still potentially miss true nodules while at the same time generating too many false positives (FP). While many earlier approaches had to rely on rather few cases for development, larger databases become now available and can be used for algorithmic development. In this paper, we address the problem of lung nodule detection via a cascaded SVM classifier. The idea is to sequentially perform two classification tasks in order to select from an extremely large pool of potential candidates the few most likely ones. As the initial pool is allowed to contain thousands of candidates, very loose criteria could be applied during this pre-selection. In this way, the chances that a true nodule is falsely rejected as a candidate are reduced significantly. The final algorithm is trained and tested on the full LIDC/IDRI database. Comparison is done against two previously published CAD systems. Overall, the algorithm achieved sensitivity of 0.859 at 2.5 FP/volume where the other two achieved sensitivity values of 0.321 and 0.625, respectively. On low dose data sets, only slight increase in the number of FP/volume was observed, while the sensitivity was not affected.

  19. Breeding maize for silage and biofuel production, an illustration of a step forward with the genome sequence.

    PubMed

    Barrière, Yves; Courtial, Audrey; Chateigner-Boutin, Anne-Laure; Denoue, Dominique; Grima-Pettenati, Jacqueline

    2016-01-01

    The knowledge of the gene families mostly impacting cell wall digestibility variations would significantly increase the efficiency of marker-assisted selection when breeding maize and grass varieties with improved silage feeding value and/or with better straw fermentability into alcohol or methane. The maize genome sequence of the B73 inbred line was released at the end of 2009, opening up new avenues to identify the genetic determinants of quantitative traits. Colocalizations between a large set of candidate genes putatively involved in secondary cell wall assembly and QTLs for cell wall digestibility (IVNDFD) were then investigated, considering physical positions of both genes and QTLs. Based on available data from six RIL progenies, 59 QTLs corresponding to 38 non-overlapping positions were matched up with a list of 442 genes distributed all over the genome. Altogether, 176 genes colocalized with IVNDFD QTLs and most often, several candidate genes colocalized at each QTL position. Frequent QTL colocalizations were found firstly with genes encoding ZmMYB and ZmNAC transcription factors, and secondly with genes encoding zinc finger, bHLH, and xylogen regulation factors. In contrast, close colocalizations were less frequent with genes involved in monolignol biosynthesis, and found only with the C4H2, CCoAOMT5, and CCR1 genes. Close colocalizations were also infrequent with genes involved in cell wall feruloylation and cross-linkages. Altogether, investigated colocalizations between candidate genes and cell wall digestibility QTLs suggested a prevalent role of regulation factors over constitutive cell wall genes on digestibility variations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

    PubMed

    Liu, X; Liu, H; Guo, Z; Luan, W

    2006-01-01

    To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

  1. An Improved WiFi Indoor Positioning Algorithm by Weighted Fusion

    PubMed Central

    Ma, Rui; Guo, Qiang; Hu, Changzhen; Xue, Jingfeng

    2015-01-01

    The rapid development of mobile Internet has offered the opportunity for WiFi indoor positioning to come under the spotlight due to its low cost. However, nowadays the accuracy of WiFi indoor positioning cannot meet the demands of practical applications. To solve this problem, this paper proposes an improved WiFi indoor positioning algorithm by weighted fusion. The proposed algorithm is based on traditional location fingerprinting algorithms and consists of two stages: the offline acquisition and the online positioning. The offline acquisition process selects optimal parameters to complete the signal acquisition, and it forms a database of fingerprints by error classification and handling. To further improve the accuracy of positioning, the online positioning process first uses a pre-match method to select the candidate fingerprints to shorten the positioning time. After that, it uses the improved Euclidean distance and the improved joint probability to calculate two intermediate results, and further calculates the final result from these two intermediate results by weighted fusion. The improved Euclidean distance introduces the standard deviation of WiFi signal strength to smooth the WiFi signal fluctuation and the improved joint probability introduces the logarithmic calculation to reduce the difference between probability values. Comparing the proposed algorithm, the Euclidean distance based WKNN algorithm and the joint probability algorithm, the experimental results indicate that the proposed algorithm has higher positioning accuracy. PMID:26334278

  2. An Improved WiFi Indoor Positioning Algorithm by Weighted Fusion.

    PubMed

    Ma, Rui; Guo, Qiang; Hu, Changzhen; Xue, Jingfeng

    2015-08-31

    The rapid development of mobile Internet has offered the opportunity for WiFi indoor positioning to come under the spotlight due to its low cost. However, nowadays the accuracy of WiFi indoor positioning cannot meet the demands of practical applications. To solve this problem, this paper proposes an improved WiFi indoor positioning algorithm by weighted fusion. The proposed algorithm is based on traditional location fingerprinting algorithms and consists of two stages: the offline acquisition and the online positioning. The offline acquisition process selects optimal parameters to complete the signal acquisition, and it forms a database of fingerprints by error classification and handling. To further improve the accuracy of positioning, the online positioning process first uses a pre-match method to select the candidate fingerprints to shorten the positioning time. After that, it uses the improved Euclidean distance and the improved joint probability to calculate two intermediate results, and further calculates the final result from these two intermediate results by weighted fusion. The improved Euclidean distance introduces the standard deviation of WiFi signal strength to smooth the WiFi signal fluctuation and the improved joint probability introduces the logarithmic calculation to reduce the difference between probability values. Comparing the proposed algorithm, the Euclidean distance based WKNN algorithm and the joint probability algorithm, the experimental results indicate that the proposed algorithm has higher positioning accuracy.

  3. High-resolution analysis of selection sweeps identified between fine-wool Merino and coarse-wool Churra sheep breeds.

    PubMed

    Gutiérrez-Gil, Beatriz; Esteban-Blanco, Cristina; Wiener, Pamela; Chitneedi, Praveen Krishna; Suarez-Vega, Aroa; Arranz, Juan-Jose

    2017-11-07

    With the aim of identifying selection signals in three Merino sheep lines that are highly specialized for fine wool production (Australian Industry Merino, Australian Merino and Australian Poll Merino) and considering that these lines have been subjected to selection not only for wool traits but also for growth and carcass traits and parasite resistance, we contrasted the OvineSNP50 BeadChip (50 K-chip) pooled genotypes of these Merino lines with the genotypes of a coarse-wool breed, phylogenetically related breed, Spanish Churra dairy sheep. Genome re-sequencing datasets of the two breeds were analyzed to further explore the genetic variation of the regions initially identified as putative selection signals. Based on the 50 K-chip genotypes, we used the overlapping selection signals (SS) identified by four selection sweep mapping analyses (that detect genetic differentiation, reduced heterozygosity and patterns of haplotype diversity) to define 18 convergence candidate regions (CCR), five associated with positive selection in Australian Merino and the remainder indicating positive selection in Churra. Subsequent analysis of whole-genome sequences from 15 Churra and 13 Merino samples identified 142,400 genetic variants (139,745 bi-allelic SNPs and 2655 indels) within the 18 defined CCR. Annotation of 1291 variants that were significantly associated with breed identity between Churra and Merino samples identified 257 intragenic variants that caused 296 functional annotation variants, 275 of which were located across 31 coding genes. Among these, four synonymous and four missense variants (NPR2_His847Arg, NCAPG_Ser585Phe, LCORL_Asp1214Glu and LCORL_Ile1441Leu) were included. Here, we report the mapping and genetic variation of 18 selection signatures that were identified between Australian Merino and Spanish Churra sheep breeds, which were validated by an additional contrast between Spanish Merino and Churra genotypes. Analysis of whole-genome sequencing datasets allowed us to identify divergent variants that may be viewed as candidates involved in the phenotypic differences for wool, growth and meat production/quality traits between the breeds analyzed. The four missense variants located in the NPR2, NCAPG and LCORL genes may be related to selection sweep regions previously identified and various QTL reported in sheep in relation to growth traits and carcass composition.

  4. Defining the role of the MADS-box gene, Zea agamous like1, in maize domestication

    USDA-ARS?s Scientific Manuscript database

    Genomic scans for genes that show the signature of past selection have been widely applied to a number of species and have identified a large number of selection candidate genes. In cultivated maize (Zea mays ssp. mays) selection scans have identified several hundred candidate domestication genes...

  5. Using Association Mapping in Teosinte (Zea Mays ssp Parviglumis) to Investigate the Function of Selection-Candidate Genes

    USDA-ARS?s Scientific Manuscript database

    Large-scale screens of the maize genome identified 48 genes that show the putative signature of artificial selection during maize domestication or improvement. These selection-candidate genes may act as quantitative trait loci (QTL) that control the phenotypic differences between maize and its proge...

  6. Financial methods for waterflooding injectate design

    DOEpatents

    Heneman, Helmuth J.; Brady, Patrick V.

    2017-08-08

    A method of selecting an injectate for recovering liquid hydrocarbons from a reservoir includes designing a plurality of injectates, calculating a net present value of each injectate, and selecting a candidate injectate based on the net present value. For example, the candidate injectate may be selected to maximize the net present value of a waterflooding operation.

  7. Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates.

    PubMed

    Braggio, Simone; Montanari, Dino; Rossi, Tino; Ratti, Emiliangelo

    2010-07-01

    As a result of their wide acceptance and conceptual simplicity, drug-like concepts are having a major influence on the drug discovery process, particularly in the selection of the 'optimal' absorption, distribution, metabolism, excretion and toxicity and physicochemical parameters space. While they have an undisputable value when assessing the potential of lead series or in evaluating inherent risk of a portfolio of drug candidates, they result much less useful in weighing up compounds for the selection of the best potential clinical candidate. We introduce the concept of drug efficiency as a new tool both to guide the drug discovery program teams during the lead optimization phase and to better assess the developability potential of a drug candidate.

  8. A first generation BAC-based physical map of the rainbow trout genome

    PubMed Central

    Palti, Yniv; Luo, Ming-Cheng; Hu, Yuqin; Genet, Carine; You, Frank M; Vallejo, Roger L; Thorgaard, Gary H; Wheeler, Paul A; Rexroad, Caird E

    2009-01-01

    Background Rainbow trout (Oncorhynchus mykiss) are the most-widely cultivated cold freshwater fish in the world and an important model species for many research areas. Coupling great interest in this species as a research model with the need for genetic improvement of aquaculture production efficiency traits justifies the continued development of genomics research resources. Many quantitative trait loci (QTL) have been identified for production and life-history traits in rainbow trout. A bacterial artificial chromosome (BAC) physical map is needed to facilitate fine mapping of QTL and the selection of positional candidate genes for incorporation in marker-assisted selection (MAS) for improving rainbow trout aquaculture production. This resource will also facilitate efforts to obtain and assemble a whole-genome reference sequence for this species. Results The physical map was constructed from DNA fingerprinting of 192,096 BAC clones using the 4-color high-information content fingerprinting (HICF) method. The clones were assembled into physical map contigs using the finger-printing contig (FPC) program. The map is composed of 4,173 contigs and 9,379 singletons. The total number of unique fingerprinting fragments (consensus bands) in contigs is 1,185,157, which corresponds to an estimated physical length of 2.0 Gb. The map assembly was validated by 1) comparison with probe hybridization results and agarose gel fingerprinting contigs; and 2) anchoring large contigs to the microsatellite-based genetic linkage map. Conclusion The production and validation of the first BAC physical map of the rainbow trout genome is described in this paper. We are currently integrating this map with the NCCCWA genetic map using more than 200 microsatellites isolated from BAC end sequences and by identifying BACs that harbor more than 300 previously mapped markers. The availability of an integrated physical and genetic map will enable detailed comparative genome analyses, fine mapping of QTL, positional cloning, selection of positional candidate genes for economically important traits and the incorporation of MAS into rainbow trout breeding programs. PMID:19814815

  9. Biocybernetic system evaluates indices of operator engagement in automated task

    NASA Technical Reports Server (NTRS)

    Pope, A. T.; Bogart, E. H.; Bartolome, D. S.

    1995-01-01

    A biocybernetic system has been developed as a method to evaluate automated flight deck concepts for compatibility with human capabilities. A biocybernetic loop is formed by adjusting the mode of operation of a task set (e.g., manual/automated mix) based on electroencephalographic (EEG) signals reflecting an operator's engagement in the task set. A critical issue for the loop operation is the selection of features of the EEG to provide an index of engagement upon which to base decisions to adjust task mode. Subjects were run in the closed-loop feedback configuration under four candidate and three experimental control definitions of an engagement index. The temporal patterning of system mode switching was observed for both positive and negative feedback of the index. The indices were judged on the basis of their relative strength in exhibiting expected feedback control system phenomena (stable operation under negative feedback and unstable operation under positive feedback). Of the candidate indices evaluated in this study, an index constructed according to the formula, beta power/(alpha power + theta power), reflected task engagement best.

  10. Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: evidence from genome-wide analyses.

    PubMed

    Crosley, E J; Elliot, M G; Christians, J K; Crespi, B J

    2013-02-01

    Recent evidence from chimpanzees and gorillas has raised doubts that preeclampsia is a uniquely human disease. The deep extravillous trophoblast (EVT) invasion and spiral artery remodeling that characterizes our placenta (and is abnormal in preeclampsia) is shared within great apes, setting Homininae apart from Hylobatidae and Old World Monkeys, which show much shallower trophoblast invasion and limited spiral artery remodeling. We hypothesize that the evolution of a more invasive placenta in the lineage ancestral to the great apes involved positive selection on genes crucial to EVT invasion and spiral artery remodeling. Furthermore, identification of placentally-expressed genes under selection in this lineage may identify novel genes involved in placental development. We tested for positive selection in approximately 18,000 genes using the ratio of non-synonymous to synonymous amino acid substitution for protein-coding DNA. DAVID Bioinformatics Resources identified biological processes enriched in positively selected genes, including processes related to EVT invasion and spiral artery remodeling. Analyses revealed 295 and 264 genes under significant positive selection on the branches ancestral to Hominidae (Human, Chimp, Gorilla, Orangutan) and Homininae (Human, Chimp, Gorilla), respectively. Gene ontology analysis of these gene sets demonstrated significant enrichments for several functional gene clusters relevant to preeclampsia risk, and sets of placentally-expressed genes that have been linked with preeclampsia and/or trophoblast invasion in other studies. Our study represents a novel approach to the identification of candidate genes and amino acid residues involved in placental pathologies by implicating them in the evolution of highly-invasive placenta. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. An Investigation on Teacher Candidates' Perspectives about Behaviors Positively Affecting Classroom Atmosphere

    ERIC Educational Resources Information Center

    Bulut Ozsezer, M. Spencer; Iflazoglu Saban, Ayten

    2016-01-01

    Problem Statement: A revision of literature shows that there are studies focusing on student and teacher perceptions of classroom atmosphere; however, no research has been found to be related to teacher candidates' perspectives on their behaviors in terms of positive classroom atmosphere. As teacher candidates are the main subject and the future…

  12. The stellar content of the Hamburg/ESO survey. IV. Selection of candidate metal-poor stars

    NASA Astrophysics Data System (ADS)

    Christlieb, N.; Schörck, T.; Frebel, A.; Beers, T. C.; Wisotzki, L.; Reimers, D.

    2008-06-01

    We present the quantitative methods used for selecting candidate metal-poor stars in the Hamburg/ESO objective-prism survey (HES). The selection is based on the strength of the Ca II K line, B-V colors (both measured directly from the digital HES spectra), as well as J-K colors from the 2 Micron All Sky Survey. The KP index for Ca II K can be measured from the HES spectra with an accuracy of 1.0 Å, and a calibration of the HES B-V colors, using CCD photometry, yields a 1-σ uncertainty of 0.07 mag for stars in the color range 0.3 < B-V < 1.4. These accuracies make it possible to reliably reject stars with [Fe/H] > -2.0 without sacrificing completeness at the lowest metallicities. A test of the selection using 1121 stars of the HK survey of Beers, Preston, and Shectman present on HES plates suggests that the completeness at [Fe/H] < -3.5 is close to 100% and that, at the same time, the contamination of the candidate sample with false positives is low: 50% of all stars with [Fe/H] > -2.5 and 97% of all stars with [Fe/H] > -2.0 are rejected. The selection was applied to 379 HES fields, covering a nominal area of 8853 deg2 of the southern high Galactic latitude sky. The candidate sample consists of 20 271 stars in the magnitude range 10 ≲ B ≲ 18. A comparison of the magnitude distribution with that of the HK survey shows that the magnitude limit of the HES sample is about 2 mag fainter. Taking the overlap of the sky areas covered by both surveys into account, it follows that the survey volume for metal-poor stars has been increased by the HES by about a factor of 10 with respect to the HK survey. We have already identified several very rare objects with the HES, including, e.g., the three most heavy-element deficient stars currently known. Based on observations collected at the European Southern Observatory, Chile (Proposal ID 145.B-0009). Tables A.1 and A.2 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/484/721

  13. Genome-wide scans for candidate genes involved in the aquatic adaptation of dolphins.

    PubMed

    Sun, Yan-Bo; Zhou, Wei-Ping; Liu, He-Qun; Irwin, David M; Shen, Yong-Yi; Zhang, Ya-Ping

    2013-01-01

    Since their divergence from the terrestrial artiodactyls, cetaceans have fully adapted to an aquatic lifestyle, which represents one of the most dramatic transformations in mammalian evolutionary history. Numerous morphological and physiological characters of cetaceans have been acquired in response to this drastic habitat transition, such as thickened blubber, echolocation, and ability to hold their breath for a long period of time. However, knowledge about the molecular basis underlying these adaptations is still limited. The sequence of the genome of Tursiops truncates provides an opportunity for a comparative genomic analyses to examine the molecular adaptation of this species. Here, we constructed 11,838 high-quality orthologous gene alignments culled from the dolphin and four other terrestrial mammalian genomes and screened for positive selection occurring in the dolphin lineage. In total, 368 (3.1%) of the genes were identified as having undergone positive selection by the branch-site model. Functional characterization of these genes showed that they are significantly enriched in the categories of lipid transport and localization, ATPase activity, sense perception of sound, and muscle contraction, areas that are potentially related to cetacean adaptations. In contrast, we did not find a similar pattern in the cow, a closely related species. We resequenced some of the positively selected sites (PSSs), within the positively selected genes, and showed that most of our identified PSSs (50/52) could be replicated. The results from this study should have important implications for our understanding of cetacean evolution and their adaptations to the aquatic environment.

  14. Development and validation of novel AAV2 random libraries displaying peptides of diverse lengths and at diverse capsid positions.

    PubMed

    Naumer, Matthias; Ying, Ying; Michelfelder, Stefan; Reuter, Antje; Trepel, Martin; Müller, Oliver J; Kleinschmidt, Jürgen A

    2012-05-01

    Libraries based on the insertion of random peptide ligands into the capsid of adeno-associated virus type 2 (AAV2) have been widely used to improve the efficiency and selectivity of the AAV vector system. However, so far only libraries of 7-mer peptide ligands have been inserted at one well-characterized capsid position. Here, we expanded the combinatorial AAV2 display system to a panel of novel AAV libraries, displaying peptides of 5, 7, 12, 19, or 26 amino acids in length at capsid position 588 or displaying 7-mer peptides at position 453, the most prominently exposed region of the viral capsid. Library selections on two unrelated cell types-human coronary artery endothelial cells and rat cardiomyoblasts-revealed the isolation of cell type-characteristic peptides of different lengths mediating strongly improved target-cell transduction, except for the 26-mer peptide ligands. Characterization of vector selectivity by transduction of nontarget cells and comparative gene-transduction analysis using a panel of 44 human tumor cell lines revealed that insertion of different-length peptides allows targeting of distinct cellular receptors for cell entry with similar efficiency, but with different selectivity. The application of such novel AAV2 libraries broadens the spectrum of targetable receptors by capsid-modified AAV vectors and provides the opportunity to choose the best suited targeting ligand for a certain application from a number of different candidates.

  15. Whole genome sequencing of turbot (Scophthalmus maximus; Pleuronectiformes): a fish adapted to demersal life

    PubMed Central

    Figueras, Antonio; Robledo, Diego; Corvelo, André; Hermida, Miguel; Pereiro, Patricia; Rubiolo, Juan A.; Gómez-Garrido, Jèssica; Carreté, Laia; Bello, Xabier; Gut, Marta; Gut, Ivo Glynne; Marcet-Houben, Marina; Forn-Cuní, Gabriel; Galán, Beatriz; García, José Luis; Abal-Fabeiro, José Luis; Pardo, Belen G.; Taboada, Xoana; Fernández, Carlos; Vlasova, Anna; Hermoso-Pulido, Antonio; Guigó, Roderic; Álvarez-Dios, José Antonio; Gómez-Tato, Antonio; Viñas, Ana; Maside, Xulio; Gabaldón, Toni; Novoa, Beatriz; Bouza, Carmen; Alioto, Tyler; Martínez, Paulino

    2016-01-01

    The turbot is a flatfish (Pleuronectiformes) with increasing commercial value, which has prompted active genomic research aimed at more efficient selection. Here we present the sequence and annotation of the turbot genome, which represents a milestone for both boosting breeding programmes and ascertaining the origin and diversification of flatfish. We compare the turbot genome with model fish genomes to investigate teleost chromosome evolution. We observe a conserved macrosyntenic pattern within Percomorpha and identify large syntenic blocks within the turbot genome related to the teleost genome duplication. We identify gene family expansions and positive selection of genes associated with vision and metabolism of membrane lipids, which suggests adaptation to demersal lifestyle and to cold temperatures, respectively. Our data indicate a quick evolution and diversification of flatfish to adapt to benthic life and provide clues for understanding their controversial origin. Moreover, we investigate the genomic architecture of growth, sex determination and disease resistance, key traits for understanding local adaptation and boosting turbot production, by mapping candidate genes and previously reported quantitative trait loci. The genomic architecture of these productive traits has allowed the identification of candidate genes and enriched pathways that may represent useful information for future marker-assisted selection in turbot. PMID:26951068

  16. Whole genome sequencing of turbot (Scophthalmus maximus; Pleuronectiformes): a fish adapted to demersal life.

    PubMed

    Figueras, Antonio; Robledo, Diego; Corvelo, André; Hermida, Miguel; Pereiro, Patricia; Rubiolo, Juan A; Gómez-Garrido, Jèssica; Carreté, Laia; Bello, Xabier; Gut, Marta; Gut, Ivo Glynne; Marcet-Houben, Marina; Forn-Cuní, Gabriel; Galán, Beatriz; García, José Luis; Abal-Fabeiro, José Luis; Pardo, Belen G; Taboada, Xoana; Fernández, Carlos; Vlasova, Anna; Hermoso-Pulido, Antonio; Guigó, Roderic; Álvarez-Dios, José Antonio; Gómez-Tato, Antonio; Viñas, Ana; Maside, Xulio; Gabaldón, Toni; Novoa, Beatriz; Bouza, Carmen; Alioto, Tyler; Martínez, Paulino

    2016-06-01

    The turbot is a flatfish (Pleuronectiformes) with increasing commercial value, which has prompted active genomic research aimed at more efficient selection. Here we present the sequence and annotation of the turbot genome, which represents a milestone for both boosting breeding programmes and ascertaining the origin and diversification of flatfish. We compare the turbot genome with model fish genomes to investigate teleost chromosome evolution. We observe a conserved macrosyntenic pattern within Percomorpha and identify large syntenic blocks within the turbot genome related to the teleost genome duplication. We identify gene family expansions and positive selection of genes associated with vision and metabolism of membrane lipids, which suggests adaptation to demersal lifestyle and to cold temperatures, respectively. Our data indicate a quick evolution and diversification of flatfish to adapt to benthic life and provide clues for understanding their controversial origin. Moreover, we investigate the genomic architecture of growth, sex determination and disease resistance, key traits for understanding local adaptation and boosting turbot production, by mapping candidate genes and previously reported quantitative trait loci. The genomic architecture of these productive traits has allowed the identification of candidate genes and enriched pathways that may represent useful information for future marker-assisted selection in turbot. © The Author 2016. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  17. The JaCVAM international validation study on the in vivo comet assay: Selection of test chemicals.

    PubMed

    Morita, Takeshi; Uno, Yoshifumi; Honma, Masamitsu; Kojima, Hajime; Hayashi, Makoto; Tice, Raymond R; Corvi, Raffaella; Schechtman, Leonard

    2015-07-01

    The Japanese Center for the Validation of Alternative Methods (JaCVAM) sponsored an international prevalidation and validation study of the in vivo rat alkaline pH comet assay. The main objective of the study was to assess the sensitivity and specificity of the assay for correctly identifying genotoxic carcinogens, as compared with the traditional rat liver unscheduled DNA synthesis assay. Based on existing carcinogenicity and genotoxicity data and chemical class information, 90 chemicals were identified as primary candidates for use in the validation study. From these 90 chemicals, 46 secondary candidates and then 40 final chemicals were selected based on a sufficiency of carcinogenic and genotoxic data, differences in chemical class or genotoxic or carcinogenic mode of action (MOA), availability, price, and ease of handling. These 40 chemicals included 19 genotoxic carcinogens, 6 genotoxic non-carcinogens, 7 non-genotoxic carcinogens and 8 non-genotoxic non-carcinogens. "Genotoxicity" was defined as positive in the Ames mutagenicity test or in one of the standard in vivo genotoxicity tests (primarily the erythrocyte micronucleus assay). These chemicals covered various chemicals classes, MOAs, and genotoxicity profiles and were considered to be suitable for the purpose of the validation study. General principles of chemical selection for validation studies are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Transgenic Parasites Stably Expressing Full-Length Plasmodium falciparum Circumsporozoite Protein as a Model for Vaccine Down-Selection in Mice Using Sterile Protection as an Endpoint

    PubMed Central

    Porter, Michael D.; Nicki, Jennifer; Pool, Christopher D.; DeBot, Margot; Illam, Ratish M.; Brando, Clara; Bozick, Brooke; De La Vega, Patricia; Angra, Divya; Spaccapelo, Roberta; Crisanti, Andrea; Murphy, Jittawadee R.; Bennett, Jason W.; Schwenk, Robert J.; Ockenhouse, Christian F.

    2013-01-01

    Circumsporozoite protein (CSP) of Plasmodium falciparum is a protective human malaria vaccine candidate. There is an urgent need for models that can rapidly down-select novel CSP-based vaccine candidates. In the present study, the mouse-mosquito transmission cycle of a transgenic Plasmodium berghei malaria parasite stably expressing a functional full-length P. falciparum CSP was optimized to consistently produce infective sporozoites for protection studies. A minimal sporozoite challenge dose was established, and protection was defined as the absence of blood-stage parasites 14 days after intravenous challenge. The specificity of protection was confirmed by vaccinating mice with multiple CSP constructs of differing lengths and compositions. Constructs that induced high NANP repeat-specific antibody titers in enzyme-linked immunosorbent assays were protective, and the degree of protection was dependent on the antigen dose. There was a positive correlation between antibody avidity and protection. The antibodies in the protected mice recognized the native CSP on the parasites and showed sporozoite invasion inhibitory activity. Passive transfer of anti-CSP antibodies into naive mice also induced protection. Thus, we have demonstrated the utility of a mouse efficacy model to down-select human CSP-based vaccine formulations. PMID:23536694

  19. Advising Doctorate Candidates and Candidates' Views during the Dissertation Process

    ERIC Educational Resources Information Center

    Hilliard, Ann T.

    2013-01-01

    In order to provide candidates with effective advisement, it is important for the advisor to continue to practice positive professional relationships and provide relevant academic support to candidates. The advisor should work closely with other faculty members and need to listen to the voices of candidates to ensure candidates' success. What…

  20. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines.

    PubMed

    Souza, Raquel P; Bonfim-Mendonça, Patrícia de S; Gimenes, Fabrícia; Ratti, Bianca A; Kaplum, Vanessa; Bruschi, Marcos L; Nakamura, Celso V; Silva, Sueli O; Maria-Engler, Silvya S; Consolaro, Marcia E L

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4',5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H 2 O 2 , decreased the Δ ψm , and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes.

  1. Oxidative Stress Triggered by Apigenin Induces Apoptosis in a Comprehensive Panel of Human Cervical Cancer-Derived Cell Lines

    PubMed Central

    Souza, Raquel P.; Gimenes, Fabrícia; Ratti, Bianca A.; Kaplum, Vanessa; Bruschi, Marcos L.; Nakamura, Celso V.; Maria-Engler, Silvya S.

    2017-01-01

    Recently, the cytotoxic effects of apigenin (4′,5,7-trihydroxyflavone), particularly its marked inhibition of cancer cell viability both in vitro and in vivo, have attracted the attention of the anticancer drug discovery field. Despite this, there are few studies of apigenin in cervical cancer, and these studies have mostly been conducted using HeLa cells. To evaluate the possibility of apigenin as a new therapeutic candidate for cervical cancer, we evaluated its cytotoxic effects in a comprehensive panel of human cervical cancer-derived cell lines including HeLa (human papillomavirus/HPV 18-positive), SiHa (HPV 16-positive), CaSki (HPV 16 and HPV 18-positive), and C33A (HPV-negative) cells in comparison to a nontumorigenic spontaneously immortalized human epithelial cell line (HaCaT). Our results demonstrated that apigenin had a selective cytotoxic effect and could induce apoptosis in all cervical cancer cell lines which were positively marked with Annexin V, but not in HaCaT (control cells). Additionally, apigenin was able to induce mitochondrial redox impairment, once it increased ROS levels and H2O2, decreased the Δψm, and increased LPO. Still, apigenin was able to inhibit migration and invasion of cancer cells. Thus, apigenin appears to be a promising new candidate as an anticancer drug for cervical cancer induced by different HPV genotypes. PMID:28191273

  2. Best-next-view algorithm for three-dimensional scene reconstruction using range images

    NASA Astrophysics Data System (ADS)

    Banta, J. E.; Zhien, Yu; Wang, X. Z.; Zhang, G.; Smith, M. T.; Abidi, Mongi A.

    1995-10-01

    The primary focus of the research detailed in this paper is to develop an intelligent sensing module capable of automatically determining the optimal next sensor position and orientation during scene reconstruction. To facilitate a solution to this problem, we have assembled a system for reconstructing a 3D model of an object or scene from a sequence of range images. Candidates for the best-next-view position are determined by detecting and measuring occlusions to the range camera's view in an image. Ultimately, the candidate which will reveal the greatest amount of unknown scene information is selected as the best-next-view position. Our algorithm uses ray tracing to determine how much new information a given sensor perspective will reveal. We have tested our algorithm successfully on several synthetic range data streams, and found the system's results to be consistent with an intuitive human search. The models recovered by our system from range data compared well with the ideal models. Essentially, we have proven that range information of physical objects can be employed to automatically reconstruct a satisfactory dynamic 3D computer model at a minimal computational expense. This has obvious implications in the contexts of robot navigation, manufacturing, and hazardous materials handling. The algorithm we developed takes advantage of no a priori information in finding the best-next-view position.

  3. Selecting candidate structures for lithium treatment : what to provide the petrographer along with concrete specimens : tech brief.

    DOT National Transportation Integrated Search

    2006-02-01

    The process of selecting candidate structures (and : appropriate components of structures) for lithium treatment : invariably involves sampling one or several components : of the structures for laboratory investigations, particularly : petrographic e...

  4. Transcriptome sequencing of Eucalyptus camaldulensis seedlings subjected to water stress reveals functional single nucleotide polymorphisms and genes under selection

    PubMed Central

    2012-01-01

    Background Water stress limits plant survival and production in many parts of the world. Identification of genes and alleles responding to water stress conditions is important in breeding plants better adapted to drought. Currently there are no studies examining the transcriptome wide gene and allelic expression patterns under water stress conditions. We used RNA sequencing (RNA-seq) to identify the candidate genes and alleles and to explore the evolutionary signatures of selection. Results We studied the effect of water stress on gene expression in Eucalyptus camaldulensis seedlings derived from three natural populations. We used reference-guided transcriptome mapping to study gene expression. Several genes showed differential expression between control and stress conditions. Gene ontology (GO) enrichment tests revealed up-regulation of 140 stress-related gene categories and down-regulation of 35 metabolic and cell wall organisation gene categories. More than 190,000 single nucleotide polymorphisms (SNPs) were detected and 2737 of these showed differential allelic expression. Allelic expression of 52% of these variants was correlated with differential gene expression. Signatures of selection patterns were studied by estimating the proportion of nonsynonymous to synonymous substitution rates (Ka/Ks). The average Ka/Ks ratio among the 13,719 genes was 0.39 indicating that most of the genes are under purifying selection. Among the positively selected genes (Ka/Ks > 1.5) apoptosis and cell death categories were enriched. Of the 287 positively selected genes, ninety genes showed differential expression and 27 SNPs from 17 positively selected genes showed differential allelic expression between treatments. Conclusions Correlation of allelic expression of several SNPs with total gene expression indicates that these variants may be the cis-acting variants or in linkage disequilibrium with such variants. Enrichment of apoptosis and cell death gene categories among the positively selected genes reveals the past selection pressures experienced by the populations used in this study. PMID:22853646

  5. The relative reliability of actively participating and passively observing raters in a simulation-based assessment for selection to specialty training in anaesthesia.

    PubMed

    Roberts, M J; Gale, T C E; Sice, P J A; Anderson, I R

    2013-06-01

    Selection to specialty training is a high-stakes assessment demanding valuable consultant time. In one initial entry level and two higher level anaesthesia selection centres, we investigated the feasibility of using staff participating in simulation scenarios, rather than observing consultants, to rate candidate performance. We compared participant and observer scores using four different outcomes: inter-rater reliability; score distributions; correlation of candidate rankings; and percentage of candidates whose selection might be affected by substituting participants' for observers' ratings. Inter-rater reliability between observers was good (correlation coefficient 0.73-0.96) but lower between participants (correlation coefficient 0.39-0.92), particularly at higher level where participants also rated candidates more favourably than did observers. Station rank orderings were strongly correlated between the rater groups at entry level (rho 0.81, p < 0.001) but weaker at the two higher level centres (rho 0.52, p = 0.018; rho 0.58, p = 0.001). Substituting participants' for observers' ratings had less effect once scores were combined with those from other selection centre stations. Selection decisions for 0-20% of candidates could have changed, depending on the numbers of training posts available. We conclude that using participating raters is feasible at initial entry level only. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

  6. School Turnaround Teachers: Selection Toolkit. Part of the School Turnaround Collection from Public Impact

    ERIC Educational Resources Information Center

    Public Impact, 2008

    2008-01-01

    This toolkit includes these separate sections: (1) Selection Preparation Guide; (2) Day-of-Interview Tools; (3) Candidate Rating Tools; and (4) Candidate Comparison and Decision Tools. Each of the sections is designed to be used at different stages of the selection process. The first section provides turnaround teacher competencies that are the…

  7. School Turnaround Leaders: Selection Toolkit. Part of the School Turnaround Collection from Public Impact

    ERIC Educational Resources Information Center

    Public Impact, 2008

    2008-01-01

    This toolkit includes the following separate sections: (1) Selection Preparation Guide; (2) Day-of-Interview Tools; (3) Candidate Rating Tools; and (4) Candidate Comparison and Decision Tools. Each of the sections is designed to be used at different stages of the selection process. The first section provides a list of competencies that would…

  8. Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle

    PubMed Central

    2011-01-01

    Background Divergently selected Lean and Fat mouse lines represent unique models for a polygenic form of resistance and susceptibility to obesity development. Previous research on these lines focused mainly on obesity-susceptible factors in the Fat line. This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes. Results Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line, although this was not reflected in elevation of total plasma or liver cholesterol. However, FPLC analysis showed that protective HDL cholesterol was elevated in Lean mice. A significant difference between the strains was also found in bile acid metabolism. Lean mice had a higher expression of Cyp8b1, a regulatory enzyme of bile acid synthesis, and the Abcb11 bile acid transporter gene responsible for export of acids to the bile. Additionally, a higher content of blood circulating bile acids was observed in Lean mice. Elevated HDL and upregulation of some bile acids synthesis and transport genes suggests enhanced reverse cholesterol transport in the Lean line - the flux of cholesterol out of the body is higher which is compensated by upregulation of endogenous cholesterol biosynthesis. Increased skeletal muscle Il6 and Dio2 mRNA levels as well as increased activity of muscle succinic acid dehydrogenase (SDH) in the Lean mice demonstrates for the first time that changes in muscle energy metabolism play important role in the Lean line phenotype determination and corroborate our previous findings of increased physical activity and thermogenesis in this line. Finally, differential expression of Abcb11 and Dio2 identifies novel strong positional candidate genes as they map within the quantitative trait loci (QTL) regions detected previously in crosses between the Lean and Fat mice. Conclusion We identified novel candidate molecular targets and metabolic changes which can at least in part explain resistance to obesity development in the Lean line. The major difference between the Lean and Fat mice was in increased liver cholesterol biosynthesis gene mRNA expression, bile acid metabolism and changes in selected muscle genes' expression in the Lean line. The liver Abcb11 and muscle Dio2 were identified as novel positional candidate genes to explain part of the phenotypic difference between the Lean and Fat lines. PMID:21291556

  9. CHROMOSPHERIC EMISSION OF PLANET CANDIDATE HOST STARS: A WAY TO IDENTIFY FALSE POSITIVES

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

    Karoff, Christoffer; Knudsen, Mads Faurschou; Albrecht, Simon

    2016-10-10

    It has been hypothesized that the presence of closely orbiting giant planets is associated with enhanced chromospheric emission of their host stars. The main cause for such a relation would likely be enhanced dynamo action induced by the planet. We present measurements of chromospheric emission in 234 planet candidate systems from the Kepler mission. This ensemble includes 37 systems with giant-planet candidates, which show a clear emission enhancement. The enhancement, however, disappears when systems that are also identified as eclipsing binary candidates are removed from the ensemble. This suggests that a large fraction of the giant-planet candidate systems with chromosphericmore » emission stronger than the Sun are not giant-planet systems, but false positives. Such false-positive systems could be tidally interacting binaries with strong chromospheric emission. This hypothesis is supported by an analysis of 188 eclipsing binary candidates that show increasing chromospheric emission as function of decreasing orbital period.« less

  10. How to choose the right operational police behavioral health specialist (OPBHS).

    PubMed

    Greenstone, James L

    2012-01-01

    A recent article (Dennis, December 2011) stressed the need to consider the factors necessary when selecting an operational police physician. It seems apparent that equal attention should be given to the selection of the Operational Police Behavioral Health Specialist or Police Psychologist (OPBHS). This is intended to round-out selection considerations for these two important and essential positions on both Special Weapons and Tactics Teams as well as on Police Hostage and Crisis Negotiations Teams. Such considerations are crucial whether these teams are operationalized together separately, or as part of the same unit. The previous outline headings, with some additions, will be utilized specifically to deal with the Operational Police Behavioral Health Specialist. Also, see Greenstone (2005). The issues to be considered for the OPBHS are: Candidate selection. (Also see Greenstone, 2005), Duties, Administrative, Clinical, Training involvement, Relationships, Liability and coverage (Dennis, 2011), Other considerations.

  11. A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

    PubMed Central

    Morton, Nicholas M.; Nelson, Yvonne B.; Michailidou, Zoi; Di Rollo, Emma M.; Ramage, Lynne; Hadoke, Patrick W. F.; Seckl, Jonathan R.; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J.; Dunbar, Donald R.

    2011-01-01

    Background Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. Results To enrich for adipose tissue obesity genes a ‘snap-shot’ pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. Conclusions A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity. PMID:21915269

  12. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

    PubMed

    Morton, Nicholas M; Nelson, Yvonne B; Michailidou, Zoi; Di Rollo, Emma M; Ramage, Lynne; Hadoke, Patrick W F; Seckl, Jonathan R; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J; Dunbar, Donald R

    2011-01-01

    Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

  13. Evidence for positive selection of taurine genes within a QTL region on chromosome X associated with testicular size in Australian Brahman cattle

    PubMed Central

    2014-01-01

    Background Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69–77 and 81–92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped. Results To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential. Conclusions Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation. PMID:24410912

  14. A multistage approach to improve performance of computer-aided detection of pulmonary embolisms depicted on CT images: preliminary investigation.

    PubMed

    Park, Sang Cheol; Chapman, Brian E; Zheng, Bin

    2011-06-01

    This study developed a computer-aided detection (CAD) scheme for pulmonary embolism (PE) detection and investigated several approaches to improve CAD performance. In the study, 20 computed tomography examinations with various lung diseases were selected, which include 44 verified PE lesions. The proposed CAD scheme consists of five basic steps: 1) lung segmentation; 2) PE candidate extraction using an intensity mask and tobogganing region growing; 3) PE candidate feature extraction; 4) false-positive (FP) reduction using an artificial neural network (ANN); and 5) a multifeature-based k-nearest neighbor for positive/negative classification. In this study, we also investigated the following additional methods to improve CAD performance: 1) grouping 2-D detected features into a single 3-D object; 2) selecting features with a genetic algorithm (GA); and 3) limiting the number of allowed suspicious lesions to be cued in one examination. The results showed that 1) CAD scheme using tobogganing, an ANN, and grouping method achieved the maximum detection sensitivity of 79.2%; 2) the maximum scoring method achieved the superior performance over other scoring fusion methods; 3) GA was able to delete "redundant" features and further improve CAD performance; and 4) limiting the maximum number of cued lesions in an examination reduced FP rate by 5.3 times. Combining these approaches, CAD scheme achieved 63.2% detection sensitivity with 18.4 FP lesions per examination. The study suggested that performance of CAD schemes for PE detection depends on many factors that include 1) optimizing the 2-D region grouping and scoring methods; 2) selecting the optimal feature set; and 3) limiting the number of allowed cueing lesions per examination.

  15. Cancer screening and early detection in the 21st century

    PubMed Central

    Murphy, Jeanne

    2017-01-01

    Objective To review the trends in and principles of cancer screening and early detection. Data Sources Journal articles, United States Preventive Services Task Force (U SPSTF) publications, professional organization position statements, evidence-based summaries Conclusion Cancer screening has contributed to decreasing the morbidity and mortality of cancer. Efforts to improve the selection of candidates for cancer screening, to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the cancer screening over time. Implications for Nursing Practice Nurses are well-positioned to lead the implementation of cancer screening recommendations in the 21st Century through their practice, research, educational efforts and advocacy. PMID:28343835

  16. Do candidate reactions relate to job performance or affect criterion-related validity? A multistudy investigation of relations among reactions, selection test scores, and job performance.

    PubMed

    McCarthy, Julie M; Van Iddekinge, Chad H; Lievens, Filip; Kung, Mei-Chuan; Sinar, Evan F; Campion, Michael A

    2013-09-01

    Considerable evidence suggests that how candidates react to selection procedures can affect their test performance and their attitudes toward the hiring organization (e.g., recommending the firm to others). However, very few studies of candidate reactions have examined one of the outcomes organizations care most about: job performance. We attempt to address this gap by developing and testing a conceptual framework that delineates whether and how candidate reactions might influence job performance. We accomplish this objective using data from 4 studies (total N = 6,480), 6 selection procedures (personality tests, job knowledge tests, cognitive ability tests, work samples, situational judgment tests, and a selection inventory), 5 key candidate reactions (anxiety, motivation, belief in tests, self-efficacy, and procedural justice), 2 contexts (industry and education), 3 continents (North America, South America, and Europe), 2 study designs (predictive and concurrent), and 4 occupational areas (medical, sales, customer service, and technological). Consistent with previous research, candidate reactions were related to test scores, and test scores were related to job performance. Further, there was some evidence that reactions affected performance indirectly through their influence on test scores. Finally, in no cases did candidate reactions affect the prediction of job performance by increasing or decreasing the criterion-related validity of test scores. Implications of these findings and avenues for future research are discussed. PsycINFO Database Record (c) 2013 APA, all rights reserved

  17. Transcriptome sequencing analysis of novel sRNAs of Kineococcus radiotolerans in response to ionizing radiation.

    PubMed

    Chen, Zhouwei; Li, Lufeng; Shan, Zhan; Huang, Hannian; Chen, Huan; Ding, Xianfeng; Guo, Jiangfeng; Liu, Lili

    2016-11-01

    Kineococcus radiotolerans is a Gram-positive, radio-resistant bacterium isolated from a radioactive environment. The small noncoding RNAs (sRNAs) in bacteria are reported to play roles in the immediate response to stress and/or the recovery from stress. The analysis of K. radiotolerans transcriptome sequencing results can identify these sRNAs in a genome-wide detection, using RNA sequencing (RNA-seq) by the deep sequencing technique. In this study, the raw data of radiation-exposed samples (RS) and control samples (CS) were acquired separately from the sequencing platform. There were 217 common sRNA candidates in the two samples screened in the genome-wide scale by bioinformatics analysis. There were 43 differentially expressed sRNA candidates, including 28 up-regulated and 15 down-regulated ones. The down-regulated sRNAs were selected for the sRNA target prediction, of which 12 sRNAs that may modulate the genes related to the transcription regulation and DNA repair were considered as the candidates involved in the radio-resistance regulation system. Copyright © 2016 Elsevier GmbH. All rights reserved.

  18. ST7612AA1, a thioacetate-ω(γ-lactam carboxamide) derivative selected from a novel generation of oral HDAC inhibitors.

    PubMed

    Giannini, Giuseppe; Vesci, Loredana; Battistuzzi, Gianfranco; Vignola, Davide; Milazzo, Ferdinando M; Guglielmi, Mario Berardino; Barbarino, Marcella; Santaniello, Mosè; Fantò, Nicola; Mor, Marco; Rivara, Silvia; Pala, Daniele; Taddei, Maurizio; Pisano, Claudio; Cabri, Walter

    2014-10-23

    A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ω-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ω-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

  19. Real-time auto-adaptive margin generation for MLC-tracked radiotherapy

    NASA Astrophysics Data System (ADS)

    Glitzner, M.; Fast, M. F.; de Senneville, B. Denis; Nill, S.; Oelfke, U.; Lagendijk, J. J. W.; Raaymakers, B. W.; Crijns, S. P. M.

    2017-01-01

    In radiotherapy, abdominal and thoracic sites are candidates for performing motion tracking. With real-time control it is possible to adjust the multileaf collimator (MLC) position to the target position. However, positions are not perfectly matched and position errors arise from system delays and complicated response of the electromechanic MLC system. Although, it is possible to compensate parts of these errors by using predictors, residual errors remain and need to be compensated to retain target coverage. This work presents a method to statistically describe tracking errors and to automatically derive a patient-specific, per-segment margin to compensate the arising underdosage on-line, i.e. during plan delivery. The statistics of the geometric error between intended and actual machine position are derived using kernel density estimators. Subsequently a margin is calculated on-line according to a selected coverage parameter, which determines the amount of accepted underdosage. The margin is then applied onto the actual segment to accommodate the positioning errors in the enlarged segment. The proof-of-concept was tested in an on-line tracking experiment and showed the ability to recover underdosages for two test cases, increasing {{V}90 %} in the underdosed area about 47 % and 41 % , respectively. The used dose model was able to predict the loss of dose due to tracking errors and could be used to infer the necessary margins. The implementation had a running time of 23 ms which is compatible with real-time requirements of MLC tracking systems. The auto-adaptivity to machine and patient characteristics makes the technique a generic yet intuitive candidate to avoid underdosages due to MLC tracking errors.

  20. Computer-aided detection of bladder mass within non-contrast-enhanced region of CT Urography (CTU)

    NASA Astrophysics Data System (ADS)

    Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Zhou, Chuan

    2016-03-01

    We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). We have previously developed methods for detection of bladder masses within the contrast-enhanced region of the bladder. In this study, we investigated methods for detection of bladder masses within the non-contrast enhanced region. The bladder was first segmented using a newly developed deep-learning convolutional neural network in combination with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensityprojection- based method. The non-contrast region was smoothed and a gray level threshold was employed to segment the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates as a prescreening step. The lesion candidates were segmented using our autoinitialized cascaded level set (AI-CALS) segmentation method, and 27 morphological features were extracted for each candidate. Stepwise feature selection with simplex optimization and leave-one-case-out resampling were used for training and validation of a false positive (FP) classifier. In each leave-one-case-out cycle, features were selected from the training cases and a linear discriminant analysis (LDA) classifier was designed to merge the selected features into a single score for classification of the left-out test case. A data set of 33 cases with 42 biopsy-proven lesions in the noncontrast enhanced region was collected. During prescreening, the system obtained 83.3% sensitivity at an average of 2.4 FPs/case. After feature extraction and FP reduction by LDA, the system achieved 81.0% sensitivity at 2.0 FPs/case, and 73.8% sensitivity at 1.5 FPs/case.

  1. 7 CFR 932.29 - Nominations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Secretary: (i) Meetings shall be held in each producer district for the purpose of selecting candidates for the member and alternate member nominations; (ii) Those candidates selected at the producer meetings... meetings called by the committee, the independent handlers shall nominate a qualified person for each...

  2. Improving mass candidate detection in mammograms via feature maxima propagation and local feature selection.

    PubMed

    Melendez, Jaime; Sánchez, Clara I; van Ginneken, Bram; Karssemeijer, Nico

    2014-08-01

    Mass candidate detection is a crucial component of multistep computer-aided detection (CAD) systems. It is usually performed by combining several local features by means of a classifier. When these features are processed on a per-image-location basis (e.g., for each pixel), mismatching problems may arise while constructing feature vectors for classification, which is especially true when the behavior expected from the evaluated features is a peaked response due to the presence of a mass. In this study, two of these problems, consisting of maxima misalignment and differences of maxima spread, are identified and two solutions are proposed. The first proposed method, feature maxima propagation, reproduces feature maxima through their neighboring locations. The second method, local feature selection, combines different subsets of features for different feature vectors associated with image locations. Both methods are applied independently and together. The proposed methods are included in a mammogram-based CAD system intended for mass detection in screening. Experiments are carried out with a database of 382 digital cases. Sensitivity is assessed at two sets of operating points. The first one is the interval of 3.5-15 false positives per image (FPs/image), which is typical for mass candidate detection. The second one is 1 FP/image, which allows to estimate the quality of the mass candidate detector's output for use in subsequent steps of the CAD system. The best results are obtained when the proposed methods are applied together. In that case, the mean sensitivity in the interval of 3.5-15 FPs/image significantly increases from 0.926 to 0.958 (p < 0.0002). At the lower rate of 1 FP/image, the mean sensitivity improves from 0.628 to 0.734 (p < 0.0002). Given the improved detection performance, the authors believe that the strategies proposed in this paper can render mass candidate detection approaches based on image location classification more robust to feature discrepancies and prove advantageous not only at the candidate detection level, but also at subsequent steps of a CAD system.

  3. Quantitative real-time PCR as a sensitive protein-protein interaction quantification method and a partial solution for non-accessible autoactivator and false-negative molecule analysis in the yeast two-hybrid system.

    PubMed

    Maier, Richard H; Maier, Christina J; Hintner, Helmut; Bauer, Johann W; Onder, Kamil

    2012-12-01

    Many functional proteomic experiments make use of high-throughput technologies such as mass spectrometry combined with two-dimensional polyacrylamide gel electrophoresis and the yeast two-hybrid (Y2H) system. Currently there are even automated versions of the Y2H system available that can be used for proteome-wide research. The Y2H system has the capacity to deliver a profusion of Y2H positive colonies from a single library screen. However, subsequent analysis of these numerous primary candidates with complementary methods can be overwhelming. Therefore, a method to select the most promising candidates with strong interaction properties might be useful to reduce the number of candidates requiring further analysis. The method described here offers a new way of quantifying and rating the performance of positive Y2H candidates. The novelty lies in the detection and measurement of mRNA expression instead of proteins or conventional Y2H genetic reporters. This method correlates well with the direct genetic reporter readouts usually used in the Y2H system, and has greater sensitivity for detecting and quantifying protein-protein interactions (PPIs) than the conventional Y2H system, as demonstrated by detection of the Y2H false-negative PPI of RXR/PPARG. Approximately 20% of all proteins are not suitable for the Y2H system, the so-called autoactivators. A further advantage of this method is the possibility to evaluate molecules that usually cannot be analyzed in the Y2H system, exemplified by a VDR-LXXLL motif peptide interaction. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. The Selection and Appointment of School Heads. A Manual of Suggestions to Boards of Trustees and Candidates. Third Edition.

    ERIC Educational Resources Information Center

    Driscoll, Eileen R.

    To assist in the selection of new private school heads, this manual provides advice to both boards of trustees and candidates. Advice directed to the board covers timing of the search and selection, announcement of the current head's resignation, search committee formation, the committee chairperson, staff assistance, search budget, job…

  5. Automatic vetting of planet candidates from ground based surveys: Machine learning with NGTS

    NASA Astrophysics Data System (ADS)

    Armstrong, David J.; Günther, Maximilian N.; McCormac, James; Smith, Alexis M. S.; Bayliss, Daniel; Bouchy, François; Burleigh, Matthew R.; Casewell, Sarah; Eigmüller, Philipp; Gillen, Edward; Goad, Michael R.; Hodgkin, Simon T.; Jenkins, James S.; Louden, Tom; Metrailler, Lionel; Pollacco, Don; Poppenhaeger, Katja; Queloz, Didier; Raynard, Liam; Rauer, Heike; Udry, Stéphane; Walker, Simon R.; Watson, Christopher A.; West, Richard G.; Wheatley, Peter J.

    2018-05-01

    State of the art exoplanet transit surveys are producing ever increasing quantities of data. To make the best use of this resource, in detecting interesting planetary systems or in determining accurate planetary population statistics, requires new automated methods. Here we describe a machine learning algorithm that forms an integral part of the pipeline for the NGTS transit survey, demonstrating the efficacy of machine learning in selecting planetary candidates from multi-night ground based survey data. Our method uses a combination of random forests and self-organising-maps to rank planetary candidates, achieving an AUC score of 97.6% in ranking 12368 injected planets against 27496 false positives in the NGTS data. We build on past examples by using injected transit signals to form a training set, a necessary development for applying similar methods to upcoming surveys. We also make the autovet code used to implement the algorithm publicly accessible. autovet is designed to perform machine learned vetting of planetary candidates, and can utilise a variety of methods. The apparent robustness of machine learning techniques, whether on space-based or the qualitatively different ground-based data, highlights their importance to future surveys such as TESS and PLATO and the need to better understand their advantages and pitfalls in an exoplanetary context.

  6. Screening for Psychopathology Versus Selecting for Suitability: Ethical and Legal Considerations

    NASA Technical Reports Server (NTRS)

    Holland, Albert W.; Galarza, Laura; Arvey, Richard; Hysong, Sylvia; Sackett, Paul; Cascio, Wayne

    2000-01-01

    The current system for psychological selection of U.S. astronauts is divided into two phases: The select-out phase and the select-in phase. The select-out phase screens candidates for psychopathology; candidates who do not meet the baseline psychiatric requirements are immediately disqualified. The select-in phase assesses candidates for suitability to fly short- and long-duration missions. Suitability ratings are given for ten factors found to be critical for short and long-duration space missions. There are qualitative differences in the purpose of the two phases (select-in vs. select-out) and in the nature of the information collected in each phase. Furthermore, there are different logistic, ethical, and legal issues related to a medical or psychiatric (select-out) screening versus a suitability (select-in) psychological screening process . The purpose of this presentation is to contrast the ethical and legal environment surrounding the select-out and select-in phases of the psychological selection system. Issues such as data collection, data storage and management, the federal statutory environment, and personnel training will be discussed. Further, a summary of the new standards for psychological testing is presented, along with their implications for astronaut selection.

  7. Automatic lung nodule graph cuts segmentation with deep learning false positive reduction

    NASA Astrophysics Data System (ADS)

    Sun, Wenqing; Huang, Xia; Tseng, Tzu-Liang Bill; Qian, Wei

    2017-03-01

    To automatic detect lung nodules from CT images, we designed a two stage computer aided detection (CAD) system. The first stage is graph cuts segmentation to identify and segment the nodule candidates, and the second stage is convolutional neural network for false positive reduction. The dataset contains 595 CT cases randomly selected from Lung Image Database Consortium and Image Database Resource Initiative (LIDC/IDRI) and the 305 pulmonary nodules achieved diagnosis consensus by all four experienced radiologists were our detection targets. Consider each slice as an individual sample, 2844 nodules were included in our database. The graph cuts segmentation was conducted in a two-dimension manner, 2733 lung nodule ROIs are successfully identified and segmented. With a false positive reduction by a seven-layer convolutional neural network, 2535 nodules remain detected while the false positive dropped to 31.6%. The average F-measure of segmented lung nodule tissue is 0.8501.

  8. Parliamentary Privilege--The Candidates. Research Brief. Edition 3

    ERIC Educational Resources Information Center

    Sutton Trust, 2015

    2015-01-01

    The research brief, "Parliamentary Privilege", looks at the educational backgrounds of candidates in winnable seats. The study included candidates selected by mid-December 2014 who were replacing serving MPs for the same party or in target seats with a reasonable possibility of winning. More than half of the candidates attended Russell…

  9. Exploring evidence of positive selection reveals genetic basis of meat quality traits in Berkshire pigs through whole genome sequencing.

    PubMed

    Jeong, Hyeonsoo; Song, Ki-Duk; Seo, Minseok; Caetano-Anollés, Kelsey; Kim, Jaemin; Kwak, Woori; Oh, Jae-Don; Kim, EuiSoo; Jeong, Dong Kee; Cho, Seoae; Kim, Heebal; Lee, Hak-Kyo

    2015-08-20

    Natural and artificial selection following domestication has led to the existence of more than a hundred pig breeds, as well as incredible variation in phenotypic traits. Berkshire pigs are regarded as having superior meat quality compared to other breeds. As the meat production industry seeks selective breeding approaches to improve profitable traits such as meat quality, information about genetic determinants of these traits is in high demand. However, most of the studies have been performed using trained sensory panel analysis without investigating the underlying genetic factors. Here we investigate the relationship between genomic composition and this phenotypic trait by scanning for signatures of positive selection in whole-genome sequencing data. We generated genomes of 10 Berkshire pigs at a total of 100.6 coverage depth, using the Illumina Hiseq2000 platform. Along with the genomes of 11 Landrace and 13 Yorkshire pigs, we identified genomic variants of 18.9 million SNVs and 3.4 million Indels in the mapped regions. We identified several associated genes related to lipid metabolism, intramuscular fatty acid deposition, and muscle fiber type which attribute to pork quality (TG, FABP1, AKIRIN2, GLP2R, TGFBR3, JPH3, ICAM2, and ERN1) by applying between population statistical tests (XP-EHH and XP-CLR). A statistical enrichment test was also conducted to detect breed specific genetic variation. In addition, de novo short sequence read assembly strategy identified several candidate genes (SLC25A14, IGF1, PI4KA, CACNA1A) as also contributing to lipid metabolism. Results revealed several candidate genes involved in Berkshire meat quality; most of these genes are involved in lipid metabolism and intramuscular fat deposition. These results can provide a basis for future research on the genomic characteristics of Berkshire pigs.

  10. George M. Low Trophy NASA's Quality and Excellence Award, 1992. Application guidelines: Small business

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Guidelines are given for the selection of small business candidates for the George M. Low Trophy, NASA's Quality and Excellence Award, 1992. Topics covered include candidate eligibility, the selection process milestone schedule, the nomination letter, and the application report.

  11. SELECTION OF CANDIDATE EUTROPHICATION MODELS FOR TOTAL MAXIMUM DAILY LOADS ANALYSES

    EPA Science Inventory

    A tiered approach was developed to evaluate candidate eutrophication models to select a common suite of models that could be used for Total Maximum Daily Loads (TMDL) analyses in estuaries, rivers, and lakes/reservoirs. Consideration for linkage to watershed models and ecologica...

  12. VizieR Online Data Catalog: KiDS Survey for solar system objects mining (Mahlke+, 2018)

    NASA Astrophysics Data System (ADS)

    Mahlke, M.; Bouy, H.; Altieri, B.; Verdoes Kleijn, G.; Carry, B.; Bertin, E.; de Jong, J. T. A.; Kuijken, K.; McFarland, J.; Valentijn, E.

    2017-10-01

    Provided are the observations of the 28,290 SSO candidates recovered from the KiDS survey. The candidates are split up into two subsamples; the first contains 20,221 candidates with an estimated false-positive content of less than 0.05%. The second sample contains 8,069 candidates with only three observations each or close to bright stars, with an estimated false-positive content of approximately 24%. Provided are the recovered positions in right ascension and declination, the observation epochs, the calculated proper motions, the magnitudes, the observation bands, and the object name and expected visual magnitude if the object was matched to a SkyBoT object (entries are empty if no match was found). (2 data files).

  13. A Study of Teacher Stereotypes: How Do Tuition-Free Teacher Candidates and General Undergraduates Think about Middle School and University Teachers in China?

    PubMed

    Zuo, Youxia; Zhao, Yufang; Peng, Chunhua; Chen, Youguo

    2017-01-01

    A tuition-free teacher candidate is an undergraduate who receives tuition-free teacher education and must work as a teacher in a middle school after their graduation. Tuition-free candidates are of the focus of many researchers; however, no study reports how tuition-free teacher candidates think about teachers. The present study explored stereotypes about middle school and university teachers held by teacher candidates. Specifically, we looked for the differences between the stereotypes held by the teacher candidates and general undergraduates. This study attempted to provide a potential tool to predict the actual willingness of teacher candidates to work as middle school teachers. University and middle school teachers were evaluated using descriptive phrases or words on a five-point Likert scale by 116 tuition-free teacher candidates and 155 general undergraduates. Exploratory factor analyses revealed a three-factor stereotype model including occupational cognition, occupational personality, and occupational emotion. Compared with general undergraduates, teacher candidates held more positive occupational personality and emotions toward middle school teachers; they held more negative occupational emotions toward university teachers. Further, the undergraduates' willingness to be middle school teachers positively correlated with positive occupational emotions and negatively correlated with negative occupational personality and emotions toward middle school teachers. This supported previous studies that individuals' professional willingness were influenced by their stereotypes about professions.

  14. A Study of Teacher Stereotypes: How Do Tuition-Free Teacher Candidates and General Undergraduates Think about Middle School and University Teachers in China?

    PubMed Central

    Zuo, Youxia; Zhao, Yufang; Peng, Chunhua; Chen, Youguo

    2017-01-01

    A tuition-free teacher candidate is an undergraduate who receives tuition-free teacher education and must work as a teacher in a middle school after their graduation. Tuition-free candidates are of the focus of many researchers; however, no study reports how tuition-free teacher candidates think about teachers. The present study explored stereotypes about middle school and university teachers held by teacher candidates. Specifically, we looked for the differences between the stereotypes held by the teacher candidates and general undergraduates. This study attempted to provide a potential tool to predict the actual willingness of teacher candidates to work as middle school teachers. University and middle school teachers were evaluated using descriptive phrases or words on a five-point Likert scale by 116 tuition-free teacher candidates and 155 general undergraduates. Exploratory factor analyses revealed a three-factor stereotype model including occupational cognition, occupational personality, and occupational emotion. Compared with general undergraduates, teacher candidates held more positive occupational personality and emotions toward middle school teachers; they held more negative occupational emotions toward university teachers. Further, the undergraduates' willingness to be middle school teachers positively correlated with positive occupational emotions and negatively correlated with negative occupational personality and emotions toward middle school teachers. This supported previous studies that individuals' professional willingness were influenced by their stereotypes about professions. PMID:28469587

  15. Getting into the Game: Helping Preservice Candidates Find Initial Teaching Positions

    ERIC Educational Resources Information Center

    Ayers, Suzan F.; Senne, Terry A.

    2011-01-01

    Many teacher candidates fumble through the job-hunting process by employing the "discovery" approach to finding a teaching position. The purpose of this article is to provide direction and guidance for securing an initial teaching position in physical education. The areas outlined in this article include (1) developing application…

  16. Save the last dance for me: unwanted serial position effects in jury evaluations.

    PubMed

    Bruine de Bruin, Wändi

    2005-03-01

    Whenever competing options are considered in sequence, their evaluations may be affected by order of appearance. Such serial position effects would threaten the fairness of competitions using jury evaluations. Randomization cannot reduce potential order effects, but it does give candidates an equal chance of being assigned to preferred serial positions. Whether, or what, serial position effects emerge may depend on the cognitive demands of the judgment task. In end-of-sequence procedures, final scores are not given until all candidates have performed, possibly burdening judges' memory. If judges' evaluations are based on how well they remember performances, serial position effects may resemble those found with free recall. Candidates may also be evaluated step-by-step, immediately after each performance. This procedure should not burden memory, though it may produce different serial position effects. Yet, this paper reports similar serial position effects with end-of-sequence and step-by-step procedures used for the Eurovision Song Contest: Ratings increased with serial position. The linear order effect was replicated in the step-by-step judgments of World and European Figure Skating Contests. It is proposed that, independent of the evaluation procedure, judges' initial impressions of sequentially appearing candidates may be formed step-by-step, yielding serial position effects.

  17. Definition of experiments and instruments for a communication/navigation research laboratory. Volume 2: Experiment selection

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The selection and definition of candidate experiments and the associated experiment instrumentation requirements are described. Information is presented that addresses the following study objectives: (1) determine specific research and technology needs in the comm/nav field through a survey of the scientific/technical community; (2) develop manned low earth orbit space screening criteria and compile lists of potential candidate experiments; (3) in Blue Book format, define and describe selected candidate experiments in sufficient detail to develop laboratory configuration designs and layouts; and (4) develop experiment time phasing criteria and recommend a payload for sortie can/early laboratory missions.

  18. Assessing the Tailored Adaptive Personality Assessment System

    DTIC Science & Technology

    2014-01-01

    and selection course. TAPAS data were collected from 1,216 Soldier-candidates attending the ARSOF course and were used to predict selection for ARSOF...were selected for ARSOF training following the course. Data were collected from February to June 2012. All respondents completed the TAPAS...the TAPAS for this purpose. Collecting additional data from ARSOF candidates would provide larger participant samples that could be used to cross

  19. 5 CFR 302.401 - Selection and appointment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... reemployment, reemployment, or regular list on which candidates have not received numerical scores, an agency... candidates have received numerical scores, the agency must make its selection for each vacancy from not more... method, an agency is not required to— (1) Accord an applicant on its priority reemployment or...

  20. MoDOT pavement preservation research program volume VI, pavement treatment trigger tables/decision trees and treatment candidate selection process.

    DOT National Transportation Integrated Search

    2015-10-01

    The objective of Task 5 was the development of pavement treatment trigger tables and the treatment candidate selection process. : The input to the trigger tables entails such factors as an overall condition indicator, smoothness, individual distress ...

  1. 14 CFR 1214.1106 - Selection of astronaut candidates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Selection of astronaut candidates. 1214.1106 Section 1214.1106 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA... be approved, as required, by JSC/ NASA management and the Associate Administrator for Space Flight...

  2. Herbal Prescriptions and Medicinal Herbs for Parkinson-Related Rigidity in Korean Medicine: Identification of Candidates Using Text Mining.

    PubMed

    Park, So Hyun; Hwang, Min Seob; Park, Hye Jin; Shin, Hwa Kyoung; Baek, Jin Ung; Choi, Byung Tae

    2018-03-27

    Dongeuibogam (DongYiBaoGian), one of the most important books in Korean medicine, comprises a comprehensive summary of all traditional medicines of North-East Asia before the 17th century. This medicinal literature was mined to establish a list of candidate herbs to treat Parkinson-related rigidity. A systematic search for terms describing Parkinson-related rigidity and candidate prescriptions for the treatment of Parkinson-related rigidity in the Dongeuibogam was performed. A high-frequency medicinal herb combination group and candidates for the treatment of Parkinson-related rigidity were also selected through an analysis of medicinal herb combination frequencies. The existing literature pertaining to the potential effects of candidate herbs for Parkinson-related rigidity was reviewed. Ten medicinal herb candidates for the treatment of Parkinson-related rigidity were selected, and their respective precedent studies were analyzed.

  3. A strategy to find novel candidate anti-Alzheimer's disease drugs by constructing interaction networks between drug targets and natural compounds in medical plants.

    PubMed

    Chen, Bi-Wen; Li, Wen-Xing; Wang, Guang-Hui; Li, Gong-Hua; Liu, Jia-Qian; Zheng, Jun-Juan; Wang, Qian; Li, Hui-Juan; Dai, Shao-Xing; Huang, Jing-Fei

    2018-01-01

    Alzheimer' disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins. TCM compounds in the top 0.5% of binding affinity scores for each target protein were selected as our research objects. Structural similarities between existing drugs from DrugBank database and selected TCM compounds as well as the druggability of our candidate compounds were studied. Finally, we searched the CNKI database to obtain studies on anti-AD Chinese plants from 2007 to 2017, and only clinical studies were included. A total of 1,476 compounds (top 0.5%) were selected as drug candidates. Most of these compounds are abundantly found in plants used for treating AD in China, especially the plants from two genera Panax and Morus. We classified the compounds by single target and multiple targets and analyzed the interactions between target proteins and compounds. Analysis of structural similarity revealed that 17 candidate anti-AD compounds were structurally identical to 14 existing approved drugs. Most of them have been reported to have a positive effect in AD. After filtering for compound druggability, we identified 11 anti-AD compounds with favorable properties, seven of which are found in anti-AD Chinese plants. Of 11 anti-AD compounds, four compounds 5,862, 5,863, 5,868, 5,869 have anti-inflammatory activity. The compound 28,814 mainly has immunoregulatory activity. The other six compounds have not yet been reported for any biology activity at present. Natural compounds from TCM provide a broad prospect for the screening of anti-AD drugs. In this work, we established networks to systematically study the connections among natural compounds, approved drugs, TCM plants and AD target proteins with the goal of identifying promising drug candidates. We hope that our study will facilitate in-depth research for the treatment of AD in Chinese medicine.

  4. Genomic signatures of parasite-driven natural selection in north European Atlantic salmon (Salmo salar).

    PubMed

    Zueva, Ksenia J; Lumme, Jaakko; Veselov, Alexey E; Kent, Matthew P; Primmer, Craig R

    2018-06-01

    Understanding the genomic basis of host-parasite adaptation is important for predicting the long-term viability of species and developing successful management practices. However, in wild populations, identifying specific signatures of parasite-driven selection often presents a challenge, as it is difficult to unravel the molecular signatures of selection driven by different, but correlated, environmental factors. Furthermore, separating parasite-mediated selection from similar signatures due to genetic drift and population history can also be difficult. Populations of Atlantic salmon (Salmo salar L.) from northern Europe have pronounced differences in their reactions to the parasitic flatworm Gyrodactylus salaris Malmberg 1957 and are therefore a good model to search for specific genomic regions underlying inter-population differences in pathogen response. We used a dense Atlantic salmon SNP array, along with extensive sampling of 43 salmon populations representing the two G. salaris response extremes (extreme susceptibility vs resistant), to screen the salmon genome for signatures of directional selection while attempting to separate the parasite effect from other factors. After combining the results from two independent genome scan analyses, 57 candidate genes potentially under positive selection were identified, out of which 50 were functionally annotated. This candidate gene set was shown to be functionally enriched for lymph node development, focal adhesion genes and anti-viral response, which suggests that the regulation of both innate and acquired immunity might be an important mechanism for salmon response to G. salaris. Overall, our results offer insights into the apparently complex genetic basis of pathogen susceptibility in salmon and highlight methodological challenges for separating the effects of various environmental factors. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Factors Influencing Candidates' Performance in English Language and Mathematics at West African Senior School Certificate Examination

    ERIC Educational Resources Information Center

    Alade, O. M.; Kuku, O. O.; Osoba, A.

    2017-01-01

    The study investigated influence of some factors on the performance of selected West African Senior School Certificate Examination (WASSCE) candidates. It also examined the relationship between these factors and candidates' performance. Factors investigated include socio-economic background of the candidates (SEB), study hours (SH), attitude…

  6. Long-lived rodents reveal signatures of positive selection in genes associated with lifespan

    PubMed Central

    Görlach, Matthias; Müller, Christine; Schwab, Matthias; Kraus, Johann; Cellerino, Alessandro; Hildebrandt, Thomas

    2018-01-01

    The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were “cellular respiration” and “metal ion homeostasis”, as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination. PMID:29570707

  7. Long-lived rodents reveal signatures of positive selection in genes associated with lifespan.

    PubMed

    Sahm, Arne; Bens, Martin; Szafranski, Karol; Holtze, Susanne; Groth, Marco; Görlach, Matthias; Calkhoven, Cornelis; Müller, Christine; Schwab, Matthias; Kraus, Johann; Kestler, Hans A; Cellerino, Alessandro; Burda, Hynek; Hildebrandt, Thomas; Dammann, Philip; Platzer, Matthias

    2018-03-01

    The genetics of lifespan determination is poorly understood. Most research has been done on short-lived animals and it is unclear if these insights can be transferred to long-lived mammals like humans. Some African mole-rats (Bathyergidae) have life expectancies that are multiple times higher than similar sized and phylogenetically closely related rodents. To gain new insights into genetic mechanisms determining mammalian lifespans, we obtained genomic and transcriptomic data from 17 rodent species and scanned eleven evolutionary branches associated with the evolution of enhanced longevity for positively selected genes (PSGs). Indicating relevance for aging, the set of 250 identified PSGs showed in liver of long-lived naked mole-rats and short-lived rats an expression pattern that fits the antagonistic pleiotropy theory of aging. Moreover, we found the PSGs to be enriched for genes known to be related to aging. Among these enrichments were "cellular respiration" and "metal ion homeostasis", as well as functional terms associated with processes regulated by the mTOR pathway: translation, autophagy and inflammation. Remarkably, among PSGs are RHEB, a regulator of mTOR, and IGF1, both central components of aging-relevant pathways, as well as genes yet unknown to be aging-associated but representing convincing functional candidates, e.g. RHEBL1, AMHR2, PSMG1 and AGER. Exemplary protein homology modeling suggests functional consequences for amino acid changes under positive selection. Therefore, we conclude that our results provide a meaningful resource for follow-up studies to mechanistically link identified genes and amino acids under positive selection to aging and lifespan determination.

  8. Infrared Thermal Testing Of Mechanical Assemblies At The Military Depot And Field Level: A Progress Report

    NASA Astrophysics Data System (ADS)

    Kaplan, Herbert

    1988-01-01

    Based on encouraging results on the Army's programs for infrared mass screening of printed circuit boards at the depot level, the US Army CECOM (Communication-Electronics Command) undertook a one-year investigation of the applicability of similar techniques to screening and diagnostics of mechanical assemblies. These included tanks, helicopters, transport vehicles and their major subassemblies (transmissions, engines, axles, etc.) at field and depot levels. Honeyhill Technical Company was tasked to classify candidate assemblies and perform preliminary measurements using Army-owned general-purpose thermal imaging equipment. The investigations yielded positive results, and it was decided to pursue a comprehensive measurements program using field-mobile equipment specifically procured for the program. This paper summarizes the results of the investigations, outlines the measurements techniques utilized, describes the classification and selection of candidate assemblies, and reports on progress toward the goals of the program.

  9. Discovery and characterization of potential prognostic biomarkers for dengue hemorrhagic fever.

    PubMed

    Poole-Smith, B Katherine; Gilbert, Alexa; Gonzalez, Andrea L; Beltran, Manuela; Tomashek, Kay M; Ward, Brian J; Hunsperger, Elizabeth A; Ndao, Momar

    2014-12-01

    Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2-5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. © The American Society of Tropical Medicine and Hygiene.

  10. Discovery and Characterization of Potential Prognostic Biomarkers for Dengue Hemorrhagic Fever

    PubMed Central

    Poole-Smith, B. Katherine; Gilbert, Alexa; Gonzalez, Andrea L.; Beltran, Manuela; Tomashek, Kay M.; Ward, Brian J.; Hunsperger, Elizabeth A.; Ndao, Momar

    2014-01-01

    Half a million patients are hospitalized with severe dengue every year, many of whom would die without timely, appropriate clinical intervention. The majority of dengue cases are uncomplicated; however, 2–5% progress to severe dengue. Severe dengue cases have been reported with increasing frequency over the last 30 years. To discover biomarkers for severe dengue, we used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry to analyze dengue virus positive serum samples from the acute phase of infection. Using this method, 16 proteins were identified as candidate biomarkers for severe dengue. From these 16 biomarkers, three candidates were selected for confirmation by enzyme-linked immunosorbent assay and Western blot: vitronectin (Vtn, 55.1 kDa), hemopexin (Hx, 52.4 kDa), and serotransferrin (Tf, 79.2 kDa). Vitronectin, Hx, and Tf best differentiated between dengue and severe dengue. PMID:25349378

  11. High Class-Imbalance in pre-miRNA Prediction: A Novel Approach Based on deepSOM.

    PubMed

    Stegmayer, Georgina; Yones, Cristian; Kamenetzky, Laura; Milone, Diego H

    2017-01-01

    The computational prediction of novel microRNA within a full genome involves identifying sequences having the highest chance of being a miRNA precursor (pre-miRNA). These sequences are usually named candidates to miRNA. The well-known pre-miRNAs are usually only a few in comparison to the hundreds of thousands of potential candidates to miRNA that have to be analyzed, which makes this task a high class-imbalance classification problem. The classical way of approaching it has been training a binary classifier in a supervised manner, using well-known pre-miRNAs as positive class and artificially defining the negative class. However, although the selection of positive labeled examples is straightforward, it is very difficult to build a set of negative examples in order to obtain a good set of training samples for a supervised method. In this work, we propose a novel and effective way of approaching this problem using machine learning, without the definition of negative examples. The proposal is based on clustering unlabeled sequences of a genome together with well-known miRNA precursors for the organism under study, which allows for the quick identification of the best candidates to miRNA as those sequences clustered with known precursors. Furthermore, we propose a deep model to overcome the problem of having very few positive class labels. They are always maintained in the deep levels as positive class while less likely pre-miRNA sequences are filtered level after level. Our approach has been compared with other methods for pre-miRNAs prediction in several species, showing effective predictivity of novel miRNAs. Additionally, we will show that our approach has a lower training time and allows for a better graphical navegability and interpretation of the results. A web-demo interface to try deepSOM is available at http://fich.unl.edu.ar/sinc/web-demo/deepsom/.

  12. Effects of Organizational Citizenship Behaviors on Selection Decisions in Employment Interviews

    ERIC Educational Resources Information Center

    Podsakoff, Nathan P.; Whiting, Steven W.; Podsakoff, Philip M.; Mishra, Paresh

    2011-01-01

    This article reports on an experiment examining the effects of job candidates' propensity to exhibit organizational citizenship behaviors (OCBs) on selection decisions made in the context of a job interview. We developed videos that manipulated candidate responses to interview questions tapping task performance and citizenship behavior content in…

  13. Research Supervisors' Perceptions of Effective Practices for Selecting Successful Research Candidates

    ERIC Educational Resources Information Center

    Blunt, R. J. S.

    2009-01-01

    This investigation elicited the perceptions of thirteen of the most successful research supervisors from one university, with a view to identifying their approaches to selecting research candidates. The supervisors were identified by the university's research office using the single criterion of having the largest number of completed research…

  14. CT Colonography with Computer-aided Detection: Recognizing the Causes of False-Positive Reader Results

    PubMed Central

    Dachman, Abraham H.; Wroblewski, Kristen; Vannier, Michael W.; Horne, John M.

    2014-01-01

    Computed tomography (CT) colonography is a screening modality used to detect colonic polyps before they progress to colorectal cancer. Computer-aided detection (CAD) is designed to decrease errors of detection by finding and displaying polyp candidates for evaluation by the reader. CT colonography CAD false-positive results are common and have numerous causes. The relative frequency of CAD false-positive results and their effect on reader performance on the basis of a 19-reader, 100-case trial shows that the vast majority of CAD false-positive results were dismissed by readers. Many CAD false-positive results are easily disregarded, including those that result from coarse mucosa, reconstruction, peristalsis, motion, streak artifacts, diverticulum, rectal tubes, and lipomas. CAD false-positive results caused by haustral folds, extracolonic candidates, diminutive lesions (<6 mm), anal papillae, internal hemorrhoids, varices, extrinsic compression, and flexural pseudotumors are almost always recognized and disregarded. The ileocecal valve and tagged stool are common sources of CAD false-positive results associated with reader false-positive results. Nondismissable CAD soft-tissue polyp candidates larger than 6 mm are another common cause of reader false-positive results that may lead to further evaluation with follow-up CT colonography or optical colonoscopy. Strategies for correctly evaluating CAD polyp candidates are important to avoid pitfalls from common sources of CAD false-positive results. ©RSNA, 2014 PMID:25384290

  15. Nursing leadership succession planning in Veterans Health Administration: creating a useful database.

    PubMed

    Weiss, Lizabeth M; Drake, Audrey

    2007-01-01

    An electronic database was developed for succession planning and placement of nursing leaders interested and ready, willing, and able to accept an assignment in a nursing leadership position. The tool is a 1-page form used to identify candidates for nursing leadership assignments. This tool has been deployed nationally, with access to the database restricted to nurse executives at every Veterans Health Administration facility for the purpose of entering the names of developed nurse leaders ready for a leadership assignment. The tool is easily accessed through the Veterans Health Administration Office of Nursing Service, and by limiting access to the nurse executive group, ensures candidates identified are qualified. Demographic information included on the survey tool includes the candidate's demographic information and other certifications/credentials. This completed information form is entered into a database from which a report can be generated, resulting in a listing of potential candidates to contact to supplement a local or Veterans Integrated Service Network wide position announcement. The data forms can be sorted by positions, areas of clinical or functional experience, training programs completed, and geographic preference. The forms can be edited or updated and/or added or deleted in the system as the need is identified. This tool allows facilities with limited internal candidates to have a resource with Department of Veterans Affairs prepared staff in which to seek additional candidates. It also provides a way for interested candidates to be considered for positions outside of their local geographic area.

  16. Disease and Surgery of the Equine Lens.

    PubMed

    Townsend, Wendy M

    2017-12-01

    Examination of the lens is critical, particularly when evaluating horses with visual impairment or performing prepurchase examinations. To adequately evaluate the lens, the pupil must be pharmacologically dilated. A cataract is any lens opacity. The size, density, and position of a cataract determine the impact on vision. Cataracts may be congenital or inherited or occur secondary to trauma or equine recurrent uveitis. Surgical removal is the only treatment option for vision impairing cataracts, but careful selection of surgical candidates is critical for successful outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Candidate gene identification of ovulation-inducing genes by RNA sequencing with an in vivo assay in zebrafish.

    PubMed

    Klangnurak, Wanlada; Fukuyo, Taketo; Rezanujjaman, M D; Seki, Masahide; Sugano, Sumio; Suzuki, Yutaka; Tokumoto, Toshinobu

    2018-01-01

    We previously reported the microarray-based selection of three ovulation-related genes in zebrafish. We used a different selection method in this study, RNA sequencing analysis. An additional eight up-regulated candidates were found as specifically up-regulated genes in ovulation-induced samples. Changes in gene expression were confirmed by qPCR analysis. Furthermore, up-regulation prior to ovulation during natural spawning was verified in samples from natural pairing. Gene knock-out zebrafish strains of one of the candidates, the starmaker gene (stm), were established by CRISPR genome editing techniques. Unexpectedly, homozygous mutants were fertile and could spawn eggs. However, a high percentage of unfertilized eggs and abnormal embryos were produced from these homozygous females. The results suggest that the stm gene is necessary for fertilization. In this study, we selected additional ovulation-inducing candidate genes, and a novel function of the stm gene was investigated.

  18. MID-INFRARED SELECTION OF ACTIVE GALACTIC NUCLEI WITH THE WIDE-FIELD INFRARED SURVEY EXPLORER. I. CHARACTERIZING WISE-SELECTED ACTIVE GALACTIC NUCLEI IN COSMOS

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

    Stern, Daniel; Assef, Roberto J.; Eisenhardt, Peter

    2012-07-01

    The Wide-field Infrared Survey Explorer (WISE) is an extremely capable and efficient black hole finder. We present a simple mid-infrared color criterion, W1 - W2 {>=} 0.8 (i.e., [3.4]-[4.6] {>=}0.8, Vega), which identifies 61.9 {+-} 5.4 active galactic nucleus (AGN) candidates per deg{sup 2} to a depth of W2 {approx} 15.0. This implies a much larger census of luminous AGNs than found by typical wide-area surveys, attributable to the fact that mid-infrared selection identifies both unobscured (type 1) and obscured (type 2) AGNs. Optical and soft X-ray surveys alone are highly biased toward only unobscured AGNs, while this simple WISEmore » selection likely identifies even heavily obscured, Compton-thick AGNs. Using deep, public data in the COSMOS field, we explore the properties of WISE-selected AGN candidates. At the mid-infrared depth considered, 160 {mu}Jy at 4.6 {mu}m, this simple criterion identifies 78% of Spitzer mid-infrared AGN candidates according to the criteria of Stern et al. and the reliability is 95%. We explore the demographics, multiwavelength properties and redshift distribution of WISE-selected AGN candidates in the COSMOS field.« less

  19. [Myonuclear domain and microtubule proteome during skeletal muscle maturation].

    PubMed

    Couturier, Nathalie; Gache, Vincent

    2017-11-01

    In the normal course of muscle fiber development, myonuclei actively position and adapt a precise localization in mature fibers, shaping MyoNuclear Domains (MNDs). Myonuclei positioning in fibers appears to be essential for muscle function as defects in MNDs settings are always associated with dysfunction (i.e., centronuclear myopathy, sarcopenia). Previous studies have shown that myonuclei positioning in fibers is reversible, suggesting that in pathologies presenting MNDs impairment, myonuclei could be re-addressed to the "correct" position in fibers and this could benefit to muscle function. Cytoskeleton networks, and particularly microtubules, have been implicated in early nuclei localization in myotubes. As the microtubule network is completely redesigned during muscle maturation, we hypothesized that "microtubules associated proteomes" would change between immature and mature fibers and contribute to a microtubule-dependent process resulting in MNDs setting and maintenance in mature fibers. We performed an in vitro biochemical approach to isolate microtubules partners in immature (myotubes) and mature myofibers. Using mass-spectrometry identification, we selected 244 candidates, differentially associated/expressed with microtubules during myofiber maturation and potentially controlling MNDs settings. We are currently conducting a siRNA screen approach on these candidates to decipher their respective implication in early and late phases of MNDs establishment, using an unbiased assay developed by our team allowing statistical analysis of MNDs regarding myonuclei content. This approach will lead to the identification of new pathways related to nuclear positioning and MNDs setting in normal condition and in myopathies associated to MNDs impairment such as CNMs. © 2017 médecine/sciences – Inserm.

  20. Genomic and Transcriptomic Associations Identify a New Insecticide Resistance Phenotype for the Selective Sweep at the Cyp6g1 Locus of Drosophila melanogaster.

    PubMed

    Battlay, Paul; Schmidt, Joshua M; Fournier-Level, Alexandre; Robin, Charles

    2016-08-09

    Scans of the Drosophila melanogaster genome have identified organophosphate resistance loci among those with the most pronounced signature of positive selection. In this study, the molecular basis of resistance to the organophosphate insecticide azinphos-methyl was investigated using the Drosophila Genetic Reference Panel, and genome-wide association. Recently released full transcriptome data were used to extend the utility of the Drosophila Genetic Reference Panel resource beyond traditional genome-wide association studies to allow systems genetics analyses of phenotypes. We found that both genomic and transcriptomic associations independently identified Cyp6g1, a gene involved in resistance to DDT and neonicotinoid insecticides, as the top candidate for azinphos-methyl resistance. This was verified by transgenically overexpressing Cyp6g1 using natural regulatory elements from a resistant allele, resulting in a 6.5-fold increase in resistance. We also identified four novel candidate genes associated with azinphos-methyl resistance, all of which are involved in either regulation of fat storage, or nervous system development. In Cyp6g1, we find a demonstrable resistance locus, a verification that transcriptome data can be used to identify variants associated with insecticide resistance, and an overlap between peaks of a genome-wide association study, and a genome-wide selective sweep analysis. Copyright © 2016 Battlay et al.

  1. Comparative transcriptome analysis and identification of candidate effectors in two related rust species (Gymnosporangium yamadae and Gymnosporangium asiaticum).

    PubMed

    Tao, Si-Qi; Cao, Bin; Tian, Cheng-Ming; Liang, Ying-Mei

    2017-08-23

    Rust fungi constitute the largest group of plant fungal pathogens. However, a paucity of data, including genomic sequences, transcriptome sequences, and associated molecular markers, hinders the development of inhibitory compounds and prevents their analysis from an evolutionary perspective. Gymnosporangium yamadae and G. asiaticum are two closely related rust fungal species, which are ecologically and economically important pathogens that cause apple rust and pear rust, respectively, proved to be devastating to orchards. In this study, we investigated the transcriptomes of these two Gymnosporangium species during the telial stage of their lifecycles. The aim of this study was to understand the evolutionary patterns of these two related fungi and to identify genes that developed by selection. The transcriptomes of G. yamadae and G. asiaticum were generated from a mixture of RNA from three biological replicates of each species. We obtained 49,318 and 54,742 transcripts, with N50 values of 1957 and 1664, for G. yamadae and G. asiaticum, respectively. We also identified a repertoire of candidate effectors and other gene families associated with pathogenicity. A total of 4947 pairs of putative orthologues between the two species were identified. Estimation of the non-synonymous/synonymous substitution rate ratios for these orthologues identified 116 pairs with Ka/Ks values greater than1 that are under positive selection and 170 pairs with Ka/Ks values of 1 that are under neutral selection, whereas the remaining 4661 genes are subjected to purifying selection. We estimate that the divergence time between the two species is approximately 5.2 Mya. This study constitutes a de novo assembly and comparative analysis between the transcriptomes of the two rust species G. yamadae and G. asiaticum. The results identified several orthologous genes, and many expressed genes were identified by annotation. Our analysis of Ka/Ks ratios identified orthologous genes subjected to positive or purifying selection. An evolutionary analysis of these two species provided a relatively precise divergence time. Overall, the information obtained in this study increases the genetic resources available for research on the genetic diversity of the Gymnosporangium genus.

  2. Active heat exchange system development for latent heat thermal energy storage

    NASA Technical Reports Server (NTRS)

    Lefrois, R. T.; Mathur, A. K.

    1980-01-01

    Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

  3. Active heat exchange system development for latent heat thermal energy storage

    NASA Astrophysics Data System (ADS)

    Lefrois, R. T.; Mathur, A. K.

    1980-04-01

    Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

  4. Configuration development study of the X-24C hypersonic research airplane, phase 2

    NASA Technical Reports Server (NTRS)

    Combs, H. G.

    1977-01-01

    The X-24C Hypersonic Research Vehicle, configured with a heat-sink structure, a launch mass limit of 31.75 Mg and powered by an LR-105 Rocket Engine plus 12 LR-101 Sustainer Engines, was found to be the more cost effective of the candidate configurations. In addition, the configuration provides the maximum off design growth potential capability and subsequently, was selected as the candidate configuration to be subjected to the design refinement study in the remaining segment of the study. Selection of this configuration was based on the analytical study conducted on the performance growth capabilities of the candidate configurations selected from the Phase 1 Study.

  5. Selection of High-Redshift QSOs using Subaru and CFHT Photometry

    NASA Astrophysics Data System (ADS)

    Jones, Victoria; White, Cameron; Hasinger, Guenther; Hu, Esther

    2018-01-01

    We present 31 high redshift (5.0 ≤ z ≤ 6.0) quasar candidates using photometry from the Subaru and Canada France Hawaii telescopes. These candidates were observed as part of the Hawaii EROsita Ecliptic Pole Survey (HEROES) of the North Ecliptic Pole in 2016 and again in 2017. The ongoing HEROES survey is gathering ground-based imaging data in preparation for the eROSITA X-Ray mission. For this selection, we utilized optical-near IR imaging data of a 36 square degree field in one narrowband and five broadband filters on Subaru’s Hyper Suprime-Cam (HSC). We also utilized less complete coverage of the field in the U and J bands from CFHT’s MegaCam and WIRCam respectively. Photometric redshifts were calculated using SED fitting techniques in comparison with stellar, quasar, and galaxy models. Selections were then made through extendedness cuts, color-color comparisons, and color-redshift plots. Follow-up spectroscopic observations of these candidates with the DEIMOS spectrograph on Keck and X-Ray observations with eROSITA in the coming years will allow for reliable classifications of our selected candidates.

  6. EST-derived SNP discovery and selective pressure analysis in Pacific white shrimp ( Litopenaeus vannamei)

    NASA Astrophysics Data System (ADS)

    Liu, Chengzhang; Wang, Xia; Xiang, Jianhai; Li, Fuhua

    2012-09-01

    Pacific white shrimp has become a major aquaculture and fishery species worldwide. Although a large scale EST resource has been publicly available since 2008, the data have not yet been widely used for SNP discovery or transcriptome-wide assessment of selective pressure. In this study, a set of 155 411 expressed sequence tags (ESTs) from the NCBI database were computationally analyzed and 17 225 single nucleotide polymorphisms (SNPs) were predicted, including 9 546 transitions, 5 124 transversions and 2 481 indels. Among the 7 298 SNP substitutions located in functionally annotated contigs, 58.4% (4 262) are non-synonymous SNPs capable of introducing amino acid mutations. Two hundred and fifty nonsynonymous SNPs in genes associated with economic traits have been identified as candidates for markers in selective breeding. Diversity estimates among the synonymous nucleotides were on average 3.49 times greater than those in non-synonymous, suggesting negative selection. Distribution of non-synonymous to synonymous substitutions (Ka/Ks) ratio ranges from 0 to 4.01, (average 0.42, median 0.26), suggesting that the majority of the affected genes are under purifying selection. Enrichment analysis identified multiple gene ontology categories under positive or negative selection. Categories involved in innate immune response and male gamete generation are rich in positively selected genes, which is similar to reports in Drosophila and primates. This work is the first transcriptome-wide assessment of selective pressure in a Penaeid shrimp species. The functionally annotated SNPs provide a valuable resource of potential molecular markers for selective breeding.

  7. 14 CFR 1214.1100 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Scope. 1214.1100 Section 1214.1100 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate... selection of astronaut candidates. It applies to all pilot and mission specialist astronaut candidate...

  8. 14 CFR 1214.1100 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Scope. 1214.1100 Section 1214.1100 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate... selection of astronaut candidates. It applies to all pilot and mission specialist astronaut candidate...

  9. 14 CFR 1214.1100 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Scope. 1214.1100 Section 1214.1100 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate... selection of astronaut candidates. It applies to all pilot and mission specialist astronaut candidate...

  10. 14 CFR 1214.1100 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Scope. 1214.1100 Section 1214.1100 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate... selection of astronaut candidates. It applies to all pilot and mission specialist astronaut candidate...

  11. 5 CFR 9901.516 - Internal placement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... candidate's performance appraisals, consideration may be given to the differences in performance appraisal... promotion was made known to all potential candidates; (B) Reassignment or reduction in band to a position with more promotion potential than a position previously held on a permanent basis in the competitive...

  12. Challenges and Concerns Faced by Doctoral Candidates Seeking Academic Positions.

    ERIC Educational Resources Information Center

    Porter, Dion; Donnell, Chandra; Buck, Tina; Edwards, Yolanda

    A panel discussion offered suggestions and recommendations for faculty and institutions of rehabilitation counseling education on more effective recruitment methods. Strategies were also considered for potential faculty members. Candidates seeking academic positions in rehabilitation counseling education face many challenges. Location of program;…

  13. The WRKY Transcription Factor Genes in Eggplant (Solanum melongena L.) and Turkey Berry (Solanum torvum Sw.)

    PubMed Central

    Yang, Xu; Deng, Cao; Zhang, Yu; Cheng, Yufu; Huo, Qiuyue; Xue, Linbao

    2015-01-01

    WRKY transcription factors, which play critical roles in stress responses, have not been characterized in eggplant or its wild relative, turkey berry. The recent availability of RNA-sequencing data provides the opportunity to examine WRKY genes from a global perspective. We identified 50 and 62 WRKY genes in eggplant (SmelWRKYs) and turkey berry (StorWRKYs), respectively, all of which could be classified into three groups (I–III) based on the WRKY protein structure. The SmelWRKYs and StorWRKYs contain ~76% and ~95% of the number of WRKYs found in other sequenced asterid species, respectively. Positive selection analysis revealed that different selection constraints could have affected the evolution of these groups. Positively-selected sites were found in Groups IIc and III. Branch-specific selection pressure analysis indicated that most WRKY domains from SmelWRKYs and StorWRKYs are conserved and have evolved at low rates since their divergence. Comparison to homologous WRKY genes in Arabidopsis revealed several potential pathogen resistance-related SmelWRKYs and StorWRKYs, providing possible candidate genetic resources for improving stress tolerance in eggplant and probably other Solanaceae plants. To our knowledge, this is the first report of a genome-wide analyses of the SmelWRKYs and StorWRKYs. PMID:25853261

  14. The WRKY transcription factor genes in eggplant (Solanum melongena L.) and Turkey Berry (Solanum torvum Sw.).

    PubMed

    Yang, Xu; Deng, Cao; Zhang, Yu; Cheng, Yufu; Huo, Qiuyue; Xue, Linbao

    2015-04-07

    WRKY transcription factors, which play critical roles in stress responses, have not been characterized in eggplant or its wild relative, turkey berry. The recent availability of RNA-sequencing data provides the opportunity to examine WRKY genes from a global perspective. We identified 50 and 62 WRKY genes in eggplant (SmelWRKYs) and turkey berry (StorWRKYs), respectively, all of which could be classified into three groups (I-III) based on the WRKY protein structure. The SmelWRKYs and StorWRKYs contain ~76% and ~95% of the number of WRKYs found in other sequenced asterid species, respectively. Positive selection analysis revealed that different selection constraints could have affected the evolution of these groups. Positively-selected sites were found in Groups IIc and III. Branch-specific selection pressure analysis indicated that most WRKY domains from SmelWRKYs and StorWRKYs are conserved and have evolved at low rates since their divergence. Comparison to homologous WRKY genes in Arabidopsis revealed several potential pathogen resistance-related SmelWRKYs and StorWRKYs, providing possible candidate genetic resources for improving stress tolerance in eggplant and probably other Solanaceae plants. To our knowledge, this is the first report of a genome-wide analyses of the SmelWRKYs and StorWRKYs.

  15. Tailor-made heart simulation predicts the effect of cardiac resynchronization therapy in a canine model of heart failure.

    PubMed

    Panthee, Nirmal; Okada, Jun-ichi; Washio, Takumi; Mochizuki, Youhei; Suzuki, Ryohei; Koyama, Hidekazu; Ono, Minoru; Hisada, Toshiaki; Sugiura, Seiryo

    2016-07-01

    Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P<0.01) or the maximum value of the derivative of left ventricular pressure (P<0.01). The optimal lead positions produced better outcomes compared with the worst positioning in all dogs studied, although there were significant variations in responses. Variations in ventricular wall thickness among the dogs may have contributed to these responses. Thus CRT simulations using the individualized three-dimensional heart models can predict acute hemodynamic improvement, and help determine the optimal positions of the pacing lead. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Positive-Negative Asymmetry in the Evaluations of Political Candidates. The Role of Features of Similarity and Affect in Voter Behavior.

    PubMed

    Falkowski, Andrzej; Jabłońska, Magdalena

    2018-01-01

    In this study we followed the extension of Tversky's research about features of similarity with its application to open sets. Unlike the original closed-set model in which a feature was shifted between a common and a distinctive set, we investigated how addition of new features and deletion of existing features affected similarity judgments. The model was tested empirically in a political context and we analyzed how positive and negative changes in a candidate's profile affect the similarity of the politician to his or her ideal and opposite counterpart. The results showed a positive-negative asymmetry in comparison judgments where enhancing negative features (distinctive for an ideal political candidate) had a greater effect on judgments than operations on positive (common) features. However, the effect was not observed for comparisons to a bad politician. Further analyses showed that in the case of a negative reference point, the relationship between similarity judgments and voting intention was mediated by the affective evaluation of the candidate.

  17. Selection of a Data Acquisition and Controls System Communications and Software Architecture for Johnson Space Center's Space Environment Simulation Laboratory Thermal and Vacuum Test Facilities

    NASA Technical Reports Server (NTRS)

    Jordan, Eric A.

    2004-01-01

    Upgrade of data acquisition and controls systems software at Johnson Space Center's Space Environment Simulation Laboratory (SESL) involved the definition, evaluation and selection of a system communication architecture and software components. A brief discussion of the background of the SESL and its data acquisition and controls systems provides a context for discussion of the requirements for each selection. Further framework is provided as upgrades to these systems accomplished in the 1990s and in 2003 are compared to demonstrate the role that technological advances have had in their improvement. Both of the selections were similar in their three phases; 1) definition of requirements, 2) identification of candidate products and their evaluation and testing and 3) selection by comparison of requirement fulfillment. The candidates for the communication architecture selection embraced several different methodologies which are explained and contrasted. Requirements for this selection are presented and the selection process is described. Several candidates for the software component of the data acquisition and controls system are identified, requirements for evaluation and selection are presented, and the evaluation process is described.

  18. Detection of genomic signatures of recent selection in commercial broiler chickens.

    PubMed

    Fu, Weixuan; Lee, William R; Abasht, Behnam

    2016-08-26

    Identification of the genomic signatures of recent selection may help uncover causal polymorphisms controlling traits relevant to recent decades of selective breeding in livestock. In this study, we aimed at detecting signatures of recent selection in commercial broiler chickens using genotype information from single nucleotide polymorphisms (SNPs). A total of 565 chickens from five commercial purebred lines, including three broiler sire (male) lines and two broiler dam (female) lines, were genotyped using the 60K SNP Illumina iSelect chicken array. To detect genomic signatures of recent selection, we applied two methods based on population comparison, cross-population extended haplotype homozygosity (XP-EHH) and cross-population composite likelihood ratio (XP-CLR), and further analyzed the results to find genomic regions under recent selection in multiple purebred lines. A total of 321 candidate selection regions spanning approximately 1.45 % of the chicken genome in each line were detected by consensus of results of both XP-EHH and XP-CLR methods. To minimize false discovery due to genetic drift, only 42 of the candidate selection regions that were shared by 2 or more purebred lines were considered as high-confidence selection regions in the study. Of these 42 regions, 20 were 50 kb or less while 4 regions were larger than 0.5 Mb. In total, 91 genes could be found in the 42 regions, among which 19 regions contained only 1 or 2 genes, and 9 regions were located at gene deserts. Our results provide a genome-wide scan of recent selection signatures in five purebred lines of commercial broiler chickens. We found several candidate genes for recent selection in multiple lines, such as SOX6 (Sex Determining Region Y-Box 6) and cTR (Thyroid hormone receptor beta). These genes may have been under recent selection due to their essential roles in growth, development and reproduction in chickens. Furthermore, our results suggest that in some candidate regions, the same or opposite alleles have been under recent selection in multiple lines. Most of the candidate genes in the selection regions are novel, and as such they should be of great interest for future research into the genetic architecture of traits relevant to modern broiler breeding.

  19. Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel

    PubMed Central

    Schmidt, Joshua M.; Battlay, Paul; Gledhill-Smith, Rebecca S.; Good, Robert T.; Lumb, Chris; Fournier-Level, Alexandre; Robin, Charles

    2017-01-01

    Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies (GWAS) to identify DDT-associated polygenes and use selective sweep analyses to assess their adaptive significance. We identify and verify two candidate DDT resistance loci. A largely uncharacterized gene, CG10737, has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1, shows compelling evidence of positive selection. PMID:28935691

  20. An interpretive review of selective sweep studies in Bos taurus cattle populations: identification of unique and shared selection signals across breeds

    PubMed Central

    Gutiérrez-Gil, Beatriz; Arranz, Juan J.; Wiener, Pamela

    2015-01-01

    This review compiles the results of 21 genomic studies of European Bos taurus breeds and thus provides a general picture of the selection signatures in taurine cattle identified by genome-wide selection-mapping scans. By performing a comprehensive summary of the results reported in the literature, we compiled a list of 1049 selection sweeps described across 37 cattle breeds (17 beef breeds, 14 dairy breeds, and 6 dual-purpose breeds), and four different beef-vs.-dairy comparisons, which we subsequently grouped into core selective sweep (CSS) regions, defined as consecutive signals within 1 Mb of each other. We defined a total of 409 CSSs across the 29 bovine autosomes, 232 (57%) of which were associated with a single-breed (Single-breed CSSs), 134 CSSs (33%) were associated with a limited number of breeds (Two-to-Four-breed CSSs) and 39 CSSs (9%) were associated with five or more breeds (Multi-breed CSSs). For each CSS, we performed a candidate gene survey that identified 291 genes within the CSS intervals (from the total list of 5183 BioMart-extracted genes) linked to dairy and meat production, stature, and coat color traits. A complementary functional enrichment analysis of the CSS positional candidates highlighted other genes related to pathways underlying behavior, immune response, and reproductive traits. The Single-breed CSSs revealed an over-representation of genes related to dairy and beef production, this was further supported by over-representation of production-related pathway terms in these regions based on a functional enrichment analysis. Overall, this review provides a comparative map of the selection sweeps reported in European cattle breeds and presents for the first time a characterization of the selection sweeps that are found in individual breeds. Based on their uniqueness, these breed-specific signals could be considered as “divergence signals,” which may be useful in characterizing and protecting livestock genetic diversity. PMID:26029239

  1. Genetic adaptation of the antibacterial human innate immunity network.

    PubMed

    Casals, Ferran; Sikora, Martin; Laayouni, Hafid; Montanucci, Ludovica; Muntasell, Aura; Lazarus, Ross; Calafell, Francesc; Awadalla, Philip; Netea, Mihai G; Bertranpetit, Jaume

    2011-07-11

    Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

  2. Genetic adaptation of the antibacterial human innate immunity network

    PubMed Central

    2011-01-01

    Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response. PMID:21745391

  3. Finding False Positives Planet Candidates Due To Background Eclipsing Binaries in K2

    NASA Astrophysics Data System (ADS)

    Mullally, Fergal; Thompson, Susan E.; Coughlin, Jeffrey; DAVE Team

    2016-06-01

    We adapt the difference image centroid approach, used for finding background eclipsing binaries, to vet K2 planet candidates. Difference image centroids were used with great success to vet planet candidates in the original Kepler mission, where the source of a transit could be identified by subtracting images of out-of-transit cadences from in-transit cadences. To account for K2's roll pattern, we reconstruct out-of-transit images from cadences that are nearby in both time and spacecraft roll angle. We describe the method and discuss some K2 planet candidates which this method suggests are false positives.

  4. Issue-Advocacy versus Candidate Advertising: Effects on Candidate Preferences and Democratic Process.

    ERIC Educational Resources Information Center

    Pfau, Michael; Holbert, R. Lance; Szabo, Erin Alison; Kaminski, Kelly

    2002-01-01

    Examines the influence of soft-money-sponsored issue-advocacy advertising in U.S. House and Senate campaigns, comparing its effects against candidate-sponsored positive advertising and contrast advertising on viewers' candidate preferences and on their attitude that reflect democratic values. Reveals no main effects for advertising approach on…

  5. Voices of Teacher Candidates of Color on White Race Evasion: "I Worried about My Safety!"

    ERIC Educational Resources Information Center

    Amos, Yukari Takimoto

    2016-01-01

    This qualitative study investigated the negative impacts minority teacher candidates receive from white teacher candidates in a required multicultural education class. The findings reveal that four teacher candidates of color had difficulty positioning themselves among the overwhelming silencing power of whiteness in the class. The white students…

  6. Status of advanced fuel candidates for Sodium Fast Reactor within the Generation IV International Forum

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

    F. Delage; J. Carmack; C. B. Lee

    2013-10-01

    The main challenge for fuels for future Sodium Fast Reactor systems is the development and qualification of a nuclear fuel sub-assembly which meets the Generation IV International Forum goals. The Advanced Fuel project investigates high burn-up minor actinide bearing fuels as well as claddings and wrappers to withstand high neutron doses and temperatures. The R&D outcome of national and collaborative programs has been collected and shared between the AF project members in order to review the capability of sub-assembly material and fuel candidates, to identify the issues and select the viable options. Based on historical experience and knowledge, both oxidemore » and metal fuels emerge as primary options to meet the performance and the reliability goals of Generation IV SFR systems. There is a significant positive experience on carbide fuels but major issues remain to be overcome: strong in-pile swelling, atmosphere required for fabrication as well as Pu and Am losses. The irradiation performance database for nitride fuels is limited with longer term R&D activities still required. The promising core material candidates are Ferritic/Martensitic (F/M) and Oxide Dispersed Strengthened (ODS) steels.« less

  7. Systematic Search for Rings around Kepler Planet Candidates: Constraints on Ring Size and Occurrence Rate

    NASA Astrophysics Data System (ADS)

    Aizawa, Masataka; Masuda, Kento; Kawahara, Hajime; Suto, Yasushi

    2018-05-01

    We perform a systematic search for rings around 168 Kepler planet candidates with sufficient signal-to-noise ratios that are selected from all of the short-cadence data. We fit ringed and ringless models to their light curves and compare the fitting results to search for the signatures of planetary rings. First, we identify 29 tentative systems, for which the ringed models exhibit statistically significant improvement over the ringless models. The light curves of those systems are individually examined, but we are not able to identify any candidate that indicates evidence for rings. In turn, we find several mechanisms of false positives that would produce ringlike signals, and the null detection enables us to place upper limits on the size of the rings. Furthermore, assuming the tidal alignment between axes of the planetary rings and orbits, we conclude that the occurrence rate of rings larger than twice the planetary radius is less than 15%. Even though the majority of our targets are short-period planets, our null detection provides statistical and quantitative constraints on largely uncertain theoretical models of the origin, formation, and evolution of planetary rings.

  8. A New Way to Confirm Planet Candidates

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-05-01

    What was the big deal behind the Kepler news conference yesterday? Its not just that the number of confirmed planets found by Kepler has more than doubled (though thats certainly exciting news!). Whats especially interesting is the way in which these new planets were confirmed.Number of planet discoveries by year since 1995, including previous non-Kepler discoveries (blue), previous Kepler discoveries (light blue) and the newly validated Kepler planets (orange). [NASA Ames/W. Stenzel; Princeton University/T. Morton]No Need for Follow-UpBefore Kepler, the way we confirmed planet candidates was with follow-up observations. The candidate could be validated either by directly imaging (which is rare) or obtaining a large number radial-velocity measurements of the wobble of the planets host star due to the planets orbit. But once Kepler started producing planet candidates, these approaches to validation became less feasible. A lot of Kepler candidates are small and orbit faint stars, making follow-up observations difficult or impossible.This problem is what inspired the development of whats known as probabilistic validation, an analysis technique that involves assessing the likelihood that the candidates signal is caused by various false-positive scenarios. Using this technique allows astronomers to estimate the likelihood of a candidate signal being a true planet detection; if that likelihood is high enough, the planet candidate can be confirmed without the need for follow-up observations.A breakdown of the catalog of Kepler Objects of Interest. Just over half had previously been identified as false positives or confirmed as candidates. 1284 are newly validated, and another 455 have FPP of1090%. [Morton et al. 2016]Probabilistic validation has been used in the past to confirm individual planet candidates in Kepler data, but now Timothy Morton (Princeton University) and collaborators have taken this to a new level: they developed the first code thats designed to do fully automated batch processing of a large number of candidates.In a recently published study the results of which were announced yesterday the teamapplied their code to the entire catalog of 7,470 Kepler objects of interest.New Planets and False PositivesThe teams code was able to successfully evaluate the total false-positive probability (FPP) for 7,056 of the objects of interest. Of these, 428 objects previously identified as candidates were found to have FPP of more than 90%, suggesting that they are most likely false positives.Periods and radii of candidate and confirmed planets in the Kepler Objects of Interest catalog. Blue circles have previously been identified as confirmed planets. Candidates (orange) are shaded by false positive probability; more transparent means more likely to be a false positive. [Morton et al. 2016]In contrast, 1,935 candidates were found to have FPP of less than 1%, and were therefore declared validated planets. Of these confirmations, 1,284 were previously unconfirmed, more than doubling Keplers previous catalog of 1,041 confirmed planets. Morton and collaborators believe that 9 of these newly confirmed planets may fall within the habitable zone of their host stars.While the announcement of 1,284 newly confirmed planets is huge, the analysis presented in this study is the real news. The code used is publicly available and can be applied to any transiting exoplanet candidate. This means that this analysis technique can be used to find batches of exoplanets in data from the extended Kepler mission (K2) or from the future TESS and PLATO transit missions.CitationTimothy D. Morton et al 2016 ApJ 822 86. doi:10.3847/0004-637X/822/2/86

  9. Identification of Genetic Differentiation between Waxy and Common Maize by SNP Genotyping

    PubMed Central

    Hao, Derong; Zhang, Zhenliang; Cheng, Yujing; Chen, Guoqing; Lu, Huhua; Mao, Yuxiang; Shi, Mingliang; Huang, Xiaolan; Zhou, Guangfei; Xue, Lin

    2015-01-01

    Waxy maize (Zea mays L. var. ceratina) is an important vegetable and economic crop that is thought to have originated from cultivated flint maize and most recently underwent divergence from common maize. In this study, a total of 110 waxy and 110 common maize inbred lines were genotyped with 3072 SNPs to evaluate the genetic diversity, population structure, and linkage disequilibrium decay as well as identify putative loci that are under positive selection. The results revealed abundant genetic diversity in the studied panel and that genetic diversity was much higher in common than in waxy maize germplasms. Principal coordinate analysis and neighbor-joining cluster analysis consistently classified the 220 accessions into two major groups and a mixed group with mixed ancestry. Subpopulation structure in both waxy and common maize sets were associated with the germplasm origin and corresponding heterotic groups. The LD decay distance (1500–2000 kb) in waxy maize was lower than that in common maize. Fourteen candidate loci were identified as under positive selection between waxy and common maize at the 99% confidence level. The information from this study can assist waxy maize breeders by enhancing parental line selection and breeding program design. PMID:26566240

  10. The glass cliff: when and why women are selected as leaders in crisis contexts.

    PubMed

    Bruckmüller, Susanne; Branscombe, Nyla R

    2010-09-01

    The glass cliff refers to women being more likely to rise to positions of organizational leadership in times of crisis than in times of success, and men being more likely to achieve those positions in prosperous times. We examine the role that (a) a gendered history of leadership and (b) stereotypes about gender and leadership play in creating the glass cliff. In Expt 1, participants who read about a company with a male history of leadership selected a male future leader for a successful organization, but chose a female future leader in times of crisis. This interaction--between company performance and gender of the preferred future leader--was eliminated for a counter-stereotypic history of female leadership. In Expt 2, stereotypically male attributes were most predictive of leader selection in a successful organization, while stereotypically female attributes were most predictive in times of crisis. Differences in the endorsement of these stereotypes, in particular with regard to the ascription of lower stereotypically female attributes to the male candidate mediated the glass cliff effect. Overall, results suggest that stereotypes about male leadership may be more important for the glass cliff effect than stereotypes about women and leadership.

  11. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed anti-diabetic target in mice selected for leanness

    PubMed Central

    Morton, Nicholas M.; Beltram, Jasmina; Carter, Roderick N.; Michailidou, Zoi; Gorjanc, Gregor; Fadden, Clare Mc; Barrios-Llerena, Martin E.; Rodriguez-Cuenca, Sergio; Gibbins, Matthew T. G.; Aird, Rhona E.; Moreno-Navarrete, José Maria; Munger, Steven C.; Svenson, Karen L.; Gastaldello, Annalisa; Ramage, Lynne; Naredo, Gregorio; Zeyda, Maximilian; Wang, Zhao V.; Howie, Alexander F.; Saari, Aila; Sipilä, Petra; Stulnig, Thomas M.; Gudnason, Vilmundur; Kenyon, Christopher J.; Seckl, Jonathan R.; Walker, Brian R.; Webster, Scott P.; Dunbar, Donald R.; Churchill, Gary A.; Vidal-Puig, Antonio; Fernandez-Real, José Manuel; Emilsson, Valur; Horvat, Simon

    2017-01-01

    Discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic Lean mouse model, selected for low adiposity over 60 generations, to identify thiosulfate sulfurtransferase (Tst, Rhodanese) as a candidate obesity-resistance gene with selectively increased adipocyte expression. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst gene deficiency markedly exacerbated diabetes whereas pharmacological TST activation ameliorated diabetes in mice in vivo. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, adipose TST mRNA correlated positively with adipose insulin sensitivity and negatively with fat mass. Genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for type 2 diabetes. PMID:27270587

  12. The Atacama Cosmology Telescope: Physical Properties and Purity of a Galaxy Cluster Sample Selected Via the Sunyaev-Zel'Dovich Effect

    NASA Technical Reports Server (NTRS)

    Menanteau, Felipe; Gonzalez, Jorge; Juin, Jean-Baptiste; Marriage, Tobias; Reese, Erik D.; Acquaviva, Viviana; Aguirre, Paula; Appel, John Willam; Baker, Andrew J.; Barrientos, L. Felipe; hide

    2010-01-01

    We present optical and X-ray properties for the first confirmed galaxy cluster sample selected by the Sunyaev-Zel'dovich Effect from 148 GHz maps over 455 square degrees of sky made with the Atacama Cosmology Telescope. These maps. coupled with multi-band imaging on 4-meter-class optical telescopes, have yielded a sample of 23 galaxy clusters with redshifts between 0.118 and 1.066. Of these 23 clusters, 10 are newly discovered. The selection of this sample is approximately mass limited and essentially independent of redshift. We provide optical positions, images, redshifts and X-ray fluxes and luminosities for the full sample, and X-ray temperatures of an important subset. The mass limit of the full sample is around 8.0 x 10(exp 14) Stellar Mass. with a number distribution that peaks around a redshift of 0.4. For the 10 highest significance SZE-selected cluster candidates, all of which are optically confirmed, the mass threshold is 1 x 10(exp 15) Stellar Mass and the redshift range is 0.167 to 1.066. Archival observations from Chandra, XMM-Newton. and ROSAT provide X-ray luminosities and temperatures that are broadly consistent with this mass threshold. Our optical follow-up procedure also allowed us to assess the purity of the ACT cluster sample. Eighty (one hundred) percent of the 148 GHz candidates with signal-to-noise ratios greater than 5.1 (5.7) are confirmed as massive clusters. The reported sample represents one of the largest SZE-selected sample of massive clusters over all redshifts within a cosmologically-significant survey volume, which will enable cosmological studies as well as future studies on the evolution, morphology, and stellar populations in the most massive clusters in the Universe.

  13. Identifying applicants suitable to a career in nursing: a value-based approach to undergraduate selection.

    PubMed

    Traynor, Marian; Galanouli, Despina; Roberts, Martin; Leonard, Lawrence; Gale, Thomas

    2017-06-01

    The aim of this study was to complement existing evidence on the suitability of Multiple Mini Interviews as a potential tool for the selection of nursing candidates on to a BSc (Hons) nursing programme. This study aimed to trial the Multiple Mini Interview approach to recruitment with a group of first year nursing students (already selected using traditional interviews). Cross-sectional validation study. This paper reports on the evaluation of the participants' detailed scores from the Multiple Mini Interview stations; their original interview scores and their end of year results. This study took place in March 2015. Scores from the seven Multiple Mini Interview stations were analysed to show the internal structure, reliability and generalizability of the stations. Original selection scores from interviews and in-course assessment were correlated with the MMI scores and variation by students' age, gender and disability status was explored. Reliability of the Multiple Mini Interview score was moderate (G = 0·52). The Multiple Mini Interview score provided better differentiation between more able students than did the original interview score but neither score was correlated with the module results. Multiple Mini Interview scores were positively associated with students' age but not their gender or disability status. The Multiple Mini Interview reported in this study offers a selection process that is based on the values and personal attributes regarded as desirable for a career in nursing and does not necessarily predict academic success. Its moderate reliability indicates the need for further improvement but it is capable of discriminating between candidates and shows little evidence of bias. © 2016 John Wiley & Sons Ltd.

  14. Genomic selection signatures in sheep from the Western Pyrenees.

    PubMed

    Ruiz-Larrañaga, Otsanda; Langa, Jorge; Rendo, Fernando; Manzano, Carmen; Iriondo, Mikel; Estonba, Andone

    2018-03-22

    The current large spectrum of sheep phenotypic diversity results from the combined product of sheep selection for different production traits such as wool, milk and meat, and its natural adaptation to new environments. In this study, we scanned the genome of 25 Sasi Ardi and 75 Latxa sheep from the Western Pyrenees for three types of regions under selection: (1) regions underlying local adaptation of Sasi Ardi semi-feral sheep, (2) regions related to a long traditional dairy selection pressure in Latxa sheep, and (3) regions experiencing the specific effect of the modern genetic improvement program established for the Latxa breed during the last three decades. Thirty-two selected candidate regions including 147 annotated genes were detected by using three statistical parameters: pooled heterozygosity H, Tajima's D, and Wright's fixation index F st . For Sasi Ardi sheep, chromosomes Ovis aries (OAR)4, 6, and 22 showed the strongest signals and harbored several candidate genes related to energy metabolism and morphology (BBS9, ELOVL3 and LDB1), immunity (NFKB2), and reproduction (H2AFZ). The major genomic difference between Sasi Ardi and Latxa sheep was on OAR6, which is known to affect milk production, with highly selected regions around the ABCG2, SPP1, LAP3, NCAPG, LCORL, and MEPE genes in Latxa sheep. The effect of the modern genetic improvement program on Latxa sheep was also evident on OAR15, on which several olfactory genes are located. We also detected several genes involved in reproduction such as ESR1 and ZNF366 that were affected by this selection program. Natural and artificial selection have shaped the genome of both Sasi Ardi and Latxa sheep. Our results suggest that Sasi Ardi traits related to energy metabolism, morphological, reproductive, and immunological features have been under positive selection to adapt this semi-feral sheep to its particular environment. The highly selected Latxa sheep for dairy production showed clear signatures of selection in genomic regions related to milk production. Furthermore, our data indicate that the selection criteria applied in the modern genetic improvement program affect immunity and reproduction traits.

  15. Genetic adaptations of the plateau zokor in high-elevation burrows.

    PubMed

    Shao, Yong; Li, Jin-Xiu; Ge, Ri-Li; Zhong, Li; Irwin, David M; Murphy, Robert W; Zhang, Ya-Ping

    2015-11-25

    The plateau zokor (Myospalax baileyi) spends its entire life underground in sealed burrows. Confronting limited oxygen and high carbon dioxide concentrations, and complete darkness, they epitomize a successful physiological adaptation. Here, we employ transcriptome sequencing to explore the genetic underpinnings of their adaptations to this unique habitat. Compared to Rattus norvegicus, genes belonging to GO categories related to energy metabolism (e.g. mitochondrion and fatty acid beta-oxidation) underwent accelerated evolution in the plateau zokor. Furthermore, the numbers of positively selected genes were significantly enriched in the gene categories involved in ATPase activity, blood vessel development and respiratory gaseous exchange, functional categories that are relevant to adaptation to high altitudes. Among the 787 genes with evidence of parallel evolution, and thus identified as candidate genes, several GO categories (e.g. response to hypoxia, oxygen homeostasis and erythrocyte homeostasis) are significantly enriched, are two genes, EPAS1 and AJUBA, involved in the response to hypoxia, where the parallel evolved sites are at positions that are highly conserved in sequence alignments from multiple species. Thus, accelerated evolution of GO categories, positive selection and parallel evolution at the molecular level provide evidences to parse the genetic adaptations of the plateau zokor for living in high-elevation burrows.

  16. Deep Learning Questions Can Help Selection of High Ability Candidates for Universities

    ERIC Educational Resources Information Center

    Mellanby, Jane; Cortina-Borja, Mario; Stein, John

    2009-01-01

    Selection of students for places at universities mainly depends on GCSE grades and predictions of A-level grades, both of which tend to favour applicants from independent schools. We have therefore developed a new type of test that would measure candidates' "deep learning" approach since this assesses the motivation and creative thinking…

  17. The Effects of Sex and Professional Experience on Superintendent Selection Decisions by School Board Chairpersons

    ERIC Educational Resources Information Center

    Jarrett, Patrick

    2017-01-01

    The purpose of this research was to examine the effects that a superintendent candidate's sex and professional background and school board chairpersons' sex have on resume screening decisions. School board chairpersons were selected randomly from across the United States to receive one of six types of hypothetical superintendent candidates'…

  18. Analysis of Additive Manufacturing for Sustainment of Naval Aviation Systems

    DTIC Science & Technology

    2017-09-01

    selection methodology to query the aviation spare-parts inventory for identification of additive manufacturing candidates. The methodology organizes...a component selection methodology to query the aviation spare-parts inventory for identification of additive manufacturing candidates. The... methodology organizes the resultant data using a top-down approach that aligns technical feasibility with programmatic objectives. Finally, a discrete event

  19. SNP discovery in candidate adaptive genes using exon capture in a free-ranging alpine ungulate

    Treesearch

    Gretchen H. Roffler; Stephen J. Amish; Seth Smith; Ted Cosart; Marty Kardos; Michael K. Schwartz; Gordon Luikart

    2016-01-01

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identify SNP markers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein-coding...

  20. Identification and association analysis of several hundred single nucleotide polymorphisms within candidate genes for back fat thickness in Italian Large White pigs using a selective genotyping approach.

    PubMed

    Fontanesi, L; Galimberti, G; Calò, D G; Fronza, R; Martelli, P L; Scotti, E; Colombo, M; Schiavo, G; Casadio, R; Buttazzoni, L; Russo, V

    2012-08-01

    Combining different approaches (resequencing of portions of 54 obesity candidate genes, literature mining for pig markers associated with fat deposition or related traits in 77 genes, and in silico mining of porcine expressed sequence tags and other sequences available in databases), we identified and analyzed 736 SNP within candidate genes to identify markers associated with back fat thickness (BFT) in Italian Large White sows. Animals were chosen using a selective genotyping approach according to their EBV for BFT (276 with most negative and 279 with most positive EBV) within a population of ≈ 12,000 pigs. Association analysis between the SNP and BFT has been carried out using the MAX test proposed for case-control studies. The designed assays were successful for 656 SNP: 370 were excluded (low call rate or minor allele frequency <5%), whereas the remaining 286 in 212 genes were taken for subsequent analyses, among which 64 showed a P(nominal) value <0.1. To deal with the multiple testing problem in a candidate gene approach, we applied the proportion of false positives (PFP) method. Thirty-eight SNP were significant (P(PFP) < 0.20). The most significant SNP was the IGF2 intron3-g.3072G>A polymorphism (P(nominal) < 1.0E-50). The second most significant SNP was the MC4R c.1426A>G polymorphism (P(nominal) = 8.0E-05). The third top SNP (P(nominal) = 6.2E-04) was the intronic TBC1D1 g.219G>A polymorphic site, in agreement with our previous results obtained in an independent study. The list of significant markers also included SNP in additional genes (ABHD16A, ABHD5, ACP2, ALMS1, APOA2, ATP1A2, CALR, COL14A1, CTSF, DARS, DECR1, ENPP1, ESR1, GH1, GHRL, GNMT, IKBKB, JAK3, MTTP, NFKBIA, NT5E, PLAT, PPARG, PPP2R5D, PRLR, RRAGD, RFC2, SDHD, SERPINF1, UBE2H, VCAM1, and WAT). Functional relationships between genes were obtained using the Ingenuity Pathway Analysis (IPA) Knowledge Base. The top scoring pathway included 19 genes with a P(nominal) < 0.1, 2 of which (IKBKB and NFKBIA) are involved in the hypothalamic IKKβ/NFκB program that could represent a key axis to affect fat deposition traits in pigs. These results represent a starting point to plan marker-assisted selection in Italian Large White nuclei for BFT. Because of similarities between humans and pigs, this study might also provide useful clues to investigate genetic factors affecting human obesity.

  1. Breeding novel solutions in the brain: a model of Darwinian neurodynamics.

    PubMed

    Szilágyi, András; Zachar, István; Fedor, Anna; de Vladar, Harold P; Szathmáry, Eörs

    2016-01-01

    Background : The fact that surplus connections and neurons are pruned during development is well established. We complement this selectionist picture by a proof-of-principle model of evolutionary search in the brain, that accounts for new variations in theory space. We present a model for Darwinian evolutionary search for candidate solutions in the brain. Methods : We combine known components of the brain - recurrent neural networks (acting as attractors), the action selection loop and implicit working memory - to provide the appropriate Darwinian architecture. We employ a population of attractor networks with palimpsest memory. The action selection loop is employed with winners-share-all dynamics to select for candidate solutions that are transiently stored in implicit working memory. Results : We document two processes: selection of stored solutions and evolutionary search for novel solutions. During the replication of candidate solutions attractor networks occasionally produce recombinant patterns, increasing variation on which selection can act. Combinatorial search acts on multiplying units (activity patterns) with hereditary variation and novel variants appear due to (i) noisy recall of patterns from the attractor networks, (ii) noise during transmission of candidate solutions as messages between networks, and, (iii) spontaneously generated, untrained patterns in spurious attractors. Conclusions : Attractor dynamics of recurrent neural networks can be used to model Darwinian search. The proposed architecture can be used for fast search among stored solutions (by selection) and for evolutionary search when novel candidate solutions are generated in successive iterations. Since all the suggested components are present in advanced nervous systems, we hypothesize that the brain could implement a truly evolutionary combinatorial search system, capable of generating novel variants.

  2. Candidate Political Philosophy: Revelations in the 1960 and 1976 Debates.

    ERIC Educational Resources Information Center

    Meadow, Robert G.; Jackson-Beeck, Marilyn

    Since voters rarely have access to a candidate's unexpurgated statements, they rely on political advertising, film footage, and media interpretations. Thus, their expectations of candidates generally reflect selective reporting and self-aggrandizement. A framework for researching the degree of understanding reached between politicians and the…

  3. 14 CFR § 1214.1100 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Scope. § 1214.1100 Section § 1214.1100 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate... selection of astronaut candidates. It applies to all pilot and mission specialist astronaut candidate...

  4. 5 CFR 337.204 - Severe shortage of candidates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... local or national labor market; (3) The existence of nationwide or geographic skills shortages; (4... geographic locations. OPM may decide independently that such a shortage exists, or may make this decision in... quality of candidates; (6) The desirability of the geographic location of the position(s); (7) The...

  5. 5 CFR 337.204 - Severe shortage of candidates.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... local or national labor market; (3) The existence of nationwide or geographic skills shortages; (4... geographic locations. OPM may decide independently that such a shortage exists, or may make this decision in... quality of candidates; (6) The desirability of the geographic location of the position(s); (7) The...

  6. 5 CFR 337.204 - Severe shortage of candidates.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... local or national labor market; (3) The existence of nationwide or geographic skills shortages; (4... geographic locations. OPM may decide independently that such a shortage exists, or may make this decision in... quality of candidates; (6) The desirability of the geographic location of the position(s); (7) The...

  7. Prevalence of Candida species in the buccal cavity of diabetic and non-diabetic individuals in and around Pondicherry.

    PubMed

    Lydia Rajakumari, M; Saravana Kumari, P

    2016-12-01

    The aim of the present study was to determine the prevalence of Candida in the buccal cavity of diabetic and non-diabetic individuals in and around Pondicherry, India and to analyse the antifungal susceptibility profile of the selected isolates. A total of 400 buccal samples, 200 each from diabetic and non-diabetic healthy individuals were included in the study. Sabouraud's dextrose agar was used for isolation of Candida species. Identification was performed through microscopy, germ tube test, sugar fermentation test, sugar assimilation test and by using Hichrome agar. Distinct and phenotypically representative colonies were selected and subjected to ITS analysis. In vitro antifungal susceptibility testing for the isolated Candida species was performed using E-test. Results revealed that the prevalence of Candida species in diabetic individuals was higher when compared with non-diabetic healthy individuals. The most predominantly isolated species in diabetic and non-diabetic individuals from buccal cavity was Candida albicans. C. tropicalis was predominant among the non-albicans Candida isolated from both diabetic and non-diabetic individuals. Among denture wearers C. glabrata was predominant. In vitro antifungal susceptibility testing shows that ketoconazole, fluconazole and itraconazole were effective against the isolated Candida species. The rate of candidal carriage in diabetic individuals is higher. Different species of Candida are present in the oral cavity of diabetic individuals. There may be a positive correlation between glycemic control and candidal colonization. In vitro antifungal susceptibility testing of Candia species are required for proper management and treatment of candidal infections. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Microfluidic Devices for Automation of Assays on Drosophila Melanogaster for Applications in Drug Discovery and Biological Studies.

    PubMed

    Ghaemi, Reza; Selvaganapathy, Ponnambalam R

    Drug discovery is a long and expensive process, which usually takes 12-15 years and could cost up to ~$1 billion. Conventional drug discovery process starts with high throughput screening and selection of drug candidates that bind to specific target associated with a disease condition. However, this process does not consider whether the chosen candidate is optimal not only for binding but also for ease of administration, distribution in the body, effect of metabolism and associated toxicity if any. A holistic approach, using model organisms early in the drug discovery process to select drug candidates that are optimal not only in binding but also suitable for administration, distribution and are not toxic is now considered as a viable way for lowering the cost and time associated with the drug discovery process. However, the conventional drug discovery assays using Drosophila are manual and required skill operator, which makes them expensive and not suitable for high-throughput screening. Recently, microfluidics has been used to automate many of the operations (e.g. sorting, positioning, drug delivery) associated with the Drosophila drug discovery assays and thereby increase their throughput. This review highlights recent microfluidic devices that have been developed for Drosophila assays with primary application towards drug discovery for human diseases. The microfluidic devices that have been reviewed in this paper are categorized based on the stage of the Drosophila that have been used. In each category, the microfluidic technologies behind each device are described and their potential biological applications are discussed.

  9. Communication Aid with Human Eyes Only

    NASA Astrophysics Data System (ADS)

    Arai, Kohei; Yajima, Kenro

    A communication aid with human eyes only is proposed. A set of candidate character is displayed onto computer screen of relatively small and light Head Mount Display: HMD that is mounted on glasses of which user wears on. When user looks at a candidate character with his/hers left eye while right eye picture is taken with small and light web camera that also is mounted on the glasses. The proposed system can selects 81 characters with two layers of 9 by 9 character candidate image. Other than these there is another selective image including control keys and frequently use of sentences. By using image matching between previously acquired template image for each candidate character and the currently acquired image, the proposed system realizes that which character in the candidates is selected. By using blinking and fix one's eye on combine together, the proposed system recognizes that user determines the selected key from the candidates. The blinking detection method employs a morphologic filter to avoid misunderstanding of dark eye detection due to eyebrows and shadows. Thus user can input sentences. User also may edit the sentences and then the sentences are read with Text to Speech: TTS software tool. Thus the system allows support conversations between handicapped and disabled persons without voice and the others peoples because only the function required for conversation is human eyes. Also the proposed system can be used as an input system for wearable computing systems. Test results by the 6 different able persons show that the proposed system does work with acceptable speed, around 1.5 second / character.

  10. The surgical residency interview: a candidate-centered, working approach.

    PubMed

    Seabott, Heather; Smith, Ryan K; Alseidi, Adnan; Thirlby, Richard C

    2012-01-01

    The interview process is a pivotal, differentiating component of the residency match. Our bias is toward a working interview, producing better fulfillment of the needs of both parties, and a more informed match selection for the candidates and program. We describe a "candidate-centered" approach for integrating applicant interviews into our daily work schedule. Applicants are informed upon accepting the interview of the working interview model. Our program offers 33 interview days over a 12-week period. A maximum of 5 applicants are hosted per day. Applicants are assigned to 1 of our general, thoracic, vascular, or plastic surgery teams. The interview day begins with the applicant changing into scrubs, attending a morning conference, and taking part in a program overview by a Chief Resident. Applicants join their host team where 4-8 hours are spent observing the operative team, on rounds and sharing lunch. The faculty and senior residents are responsible for interviewing and evaluating applicants though the Electronic Residency Application Service. A total of 13 surgeons are involved in the interview process resulting in broad-based evaluations. Each surgeon interviewed between 3 and 12 applicants. Faculty rate this interview approach highly because it allows them to maintain a rigorous operative schedule while interacting with applicants. Current residents are engaged in welcoming applicants to view the program. Faculty and residents believe cooperating in a real world manner aids their assessment of the applicant. Applicants routinely provide positive feedback, relaying this approach is informative, transparent, and should be the "standard." Applicants believe they are presented a realistic view of the program. Ultimately, this candidate-centered process may be attributable to our resident cohort who exhibit high satisfaction, excellent resident morale, and very low dropout rate. We present a candidate-centered, working interview approach used in the selection of general surgery residents. While it may require more resources than the traditional approach, it harbors advantages for the applicant and the program. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  11. ZP Domain Proteins in the Abalone Egg Coat Include a Paralog of VERL under Positive Selection That Binds Lysin and 18-kDa Sperm Proteins

    PubMed Central

    Aagaard, Jan E.; Vacquier, Victor D.; MacCoss, Michael J.; Swanson, Willie J.

    2010-01-01

    Identifying fertilization molecules is key to our understanding of reproductive biology, yet only a few examples of interacting sperm and egg proteins are known. One of the best characterized comes from the invertebrate archeogastropod abalone (Haliotis spp.), where sperm lysin mediates passage through the protective egg vitelline envelope (VE) by binding to the VE protein vitelline envelope receptor for lysin (VERL). Rapid adaptive divergence of abalone lysin and VERL are an example of positive selection on interacting fertilization proteins contributing to reproductive isolation. Previously, we characterized a subset of the abalone VE proteins that share a structural feature, the zona pellucida (ZP) domain, which is common to VERL and the egg envelopes of vertebrates. Here, we use additional expressed sequence tag sequencing and shotgun proteomics to characterize this family of proteins in the abalone egg VE. We expand 3-fold the number of known ZP domain proteins present within the VE (now 30 in total) and identify a paralog of VERL (vitelline envelope zona pellucida domain protein [VEZP] 14) that contains a putative lysin-binding motif. We find that, like VERL, the divergence of VEZP14 among abalone species is driven by positive selection on the lysin-binding motif alone and that these paralogous egg VE proteins bind a similar set of sperm proteins including a rapidly evolving 18-kDa paralog of lysin, which may mediate sperm–egg fusion. This work identifies an egg coat paralog of VERL under positive selection and the candidate sperm proteins with which it may interact during abalone fertilization. PMID:19767347

  12. Improving the Accuracy of Planet Occurrence Rates from Kepler Using Approximate Bayesian Computation

    NASA Astrophysics Data System (ADS)

    Hsu, Danley C.; Ford, Eric B.; Ragozzine, Darin; Morehead, Robert C.

    2018-05-01

    We present a new framework to characterize the occurrence rates of planet candidates identified by Kepler based on hierarchical Bayesian modeling, approximate Bayesian computing (ABC), and sequential importance sampling. For this study, we adopt a simple 2D grid in planet radius and orbital period as our model and apply our algorithm to estimate occurrence rates for Q1–Q16 planet candidates orbiting solar-type stars. We arrive at significantly increased planet occurrence rates for small planet candidates (R p < 1.25 R ⊕) at larger orbital periods (P > 80 day) compared to the rates estimated by the more common inverse detection efficiency method (IDEM). Our improved methodology estimates that the occurrence rate density of small planet candidates in the habitable zone of solar-type stars is {1.6}-0.5+1.2 per factor of 2 in planet radius and orbital period. Additionally, we observe a local minimum in the occurrence rate for strong planet candidates marginalized over orbital period between 1.5 and 2 R ⊕ that is consistent with previous studies. For future improvements, the forward modeling approach of ABC is ideally suited to incorporating multiple populations, such as planets, astrophysical false positives, and pipeline false alarms, to provide accurate planet occurrence rates and uncertainties. Furthermore, ABC provides a practical statistical framework for answering complex questions (e.g., frequency of different planetary architectures) and providing sound uncertainties, even in the face of complex selection effects, observational biases, and follow-up strategies. In summary, ABC offers a powerful tool for accurately characterizing a wide variety of astrophysical populations.

  13. Sequence analyses of the distal-less homeobox gene family in East African cichlid fishes reveal signatures of positive selection.

    PubMed

    Diepeveen, Eveline T; Kim, Fabienne D; Salzburger, Walter

    2013-07-17

    Gen(om)e duplication events are hypothesized as key mechanisms underlying the origin of phenotypic diversity and evolutionary innovation. The diverse and species-rich lineage of teleost fishes is a renowned example of this scenario, because of the fish-specific genome duplication. Gene families, generated by this and other gene duplication events, have been previously found to play a role in the evolution and development of innovations in cichlid fishes - a prime model system to study the genetic basis of rapid speciation, adaptation and evolutionary innovation. The distal-less homeobox genes are particularly interesting candidate genes for evolutionary novelties, such as the pharyngeal jaw apparatus and the anal fin egg-spots. Here we study the dlx repertoire in 23 East African cichlid fishes to determine the rate of evolution and the signatures of selection pressure. Four intact dlx clusters were retrieved from cichlid draft genomes. Phylogenetic analyses of these eight dlx loci in ten teleost species, followed by an in-depth analysis of 23 East African cichlid species, show that there is disparity in the rates of evolution of the dlx paralogs. Dlx3a and dlx4b are the fastest evolving dlx genes, while dlx1a and dlx6a evolved more slowly. Subsequent analyses of the nonsynonymous-synonymous substitution rate ratios indicate that dlx3b, dlx4a and dlx5a evolved under purifying selection, while signs of positive selection were found for dlx1a, dlx2a, dlx3a and dlx4b. Our results indicate that the dlx repertoire of teleost fishes and cichlid fishes in particular, is shaped by differential selection pressures and rates of evolution after gene duplication. Although the divergence of the dlx paralogs are putative signs of new or altered functions, comparisons with available expression patterns indicate that the three dlx loci under strong purifying selection, dlx3b, dlx4a and dlx5a, are transcribed at high levels in the cichlids' pharyngeal jaw and anal fin. The dlx paralogs emerge as excellent candidate genes for the development of evolutionary innovations in cichlids, although further functional analyses are necessary to elucidate their respective contribution.

  14. The transcriptional landscape of αβ T cell differentiation

    PubMed Central

    Mingueneau, Michael; Kreslavsky, Taras; Gray, Daniel; Heng, Tracy; Cruse, Richard; Ericson, Jeffrey; Bendall, Sean; Spitzer, Matt; Nolan, Garry; Kobayashi, Koichi; von Boehmer, Harald; Mathis, Diane; Benoist, Christophe

    2013-01-01

    αβT cell differentiation from thymic precursors is a complex process, explored here with the breadth of ImmGen expression datasets, analyzing how differentiation of thymic precursors gives rise to transcriptomes. After surprisingly gradual changes though early T commitment, transit through the CD4+CD8+ stage involves a shutdown or rare breadth, and correlating tightly with MYC. MHC-driven selection promotes a large-scale transcriptional reactivation. We identify distinct signatures that mark cells destined for positive selection versus apoptotic deletion. Differential expression of surprisingly few genes accompany CD4 or CD8 commitment, a similarity that carries through to peripheral T cells and their activation, revealed by mass cytometry phosphoproteomics. The novel transcripts identified as candidate mediators of key transitions help define the “known unknown” of thymocyte differentiation. PMID:23644507

  15. Combining experimental evolution with next-generation sequencing: a powerful tool to study adaptation from standing genetic variation.

    PubMed

    Schlötterer, C; Kofler, R; Versace, E; Tobler, R; Franssen, S U

    2015-05-01

    Evolve and resequence (E&R) is a new approach to investigate the genomic responses to selection during experimental evolution. By using whole genome sequencing of pools of individuals (Pool-Seq), this method can identify selected variants in controlled and replicable experimental settings. Reviewing the current state of the field, we show that E&R can be powerful enough to identify causative genes and possibly even single-nucleotide polymorphisms. We also discuss how the experimental design and the complexity of the trait could result in a large number of false positive candidates. We suggest experimental and analytical strategies to maximize the power of E&R to uncover the genotype-phenotype link and serve as an important research tool for a broad range of evolutionary questions.

  16. Discovering Cepheid and RR Lyrae Stars: Pan-STARRS Science Archive @ STScI and Robotically Controlled Telescopes

    NASA Astrophysics Data System (ADS)

    Johnson, Elizabeth; Strolger, Louis-Gregory; Engle, Scott G.; Anderson, Richard I.; Rest, Armin; Calamida, Annalisa; Dosovitz Fox, Ori; Laney, David

    2017-01-01

    Cepheid and RR Lyrae stars are an integral part of the cosmic distance ladder and are also useful for studying galactic structure and stellar ages. This project aims to greatly expand the number of known periodic variables in our galaxy by identifying candidates in the PanSTARRS-1 3pi catalog, and carrying out systematically targeted characterization with robotically controlled telescopes. Candidate targets are selected from available detection tables based on color and variability indices and are then fully vetted using robotic telescopes: the RCT 1.3 meter (Kitt Peak National Observatory) and RATIR 1.5 meter (Mexico). Here we present work to develop a full, semi-automated prescription for candidate selection, targeted follow-up photometry, cataloging, and classification, which allows the review of approximately 25 variable candidates every two weeks. We make comparisons of our sample selection and purity from a similar study based on Pan-STARRS data (Hernitschek et al. 2016), as well as candidates identified in Gaia DR1. The goal, through continued observation and analysis, is to identify at least 10,000 new variables, hundreds of which will be new Cepheid and RR Lyrae stars.

  17. Academic Self-Efficacy Perceptions of Teacher Candidates

    ERIC Educational Resources Information Center

    Yesilyurt, Etem

    2013-01-01

    This study aims determining academic self-efficacy perception of teacher candidates. It is survey model. Population of the study consists of teacher candidates in 2010-2011 academic years at Ahmet Kelesoglu Education Faculty of Education Formation of Selcuk University. A simple random sample was selected as sampling method and the study was…

  18. 14 CFR 1214.1104 - Evaluation and ranking of highly qualified candidates.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Evaluation and ranking of highly qualified candidates. 1214.1104 Section 1214.1104 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate Recruitment and Selection Program § 1214.1104 Evaluation and...

  19. 14 CFR 1214.1104 - Evaluation and ranking of highly qualified candidates.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Evaluation and ranking of highly qualified candidates. 1214.1104 Section 1214.1104 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT NASA Astronaut Candidate Recruitment and Selection Program § 1214.1104 Evaluation and...

  20. CD44-positive cells are candidates for astrocyte precursor cells in developing mouse cerebellum.

    PubMed

    Cai, Na; Kurachi, Masashi; Shibasaki, Koji; Okano-Uchida, Takayuki; Ishizaki, Yasuki

    2012-03-01

    Neural stem cells are generally considered to be committed to becoming precursor cells before terminally differentiating into either neurons or glial cells during neural development. Neuronal and oligodendrocyte precursor cells have been identified in several areas in the murine central nervous system. The presence of astrocyte precursor cells (APCs) is not so well understood. The present study provides several lines of evidence that CD44-positive cells are APCs in the early postnatal mouse cerebellum. In developing mouse cerebellum, CD44-positive cells, mostly located in the white matter, were positive for the markers of the astrocyte lineage, but negative for the markers of mature astrocytes. CD44-positive cells were purified from postnatal cerebellum by fluorescence-activated cell sorting and characterized in vitro. In the absence of any signaling molecule, many cells died by apoptosis. The surviving cells gradually expressed glial fibrillary acidic protein, a marker for mature astrocytes, indicating that differentiation into mature astrocytes is the default program for these cells. The cells produced no neurospheres nor neurons nor oligodendrocytes under any condition examined, indicating these cells are not neural stem cells. Leukemia inhibitory factor greatly promoted astrocytic differentiation of CD44-positive cells, whereas bone morphogenetic protein 4 (BMP4) did not. Fibroblast growth factor-2 was a potent mitogen for these cells, but was insufficient for survival. BMP4 inhibited activation of caspase-3 and greatly promoted survival, suggesting a novel role for BMP4 in the control of development of astrocytes in cerebellum. We isolated and characterized only CD44 strongly positive large cells and discarded small and/or CD44 weakly positive cells in this study. Further studies are necessary to characterize these cells to help determine whether CD44 is a selective and specific marker for APCs in the developing mouse cerebellum. In conclusion, we succeeded in preparing APC candidates from developing mouse cerebellum, characterized them in vitro, and found that BMPs are survival factors for these cells.

  1. Improvement of a method for positioning of pithead by considering motion of the surface water

    NASA Astrophysics Data System (ADS)

    Yi, H.; Lee, D. K.

    2016-12-01

    Underground mining has weakness compared with open pit mining in aspects of efficiency, economy and working environment. However, the method has applied for the development of a deep orebody. Development plan is established when the economic valuation and technical analysis of the deposits is completed through exploration of mineral resources. Development is a process to open a passage from the ground surface to the orebody as one of the steps of mining process. In the planning, there are details such as pithead positioning, mining method selection, and shaft design, etc. Among these, pithead positioning is implemented by considering infrastructures, watershed, geology, and economy. In this study, we propose a method to consider the motion of the surface waters in order to improve the existing pithead positioning techniques. The method contemplates the terrain around the mine and makes the surface water flow information. Then, the drainage treatment cost for each candidate location of pithead is suggested. This study covers the concept and design of the scheme.

  2. Designing Superoxide-Generating Quantum Dots for Selective Light-Activated Nanotherapy.

    PubMed

    Goodman, Samuel M; Levy, Max; Li, Fei-Fei; Ding, Yuchen; Courtney, Colleen M; Chowdhury, Partha P; Erbse, Annette; Chatterjee, Anushree; Nagpal, Prashant

    2018-01-01

    The rapid emergence of superbugs, or multi-drug resistant (MDR) organisms, has prompted a search for novel antibiotics, beyond traditional small-molecule therapies. Nanotherapeutics are being investigated as alternatives, and recently superoxide-generating quantum dots (QDs) have been shown as important candidates for selective light-activated therapy, while also potentiating existing antibiotics against MDR superbugs. Their therapeutic action is selective, can be tailored by simply changing their quantum-confined conduction-valence band (CB-VB) positions and alignment with different redox half-reactions-and hence their ability to generate specific radical species in biological media. Here, we show the design of superoxide-generating QDs using optimal QD material and size well-matched to superoxide redox potential, charged ligands to modulate their uptake in cells and selective redox interventions, and core/shell structures to improve their stability for therapeutic action. We show that cadmium telluride (CdTe) QDs with conduction band (CB) position at -0.5 V with respect to Normal Hydrogen Electron (NHE) and visible 2.4 eV bandgap generate a large flux of selective superoxide radicals, thereby demonstrating the effective light-activated therapy. Although the positively charged QDs demonstrate large cellular uptake, they bind indiscriminately to cell surfaces and cause non-selective cell death, while negatively charged and zwitterionic QD ligands reduce the uptake and allow selective therapeutic action via interaction with redox species. The stability of designed QDs in biologically-relevant media increases with the formation of core-shell QD structures, but an appropriate design of core-shell structures is needed to minimize any reduction in charge injection efficiency to adsorbed oxygen molecules (to form superoxide) and maintain similar quantitative generation of tailored redox species, as measured using electron paramagnetic resonance (EPR) spectroscopy and electrochemical impedance spectroscopy (EIS). Using these findings, we demonstrate the rational design of QDs as selective therapeutic to kill more than 99% of a priority class I pathogen, thus providing an effective therapy against MDR superbugs.

  3. Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies.

    PubMed

    Bezençon, Olivier; Heidmann, Bibia; Siegrist, Romain; Stamm, Simon; Richard, Sylvia; Pozzi, Davide; Corminboeuf, Olivier; Roch, Catherine; Kessler, Melanie; Ertel, Eric A; Reymond, Isabelle; Pfeifer, Thomas; de Kanter, Ruben; Toeroek-Schafroth, Michael; Moccia, Luca G; Mawet, Jacques; Moon, Richard; Rey, Markus; Capeleto, Bruno; Fournier, Elvire

    2017-12-14

    We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.

  4. BALLERINA - doing Pirouettes for the Gamma-Bursts

    NASA Astrophysics Data System (ADS)

    Lund, Niels; Ballerina Consortium

    1998-12-01

    BALLERINA is a satellite project currently selected (together with 3 other candidates) for a five month phase-A study within the Danish Small-Satellite Programme. BALLERINA combines an all-sky monitor yielding instantaneous half-degree size error boxes with rapid maneuverability and a wide field X-ray telescope. The project aims to study the transition phase from the gamma-burst to the afterglow phase, and to distribute sub-arcminute positions for the bursts in near real time. We expect to be able to lock-on to the source with the X-ray telescope in less than 3 minutes from the trigger, and to provide the accurate burst position to the general astronomical community within 10 minutes. While waiting for the bursts we plan to study other transient and persistent X-ray sources .

  5. Lessons from the Performing Arts: Can Auditioning Improve the Selection Process in University Administration Preparation Programs in the 21st Century?

    ERIC Educational Resources Information Center

    Jones, Gary; Creighton, Theodore B.

    With approximately 50 percent of school administrators retiring over the next 10 years, school leader preparation programs are under pressure to admit adequate numbers of candidates to justify their costs and continued existence. Candidate recruitment and selection suffer, however, from ongoing practical problems including the use of grade-point…

  6. A Discovery of a Candidate Companion to a Transiting System KOI-94: A Direct Imaging Study for a Possibility of a False Positive

    NASA Technical Reports Server (NTRS)

    Takahashi, Yasuhiro; Narita, Norio; Hirano, Teruyuki; Kuzuhara, Masayuki; Tamura, Motohide; Kudo, Tomoyuki; Kusakabe, Nobuhiko; Hashimoto, Jun; Sato, Bun'ei; Abe, Lyu; hide

    2013-01-01

    We report a discovery of a companion candidate around one of Kepler Objects of Interest (KOIs), KOI-94, and results of our quantitative investigation of the possibility that planetary candidates around KOI-94 are false positives. KOI-94 has a planetary system in which four planetary detections have been reported by Kepler, suggesting that this system is intriguing to study the dynamical evolutions of planets. However, while two of those detections (KOI-94.01 and 03) have been made robust by previous observations, the others (KOI-94.02 and 04) are marginal detections, for which future confirmations with various techniques are required. We have conducted high-contrast direct imaging observations with Subaru/HiCIAO in H band and detected a faint object located at a separation of approximately 0.6 sec from KOI-94. The object has a contrast of approximately 1 × 10(exp -3) in H band, and corresponds to an M type star on the assumption that the object is at the same distance of KOI-94. Based on our analysis, KOI-94.02 is likely to be a real planet because of its transit depth, while KOI-94.04 can be a false positive due to the companion candidate. The success in detecting the companion candidate suggests that high-contrast direct imaging observations are important keys to examine false positives of KOIs. On the other hand, our transit light curve reanalyses lead to a better period estimate of KOI-94.04 than that on the KOI catalogue and show that the planetary candidate has the same limb darkening parameter value as the other planetary candidates in the KOI-94 system, suggesting that KOI-94.04 is also a real planet in the system.

  7. Radio stars - A possible link between the Hipparcos optical reference frame and an extra-galactic very long baseline interferometry reference frame

    NASA Technical Reports Server (NTRS)

    Lestrade, J.-F.; Preston, R. A.; Slade, M. A.

    1983-01-01

    The concept of typing the Hipparcos optical and the JPL VLBI frames of reference by means of VLBI measurements of the positions and proper motions of the radio components of some bright stars is considered. The properties of the thermal and non-thermal radio-stars are discussed and 22 candidate stars are selected to achieve this tie. A description is given of the first VLBI attempt to detect these stars on the intercontinental baselines of the Deep Space Network with the Mark II recording system.

  8. A Review of Selected Candidate Endophenotypes for Depression

    PubMed Central

    Goldstein, Brandon L.; Klein, Daniel N.

    2014-01-01

    Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. PMID:25006008

  9. [Multiple mini interviews before the occupation of main training posts in paediatrics].

    PubMed

    Hertel, Niels Thomas; Bjerager, Mia; Boas, Malene; Boisen, Kirsten A; Børch, Klaus; Frederiksen, Marianne Sjølin; Holm, Kirsten; Grum-Nymann, Anette; Johnsen, Martin M; Whitehouse, Stine; Balslev, Thomas

    2013-09-09

    Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

  10. The genetic basis of adaptive pigmentation variation in Drosophila melanogaster.

    PubMed

    Pool, John E; Aquadro, Charles F

    2007-07-01

    In a broad survey of Drosophila melanogaster population samples, levels of abdominal pigmentation were found to be highly variable and geographically differentiated. A strong positive correlation was found between dark pigmentation and high altitude, suggesting adaptation to specific environments. DNA sequence polymorphism at the candidate gene ebony revealed a clear association with the pigmentation of homozygous third chromosome lines. The darkest lines sequenced had nearly identical haplotypes spanning 14.5 kb upstream of the protein-coding exons of ebony. Thus, natural selection may have elevated the frequency of an allele that confers dark abdominal pigmentation by influencing the regulation of ebony.

  11. Selection signatures in four lignin genes from switchgrass populations divergently selected for in vitro dry matter digestibility

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

    Chen, Shiyu; Kaeppler, Shawn M.; Vogel, Kenneth P.

    Switchgrass is undergoing development as a dedicated cellulosic bioenergy crop. Fermentation of lignocellulosic biomass to ethanol in a bioenergy system or to volatile fatty acids in a livestock production system is strongly and negatively influenced by lignification of cell walls. This study detects specific loci that exhibit selection signatures across switchgrass breeding populations that differ in in vitro dry matter digestibility (IVDMD), ethanol yield, and lignin concentration. Allele frequency changes in candidate genes were used to detect loci under selection. Out of the 183 polymorphisms identified in the four candidate genes, twenty-five loci in the intron regions and four locimore » in coding regions were found to display a selection signature. All loci in the coding regions are synonymous substitutions. Selection in both directions were observed on polymorphisms that appeared to be under selection. Genetic diversity and linkage disequilibrium within the candidate genes were low. The recurrent divergent selection caused excessive moderate allele frequencies in the cycle 3 reduced lignin population as compared to the base population. As a result, this study provides valuable insight on genetic changes occurring in short-term selection in the polyploid populations, and discovered potential markers for breeding switchgrass with improved biomass quality.« less

  12. Selection signatures in four lignin genes from switchgrass populations divergently selected for in vitro dry matter digestibility

    DOE PAGES

    Chen, Shiyu; Kaeppler, Shawn M.; Vogel, Kenneth P.; ...

    2016-11-28

    Switchgrass is undergoing development as a dedicated cellulosic bioenergy crop. Fermentation of lignocellulosic biomass to ethanol in a bioenergy system or to volatile fatty acids in a livestock production system is strongly and negatively influenced by lignification of cell walls. This study detects specific loci that exhibit selection signatures across switchgrass breeding populations that differ in in vitro dry matter digestibility (IVDMD), ethanol yield, and lignin concentration. Allele frequency changes in candidate genes were used to detect loci under selection. Out of the 183 polymorphisms identified in the four candidate genes, twenty-five loci in the intron regions and four locimore » in coding regions were found to display a selection signature. All loci in the coding regions are synonymous substitutions. Selection in both directions were observed on polymorphisms that appeared to be under selection. Genetic diversity and linkage disequilibrium within the candidate genes were low. The recurrent divergent selection caused excessive moderate allele frequencies in the cycle 3 reduced lignin population as compared to the base population. As a result, this study provides valuable insight on genetic changes occurring in short-term selection in the polyploid populations, and discovered potential markers for breeding switchgrass with improved biomass quality.« less

  13. Assessment of Positive Psychology Course According to Comments and Life Satisfaction Levels of Counselor Candidates

    ERIC Educational Resources Information Center

    Bas, Asli Uz

    2016-01-01

    The purpose of this study was to assess the "Positive Psychology" course according to comments and life satisfaction levels of counselor candidates. The course was offered in Guidance and Psychological Counseling undergraduate program as an elective course. The participants of the study were 56 senior undergraduate students attended…

  14. Comparative transcriptome analyses of flower development in four species of Achimenes (Gesneriaceae).

    PubMed

    Roberts, Wade R; Roalson, Eric H

    2017-03-20

    Flowers have an amazingly diverse display of colors and shapes, and these characteristics often vary significantly among closely related species. The evolution of diverse floral form can be thought of as an adaptive response to pollination and reproduction, but it can also be seen through the lens of morphological and developmental constraints. To explore these interactions, we use RNA-seq across species and development to investigate gene expression and sequence evolution as they relate to the evolution of the diverse flowers in a group of Neotropical plants native to Mexico-magic flowers (Achimenes, Gesneriaceae). The assembled transcriptomes contain between 29,000 and 42,000 genes expressed during development. We combine sequence orthology and coexpression clustering with analyses of protein evolution to identify candidate genes for roles in floral form evolution. Over 25% of transcripts captured were distinctive to Achimenes and overrepresented by genes involved in transcription factor activity. Using a model-based clustering approach we find dynamic, temporal patterns of gene expression among species. Selection tests provide evidence of positive selection in several genes with roles in pigment production, flowering time, and morphology. Combining these approaches to explore genes related to flower color and flower shape, we find distinct patterns that correspond to transitions of floral form among Achimenes species. The floral transcriptomes developed from four species of Achimenes provide insight into the mechanisms involved in the evolution of diverse floral form among closely related species with different pollinators. We identified several candidate genes that will serve as an important and useful resource for future research. High conservation of sequence structure, patterns of gene coexpression, and detection of positive selection acting on few genes suggests that large phenotypic differences in floral form may be caused by genetic differences in a small set of genes. Our characterized floral transcriptomes provided here should facilitate further analyses into the genomics of flower development and the mechanisms underlying the evolution of diverse flowers in Achimenes and other Neotropical Gesneriaceae.

  15. A novel machine learning-enabled framework for instantaneous heart rate monitoring from motion-artifact-corrupted electrocardiogram signals.

    PubMed

    Zhang, Qingxue; Zhou, Dian; Zeng, Xuan

    2016-11-01

    This paper proposes a novel machine learning-enabled framework to robustly monitor the instantaneous heart rate (IHR) from wrist-electrocardiography (ECG) signals continuously and heavily corrupted by random motion artifacts in wearable applications. The framework includes two stages, i.e. heartbeat identification and refinement, respectively. In the first stage, an adaptive threshold-based auto-segmentation approach is proposed to select out heartbeat candidates, including the real heartbeats and large amounts of motion-artifact-induced interferential spikes. Then twenty-six features are extracted for each candidate in time, spatial, frequency and statistical domains, and evaluated by a spare support vector machine (SVM) to select out ten critical features which can effectively reveal residual heartbeat information. Afterwards, an SVM model, created on the training data using the selected feature set, is applied to find high confident heartbeats from a large number of candidates in the testing data. In the second stage, the SVM classification results are further refined by two steps: (1) a rule-based classifier with two attributes named 'continuity check' and 'locality check' for outlier (false positives) removal, and (2) a heartbeat interpolation strategy for missing-heartbeat (false negatives) recovery. The framework is evaluated on a wrist-ECG dataset acquired by a semi-customized platform and also a public dataset. When the signal-to-noise ratio is as low as  -7 dB, the mean absolute error of the estimated IHR is 1.4 beats per minute (BPM) and the root mean square error is 6.5 BPM. The proposed framework greatly outperforms well-established approaches, demonstrating that it can effectively identify the heartbeats from ECG signals continuously corrupted by intense motion artifacts and robustly estimate the IHR. This study is expected to contribute to robust long-term wearable IHR monitoring for pervasive heart health and fitness management.

  16. Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product.

    PubMed

    Thevis, Mario; Geyer, Hans; Kamber, Matthias; Schänzer, Wilhelm

    2009-08-01

    Non-steroidal and tissue-selective anabolic agents such as selective androgen receptor modulators (SARMs) represent a promising class of therapeutics for the treatment of various diseases such as sarcopenia or cancer cachexia. Advanced compounds of SARMs are based on an arylpropionamide-derived structure and leading drug candidates have successfully completed phase-II-clinical trials. Although none of these therapeutics have been approved, their performance-enhancing qualities and the black-market availability of these products makes them a viable target for misuse in the athletic community. In 2008, SARMs were added to the Prohibited List established by the World Anti-Doping Agency (WADA). That SARMs are the subject of misuse even without clinical approval was proved for the first time by the detection of the drug candidate Andarine (also referred to as S-4, S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide), advertised, sold and supplied via the Internet. The oily liquids, declared as green tea extracts and face moisturizer, were assayed using state-of-the-art analytical procedures and S-4 was found at concentrations of approximately 150 mg/mL. The authenticity of the product was demonstrated in comparison to reference material by liquid chromatography, high resolution/high accuracy (tandem) mass spectrometry using positive and negative electrospray ionization, and comparison to reference material. Moreover, an impurity resulting from poor product purification was detected, accounting for approximately 10% of S-4. This consisted of 2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-3-(4-nitro-3-trifluoromethyl-phenylamino)-propionamide. The ease of purchasing non-approved drug candidates that could potentially increase athletic performance demonstrates the need to operate proactively in the continued fight against doping. The early inclusion of emerging drugs into routine sports drug testing procedures is a key element of preventive doping research, limiting the options for cheating athletes who aim to undermine the doping control system. Copyright 2009 John Wiley & Sons, Ltd.

  17. Readability and Content of Patient Education Material Related to Implantable Cardioverter Defibrillators

    PubMed Central

    Strachan, Patricia H.; de Laat, Sonya; Carroll, Sandra L.; Schwartz, Lisa; Vaandering, Katie; Toor, Gurjit K.; Arthur, Heather M.

    2012-01-01

    Background Implantable cardioverter defibrillators (ICDs) are increasingly offered to patients for primary prevention of sudden cardiac death. Candidates for ICD receive ICD-related patient education material when they make decisions to consent or decline a primary prevention ICD. Printed patient education material directed at ICD candidates has not been the focus of direct appraisal. Objective We evaluated the readability and content of ICD-related print education materials made available to patients who were enrolled in a study involving patient decision making for ICD from 3 ICD sites in southern Ontario, Canada. Methods All ICD print materials referred to during interviews and/or that were available in ICD site waiting rooms were collected for analysis. Readability testing was conducted using the SMOG (“simple measurement of gobbledygook”) and Fry methods. The material was evaluated according to selected plain-language criteria, thematic content analysis, and rhetoric analysis. Results Twenty-one print materials were identified and analyzed. Documents were authored by device manufacturers, tertiary care hospitals, and cardiac support organizations. Although many documents adhered to plain-language recommendations, text-reading levels were higher than recommended. Twelve major content themes were identified. Content focused heavily on the positive aspects of living with the device to the exclusion of other possible information that could be relevant to the decisions that patients made. Conclusions Print-based patient education materials for ICD candidates are geared to a highly literate population. The focus on positive information to the exclusion of potentially negative aspects of the ICD, or alternatives to accepting 1, could influence and/or confuse patients about the purpose and implications of this medical device. Development of print materials is indicated that includes information about possible problems and that would be relevant for the multicultural and debilitated population who may require ICDs. The findings are highly relevant for nurses who care for primary prevention ICD candidates. PMID:21926915

  18. Gastroenterology - Evolution of specialty choice in recent years.

    PubMed

    Curbelo, José; Galván-Román, José-María; Sánchez-Lasheras, Fernando; Romeo, Jose María; Fernández-Somoano, Ana; Villacampa, Tomás; Baladrón, Jaime

    2017-09-01

    Gastroenterology is one of the medical specialties offered to residency training candidates each year. This project analyzes the data associated with the choice of a Gastroenterology residency program in recent years. Data related to specialty selection were obtained from official reports with regard to the allocation of residency places by the Spanish Ministry of Health, Social Services and Equality. Information was collected from various teaching centers via their training guides, the Spanish National Catalogue of Hospitals and the National Transplant Organization. The median consecutive number involved in the choice of Gastroenterology training has decreased year after year, and this specialty is now positioned among the five most commonly selected residency programs in 2015. The median number of hospitals with a higher number of beds, adult liver transplantation activities and dedicated GI bleeding units is significantly lower. This is also true when centers are analyzed according to the presence of specific Gastroenterology on-call shifts for residents or their association with medical schools. Data from the past five years highlight Madrid, Aragón and the Basque Country as the autonomous communities where Gastroenterology is the most popular. Centers selected by candidates with the lowest median consecutive numbers from 2011-2015 included the university hospitals Ramón y Cajal, Santiago de Compostela and Gregorio Marañón. Gastroenterology has gradually escalated in the ranking of residency choices and is now one of the five most popular options. Potential residents prefer larger centers with complex-care patients and more research activity.

  19. Anton permselective membrane

    NASA Technical Reports Server (NTRS)

    Alexander, S. S.; Hodgdon, R. B.; Waite, W. A.

    1979-01-01

    Experimental composite membranes were synthesized on a lab scale consisting of a thin layer of anion permselective resin supported by and bonded to a porous physically strong and conductive substrate film. These showed good selectivity and also substantially lower electrical resistivities than the homogenous candidate membranes optimized in the previous contract. A wide range of resin porosities were examined for three candidate membrane systems, CDIL, CP4L, and A3L to identify the formulation giving the best overall redox cell performance. Candidate anion membranes showed large increases in resistivity after a short time of immersion in concentrated FeCl/HCl solution. Largely on the basis of resistance stability the CDIL formulation was selected as prime candidate and about thirty-five membranes (one foot square) were produced for experimental static and dynamic evaluation.

  20. Two new discipline-independent indices to quantify individual's scientific research output

    NASA Astrophysics Data System (ADS)

    Valentinuzzi, M. E.; Laciar, E.; Atrio, J. L.

    2007-11-01

    Interest in quantitative measurement of scientific output has been steadily growing because of increasing needs in the evaluation of candidates for new positions and promotions in academic careers. Recently, a new index H was proposed; it is based on an hyperbolic relationship between the number of citations and the number of papers of a given investigator, which intersects with the equality straight line. The crossing point gives the number of papers that received at least H references in a predetermined period of time. Such index neglects the contribution of the less cited papers and depends strongly on the discipline. Herein, using Hirsch's crossing point idea, we propose two new normalized indices, selectivity S and amplitude A, that are independent on the discipline and that take into account the whole spectrum of published and cited papers. The proposed method was applied to 100 scientists using information obtained from SCOPUS. The potential function appeared as the best fit to the data. Correlation coefficients were always high (r = 0.79 ± 0.11). Most of the authors displayed a marked selectivity because a typical researcher concentrates only on a single subject or perhaps a few while a wide reach did not predominate. In conclusion, these parameters are proposed as a way to complement the scientific evaluation process of a candidate.

  1. Genetic Modification of Oncolytic Newcastle Disease Virus for Cancer Therapy.

    PubMed

    Cheng, Xing; Wang, Weijia; Xu, Qi; Harper, James; Carroll, Danielle; Galinski, Mark S; Suzich, JoAnn; Jin, Hong

    2016-06-01

    Clinical development of a mesogenic strain of Newcastle disease virus (NDV) as an oncolytic agent for cancer therapy has been hampered by its select agent status due to its pathogenicity in avian species. Using reverse genetics, we have generated a lead candidate oncolytic NDV based on the mesogenic NDV-73T strain that is no longer classified as a select agent for clinical development. This recombinant NDV has a modification at the fusion protein (F) cleavage site to reduce the efficiency of F protein cleavage and an insertion of a 198-nucleotide sequence into the HN-L intergenic region, resulting in reduced viral gene expression and replication in avian cells but not in mammalian cells. In mammalian cells, except for viral polymerase (L) gene expression, viral gene expression is not negatively impacted or increased by the HN-L intergenic insertion. Furthermore, the virus can be engineered to express a foreign gene while still retaining the ability to grow to high titers in cell culture. The recombinant NDV selectively replicates in and kills tumor cells and is able to drive potent tumor growth inhibition following intratumoral or intravenous administration in a mouse tumor model. The candidate is well positioned for clinical development as an oncolytic virus. Avian paramyxovirus type 1, NDV, has been an attractive oncolytic agent for cancer virotherapy. However, this virus can cause epidemic disease in poultry, and concerns about the potential environmental and economic impact of an NDV outbreak have precluded its clinical development. Here we describe generation and characterization of a highly potent oncolytic NDV variant that is unlikely to cause Newcastle disease in its avian host, representing an essential step toward moving NDV forward as an oncolytic agent. Several attenuation mechanisms have been genetically engineered into the recombinant NDV that reduce chicken pathogenicity to a level that is acceptable worldwide without impacting viral production in cell culture. The selective tumor replication of this recombinant NDV, both in vitro and in vivo, along with efficient tumor cell killing makes it an attractive oncolytic virus candidate that may provide clinical benefit to patients. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Perceived Social Support and Assertiveness as a Predictor of Candidates Psychological Counselors' Psychological Well-Being

    ERIC Educational Resources Information Center

    Ates, Bünyamin

    2016-01-01

    In this research, to what extent the variables of perceived social support (family, friends and special people) and assertiveness predicted the psychological well-being levels of candidate psychological counselors. The research group of this study included totally randomly selected 308 candidate psychological counselors including 174 females…

  3. MAT@USC Candidates and Latino English Language Learners

    ERIC Educational Resources Information Center

    Lomeli, Cynthia Leticia

    2012-01-01

    The purpose of this study was to further understand the perceptions of MAT@USC teacher candidates and how their perceptions and previous experiences affect the educational experiences of Latino English language learners. Three questions were developed to guide this study: (1) What are the perceptions of MAT@USC candidates in selected courses…

  4. Milagro Observations of Potential TeV Emitters

    NASA Technical Reports Server (NTRS)

    Abdo, A. A.; Abeysekara, A. U.; Allen, B. T.; Aune, T.; Barber, A. S.; Berley, D.; Braun, J.; Chen, C.; Christopher, G. E.; DeYoung, T.; hide

    2014-01-01

    This paper reports the results from three targeted searches of Milagro TeV sky maps: two extragalactic point source lists and one pulsar source list. The first extragalactic candidate list consists of 709 candidates selected from the Fermi-LAT 2FGL catalog. The second extragalactic candidate list contains 31 candidates selected from the TeVCat source catalog that have been detected by imaging atmospheric Cherenkov telescopes (IACTs). In both extragalactic candidate lists Mkn 421 was the only source detected by Milagro. This paper presents the Milagro TeV flux for Mkn 421 and flux limits for the brighter Fermi- LAT extragalactic sources and for all TeVCat candidates. The pulsar list extends a previously published Milagro targeted search for Galactic sources. With the 32 new gamma-ray pulsars identified in 2FGL, the number of pulsars that are studied by both Fermi-LAT and Milagro is increased to 52. In this sample, we find that the probability of Milagro detecting a TeV emission coincident with a pulsar increases with the GeV flux observed by the Fermi-LAT in the energy range from 0.1 GeV to 100 GeV.

  5. The cld mutation: narrowing the critical chromosomal region and selecting candidate genes.

    PubMed

    Péterfy, Miklós; Mao, Hui Z; Doolittle, Mark H

    2006-10-01

    Combined lipase deficiency (cld) is a recessive, lethal mutation specific to the tw73 haplotype on mouse Chromosome 17. While the cld mutation results in lipase proteins that are inactive, aggregated, and retained in the endoplasmic reticulum (ER), it maps separately from the lipase structural genes. We have narrowed the gene critical region by about 50% using the tw18 haplotype for deletion mapping and a recombinant chromosome used originally to map cld with respect to the phenotypic marker tf. The region now extends from 22 to 25.6 Mbp on the wild-type chromosome, currently containing 149 genes and 50 expressed sequence tags (ESTs). To identify the affected gene, we have selected candidates based on their known role in associated biological processes, cellular components, and molecular functions that best fit with the predicted function of the cld gene. A secondary approach was based on differences in mRNA levels between mutant (cld/cld) and unaffected (+/cld) cells. Using both approaches, we have identified seven functional candidates with an ER localization and/or an involvement in protein maturation and folding that could explain the lipase deficiency, and six expression candidates that exhibit large differences in mRNA levels between mutant and unaffected cells. Significantly, two genes were found to be candidates with regard to both function and expression, thus emerging as the strongest candidates for cld. We discuss the implications of our mapping results and our selection of candidates with respect to other genes, deletions, and mutations occurring in the cld critical region.

  6. Rising to the challenge: acute stress appraisals and selection centre performance in applicants to postgraduate specialty training in anaesthesia.

    PubMed

    Roberts, Martin J; Gale, Thomas C E; McGrath, John S; Wilson, Mark R

    2016-05-01

    The ability to work under pressure is a vital non-technical skill for doctors working in acute medical specialties. Individuals who evaluate potentially stressful situations as challenging rather than threatening may perform better under pressure and be more resilient to stress and burnout. Training programme recruitment processes provide an important opportunity to examine applicants' reactions to acute stress. In the context of multi-station selection centres for recruitment to anaesthesia training programmes, we investigated the factors influencing candidates' pre-station challenge/threat evaluations and the extent to which their evaluations predicted subsequent station performance. Candidates evaluated the perceived stress of upcoming stations using a measure of challenge/threat evaluation-the cognitive appraisal ratio (CAR)-and consented to release their demographic details and station scores. Using regression analyses we determined which candidate and station factors predicted variation in the CAR and whether, after accounting for these factors, the CAR predicted candidate performance in the station. The CAR was affected by the nature of the station and candidate gender, but not age, ethnicity, country of training or clinical experience. Candidates perceived stations involving work related tasks as more threatening. After controlling for candidates' demographic and professional profiles, the CAR significantly predicted station performance: 'challenge' evaluations were associated with better performance, though the effect was weak. Our selection centre model can help recruit prospective anaesthetists who are able to rise to the challenge of performing in stressful situations but results do not support the direct use of challenge/threat data for recruitment decisions.

  7. Design, analysis and test verification of advanced encapsulation systems

    NASA Technical Reports Server (NTRS)

    Garcia, A., III; Kallis, J. M.; Trucker, D. C.

    1983-01-01

    Analytical models were developed to perform optical, thermal, electrical and structural analyses on candidate encapsulation systems. From these analyses several candidate encapsulation systems were selected for qualification testing.

  8. QTL mapping and candidate genes for resistance to Fusarium ear rot and fumonisin contamination in maize.

    PubMed

    Maschietto, Valentina; Colombi, Cinzia; Pirona, Raul; Pea, Giorgio; Strozzi, Francesco; Marocco, Adriano; Rossini, Laura; Lanubile, Alessandra

    2017-01-21

    Fusarium verticillioides is a common maize pathogen causing ear rot (FER) and contamination of the grains with the fumonisin B1 (FB1) mycotoxin. Resistance to FER and FB1 contamination are quantitative traits, affected by environmental conditions, and completely resistant maize genotypes to the pathogen are so far unknown. In order to uncover genomic regions associated to reduced FER and FB1 contamination and identify molecular markers for assisted selection, an F 2:3 population of 188 progenies was developed crossing CO441 (resistant) and CO354 (susceptible) genotypes. FER severity and FB1 contamination content were evaluated over 2 years and sowing dates (early and late) in ears artificially inoculated with F. verticillioides by the use of either side-needle or toothpick inoculation techniques. Weather conditions significantly changed in the two phenotyping seasons and FER and FB1 content distribution significantly differed in the F 3 progenies according to the year and the sowing time. Significant positive correlations (P < 0.01) were detected between FER and FB1 contamination, ranging from 0.72 to 0.81. A low positive correlation was determined between FB1 contamination and silking time (DTS). A genetic map was generated for the cross, based on 41 microsatellite markers and 342 single nucleotide polymorphisms (SNPs) derived from Genotyping-by-Sequencing (GBS). QTL analyses revealed 15 QTLs for FER, 17 QTLs for FB1 contamination and nine QTLs for DTS. Eight QTLs located on linkage group (LG) 1, 2, 3, 6, 7 and 9 were in common between FER and FB1, making possible the selection of genotypes with both low disease severity and low fumonisin contamination. Moreover, five QTLs on LGs 1, 2, 4, 5 and 9 located close to previously reported QTLs for resistance to other mycotoxigenic fungi. Finally, 24 candidate genes for resistance to F. verticillioides are proposed combining previous transcriptomic data with QTL mapping. This study identified a set of QTLs and candidate genes that could accelerate breeding for resistance of maize lines showing reduced disease severity and low mycotoxin contamination determined by F. verticillioides.

  9. Identification of genomic regions associated with feed efficiency in Nelore cattle.

    PubMed

    de Oliveira, Priscila S N; Cesar, Aline S M; do Nascimento, Michele L; Chaves, Amália S; Tizioto, Polyana C; Tullio, Rymer R; Lanna, Dante P D; Rosa, Antonio N; Sonstegard, Tad S; Mourao, Gerson B; Reecy, James M; Garrick, Dorian J; Mudadu, Maurício A; Coutinho, Luiz L; Regitano, Luciana C A

    2014-09-26

    Feed efficiency is jointly determined by productivity and feed requirements, both of which are economically relevant traits in beef cattle production systems. The objective of this study was to identify genes/QTLs associated with components of feed efficiency in Nelore cattle using Illumina BovineHD BeadChip (770 k SNP) genotypes from 593 Nelore steers. The traits analyzed included: average daily gain (ADG), dry matter intake (DMI), feed-conversion ratio (FCR), feed efficiency (FE), residual feed intake (RFI), maintenance efficiency (ME), efficiency of gain (EG), partial efficiency of growth (PEG) and relative growth rate (RGR). The Bayes B analysis was completed with Gensel software parameterized to fit fewer markers than animals. Genomic windows containing all the SNP loci in each 1 Mb that accounted for more than 1.0% of genetic variance were considered as QTL region. Candidate genes within windows that explained more than 1% of genetic variance were selected by putative function based on DAVID and Gene Ontology. Thirty-six QTL (1-Mb SNP window) were identified on chromosomes 1, 2, 3, 5, 6, 7, 8, 9, 10, 12, 14, 15, 16, 18, 19, 20, 21, 22, 24, 25 and 26 (UMD 3.1). The amount of genetic variance explained by individual QTL windows for feed efficiency traits ranged from 0.5% to 9.07%. Some of these QTL minimally overlapped with previously reported feed efficiency QTL for Bos taurus. The QTL regions described in this study harbor genes with biological functions related to metabolic processes, lipid and protein metabolism, generation of energy and growth. Among the positional candidate genes selected for feed efficiency are: HRH4, ALDH7A1, APOA2, LIN7C, CXADR, ADAM12 and MAP7. Some genomic regions and some positional candidate genes reported in this study have not been previously reported for feed efficiency traits in Bos indicus. Comparison with published results indicates that different QTLs and genes may be involved in the control of feed efficiency traits in this Nelore cattle population, as compared to Bos taurus cattle.

  10. Justice Can Further Improve Its Monitoring of Changes in State/Local Voting Laws.

    DTIC Science & Technology

    1983-12-19

    voter quali- fications and eligibility; registration, bal- loting and vote counting procedures; and the eligibility or method of selecting candidates...voter qualifications and eligibility; registration, balloting, and vote counting procedures; and the eligibility or method of *$ selecting candidates...reapportionments, -* annexations, method -of-election, and bilingual assistance to mi- nority language groups. Forty-nine of the withdrawals occurred after the

  11. Frequentist Model Averaging in Structural Equation Modelling.

    PubMed

    Jin, Shaobo; Ankargren, Sebastian

    2018-06-04

    Model selection from a set of candidate models plays an important role in many structural equation modelling applications. However, traditional model selection methods introduce extra randomness that is not accounted for by post-model selection inference. In the current study, we propose a model averaging technique within the frequentist statistical framework. Instead of selecting an optimal model, the contributions of all candidate models are acknowledged. Valid confidence intervals and a [Formula: see text] test statistic are proposed. A simulation study shows that the proposed method is able to produce a robust mean-squared error, a better coverage probability, and a better goodness-of-fit test compared to model selection. It is an interesting compromise between model selection and the full model.

  12. Is orthopedics more competitive today than when my attending matched? An analysis of National Resident Matching Program data for orthopedic PGY1 applicants from 1984 to 2011.

    PubMed

    Karnes, Jonathan M; Mayerson, Joel L; Scharschmidt, Thomas J

    2014-01-01

    This study evaluated supply and demand trends for orthopedic postgraduate year 1 (PGY1) positions from 1984 to 2011 for the purpose of estimating national intercandidate competition over time. National Resident Matching Program (NRMP) data for orthopedic surgery from 1984 to 2011 were collected. Proxy variables including (total number of orthopedic applicants/number of orthopedic PGY1 positions), (number of US senior applicants to orthopedics/number of orthopedic PGY1 positions), (number of US seniors matching into orthopedics/number of US senior orthopedic applicants), (total number of matched orthopedic applicants/total number of orthopedic applicants), and (total number of US applicants who fail to match into orthopedics/total number of US senior applicants into orthopedics) as well as average United States Medical Licensing Examination Step 1 scores were used to gauge the level of competition between candidates and were compared over time. Academic medical center in the Midwestern United States. Medical professors and medical students. The NRMP data suggested that the number of positions per applicant decreased or remained stable since 1984 and that the percentage of applicants who did not match was no higher now than in the past. This finding was primarily because of the relative decrease in the ratio of applicants to available PGY1 positions, which stems from the number of positions increasing more rapidly than the number of applicants. The NRMP data from 1984 to 2011 supported our hypothesis that intercandidate competition intensity for orthopedic PGY1 positions has not increased over time. The misconception that orthopedics is becoming more competitive likely arises from the increased number of applications submitted per candidate and the resulting relative importance placed on objective criteria such as United States Medical Licensing Examination Step 1 scores when programs select interview cohorts. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  13. Genome-Wide Specific Selection in Three Domestic Sheep Breeds.

    PubMed

    Wang, Huihua; Zhang, Li; Cao, Jiaxve; Wu, Mingming; Ma, Xiaomeng; Liu, Zhen; Liu, Ruizao; Zhao, Fuping; Wei, Caihong; Du, Lixin

    2015-01-01

    Commercial sheep raised for mutton grow faster than traditional Chinese sheep breeds. Here, we aimed to evaluate genetic selection among three different types of sheep breed: two well-known commercial mutton breeds and one indigenous Chinese breed. We first combined locus-specific branch lengths and di statistical methods to detect candidate regions targeted by selection in the three different populations. The results showed that the genetic distances reached at least medium divergence for each pairwise combination. We found these two methods were highly correlated, and identified many growth-related candidate genes undergoing artificial selection. For production traits, APOBR and FTO are associated with body mass index. For meat traits, ALDOA, STK32B and FAM190A are related to marbling. For reproduction traits, CCNB2 and SLC8A3 affect oocyte development. We also found two well-known genes, GHR (which affects meat production and quality) and EDAR (associated with hair thickness) were associated with German mutton merino sheep. Furthermore, four genes (POL, RPL7, MSL1 and SHISA9) were associated with pre-weaning gain in our previous genome-wide association study. Our results indicated that combine locus-specific branch lengths and di statistical approaches can reduce the searching ranges for specific selection. And we got many credible candidate genes which not only confirm the results of previous reports, but also provide a suite of novel candidate genes in defined breeds to guide hybridization breeding.

  14. Pond Identification, Classification, and Inundation Dynamics at St. Marks National Wildlife Refuge in northwest Florida, USA

    NASA Astrophysics Data System (ADS)

    Riley, J. W.; Calhoun, D.; Barichivich, J.

    2012-12-01

    The persistence and resilience of amphibian communities is largely dependent on adequate breeding habitat. This is especially important for threatened and endangered species that may often exist as isolated populations and have specific requirements for breeding. A study currently being conducted by the U.S. Geological Survey is investigating the feasibility of a repatriation effort of the Striped Newt (Notophthalmus perstriatus), a federal candidate species, within the St. Marks National Wildlife Refuge (SMNWR) in northwest Florida. This amphibian species requires ponds that are free of fishes and, for this reason, generally chooses ephemeral ponds as breeding sites. The delineation of potential breeding habitat is a first step in selecting candidate areas for repatriation. To achieve this, a LIDAR (Light Detection and Ranging) derived digital elevation model (DEM) and a topographic position index (TPI) classification scheme was used to identify and classify isolated depressions across the landscape. The TPI evaluates the difference in elevation from a central DEM cell to the mean elevation of a neighborhood of surrounding DEM cells and is a robust tool for locating depressional features within a landscape. These candidate depression features were then screened to remove large perennial ponds and smaller connected ponds from further consideration. In addition, the perimeters of twenty-two field identified ephemeral ponds were surveyed with a high precision RTK GPS (Real Time Kinematic Global Positioning System) unit to provide a calibration dataset to evaluate the performance of the feature identification method. This set of ponds was also instrumented with water-level recorders to investigate inundation dynamics across a wide range of hydrologic conditions. We anticipate being able to classify pond hydroperiod—thus each pond's potential as breeding habitat—at the monitored locations through this combination of approaches. Using estimates of pond size, morphology, and landscape position derived from the DEM, the classifications will be extended to other ponds on the refuge.

  15. The Perception and Costs of the Interview Process for Plastic Surgery Residency Programs: Can the Process Be Streamlined?

    PubMed

    Susarla, Srinivas M; Swanson, Edward W; Slezak, Sheri; Lifchez, Scott D; Redett, Richard J

    2017-01-01

    The purpose of this study was to assess applicant perceptions and costs associated with the interview process for plastic surgery residency positions. This was a cross-sectional survey of applicants to the integrated- and independent-track residencies at the authors' institution. All applicants who were interviewed were invited to complete a Web-based survey on costs and perceptions of various components of the interview process. Descriptive and bivariate statistics were computed to compare applicants to the two program tracks. Fifty-three applicants were interviewed for residency positions; 48 completed a survey (90.5 percent response rate). Thirty-four applicants were candidates for the integrated program; 16 applicants were candidates for the independent program. The program spent $2763 per applicant interviewed; 63 percent of applicants spent more than $5000 on the interview process. More than 70 percent of applicants missed more than 7 days of work to attend interviews. Independent applicants felt less strongly that interviews were critical to the selection process and placed less value on physically visiting the hospital and direct, in-person interaction. Applicants placed little value on program informational talks. Applicants who had experience with virtual interviews felt more positively about the format of a video interview relative to those who did not. The residency interview process is resource intensive for programs and applicants. Removing informational talks may improve the process. Making physical tours and in-person interviews optional are other alternatives that merit future study.

  16. Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA)

    PubMed Central

    Tijono, S M; Guo, K; Henare, K; Palmer, B D; Wang, L-C S; Albelda, S M; Ching, L-M

    2013-01-01

    Background: Species selectivity of DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan) for murine cells over human cells could explain in part the recent disappointing phase III trials clinical results when preclinical studies were so promising. To identify analogues with greater human clinical potential, we compared the activity of xanthenone-4-acetic acid (XAA) analogues in murine or human cellular models. Methods: Analogues with a methyl group systematically substituted at different positions of the XAA backbone were evaluated for cytokine induction in cultured murine or human leukocytes; and for anti-vascular effects on endothelial cells on matrigel. In vivo antitumour activity and cytokine production by stromal or cancer cells was measured in human A375 and HCT116 xenografts. Results: Mono-methyl XAA analogues with substitutions at the seventh and eighth positions were the most active in stimulating human leukocytes to produce IL-6 and IL-8; and for inhibition of tube formation by ECV304 human endothelial-like cells, while 5- and 6-substituted analogues were the most active in murine cell systems. Conclusion: Xanthenone-4-acetic acid analogues exhibit extreme species selectivity. Analogues that are the most active in human systems are inactive in murine models, highlighting the need for the use of appropriate in vivo animal models in selecting clinical candidates for this class of compounds. PMID:23481185

  17. Finding Hidden Quasars with UKIDSS and AAOmega

    NASA Astrophysics Data System (ADS)

    Maddox, Natasha; Hewett, P. C.; Warren, S. J.; Croom, S. M.

    2007-05-01

    The number of luminous quasars that have thus far eluded optical surveys is a subject of ongoing debate. Dust reddening and significant host galaxy light tend to exclude candidates from traditional UV-excess selection. UKIDSS, the near-infrared counterpart to SDSS, has started to provide the large area NIR data required to quantify the number of quasars missing from optical surveys. The quasar candidate list was chosen from the Early Data Release of the UKIDSS Large Area Survey (LAS), which aims to cover 2000 square degrees in two years. Requiring each object to have K<17, J<19.5 (the detection limit of the LAS) and a detection in SDSS were the only restrictions imposed on the candidates. A simple cut in gJK colour space, exploiting the K-band excess of quasars compared to stars, then separates the quasar candidates from the stellar locus. Optical-NIR colour selection with relaxed restrictions on morphology is less sensitive to dust reddening, so provides a more complete candidate list, suitable for follow-up observation with the new AAOmega spectrograph on the Anglo-Australian Telescope. With spectroscopic observations covering nearly 20 square degrees taken at the AAT, this is by far the largest K-band selected quasar sample to date. Many new quasars have been identified, in addition to known quasars being recovered. Several of the newly discovered quasars lie in regions of colour space typically excluded by UV selection. This study highlights the effectiveness of the K-excess technique in selecting quasars that do not necessarily exhibit the classic UV excess, either due to intrinsic SED shape or dust reddening. Combining upcoming UKIDSS data releases with scheduled AAT observations will increase the area surveyed by several times, thus moving closer to fully quantifying the number of luminous, reddened quasars.

  18. Photometric Study of Massive Evolved Galaxies in the CANDELS GOODS-S at z>3

    NASA Astrophysics Data System (ADS)

    Nayyeri, Hooshang; Mobasher, B.; Ferguson, H. C.; Wiklind, T.; Hemmati, S.; De Barros, S.; Fontana, A.; Dahlen, T.; Koekemoer, A. M.

    2014-01-01

    According to the hierarchical models, galaxies assemble their mass through time with the most massive and evolved systems found in the more recent times and in the most massive dark matter halos. Understanding the evolution of mass assembly with cosmic time plays a central role in observational astronomy. Here, we use the very deep near Infra-red HST/WFC3 observations by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) to study passively evolving, old and massive systems at high redshifts. For this we utilize the pronounced Balmer Break (an age dependent diagnostic at rest-frame 3648Å) in post-starburst galaxies to devise a Balmer Break Galaxy (BBG) selection. We use the CANDELS WFC3 1.6 μm selected catalog in the GOODS-S, generated with TFIT algorithm suitable for mixed resolution data sets, to select the candidates. We identified 24 sources as candidates for evolved systems in the redshift 3.5

  19. Bias against foreign-born or foreign-trained doctors: experimental evidence.

    PubMed

    Louis, Winnifred R; Lalonde, Richard N; Esses, Victoria M

    2010-12-01

    Bias against foreign-born or -trained medical students and doctors is not well understood, despite its documented impact on recruitment, integration and retention. This research experimentally examines the interaction of location of medical education and nationality in evaluations of doctors' competence and trustworthiness. A convenience sample of prospective patients evaluated fictitious candidates for a position as a doctor in community practice at a new local health clinic. All applicants were described as having the same personality profile, legal qualifications to practise, a multi-degree education and relevant work experience. The location of medical education (the candidate's home country or the UK) and national background (Australia or Pakistan) of the applicants were independently experimentally manipulated. Consistent with previous research on skills discounting and bias, foreign-born candidates were evaluated less favourably than native-born candidates, despite their comparable education level, work experience and personality. However, overseas medical education obtained in the First World both boosted evaluations (of competence and trustworthiness) and attenuated bias based on nationality. The present findings demonstrate the selective discounting of foreign-born doctors' credentials. The data show an interaction of location of medical education and birth nationality in bias against foreign doctors. On an applied level, the data document that the benefits of medical education obtained in the First World can extend beyond its direct outcomes (high-quality training and institutional recognition) to the indirect benefit of the attenuation of patient bias based on nationality. © Blackwell Publishing Ltd 2010.

  20. Design criteria and candidate electrical power systems for a reusable Space Shuttle booster.

    NASA Technical Reports Server (NTRS)

    Merrifield, D. V.

    1972-01-01

    This paper presents the results of a preliminary study to establish electrical power requirements, investigate candidate power sources, and select a representative power generation concept for the NASA Space Shuttle booster stage. Design guidelines and system performance requirements are established. Candidate power sources and combinations thereof are defined and weight estimates made. The selected power source concept utilizes secondary silver-zinc batteries, engine-driven alternators with constant speed drive, and an airbreathing gas turbine. The need for cost optimization, within safety, reliability, and performance constraints, is emphasized as being the most important criteria in design of the final system.

  1. Understanding and Negotiating the Phone Interview.

    ERIC Educational Resources Information Center

    Durand, Alain-Philippe

    2002-01-01

    Discusses telephone interviews with candidates seeking positions in foreign language departments, where there is only voice and language with which to represent oneself to a search committee and by which to judge their responses. Suggests ways candidates can create a favorable impression and points out that one advantage of the candidate's…

  2. GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2).

    PubMed

    Crawford, Terry D; Audia, James E; Bellon, Steve; Burdick, Daniel J; Bommi-Reddy, Archana; Côté, Alexandre; Cummings, Richard T; Duplessis, Martin; Flynn, E Megan; Hewitt, Michael; Huang, Hon-Ren; Jayaram, Hariharan; Jiang, Ying; Joshi, Shivangi; Kiefer, James R; Murray, Jeremy; Nasveschuk, Christopher G; Neiss, Arianne; Pardo, Eneida; Romero, F Anthony; Sandy, Peter; Sims, Robert J; Tang, Yong; Taylor, Alexander M; Tsui, Vickie; Wang, Jian; Wang, Shumei; Wang, Yongyun; Xu, Zhaowu; Zawadzke, Laura; Zhu, Xiaoqin; Albrecht, Brian K; Magnuson, Steven R; Cochran, Andrea G

    2017-07-13

    The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

  3. A hierarchical two-phase framework for selecting genes in cancer datasets with a neuro-fuzzy system.

    PubMed

    Lim, Jongwoo; Wang, Bohyun; Lim, Joon S

    2016-04-29

    Finding the minimum number of appropriate biomarkers for specific targets such as a lung cancer has been a challenging issue in bioinformatics. We propose a hierarchical two-phase framework for selecting appropriate biomarkers that extracts candidate biomarkers from the cancer microarray datasets and then selects the minimum number of appropriate biomarkers from the extracted candidate biomarkers datasets with a specific neuro-fuzzy algorithm, which is called a neural network with weighted fuzzy membership function (NEWFM). In this context, as the first phase, the proposed framework is to extract candidate biomarkers by using a Bhattacharyya distance method that measures the similarity of two discrete probability distributions. Finally, the proposed framework is able to reduce the cost of finding biomarkers by not receiving medical supplements and improve the accuracy of the biomarkers in specific cancer target datasets.

  4. Health Information Technology Coordination to Support Patient-centered Care Coordination.

    PubMed

    Steichen, O; Gregg, W

    2015-08-13

    To select papers published in 2014, illustrating how information technology can contribute to and improve patient-centered care coordination. The two section editors performed a literature review from Medline and Web of Science to select a list of candidate best papers on the use of information technology for patient-centered care coordination. These papers were peer-reviewed by external reviewers and three of them were selected as "best papers". The first selected paper reports a qualitative study exploring the gap between current practices of care coordination in various settings and idealized longitudinal care plans. The second selected paper illustrates several unintended consequences of HIT designed to improve care coordination. The third selected paper shows that advanced analytic techniques in medical informatics can be instrumental in studying patient-centered care coordination. The realization of true patient-centered care coordination is dependent upon a number of factors. Standardization of clinical documentation and HIT interoperability across organization and settings is a critical prerequisite for HIT to support patient-centered care coordination. Enabling patient involvement is an efficient means for goal setting and health information sharing. Additionally, unintended consequences of HIT tools (both positive and negative) must be measured and taken into account for quality improvement.

  5. Vaccine candidates for malaria: what's new?

    PubMed

    Takashima, Eizo; Morita, Masayuki; Tsuboi, Takafumi

    2016-01-01

    Although it is more than a decade since the parasite genome information was obtained, standardized novel genome-wide selection/prioritization strategies for candidacy of malaria vaccine antigens are still sought. In the quest to systematically identify candidates, it is impossible to overemphasize the usefulness of wheat germ cell-free technology in expressing quality proteins for the post-genome vaccine candidate discovery.

  6. Multiple Leader Candidate and Competitive Position Allocation for Robust Formation against Member Robot Faults

    PubMed Central

    Kwon, Ji-Wook; Kim, Jin Hyo; Seo, Jiwon

    2015-01-01

    This paper proposes a Multiple Leader Candidate (MLC) structure and a Competitive Position Allocation (CPA) algorithm which can be applicable for various applications including environmental sensing. Unlike previous formation structures such as virtual-leader and actual-leader structures with position allocation including a rigid allocation and an optimization based allocation, the formation employing the proposed MLC structure and CPA algorithm is robust against the fault (or disappearance) of the member robots and reduces the entire cost. In the MLC structure, a leader of the entire system is chosen among leader candidate robots. The CPA algorithm is the decentralized position allocation algorithm that assigns the robots to the vertex of the formation via the competition of the adjacent robots. The numerical simulations and experimental results are included to show the feasibility and the performance of the multiple robot system employing the proposed MLC structure and the CPA algorithm. PMID:25954956

  7. THE HUNT FOR EXOMOONS WITH KEPLER (HEK). II. ANALYSIS OF SEVEN VIABLE SATELLITE-HOSTING PLANET CANDIDATES

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

    Kipping, D. M.; Hartman, J.; Bakos, G. A.

    2013-06-20

    From the list of 2321 transiting planet candidates announced by the Kepler Mission, we select seven targets with favorable properties for the capacity to dynamically maintain an exomoon and present a detectable signal. These seven candidates were identified through our automatic target selection (TSA) algorithm and target selection prioritization (TSP) filtering, whereby we excluded systems exhibiting significant time-correlated noise and focused on those with a single transiting planet candidate of radius less than 6 R{sub Circled-Plus }. We find no compelling evidence for an exomoon around any of the seven Kepler Objects of Interest (KOIs) but constrain the satellite-to-planet massmore » ratios for each. For four of the seven KOIs, we estimate a 95% upper quantile of M{sub S} /M{sub P} < 0.04, which given the radii of the candidates, likely probes down to sub-Earth masses. We also derive precise transit times and durations for each candidate and find no evidence for dynamical variations in any of the KOIs. With just a few systems analyzed thus far in the ongoing ''Hunt for Exomoons with Kepler'' (HEK) project, projections on eta-moon would be premature, but a high frequency of large moons around Super-Earths/Mini-Neptunes would be premature, but a high frequency of large moons around Super-Earths/Mini-Neptunes would appear to be incommensurable with our results so far.« less

  8. The Influence of Endmember Selection Method in Extracting Impervious Surface from Airborne Hyperspectral Imagery

    NASA Astrophysics Data System (ADS)

    Wang, J.; Feng, B.

    2016-12-01

    Impervious surface area (ISA) has long been studied as an important input into moisture flux models. In general, ISA impedes groundwater recharge, increases stormflow/flood frequency, and alters in-stream and riparian habitats. Urban area is recognized as one of the richest ISA environment. Urban ISA mapping assists flood prevention and urban planning. Hyperspectral imagery (HI), for its ability to detect subtle spectral signature, becomes an ideal candidate in urban ISA mapping. To map ISA from HI involves endmember (EM) selection. The high degree of spatial and spectral heterogeneity of urban environment puts great difficulty in this task: a compromise point is needed between the automatic degree and the good representativeness of the method. The study tested one manual and two semi-automatic EM selection strategies. The manual and the first semi-automatic methods have been widely used in EM selection. The second semi-automatic EM selection method is rather new and has been only proposed for moderate spatial resolution satellite. The manual method visually selected the EM candidates from eight landcover types in the original image. The first semi-automatic method chose the EM candidates using a threshold over the pixel purity index (PPI) map. The second semi-automatic method used the triangle shape of the HI scatter plot in the n-Dimension visualizer to identify the V-I-S (vegetation-impervious surface-soil) EM candidates: the pixels locate at the triangle points. The initial EM candidates from the three methods were further refined by three indexes (EM average RMSE, minimum average spectral angle, and count based EM selection) and generated three spectral libraries, which were used to classify the test image. Spectral angle mapper was applied. The accuracy reports for the classification results were generated. The overall accuracy are 85% for the manual method, 81% for the PPI method, and 87% for the V-I-S method. The V-I-S EM selection method performs best in this study. This fact proves the value of V-I-S EM selection method in not only moderate spatial resolution satellite image but also the more and more accessible high spatial resolution airborne image. This semi-automatic EM selection method can be adopted into a wide range of remote sensing images and provide ISA map for hydrology analysis.

  9. Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): a very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes.

    PubMed

    Madar, David J; Kopecka, Hana; Pireh, Daisy; Yong, Hong; Pei, Zhonghua; Li, Xiaofeng; Wiedeman, Paul E; Djuric, Stevan W; Von Geldern, Thomas W; Fickes, Michael G; Bhagavatula, Lakshmi; McDermott, Todd; Wittenberger, Steven; Richards, Steven J; Longenecker, Kenton L; Stewart, Kent D; Lubben, Thomas H; Ballaron, Stephen J; Stashko, Michael A; Long, Michelle A; Wells, Heidi; Zinker, Bradley A; Mika, Amanda K; Beno, David W A; Kempf-Grote, Anita J; Polakowski, James; Segreti, Jason; Reinhart, Glenn A; Fryer, Ryan M; Sham, Hing L; Trevillyan, James M

    2006-10-19

    Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.

  10. BANYAN. V. A SYSTEMATIC ALL-SKY SURVEY FOR NEW VERY LATE-TYPE LOW-MASS STARS AND BROWN DWARFS IN NEARBY YOUNG MOVING GROUPS

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

    Gagné, Jonathan; Lafrenière, David; Doyon, René

    2015-01-10

    We present the BANYAN All-Sky Survey (BASS) catalog, consisting of 228 new late-type (M4-L6) candidate members of nearby young moving groups (YMGs) with an expected false-positive rate of ∼13%. This sample includes 79 new candidate young brown dwarfs and 22 planetary-mass objects. These candidates were identified through the first systematic all-sky survey for late-type low-mass stars and brown dwarfs in YMGs. We cross-matched the Two Micron All Sky Survey and AllWISE catalogs outside of the galactic plane to build a sample of 98,970 potential ≥M5 dwarfs in the solar neighborhood and calculated their proper motions with typical precisions of 5-15more » mas yr{sup –1}. We selected highly probable candidate members of several YMGs from this sample using the Bayesian Analysis for Nearby Young AssociatioNs II tool (BANYAN II). We used the most probable statistical distances inferred from BANYAN II to estimate the spectral type and mass of these candidate YMG members. We used this unique sample to show tentative signs of mass segregation in the AB Doradus moving group and the Tucana-Horologium and Columba associations. The BASS sample has already been successful in identifying several new young brown dwarfs in earlier publications, and will be of great interest in studying the initial mass function of YMGs and for the search of exoplanets by direct imaging; the input sample of potential close-by ≥M5 dwarfs will be useful to study the kinematics of low-mass stars and brown dwarfs and search for new proper motion pairs.« less

  11. Detection of haplotypes associated with prenatal death in dairy cattle and identification of deleterious mutations in GART, SHBG and SLC37A2.

    PubMed

    Fritz, Sébastien; Capitan, Aurelien; Djari, Anis; Rodriguez, Sabrina C; Barbat, Anne; Baur, Aurélia; Grohs, Cécile; Weiss, Bernard; Boussaha, Mekki; Esquerré, Diane; Klopp, Christophe; Rocha, Dominique; Boichard, Didier

    2013-01-01

    The regular decrease of female fertility over time is a major concern in modern dairy cattle industry. Only half of this decrease is explained by indirect response to selection on milk production, suggesting the existence of other factors such as embryonic lethal genetic defects. Genomic regions harboring recessive deleterious mutations were detected in three dairy cattle breeds by identifying frequent haplotypes (>1%) showing a deficit in homozygotes among Illumina Bovine 50k Beadchip haplotyping data from the French genomic selection database (47,878 Holstein, 16,833 Montbéliarde, and 11,466 Normande animals). Thirty-four candidate haplotypes (p<10(-4)) including previously reported regions associated with Brachyspina, CVM, HH1, and HH3 in Holstein breed were identified. Haplotype length varied from 1 to 4.8 Mb and frequencies from 1.7 up to 9%. A significant negative effect on calving rate, consistent in heifers and in lactating cows, was observed for 9 of these haplotypes in matings between carrier bulls and daughters of carrier sires, confirming their association with embryonic lethal mutations. Eight regions were further investigated using whole genome sequencing data from heterozygous bull carriers and control animals (45 animals in total). Six strong candidate causative mutations including polymorphisms previously reported in FANCI (Brachyspina), SLC35A3 (CVM), APAF1 (HH1) and three novel mutations with very damaging effect on the protein structure, according to SIFT and Polyphen-2, were detected in GART, SHBG and SLC37A2 genes. In conclusion, this study reveals a yet hidden consequence of the important inbreeding rate observed in intensively selected and specialized cattle breeds. Counter-selection of these mutations and management of matings will have positive consequences on female fertility in dairy cattle.

  12. Using a situational judgement test for selection into dental core training: a preliminary analysis.

    PubMed

    Rowett, E; Patterson, F; Cousans, F; Elley, K

    2017-05-12

    Objective and setting This paper describes the evaluation of a pilot situational judgement test (SJT) for selection into UK Dental Core Training (DCT). The SJT's psychometric properties, group differences based on gender and ethnicity, and candidate reactions were assessed.Methods The SJT targets four non-academic attributes important for success in DCT. Data were collected alongside live selection processes from five Health Education England local teams in the UK (N = 386). Candidates completed the pilot SJT and an evaluation questionnaire to examine their reactions to the test.Results SJT scores were relatively normally distributed and showed acceptable levels of internal reliability (α = 0.68). Difficulty level and partial correlations between scenarios and SJT total score were in the expected ranges (64.61% to 90.03% and r = 0.06 to 0.41, respectively). No group differences were found for gender, and group differences between White and BME candidates were minimal. Most candidates perceived the SJT as relevant to the target role, appropriate and fair.Conclusions This study demonstrated the potential suitability of an SJT for use in DCT selection. Future research should replicate these preliminary findings in other cohorts, and assess the predictive validity of the SJT for predicting key training and practice-based outcomes.

  13. EIGHT HUNDRED NEW CANDIDATES FOR GLOBULAR CLUSTERS IN NGC 5128 (Centaurus A)

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

    Harris, Gretchen L. H.; Johnston, Kyle; Kazemzadeh, Farnoud

    2012-04-15

    We have used new wide-field imaging with the Magellan IMACS camera to search for globular cluster (GC) candidates around NGC 5128, the nearest giant E galaxy. The imaging data are in the B and R broadband filters and cover a 1.55 deg{sup 2} field centered on the galaxy, corresponding to an area about 90 Multiplication-Sign 90 kpc{sup 2} at the distance of NGC 5128. All the fields were taken under exceptionally high-quality seeing conditions (FWHM = 0.''4-0.''5 in R). Using this material we are able, for the first time in the literature, to construct a homogeneous list of GC candidatesmore » covering a wide span of the NGC 5128 halo and unusually free of field contaminants (foreground stars and faint background galaxies). Selecting the measured objects by color, magnitude, ellipticity, and profile size gives us a final catalog of 833 new high-quality GC candidates brighter than R = 21 (0.8 mag fainter than the standard GC luminosity function turnover point). The measured positions have better than 0.''2 precision in both coordinates. This list can be used as the basis for spectroscopic follow-up, leading to a more comprehensive kinematic and dynamic study of the halo.« less

  14. Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation

    PubMed Central

    Hériché, Jean-Karim; Lees, Jon G.; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M. Julia; Hossain, M. Julius; Adler, Priit; Fernández, José M.; Krallinger, Martin; Haering, Christian H.; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A.; Orengo, Christine; Ellenberg, Jan

    2014-01-01

    The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848

  15. Fifty Years of Pulsar Candidate Selection: From simple filters to a new principled real-time classification approach

    NASA Astrophysics Data System (ADS)

    Lyon, R. J.; Stappers, B. W.; Cooper, S.; Brooke, J. M.; Knowles, J. D.

    2016-06-01

    Improving survey specifications are causing an exponential rise in pulsar candidate numbers and data volumes. We study the candidate filters used to mitigate these problems during the past fifty years. We find that some existing methods such as applying constraints on the total number of candidates collected per observation, may have detrimental effects on the success of pulsar searches. Those methods immune to such effects are found to be ill-equipped to deal with the problems associated with increasing data volumes and candidate numbers, motivating the development of new approaches. We therefore present a new method designed for on-line operation. It selects promising candidates using a purpose-built tree-based machine learning classifier, the Gaussian Hellinger Very Fast Decision Tree (GH-VFDT), and a new set of features for describing candidates. The features have been chosen so as to I) maximise the separation between candidates arising from noise and those of probable astrophysical origin, and II) be as survey-independent as possible. Using these features our new approach can process millions of candidates in seconds (˜1 million every 15 seconds), with high levels of pulsar recall (90%+). This technique is therefore applicable to the large volumes of data expected to be produced by the Square Kilometre Array (SKA). Use of this approach has assisted in the discovery of 20 new pulsars in data obtained during the LOFAR Tied-Array All-Sky Survey (LOTAAS).

  16. Candidate high-z protoclusters among the Planck compact sources, as revealed by Herschel-SPIRE

    NASA Astrophysics Data System (ADS)

    Greenslade, J.; Clements, D. L.; Cheng, T.; De Zotti, G.; Scott, D.; Valiante, E.; Eales, S.; Bremer, M. N.; Dannerbauer, H.; Birkinshaw, M.; Farrah, D.; Harrison, D. L.; Michałowski, M. J.; Valtchanov, I.; Oteo, I.; Baes, M.; Cooray, A.; Negrello, M.; Wang, L.; van der Werf, P.; Dunne, L.; Dye, S.

    2018-05-01

    By determining the nature of all the Planck compact sources within 808.4 deg2 of large Herschel surveys, we have identified 27 candidate protoclusters of dusty star-forming galaxies (DSFGs) that are at least 3σ overdense in either 250, 350, or 500 μm sources. We find roughly half of all the Planck compact sources are resolved by Herschel into multiple discrete objects, with the other half remaining unresolved by Herschel. We find a significant difference between versions of the Planck catalogues, with earlier releases hosting a larger fraction of candidate protoclusters and Galactic cirrus than later releases, which we ascribe to a difference in the filters used in the creation of the three catalogues. We find a surface density of DSFG candidate protoclusters of (3.3 ± 0.7) × 10-2 sources deg-2, in good agreement with previous similar studies. We find that a Planck colour selection of S857/S545 < 2 works well to select candidate protoclusters, but can miss protoclusters at z < 2. The Herschel colours of individual candidate protocluster members indicate our candidate protoclusters all likely all lie at z > 1. Our candidate protoclusters are a factor of 5 times brighter at 353 GHz than expected from simulations, even in the most conservative estimates. Further observations are needed to confirm whether these candidate protoclusters are physical clusters, multiple protoclusters along the line of sight, or chance alignments of unassociated sources.

  17. Situational judgement tests in medical education and training: Research, theory and practice: AMEE Guide No. 100.

    PubMed

    Patterson, Fiona; Zibarras, Lara; Ashworth, Vicki

    2016-01-01

    Why use SJTs? Traditionally, selection into medical education professions has focused primarily upon academic ability alone. This approach has been questioned more recently, as although academic attainment predicts performance early in training, research shows it has less predictive power for demonstrating competence in postgraduate clinical practice. Such evidence, coupled with an increasing focus on individuals working in healthcare roles displaying the core values of compassionate care, benevolence and respect, illustrates that individuals should be selected on attributes other than academic ability alone. Moreover, there are mounting calls to widen access to medicine, to ensure that selection methods do not unfairly disadvantage individuals from specific groups (e.g. regarding ethnicity or socio-economic status), so that the future workforce adequately represents society as a whole. These drivers necessitate a method of assessment that allows individuals to be selected on important non-academic attributes that are desirable in healthcare professionals, in a fair, reliable and valid way. What are SJTs? Situational judgement tests (SJTs) are tests used to assess individuals' reactions to a number of hypothetical role-relevant scenarios, which reflect situations candidates are likely to encounter in the target role. These scenarios are based on a detailed analysis of the role and should be developed in collaboration with subject matter experts, in order to accurately assess the key attributes that are associated with competent performance. From a theoretical perspective, SJTs are believed to measure prosocial Implicit Trait Policies (ITPs), which are shaped by socialisation processes that teach the utility of expressing certain traits in different settings such as agreeable expressions (e.g. helping others in need), or disagreeable actions (e.g. advancing ones own interest at others, expense). Are SJTs reliable, valid and fair? Several studies, including good quality meta-analytic and longitudinal research, consistently show that SJTs used in many different occupational groups are reliable and valid. Although there is over 40 years of research evidence available on SJTs, it is only within the past 10 years that SJTs have been used for recruitment into medicine. Specifically, evidence consistently shows that SJTs used in medical selection have good reliability, and predict performance across a range of medical professions, including performance in general practice, in early years (foundation training as a junior doctor) and for medical school admissions. In addition, SJTs have been found to have significant added value (incremental validity) over and above other selection methods such as knowledge tests, measures of cognitive ability, personality tests and application forms. Regarding differential attainment, generally SJTs have been found to have lower adverse impact compared to other selection methods, such as cognitive ability tests. SJTs have the benefit of being appropriate both for use in selection where candidates are novices (i.e. have no prior role experience or knowledge such as in medical school admissions) as well as settings where candidates have substantial job knowledge and specific experience (as in postgraduate recruitment for more senior roles). An SJT specification (e.g. scenario content, response instructions and format) may differ depending on the level of job knowledge required. Research consistently shows that SJTs are usually found to be positively received by candidates compared to other selection tests such as cognitive ability and personality tests. Practically, SJTs are difficult to design effectively, and significant expertise is required to build a reliable and valid SJT. Once designed however, SJTs are cost efficient to administer to large numbers of candidates compared to other tests of non-academic attributes (e.g. personal statements, structured interviews), as they are standardised and can be computer-delivered and machine-marked.

  18. Hit-to-lead development of the chamigrane endoperoxide merulin A for the treatment of African sleeping sickness.

    PubMed

    Navarro, Gabriel; Chokpaiboon, Supchar; De Muylder, Geraldine; Bray, Walter M; Nisam, Sean C; McKerrow, James H; Pudhom, Khanitha; Linington, Roger G

    2012-01-01

    Human African trypanosomiasis (HAT) is an infectious disease with a large global health burden occurring primarily in Central and Eastern Africa. Most current treatments have poor blood brain barrier (BBB) penetration, which prevent them from targeting the most lethal stage of the infection. In addition, current therapeutics suffer from a variety of limitations ranging from serious side effects to difficulties with treatment administration. Therefore it is of crucial importance to find new treatments that are safe, affordable, and effective against both sub-species of Trypanosoma brucei. Semi-synthetic derivatization of the fungally-derived natural product merulin A (1) has led to the discovery of new development candidates for the protozoan parasite T. brucei, the causative agent of HAT. Creation of an initial SAR library based around the merulin scaffold revealed several key features required for activity, including the endoperoxide bridge, as well as one position suitable for further derivatization. Subsequent synthesis of a 20-membered analogue library, guided by the addition of acyl groups that improve the drug-like properties of the merulin A core, resulted in the development of compound 12 with an IC(50) of 60 nM against T. brucei, and a selectivity index greater than 300-fold against HeLa and immortalized glial cells. We report the semi-synthetic optimization of the merulin class of endoperoxide natural products as development candidates against T. brucei. We have identified compounds with low nM antiparasitic activities and high selectivity indices against HeLa cells. These compounds can be produced economically in large quantities via a one step derivatization from the microbial fermentation broth isolate, making them encouraging lead candidates for further development.

  19. Computer-aided detection of bladder masses in CT urography (CTU)

    NASA Astrophysics Data System (ADS)

    Cha, Kenny H.; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Caoili, Elaine M.; Cohan, Richard H.; Weizer, Alon; Samala, Ravi K.

    2017-03-01

    We are developing a computer-aided detection system for bladder cancer in CT urography (CTU). We have previously developed methods for detection of bladder masses within the contrast-enhanced and the non-contrastenhanced regions of the bladder individually. In this study, we investigated methods for detection of bladder masses within the entire bladder. The bladder was segmented using our method that combined deep-learning convolutional neural network with level sets. The non-contrast-enhanced region was separated from the contrast-enhanced region with a maximum-intensity-projection-based method. The non-contrast region was smoothed and gray level threshold was applied to the contrast and non-contrast regions separately to extract the bladder wall and potential masses. The bladder wall was transformed into a straightened thickness profile, which was analyzed to identify lesion candidates in a prescreening step. The candidates were mapped back to the 3D CT volume and segmented using our auto-initialized cascaded level set (AI-CALS) segmentation method. Twenty-seven morphological features were extracted for each candidate. A data set of 57 patients with 71 biopsy-proven bladder lesions was used, which was split into independent training and test sets: 42 training cases with 52 lesions, and 15 test cases with 19 lesions. Using the training set, feature selection was performed and a linear discriminant (LDA) classifier was designed to merge the selected features for classification of bladder lesions and false positives. The trained classifier was evaluated with the test set. FROC analysis showed that the system achieved a sensitivity of 86.5% at 3.3 FPs/case for the training set, and 84.2% at 3.7 FPs/case for the test set.

  20. Beam orientation optimization for intensity-modulated radiation therapy using mixed integer programming

    NASA Astrophysics Data System (ADS)

    Yang, Ruijie; Dai, Jianrong; Yang, Yong; Hu, Yimin

    2006-08-01

    The purpose of this study is to extend an algorithm proposed for beam orientation optimization in classical conformal radiotherapy to intensity-modulated radiation therapy (IMRT) and to evaluate the algorithm's performance in IMRT scenarios. In addition, the effect of the candidate pool of beam orientations, in terms of beam orientation resolution and starting orientation, on the optimized beam configuration, plan quality and optimization time is also explored. The algorithm is based on the technique of mixed integer linear programming in which binary and positive float variables are employed to represent candidates for beam orientation and beamlet weights in beam intensity maps. Both beam orientations and beam intensity maps are simultaneously optimized in the algorithm with a deterministic method. Several different clinical cases were used to test the algorithm and the results show that both target coverage and critical structures sparing were significantly improved for the plans with optimized beam orientations compared to those with equi-spaced beam orientations. The calculation time was less than an hour for the cases with 36 binary variables on a PC with a Pentium IV 2.66 GHz processor. It is also found that decreasing beam orientation resolution to 10° greatly reduced the size of the candidate pool of beam orientations without significant influence on the optimized beam configuration and plan quality, while selecting different starting orientations had large influence. Our study demonstrates that the algorithm can be applied to IMRT scenarios, and better beam orientation configurations can be obtained using this algorithm. Furthermore, the optimization efficiency can be greatly increased through proper selection of beam orientation resolution and starting beam orientation while guaranteeing the optimized beam configurations and plan quality.

  1. Candidal carriage predicts candidiasis during topical immunosuppressive therapy: a preliminary retrospective cohort study.

    PubMed

    Tejani, Sara; Sultan, Ahmed; Stojanov, Ivan; Woo, Sook-Bin

    2016-10-01

    To determine (1) the prevalence of candidal carriage in patients with oral mucosal disease to be treated with topical immunosuppressive therapy, and (2) the incidence of oral candidiasis among carriers and noncarriers after initiation of therapy to assess any correlation between carriage and the development of candidiasis. Records of patients who underwent swab cultures for Candida between January 2009 and October 2014 at the Brigham and Women's Hospital in Boston, Massachusetts, were retrospectively reviewed. The prevalence of candidal carriage and incidence of candidiasis were determined by using descriptive statistics. Of 99 evaluable patients, 20 (20.2%) were Candida positive and 79 (79.8%) were Candida negative. Of 44 patients with follow-up, 7 (15.9%) were Candida positive and 37 (84.1%) were Candida negative; five (11.4%) developed candidiasis. Four of seven (57.1%) Candida-positive patients developed candidiasis, whereas only one of 37 (2.7%) Candida-negative patients developed candidiasis (P = .0012). The overall prevalence of candidal carriage was low (20.2%), and there was a significant difference in the incidence of candidiasis between carriers and noncarriers (P = .0012) after topical immunosuppressive therapy. Therefore, patients who are candidal carriers should be monitored closely for the development of secondary candidiasis and may be candidates for prophylactic antifungal therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Accurate indel prediction using paired-end short reads

    PubMed Central

    2013-01-01

    Background One of the major open challenges in next generation sequencing (NGS) is the accurate identification of structural variants such as insertions and deletions (indels). Current methods for indel calling assign scores to different types of evidence or counter-evidence for the presence of an indel, such as the number of split read alignments spanning the boundaries of a deletion candidate or reads that map within a putative deletion. Candidates with a score above a manually defined threshold are then predicted to be true indels. As a consequence, structural variants detected in this manner contain many false positives. Results Here, we present a machine learning based method which is able to discover and distinguish true from false indel candidates in order to reduce the false positive rate. Our method identifies indel candidates using a discriminative classifier based on features of split read alignment profiles and trained on true and false indel candidates that were validated by Sanger sequencing. We demonstrate the usefulness of our method with paired-end Illumina reads from 80 genomes of the first phase of the 1001 Genomes Project ( http://www.1001genomes.org) in Arabidopsis thaliana. Conclusion In this work we show that indel classification is a necessary step to reduce the number of false positive candidates. We demonstrate that missing classification may lead to spurious biological interpretations. The software is available at: http://agkb.is.tuebingen.mpg.de/Forschung/SV-M/. PMID:23442375

  3. Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance.

    PubMed

    Jann, Oliver C; Werling, Dirk; Chang, Jung-Su; Haig, David; Glass, Elizabeth J

    2008-10-20

    There is accumulating evidence that polymorphism in Toll-like receptor (TLR) genes might be associated with disease resistance or susceptibility traits in livestock. Polymorphic sites affecting TLR function should exhibit signatures of positive selection, identified as a high ratio of non-synonymous to synonymous nucleotide substitutions (omega). Phylogeny based models of codon substitution based on estimates of omega for each amino acid position can therefore offer a valuable tool to predict sites of functional relevance. We have used this approach to identify such polymorphic sites within the bovine TLR2 genes from ten Bos indicus and Bos taurus cattle breeds. By analysing TLR2 gene phylogeny in a set of mammalian species and a subset of ruminant species we have estimated the selective pressure on individual sites and domains and identified polymorphisms at sites of putative functional importance. The omega were highest in the mammalian TLR2 domains thought to be responsible for ligand binding and lowest in regions responsible for heterodimerisation with other TLR-related molecules. Several positively-selected sites were detected in or around ligand-binding domains. However a comparison of the ruminant subset of TLR2 sequences with the whole mammalian set of sequences revealed that there has been less selective pressure among ruminants than in mammals as a whole. This suggests that there have been functional changes during ruminant evolution. Twenty newly-discovered non-synonymous polymorphic sites were identified in cattle. Three of them were localised at positions shaped by positive selection in the ruminant dataset (Leu227Phe, His305Pro, His326Gln) and in domains involved in the recognition of ligands. His326Gln is of particular interest as it consists of an exchange of differentially-charged amino acids at a position which has previously been shown to be crucial for ligand binding in human TLR2. Within bovine TLR2, polymorphisms at amino acid positions 227, 305 and 326 map to functionally important sites of TLR2 and should be considered as candidate SNPs for immune related traits in cattle. A final proof of their functional relevance requires further studies to determine their functional effect on the immune response after stimulation with relevant ligands and/or their association with immune related traits in animals.

  4. Comparative Transcriptome of Wild Type and Selected Strains of the Microalgae Tisochrysis lutea Provides Insights into the Genetic Basis, Lipid Metabolism and the Life Cycle

    PubMed Central

    Carrier, Gregory; Garnier, Matthieu; Le Cunff, Loïc; Bougaran, Gaël; Probert, Ian; De Vargas, Colomban; Corre, Erwan; Cadoret, Jean-Paul; Saint-Jean, Bruno

    2014-01-01

    The applied exploitation of microalgae cultures has to date almost exclusively involved the use of wild type strains, deposited over decades in dedicated culture collections. Concomitantly, the concept of improving algae with selection programs for particular specific purposes is slowly emerging. Studying since a decade an economically and ecologically important haptophyte Tisochrysis lutea (Tiso), we took advantage of the availability of wild type (Tiso-Wt) and selected (Tiso-S2M2) strains to conduct a molecular variations study. This endeavour presented substantial challenges: the genome assembly was not yet available, the life cycle unknown and genetic diversity of Tiso-Wt poorly documented. This study brings the first molecular data in order to set up a selection strategy for that microalgae. Following high-throughput Illumina sequencing, transcriptomes of Tiso-Wt and Tiso-S2M2 were de novo assembled and annotated. Genetic diversity between both strains was analyzed and revealed a clear conservation, while a comparison of transcriptomes allowed identification of polymorphisms resulting from the selection program. Of 34,374 transcripts, 291 were differentially expressed and 165 contained positional polymorphisms (SNP, Indel). We focused on lipid over-accumulation of the Tiso-S2M2 strain and 8 candidate genes were identified by combining analysis of positional polymorphism, differential expression levels, selection signature and by study of putative gene function. Moreover, genetic analysis also suggests the existence of a sexual cycle and genetic recombination in Tisochrysis lutea. PMID:24489800

  5. Patterns of Ancestry, Signatures of Natural Selection, and Genetic Association with Stature in Western African Pygmies

    PubMed Central

    Jarvis, Joseph P.; Ferwerda, Bart; Froment, Alain; Bodo, Jean-Marie; Beggs, William; Hoffman, Gabriel; Mezey, Jason; Tishkoff, Sarah A.

    2012-01-01

    African Pygmy groups show a distinctive pattern of phenotypic variation, including short stature, which is thought to reflect past adaptation to a tropical environment. Here, we analyze Illumina 1M SNP array data in three Western Pygmy populations from Cameroon and three neighboring Bantu-speaking agricultural populations with whom they have admixed. We infer genome-wide ancestry, scan for signals of positive selection, and perform targeted genetic association with measured height variation. We identify multiple regions throughout the genome that may have played a role in adaptive evolution, many of which contain loci with roles in growth hormone, insulin, and insulin-like growth factor signaling pathways, as well as immunity and neuroendocrine signaling involved in reproduction and metabolism. The most striking results are found on chromosome 3, which harbors a cluster of selection and association signals between approximately 45 and 60 Mb. This region also includes the positional candidate genes DOCK3, which is known to be associated with height variation in Europeans, and CISH, a negative regulator of cytokine signaling known to inhibit growth hormone-stimulated STAT5 signaling. Finally, pathway analysis for genes near the strongest signals of association with height indicates enrichment for loci involved in insulin and insulin-like growth factor signaling. PMID:22570615

  6. Identification of precision treatment strategies for relapsed/refractory multiple myeloma by functional drug sensitivity testing.

    PubMed

    Majumder, Muntasir Mamun; Silvennoinen, Raija; Anttila, Pekka; Tamborero, David; Eldfors, Samuli; Yadav, Bhagwan; Karjalainen, Riikka; Kuusanmäki, Heikki; Lievonen, Juha; Parsons, Alun; Suvela, Minna; Jantunen, Esa; Porkka, Kimmo; Heckman, Caroline A

    2017-08-22

    Novel agents have increased survival of multiple myeloma (MM) patients, however high-risk and relapsed/refractory patients remain challenging to treat and their outcome is poor. To identify novel therapies and aid treatment selection for MM, we assessed the ex vivo sensitivity of 50 MM patient samples to 308 approved and investigational drugs. With the results we i) classified patients based on their ex vivo drug response profile; ii) identified and matched potential drug candidates to recurrent cytogenetic alterations; and iii) correlated ex vivo drug sensitivity to patient outcome. Based on their drug sensitivity profiles, MM patients were stratified into four distinct subgroups with varied survival outcomes. Patients with progressive disease and poor survival clustered in a drug response group exhibiting high sensitivity to signal transduction inhibitors. Del(17p) positive samples were resistant to most drugs tested with the exception of histone deacetylase and BCL2 inhibitors. Samples positive for t(4;14) were highly sensitive to immunomodulatory drugs, proteasome inhibitors and several targeted drugs. Three patients treated based on the ex vivo results showed good response to the selected treatments. Our results demonstrate that ex vivo drug testing may potentially be applied to optimize treatment selection and achieve therapeutic benefit for relapsed/refractory MM.

  7. A neural basis for the effect of candidate appearance on election outcomes.

    PubMed

    Spezio, Michael L; Rangel, Antonio; Alvarez, Ramon Michael; O'Doherty, John P; Mattes, Kyle; Todorov, Alexander; Kim, Hackjin; Adolphs, Ralph

    2008-12-01

    Election outcomes correlate with judgments based on a candidate's visual appearance, suggesting that the attributions viewers make based on appearance, so-called thin-slice judgments, influence voting. Yet, it is not known whether the effect of appearance on voting is more strongly influenced by positive or negative attributions, nor which neural mechanisms subserve this effect. We conducted two independent brain imaging studies to address this question. In Study 1, images of losing candidates elicited greater activation in the insula and ventral anterior cingulate than images of winning candidates. Winning candidates elicited no differential activation at all. This suggests that negative attributions from appearance exert greater influence on voting than do positive. We further tested this hypothesis in Study 2 by asking a separate group of participants to judge which unfamiliar candidate in a pair looked more attractive, competent, deceitful and threatening. When negative attribution processing was enhanced (specifically, under judgment of threat), images of losing candidates again elicited greater activation in the insula and ventral anterior cingulate. Together, these findings support the view that negative attributions play a critical role in mediating the effects of appearance on voter decisions, an effect that may be of special importance when other information is absent.

  8. Political partisanship influences perception of biracial candidates' skin tone

    PubMed Central

    Caruso, Eugene M.; Mead, Nicole L.; Balcetis, Emily

    2009-01-01

    People tend to view members of their own political group more positively than members of a competing political group. In this article, we demonstrate that political partisanship influences people's visual representations of a biracial political candidate's skin tone. In three studies, participants rated the representativeness of photographs of a hypothetical (Study 1) or real (Barack Obama; Studies 2 and 3) biracial political candidate. Unbeknownst to participants, some of the photographs had been altered to make the candidate's skin tone either lighter or darker than it was in the original photograph. Participants whose partisanship matched that of the candidate they were evaluating consistently rated the lightened photographs as more representative of the candidate than the darkened photographs, whereas participants whose partisanship did not match that of the candidate showed the opposite pattern. For evaluations of Barack Obama, the extent to which people rated lightened photographs as representative of him was positively correlated with their stated voting intentions and reported voting behavior in the 2008 Presidential election. This effect persisted when controlling for political ideology and racial attitudes. These results suggest that people's visual representations of others are related to their own preexisting beliefs and to the decisions they make in a consequential context. PMID:19934033

  9. Political partisanship influences perception of biracial candidates' skin tone.

    PubMed

    Caruso, Eugene M; Mead, Nicole L; Balcetis, Emily

    2009-12-01

    People tend to view members of their own political group more positively than members of a competing political group. In this article, we demonstrate that political partisanship influences people's visual representations of a biracial political candidate's skin tone. In three studies, participants rated the representativeness of photographs of a hypothetical (Study 1) or real (Barack Obama; Studies 2 and 3) biracial political candidate. Unbeknownst to participants, some of the photographs had been altered to make the candidate's skin tone either lighter or darker than it was in the original photograph. Participants whose partisanship matched that of the candidate they were evaluating consistently rated the lightened photographs as more representative of the candidate than the darkened photographs, whereas participants whose partisanship did not match that of the candidate showed the opposite pattern. For evaluations of Barack Obama, the extent to which people rated lightened photographs as representative of him was positively correlated with their stated voting intentions and reported voting behavior in the 2008 Presidential election. This effect persisted when controlling for political ideology and racial attitudes. These results suggest that people's visual representations of others are related to their own preexisting beliefs and to the decisions they make in a consequential context.

  10. Patterns of Nucleotide Diversity at the Regions Encompassing the Drosophila Insulin-Like Peptide (dilp) Genes: Demography vs. Positive Selection in Drosophila melanogaster

    PubMed Central

    Guirao-Rico, Sara; Aguadé, Montserrat

    2013-01-01

    In Drosophila, the insulin-signaling pathway controls some life history traits, such as fertility and lifespan, and it is considered to be the main metabolic pathway involved in establishing adult body size. Several observations concerning variation in body size in the Drosophila genus are suggestive of its adaptive character. Genes encoding proteins in this pathway are, therefore, good candidates to have experienced adaptive changes and to reveal the footprint of positive selection. The Drosophila insulin-like peptides (DILPs) are the ligands that trigger the insulin-signaling cascade. In Drosophila melanogaster, there are several peptides that are structurally similar to the single mammalian insulin peptide. The footprint of recent adaptive changes on nucleotide variation can be unveiled through the analysis of polymorphism and divergence. With this aim, we have surveyed nucleotide sequence variation at the dilp1-7 genes in a natural population of D. melanogaster. The comparison of polymorphism in D. melanogaster and divergence from D. simulans at different functional classes of the dilp genes provided no evidence of adaptive protein evolution after the split of the D. melanogaster and D. simulans lineages. However, our survey of polymorphism at the dilp gene regions of D. melanogaster has provided some evidence for the action of positive selection at or near these genes. The regions encompassing the dilp1-4 genes and the dilp6 gene stand out as likely affected by recent adaptive events. PMID:23308258

  11. Vision-Based Traffic Data Collection Sensor for Automotive Applications

    PubMed Central

    Llorca, David F.; Sánchez, Sergio; Ocaña, Manuel; Sotelo, Miguel. A.

    2010-01-01

    This paper presents a complete vision sensor onboard a moving vehicle which collects the traffic data in its local area in daytime conditions. The sensor comprises a rear looking and a forward looking camera. Thus, a representative description of the traffic conditions in the local area of the host vehicle can be computed. The proposed sensor detects the number of vehicles (traffic load), their relative positions and their relative velocities in a four-stage process: lane detection, candidates selection, vehicles classification and tracking. Absolute velocities (average road speed) and global positioning are obtained after combining the outputs provided by the vision sensor with the data supplied by the CAN Bus and a GPS sensor. The presented experiments are promising in terms of detection performance and accuracy in order to be validated for applications in the context of the automotive industry. PMID:22315572

  12. Vision-based traffic data collection sensor for automotive applications.

    PubMed

    Llorca, David F; Sánchez, Sergio; Ocaña, Manuel; Sotelo, Miguel A

    2010-01-01

    This paper presents a complete vision sensor onboard a moving vehicle which collects the traffic data in its local area in daytime conditions. The sensor comprises a rear looking and a forward looking camera. Thus, a representative description of the traffic conditions in the local area of the host vehicle can be computed. The proposed sensor detects the number of vehicles (traffic load), their relative positions and their relative velocities in a four-stage process: lane detection, candidates selection, vehicles classification and tracking. Absolute velocities (average road speed) and global positioning are obtained after combining the outputs provided by the vision sensor with the data supplied by the CAN Bus and a GPS sensor. The presented experiments are promising in terms of detection performance and accuracy in order to be validated for applications in the context of the automotive industry.

  13. VizieR Online Data Catalog: 1876 open clusters multimembership catalog (Sampedro+, 2017)

    NASA Astrophysics Data System (ADS)

    Sampedro, L.; Dias, W. S.; Alfaro, E. J.; Monteiro, H.; Molino, A.

    2017-10-01

    We use version 3.5 of the New Optically Visible Open Clusters and Candidates catalogue (hereafter DAML02; Dias et al., 2002, Cat. B/ocl), to select a sample of 2167 open clusters to be analysed. The stellar positions and the proper motions are taken from the UCAC4 (Zacharias et al., 2013, Cat. I/322). The catalogue contains data for over 113 million stars (105 million of them with proper-motion data), and is complete down to magnitude R=16. The positional accuracy of the listed objects is about 15-100mas per coordinate, depending on the magnitude. Formal errors in proper motions range from about 1 to 10mas/yr, depending on the magnitude and the observational history. Systematic errors in the proper motions are estimated to be about 1-4mas/yr. (2 data files).

  14. 76 FR 4896 - Call for Candidates

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-27

    ... designated to establish generally accepted accounting principles for federal government entities. Generally, non-federal Board members are selected from the general financial community, the accounting and... FEDERAL ACCOUNTING STANDARDS ADVISORY BOARD Call for Candidates AGENCY: Federal Accounting...

  15. Toward a formalization of the process to select IMIA Yearbook best papers.

    PubMed

    Lamy, J-B; Séroussi, B; Griffon, N; Kerdelhué, G; Jaulent, M-C; Bouaud, J

    2015-01-01

    Each year, the International Medical Informatics Association Yearbook recognizes significant scientific papers, labelled as "best papers", published the previous year in the subfields of biomedical informatics that correspond to the different section topics of the journal. For each section, about fifteen pre-selected "candidate" best papers are externally peer-reviewed to select the actual best papers. Although based on the available literature, little is known about the pre-selection process. To move toward an explicit formalization of the candidate best papers selection process to reduce variability in the literature search across sections and over years. A methodological framework is proposed to build for each section topic specific queries tailored to PubMed and Web of Science citation databases. The two sets of returned papers are merged and reviewed by two independent section editors and citations are tagged as "discarded", "pending", and "kept". A protocolized consolidation step is then jointly conducted to resolve conflicts. A bibliographic software tool, BibReview, was developed to support the whole process. The proposed search strategy was fully applied to the Decision Support section of the 2013 edition of the Yearbook. For this section, 1124 references were returned (689 PubMed-specific, 254 WoS-specific, 181 common to both databases) among which the 15 candidate best papers were selected. The search strategy for determining candidate best papers for an IMIA Yearbook's section is now explicitly specified and allows for reproducibility. However, some aspects of the whole process remain reviewer-dependent, mostly because there is no characterization of a "best paper".

  16. Insights into DDT Resistance from the Drosophila melanogaster Genetic Reference Panel.

    PubMed

    Schmidt, Joshua M; Battlay, Paul; Gledhill-Smith, Rebecca S; Good, Robert T; Lumb, Chris; Fournier-Level, Alexandre; Robin, Charles

    2017-11-01

    Insecticide resistance is considered a classic model of microevolution, where a strong selective agent is applied to a large natural population, resulting in a change in frequency of alleles that confer resistance. While many insecticide resistance variants have been characterized at the gene level, they are typically single genes of large effect identified in highly resistant pest species. In contrast, multiple variants have been implicated in DDT resistance in Drosophila melanogaster ; however, only the Cyp6g1 locus has previously been shown to be relevant to field populations. Here we use genome-wide association studies (GWAS) to identify DDT-associated polygenes and use selective sweep analyses to assess their adaptive significance. We identify and verify two candidate DDT resistance loci. A largely uncharacterized gene, CG10737 , has a function in muscles that ameliorates the effects of DDT, while a putative detoxifying P450, Cyp6w1 , shows compelling evidence of positive selection. Copyright © 2017 by the Genetics Society of America.

  17. Stellar Stream Candidates in the Solar Neighborhood Found in the LAMOST DR3 and TGAS

    NASA Astrophysics Data System (ADS)

    Liang, X. L.; Zhao, J. K.; Oswalt, T. D.; Chen, Y. Q.; Zhang, L.; Zhao, G.

    2017-08-01

    We have cross-matched the LAMOST DR3 with the Gaia DR1 TGAS catalogs and obtained a sample of 166,827 stars with reliable kinematics. A technique based on the wavelet transform was applied to detect significant overdensities in velocity space among five subsamples divided by spatial position. In total, 16 significant overdensities of stars with very similar kinematics were identified. Among these, four are new stream candidates and the rest are previously known groups. Both the U-V velocity and metallicity distributions of the local sample show a clear gap between the Hercules structure and the Hyades-Pleiades structure. The U-V positions of these peaks shift with the spatial position. Following a description of our analysis, we speculate on possible origins of our stream candidates.

  18. Finding the Right Candidate for the Right Position: A Fast NMR-Assisted Combinatorial Method for Optimizing Nucleic Acids Binders.

    PubMed

    Jiménez-Moreno, Ester; Montalvillo-Jiménez, Laura; Santana, Andrés G; Gómez, Ana M; Jiménez-Osés, Gonzalo; Corzana, Francisco; Bastida, Agatha; Jiménez-Barbero, Jesús; Cañada, Francisco Javier; Gómez-Pinto, Irene; González, Carlos; Asensio, Juan Luis

    2016-05-25

    Development of strong and selective binders from promiscuous lead compounds represents one of the most expensive and time-consuming tasks in drug discovery. We herein present a novel fragment-based combinatorial strategy for the optimization of multivalent polyamine scaffolds as DNA/RNA ligands. Our protocol provides a quick access to a large variety of regioisomer libraries that can be tested for selective recognition by combining microdialysis assays with simple isotope labeling and NMR experiments. To illustrate our approach, 20 small libraries comprising 100 novel kanamycin-B derivatives have been prepared and evaluated for selective binding to the ribosomal decoding A-Site sequence. Contrary to the common view of NMR as a low-throughput technique, we demonstrate that our NMR methodology represents a valuable alternative for the detection and quantification of complex mixtures, even integrated by highly similar or structurally related derivatives, a common situation in the context of a lead optimization process. Furthermore, this study provides valuable clues about the structural requirements for selective A-site recognition.

  19. Alleviation of Multiple Asthmatic Pathologic Features with Orally Available and Subtype Selective GABAA Receptor Modulators.

    PubMed

    Forkuo, Gloria S; Nieman, Amanda N; Yuan, Nina Y; Kodali, Revathi; Yu, Olivia B; Zahn, Nicolas M; Jahan, Rajwana; Li, Guanguan; Stephen, Michael Rajesh; Guthrie, Margaret L; Poe, Michael M; Hartzler, Benjamin D; Harris, Ted W; Yocum, Gene T; Emala, Charles W; Steeber, Douglas A; Stafford, Douglas C; Cook, James M; Arnold, Leggy A

    2017-06-05

    We describe pharmacokinetic and pharmacodynamic properties of two novel oral drug candidates for asthma. Phenolic α 4 β 3 γ 2 GABA A R selective compound 1 and acidic α 5 β 3 γ 2 selective GABA A R positive allosteric modulator compound 2 relaxed airway smooth muscle ex vivo and attenuated airway hyperresponsiveness (AHR) in a murine model of asthma. Importantly, compound 2 relaxed acetylcholine contracted human tracheal airway smooth muscle strips. Oral treatment of compounds 1 and 2 decreased eosinophils in bronchoalveolar lavage fluid in ovalbumin sensitized and challenged mice, thus exhibiting anti-inflammatory properties. Additionally, compound 1 reduced the number of lung CD4 + T lymphocytes and directly modulated their transmembrane currents by acting on GABA A Rs. Excellent pharmacokinetic properties were observed, including long plasma half-life (up to 15 h), oral availability, and extremely low brain distribution. In conclusion, we report the selective targeting of GABA A Rs expressed outside the brain and demonstrate reduction of AHR and airway inflammation with two novel orally available GABA A R ligands.

  20. Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

    PubMed

    Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

    2018-01-01

    This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

  1. Current State of Colorectal Surgery Training: A Survey of Program Directors, Current and Recently Matched Colorectal Residents, and Recent Colorectal Graduates.

    PubMed

    Bailey, Matthew B; Miller, Peter E; Pawlak, Stephanie E; Thomas, Michael S; Beck, David E; Vargas, H David; Whitlow, Charles B; Margolin, David A

    2016-02-01

    Colorectal residency has become one of the more competitive postgraduate training opportunities; however, little information is available to guide potential applicants in gauging their competitiveness. The aim of this study was to identify the current trends colorectal residency training and to identify what factors are considered most important in ranking a candidate highly. We hypothesized that there was a difference in what program directors, current and recently matched colorectal residents, and recent graduates consider most important in making a candidate competitive for a colorectal residency position. Three 10-question anonymous surveys were sent to 59 program directors, 87 current and recently matched colorectal residents, and 119 recent graduates in March 2015. The study was conducted as an anonymous internet survey. Current trends in applying for a colorectal residency, competitiveness of recent colorectal residents, factors considered most important in ranking a candidate highly, and what future colorectal surgeons can expect after finishing their training were measured. The study had an overall response rate of 43%, with 28 (47%) of 59 program directors, 46 (53%) of 87 current and recently matched colorectal residents, and 39 (33%) of 119 recent graduates responding. The majority of program directors felt that a candidate's performance during the interview process was the most important factor in making a candidate competitive, followed by contact from a colleague, letters of recommendation, American Board of Surgery In-Training Exam scores, and number of publications/presentations. The majority of current and recently matched colorectal residents felt that a recommendation/telephone call from a colleague was the most important factor, whereas the majority of recent graduates favored letters of recommendation as the most important factor in ranking a candidate highly. Limitations to the study include its small sample size, selection bias, responder bias, and misclassification bias. There are differences in what program directors and current/recent residents consider most important in making an applicant competitive for colorectal residency.

  2. CT colonography: influence of 3D viewing and polyp candidate features on interpretation with computer-aided detection.

    PubMed

    Shi, Rong; Schraedley-Desmond, Pamela; Napel, Sandy; Olcott, Eric W; Jeffrey, R Brooke; Yee, Judy; Zalis, Michael E; Margolis, Daniel; Paik, David S; Sherbondy, Anthony J; Sundaram, Padmavathi; Beaulieu, Christopher F

    2006-06-01

    To retrospectively determine if three-dimensional (3D) viewing improves radiologists' accuracy in classifying true-positive (TP) and false-positive (FP) polyp candidates identified with computer-aided detection (CAD) and to determine candidate polyp features that are associated with classification accuracy, with known polyps serving as the reference standard. Institutional review board approval and informed consent were obtained; this study was HIPAA compliant. Forty-seven computed tomographic (CT) colonography data sets were obtained in 26 men and 10 women (age range, 42-76 years). Four radiologists classified 705 polyp candidates (53 TP candidates, 652 FP candidates) identified with CAD; initially, only two-dimensional images were used, but these were later supplemented with 3D rendering. Another radiologist unblinded to colonoscopy findings characterized the features of each candidate, assessed colon distention and preparation, and defined the true nature of FP candidates. Receiver operating characteristic curves were used to compare readers' performance, and repeated-measures analysis of variance was used to test features that affect interpretation. Use of 3D viewing improved classification accuracy for three readers and increased the area under the receiver operating characteristic curve to 0.96-0.97 (P<.001). For TP candidates, maximum polyp width (P=.038), polyp height (P=.019), and preparation (P=.004) significantly affected accuracy. For FP candidates, colonic segment (P=.007), attenuation (P<.001), surface smoothness (P<.001), distention (P=.034), preparation (P<.001), and true nature of candidate lesions (P<.001) significantly affected accuracy. Use of 3D viewing increases reader accuracy in the classification of polyp candidates identified with CAD. Polyp size and examination quality are significantly associated with accuracy. Copyright (c) RSNA, 2006.

  3. Production of JP-8-Based Hydrogen and Advanced Tactical Fuels for the U.S. Military

    DTIC Science & Technology

    2009-09-24

    system in pilot plant gasifier. Table 14. Summary of the Gravimetric Analysis of Tar (heavier than benzene) and PM Sampled from Hot and Cold Side...thorough technoeconomic assessment and analysis of available feedstocks prior to a candidate biomass being selected for energy generation or product...application will also require a thorough technoeconomic assessment and analysis of available feedstocks prior to a candidate biomass being selected

  4. Method for determining gene knockouts

    DOEpatents

    Maranas, Costas D [Port Matilda, PA; Burgard, Anthony R [State College, PA; Pharkya, Priti [State College, PA

    2011-09-27

    A method for determining candidates for gene deletions and additions using a model of a metabolic network associated with an organism, the model includes a plurality of metabolic reactions defining metabolite relationships, the method includes selecting a bioengineering objective for the organism, selecting at least one cellular objective, forming an optimization problem that couples the at least one cellular objective with the bioengineering objective, and solving the optimization problem to yield at least one candidate.

  5. Method for determining gene knockouts

    DOEpatents

    Maranas, Costa D; Burgard, Anthony R; Pharkya, Priti

    2013-06-04

    A method for determining candidates for gene deletions and additions using a model of a metabolic network associated with an organism, the model includes a plurality of metabolic reactions defining metabolite relationships, the method includes selecting a bioengineering objective for the organism, selecting at least one cellular objective, forming an optimization problem that couples the at least one cellular objective with the bioengineering objective, and solving the optimization problem to yield at least one candidate.

  6. Data-Driven Surface Traversability Analysis for Mars 2020 Landing Site Selection

    NASA Technical Reports Server (NTRS)

    Ono, Masahiro; Rothrock, Brandon; Almeida, Eduardo; Ansar, Adnan; Otero, Richard; Huertas, Andres; Heverly, Matthew

    2015-01-01

    The objective of this paper is three-fold: 1) to describe the engineering challenges in the surface mobility of the Mars 2020 Rover mission that are considered in the landing site selection processs, 2) to introduce new automated traversability analysis capabilities, and 3) to present the preliminary analysis results for top candidate landing sites. The analysis capabilities presented in this paper include automated terrain classification, automated rock detection, digital elevation model (DEM) generation, and multi-ROI (region of interest) route planning. These analysis capabilities enable to fully utilize the vast volume of high-resolution orbiter imagery, quantitatively evaluate surface mobility requirements for each candidate site, and reject subjectivity in the comparison between sites in terms of engineering considerations. The analysis results supported the discussion in the Second Landing Site Workshop held in August 2015, which resulted in selecting eight candidate sites that will be considered in the third workshop.

  7. Candidate Species Selection: Cultural and Photosynthetic Aspects

    NASA Technical Reports Server (NTRS)

    Mitchell, C. A.

    1982-01-01

    Cultural information is provided for a data base that will be used to select candidate crop species for a controlled ecological life support system (CELSS). Lists of food crops which will satisfy most nutritional requirements of humans and also fit within the scope of cultural restrictions that logically would apply to a closed, regenerating system were generated. Cultural and environmental conditions that will allow the most rapid production of edible biomass from candidate species in the shortest possible time are identified. Cultivars which are most productive in terms of edible biomass production by (CE) conditions, and which respond to the ever-closed approach to optimization realized by each shortened production cycle are selected. The experimental approach with lettuce was to grow the crop hydroponically in a growth chamber and to manipulate such variables as light level and duration, day/night temperature, and nutrient form and level in the solution culture.

  8. Genomic resources and their influence on the detection of the signal of positive selection in genome scans.

    PubMed

    Manel, S; Perrier, C; Pratlong, M; Abi-Rached, L; Paganini, J; Pontarotti, P; Aurelle, D

    2016-01-01

    Genome scans represent powerful approaches to investigate the action of natural selection on the genetic variation of natural populations and to better understand local adaptation. This is very useful, for example, in the field of conservation biology and evolutionary biology. Thanks to Next Generation Sequencing, genomic resources are growing exponentially, improving genome scan analyses in non-model species. Thousands of SNPs called using Reduced Representation Sequencing are increasingly used in genome scans. Besides, genome sequences are also becoming increasingly available, allowing better processing of short-read data, offering physical localization of variants, and improving haplotype reconstruction and data imputation. Ultimately, genome sequences are also becoming the raw material for selection inferences. Here, we discuss how the increasing availability of such genomic resources, notably genome sequences, influences the detection of signals of selection. Mainly, increasing data density and having the information of physical linkage data expand genome scans by (i) improving the overall quality of the data, (ii) helping the reconstruction of demographic history for the population studied to decrease false-positive rates and (iii) improving the statistical power of methods to detect the signal of selection. Of particular importance, the availability of a high-quality reference genome can improve the detection of the signal of selection by (i) allowing matching the potential candidate loci to linked coding regions under selection, (ii) rapidly moving the investigation to the gene and function and (iii) ensuring that the highly variable regions of the genomes that include functional genes are also investigated. For all those reasons, using reference genomes in genome scan analyses is highly recommended. © 2015 John Wiley & Sons Ltd.

  9. A review of selected candidate endophenotypes for depression.

    PubMed

    Goldstein, Brandon L; Klein, Daniel N

    2014-07-01

    Endophenotypes are proposed to occupy an intermediate position in the pathway between genotype and phenotype in genetically complex disorders such as depression. To be considered an endophenotype, a construct must meet a set of criteria proposed by Gottesman and Gould (2003). In this qualitative review, we summarize evidence for each criterion for several putative endophenotypes for depression: neuroticism, morning cortisol, frontal asymmetry of cortical electrical activity, reward learning, and biases of attention and memory. Our review indicates that while there is strong support for some depression endophenotypes, other putative endophenotypes lack data or have inconsistent findings for core criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Preliminary performance analysis of an interplanetary navigation system using asteroid based beacons

    NASA Technical Reports Server (NTRS)

    Jee, J. Rodney; Khatib, Ahmad R.; Muellerschoen, Ronald J.; Williams, Bobby G.; Vincent, Mark A.

    1988-01-01

    A futuristic interplanetary navigation system using transmitters placed on selected asteroids is introduced. This network of space beacons is seen as a needed alternative to the overly burdened Deep Space Network. Covariance analyses on the potential performance of these space beacons located on a candidate constellation of eight real asteroids are initiated. Simplified analytic calculations are performed to determine limiting accuracies attainable with the network for geometric positioning. More sophisticated computer simulations are also performed to determine potential accuracies using long arcs of range and Doppler data from the beacons. The results from these computations show promise for this navigation system.

  11. The genetic basis of adaptive pigmentation variation in Drosophila melanogaster

    PubMed Central

    Pool, John E.; Aquadro, Charles F.

    2009-01-01

    In a broad survey of Drosophila melanogaster population samples, levels of abdominal pigmentation were found to be highly variable and geographically differentiated. A strong positive correlation was found between dark pigmentation and high altitude, suggesting adaptation to specific environments. DNA sequence polymorphism at the candidate gene ebony revealed a clear association with the pigmentation of homozygous third chromosome lines. The darkest lines sequenced had nearly identical haplotypes spanning 14.5 kilobases upstream of the protein-coding exons of ebony. Thus, natural selection may have elevated the frequency of an allele that confers dark abdominal pigmentation by influencing the regulation of ebony. PMID:17614900

  12. A Correlation Between the Characteristics of Candidates and Performance on the Uniform CPA Examination.

    ERIC Educational Resources Information Center

    Zook, Donald R.; Bremser, Wayne G.

    1982-01-01

    This study examined the relationship between successful performance on the auditing, theory, and practice parts of the certified public accountant examination and selected characteristics possessed by CPA candidates. (Author/CT)

  13. The Selection of RR Lyrae Stars Using POSS and SDSS

    NASA Astrophysics Data System (ADS)

    Fraser, Oliver J.; Barton, J. R.; Oldfield, B. J.; Biesiadzinski, T. P.; Horning, D. A.; Baerny, J. K.; Kiuchi, F.; Krogsrud, D.; Longhurst, D. S.; McCommas, L. P.; Scheidt, J. A.; Covarrubias, R.; Covey, K.; Laws, C.; Sesar, B.; Ivezic, Z.

    2006-12-01

    We test a method for identifying candidate RR Lyrae stars based on a comparison of POSS and SDSS photometry (Sesar et. al. 2005). Our candidate stars range in SDSS g magnitude from 14.4--16, or a distance of 6--12 kpc. Follow-up photometry obtained at Manastash Ridge Observatory typically includes 30-40 points per light curve. We find that at least two thirds of our sample of 23 objects are clearly variable, with light curves consistent with RR Lyrae. Candidate RR Lyrae were selected using stars that had brightened at least 0.3 magnitudes between POSS and SDSS, and which had SDSS magnitudes and colors consistent with the cuts in Ivezic et al. 2004.

  14. The Left and Minority Representation: The Labour Party, Muslim Candidates, and Inclusion Tradeoffs

    PubMed Central

    Dancygier, Rafaela

    2014-01-01

    As ethnic diversity rises across Europe, the Left faces a trade-off between incorporating new minorities while retaining support from settled, working-class voters. Focusing on the Labour Party’s selection of Muslims and employing a dataset containing over 42,000 local election candidates in England, this article argues that inclusion is less likely where core voters are most concerned about the representation of Muslims’ material and religious interests: economically deprived areas with sizable Muslim populations. It shows that in these areas Muslim candidates underperform at the polls and Labour Parties are less likely to choose Muslim candidates here as a result. Selection thus varies based on the economic and cultural threats that Muslim representation poses to the Left’s core constituency. These findings contribute to our understanding of the forces that shape ethnic minority political incorporation across contexts. PMID:24634537

  15. Evolution of disease response genes in loblolly pine: insights from candidate genes.

    PubMed

    Ersoz, Elhan S; Wright, Mark H; González-Martínez, Santiago C; Langley, Charles H; Neale, David B

    2010-12-06

    Host-pathogen interactions that may lead to a competitive co-evolution of virulence and resistance mechanisms present an attractive system to study molecular evolution because strong, recent (or even current) selective pressure is expected at many genomic loci. However, it is unclear whether these selective forces would act to preserve existing diversity, promote novel diversity, or reduce linked neutral diversity during rapid fixation of advantageous alleles. In plants, the lack of adaptive immunity places a larger burden on genetic diversity to ensure survival of plant populations. This burden is even greater if the generation time of the plant is much longer than the generation time of the pathogen. Here, we present nucleotide polymorphism and substitution data for 41 candidate genes from the long-lived forest tree loblolly pine, selected primarily for their prospective influences on host-pathogen interactions. This dataset is analyzed together with 15 drought-tolerance and 13 wood-quality genes from previous studies. A wide range of neutrality tests were performed and tested against expectations from realistic demographic models. Collectively, our analyses found that axr (auxin response factor), caf1 (chromatin assembly factor) and gatabp1 (gata binding protein 1) candidate genes carry patterns consistent with directional selection and erd3 (early response to drought 3) displays patterns suggestive of a selective sweep, both of which are consistent with the arm-race model of disease response evolution. Furthermore, we have identified patterns consistent with diversifying selection at erf1-like (ethylene responsive factor 1), ccoaoemt (caffeoyl-CoA-O-methyltransferase), cyp450-like (cytochrome p450-like) and pr4.3 (pathogen response 4.3), expected under the trench-warfare evolution model. Finally, a drought-tolerance candidate related to the plant cell wall, lp5, displayed patterns consistent with balancing selection. In conclusion, both arms-race and trench-warfare models seem compatible with patterns of polymorphism found in different disease-response candidate genes, indicating a mixed strategy of disease tolerance evolution for loblolly pine, a major tree crop in southeastern United States.

  16. Postdoctoral Fellow | Center for Cancer Research

    Cancer.gov

    The positions will provide excellent training opportunities in mucosal immunology.  The ideal candidates must be able to work independently and have demonstrated abilities in clear scientific project planning and reporting.  Experience in multiparameter flow cytometry, gene expression analysis, intestinal cell isolation, and mouse models of disease is desirable.  One position will be preferentially given to candidate with experience in non-human primate models.  

  17. Morph-X-Select: Morphology-based tissue aptamer selection for ovarian cancer biomarker discovery

    PubMed Central

    Wang, Hongyu; Li, Xin; Volk, David E.; Lokesh, Ganesh L.-R.; Elizondo-Riojas, Miguel-Angel; Li, Li; Nick, Alpa M.; Sood, Anil K.; Rosenblatt, Kevin P.; Gorenstein, David G.

    2016-01-01

    High affinity aptamer-based biomarker discovery has the advantage of simultaneously discovering an aptamer affinity reagent and its target biomarker protein. Here, we demonstrate a morphology-based tissue aptamer selection method that enables us to use tissue sections from individual patients and identify high-affinity aptamers and their associated target proteins in a systematic and accurate way. We created a combinatorial DNA aptamer library that has been modified with thiophosphate substitutions of the phosphate ester backbone at selected 5′dA positions for enhanced nuclease resistance and targeting. Based on morphological assessment, we used image-directed laser microdissection (LMD) to dissect regions of interest bound with the thioaptamer (TA) library and further identified target proteins for the selected TAs. We have successfully identified and characterized the lead candidate TA, V5, as a vimentin-specific sequence that has shown specific binding to tumor vasculature of human ovarian tissue and human microvascular endothelial cells. This new Morph-X-Select method allows us to select high-affinity aptamers and their associated target proteins in a specific and accurate way, and could be used for personalized biomarker discovery to improve medical decision-making and to facilitate the development of targeted therapies to achieve more favorable outcomes. PMID:27839510

  18. Automated detection of lung nodules with three-dimensional convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Pérez, Gustavo; Arbeláez, Pablo

    2017-11-01

    Lung cancer is the cancer type with highest mortality rate worldwide. It has been shown that early detection with computer tomography (CT) scans can reduce deaths caused by this disease. Manual detection of cancer nodules is costly and time-consuming. We present a general framework for the detection of nodules in lung CT images. Our method consists of the pre-processing of a patient's CT with filtering and lung extraction from the entire volume using a previously calculated mask for each patient. From the extracted lungs, we perform a candidate generation stage using morphological operations, followed by the training of a three-dimensional convolutional neural network for feature representation and classification of extracted candidates for false positive reduction. We perform experiments on the publicly available LIDC-IDRI dataset. Our candidate extraction approach is effective to produce precise candidates with a recall of 99.6%. In addition, false positive reduction stage manages to successfully classify candidates and increases precision by a factor of 7.000.

  19. Luminous Obscured AGN Unveiled in the Stripe 82 X-ray Survey

    NASA Astrophysics Data System (ADS)

    LaMassa, Stephanie; Glikman, Eilat; Brusa, Marcella; Rigby, Jane; Tasnim Ananna, Tonima; Stern, Daniel; Lira, Paulina; Urry, Meg; Salvato, Mara; Alexandroff, Rachael; Allevato, Viola; Cardamone, Carolin; Civano, Francesca Maria; Coppi, Paolo; Farrah, Duncan; Komossa, S.; Lanzuisi, Giorgio; Marchesi, Stefano; Richards, Gordon; Trakhtenbrot, Benny; Treister, Ezequiel

    2018-01-01

    Stripe 82X is a wide-area (30 deg2) X-ray survey overlapping the legacy Sloan Digital Sky Survey (SDSS) Stripe 82 field, designed to uncover rare, high luminosity active galactic nuclei (AGN). We report on the results of an on-going near-infrared (NIR) spectroscopic campaign to follow-up reddened AGN candidates with Palomar TripleSpec, Keck NIRSPEC, and Gemini GNIRS. We identified 8 AGN in our bright NIR sample (K < 16, Vega), selected to have red R-K colors (> 4, Vega); four of these sources had existing optical spectra in SDSS. We targeted four out of 34 obscured AGN candidates in our faint NIR sample (K > 17, Vega), all of which are undetected in the single-epoch SDSS imaging, making them the best candidates for the most obscured and/or the most distant reddend AGN in Stripe 82X. All twelve sources are Type 1 AGN, with the FWHM of at least one permitted emission line exceeding 1300 km/s. We find that our nearly complete bright NIR sample (12/13 obscured AGN candidates have spectroscopic redshifts) is more distant (z > 0.5) than a matched sample of blue Type 1 AGN from Stripe 82X; these AGN tend to be more luminous than their blue, unobscured counterparts. Results from our pilot program of faint NIR-selected obscured AGN candidates demonstrate that our selection recovers reddened quasars missed by SDSS.

  20. 11 CFR 100.2 - Election (2 U.S.C. 431(1)).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... office as independent candidates, or without nomination by a major party (as defined in 26 U.S.C. 9002(6..., as a direct result of which candidates are nominated, in accordance with applicable State law, for... candidate: (i) The day prescribed by applicable State law as the last day to qualify for a position on the...

  1. Applications of machine-learning algorithms for infrared colour selection of Galactic Wolf-Rayet stars

    NASA Astrophysics Data System (ADS)

    Morello, Giuseppe; Morris, P. W.; Van Dyk, S. D.; Marston, A. P.; Mauerhan, J. C.

    2018-01-01

    We have investigated and applied machine-learning algorithms for infrared colour selection of Galactic Wolf-Rayet (WR) candidates. Objects taken from the Spitzer Galactic Legacy Infrared Midplane Survey Extraordinaire (GLIMPSE) catalogue of the infrared objects in the Galactic plane can be classified into different stellar populations based on the colours inferred from their broad-band photometric magnitudes [J, H and Ks from 2 Micron All Sky Survey (2MASS), and the four Spitzer/IRAC bands]. The algorithms tested in this pilot study are variants of the k-nearest neighbours approach, which is ideal for exploratory studies of classification problems where interrelations between variables and classes are complicated. The aims of this study are (1) to provide an automated tool to select reliable WR candidates and potentially other classes of objects, (2) to measure the efficiency of infrared colour selection at performing these tasks and (3) to lay the groundwork for statistically inferring the total number of WR stars in our Galaxy. We report the performance results obtained over a set of known objects and selected candidates for which we have carried out follow-up spectroscopic observations, and confirm the discovery of four new WR stars.

  2. Collaboration between research scientists and educators in implementation of a Masters program for training new Earth Science teachers in New York State

    NASA Astrophysics Data System (ADS)

    Nadeau, P. A.; Flores, K. E.; Zirakparvar, N. A.; Grcevich, J.; Ustunisik, G. K.; Kinzler, R. J.; Macdonald, M.; Mathez, E. A.; Mac Low, M.

    2012-12-01

    Educators and research scientists at the American Museum of Natural History are collaborating to implement a teacher education program with the goal of addressing a critical shortage of qualified Earth Science teachers in New York State (NYS), particularly in high-needs schools with diverse populations. This pilot program involves forging a one-of-a-kind partnership between a world-class research museum and high-needs schools in New York City. By placing teaching candidates in such schools, the project has potential to engage, motivate, and improve Earth Science achievement and interest in STEM careers of thousands of students from traditionally underrepresented populations including English language learners, special education students, and racial minority groups. The program, which is part of the state's Race to the Top initiative, is approved by the NYS Board of Regents and will prepare a total of 50 candidates in two cohorts to earn a Board of Regents-awarded Masters of Arts in Teaching (MAT) degree with a specialization in Earth Science for grades 7-12. The museum is in a unique position of being able to break traditional educational barriers as a result of a long history of interdisciplinary collaborations between educators and research scientists, as well as being the only stand-alone science graduate degree-granting museum in the United States. The intensive 15-month curriculum for MAT candidates comprises one summer of museum teaching residency, a full academic year of residency in high-needs public schools, one summer of science research residency, and concurrent graduate-level courses in Earth and space sciences, pedagogy, and adolescent psychology. We emphasize field-based geological studies and experiential learning, in contrast to many traditional teacher education programs. In an effort to ensure that MAT candidates have a robust knowledge base in Earth science, and per NYS Department of Education requirements, we selected candidates with strong backgrounds in fields including geology, meteorology, and environmental science and engineering. Program faculty includes curators and post-doctoral fellows specializing in geology, astrophysics, and paleontology, and doctoral-level Education faculty, who work side by side across disciplines to develop and co-teach courses. With the first cohort of teaching candidates having entered the program in June of 2012, the MAT program is still in the early stages. Current teacher candidates have a wide variety of scientific expertise, come from diverse geographic localities, range from recent bachelors graduates to career changers, and thus far have provided much positive feedback about their experiences with the MAT curriculum. Here we report on the first 6 months of the program.

  3. An active learning representative subset selection method using net analyte signal.

    PubMed

    He, Zhonghai; Ma, Zhenhe; Luan, Jingmin; Cai, Xi

    2018-05-05

    To guarantee accurate predictions, representative samples are needed when building a calibration model for spectroscopic measurements. However, in general, it is not known whether a sample is representative prior to measuring its concentration, which is both time-consuming and expensive. In this paper, a method to determine whether a sample should be selected into a calibration set is presented. The selection is based on the difference of Euclidean norm of net analyte signal (NAS) vector between the candidate and existing samples. First, the concentrations and spectra of a group of samples are used to compute the projection matrix, NAS vector, and scalar values. Next, the NAS vectors of candidate samples are computed by multiplying projection matrix with spectra of samples. Scalar value of NAS is obtained by norm computation. The distance between the candidate set and the selected set is computed, and samples with the largest distance are added to selected set sequentially. Last, the concentration of the analyte is measured such that the sample can be used as a calibration sample. Using a validation test, it is shown that the presented method is more efficient than random selection. As a result, the amount of time and money spent on reference measurements is greatly reduced. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. An active learning representative subset selection method using net analyte signal

    NASA Astrophysics Data System (ADS)

    He, Zhonghai; Ma, Zhenhe; Luan, Jingmin; Cai, Xi

    2018-05-01

    To guarantee accurate predictions, representative samples are needed when building a calibration model for spectroscopic measurements. However, in general, it is not known whether a sample is representative prior to measuring its concentration, which is both time-consuming and expensive. In this paper, a method to determine whether a sample should be selected into a calibration set is presented. The selection is based on the difference of Euclidean norm of net analyte signal (NAS) vector between the candidate and existing samples. First, the concentrations and spectra of a group of samples are used to compute the projection matrix, NAS vector, and scalar values. Next, the NAS vectors of candidate samples are computed by multiplying projection matrix with spectra of samples. Scalar value of NAS is obtained by norm computation. The distance between the candidate set and the selected set is computed, and samples with the largest distance are added to selected set sequentially. Last, the concentration of the analyte is measured such that the sample can be used as a calibration sample. Using a validation test, it is shown that the presented method is more efficient than random selection. As a result, the amount of time and money spent on reference measurements is greatly reduced.

  5. Genetic reprogramming of human amniotic cells with episomal vectors: neural rosettes as sentinels in candidate selection for validation assays.

    PubMed

    Wilson, Patricia G; Payne, Tiffany

    2014-01-01

    The promise of genetic reprogramming has prompted initiatives to develop banks of induced pluripotent stem cells (iPSCs) from diverse sources. Sentinel assays for pluripotency could maximize available resources for generating iPSCs. Neural rosettes represent a primitive neural tissue that is unique to differentiating PSCs and commonly used to identify derivative neural/stem progenitors. Here, neural rosettes were used as a sentinel assay for pluripotency in selection of candidates to advance to validation assays. Candidate iPSCs were generated from independent populations of amniotic cells with episomal vectors. Phase imaging of living back up cultures showed neural rosettes in 2 of the 5 candidate populations. Rosettes were immunopositive for the Sox1, Sox2, Pax6 and Pax7 transcription factors that govern neural development in the earliest stage of development and for the Isl1/2 and Otx2 transcription factors that are expressed in the dorsal and ventral domains, respectively, of the neural tube in vivo. Dissociation of rosettes produced cultures of differentiation competent neural/stem progenitors that generated immature neurons that were immunopositive for βIII-tubulin and glia that were immunopositive for GFAP. Subsequent validation assays of selected candidates showed induced expression of endogenous pluripotency genes, epigenetic modification of chromatin and formation of teratomas in immunodeficient mice that contained derivatives of the 3 embryonic germ layers. Validated lines were vector-free and maintained a normal karyotype for more than 60 passages. The credibility of rosette assembly as a sentinel assay for PSCs is supported by coordinate loss of nuclear-localized pluripotency factors Oct4 and Nanog in neural rosettes that emerge spontaneously in cultures of self-renewing validated lines. Taken together, these findings demonstrate value in neural rosettes as sentinels for pluripotency and selection of promising candidates for advance to validation assays.

  6. Genetic reprogramming of human amniotic cells with episomal vectors: neural rosettes as sentinels in candidate selection for validation assays

    PubMed Central

    Payne, Tiffany

    2014-01-01

    The promise of genetic reprogramming has prompted initiatives to develop banks of induced pluripotent stem cells (iPSCs) from diverse sources. Sentinel assays for pluripotency could maximize available resources for generating iPSCs. Neural rosettes represent a primitive neural tissue that is unique to differentiating PSCs and commonly used to identify derivative neural/stem progenitors. Here, neural rosettes were used as a sentinel assay for pluripotency in selection of candidates to advance to validation assays. Candidate iPSCs were generated from independent populations of amniotic cells with episomal vectors. Phase imaging of living back up cultures showed neural rosettes in 2 of the 5 candidate populations. Rosettes were immunopositive for the Sox1, Sox2, Pax6 and Pax7 transcription factors that govern neural development in the earliest stage of development and for the Isl1/2 and Otx2 transcription factors that are expressed in the dorsal and ventral domains, respectively, of the neural tube in vivo. Dissociation of rosettes produced cultures of differentiation competent neural/stem progenitors that generated immature neurons that were immunopositive for βIII-tubulin and glia that were immunopositive for GFAP. Subsequent validation assays of selected candidates showed induced expression of endogenous pluripotency genes, epigenetic modification of chromatin and formation of teratomas in immunodeficient mice that contained derivatives of the 3 embryonic germ layers. Validated lines were vector-free and maintained a normal karyotype for more than 60 passages. The credibility of rosette assembly as a sentinel assay for PSCs is supported by coordinate loss of nuclear-localized pluripotency factors Oct4 and Nanog in neural rosettes that emerge spontaneously in cultures of self-renewing validated lines. Taken together, these findings demonstrate value in neural rosettes as sentinels for pluripotency and selection of promising candidates for advance to validation assays. PMID:25426336

  7. CNNdel: Calling Structural Variations on Low Coverage Data Based on Convolutional Neural Networks

    PubMed Central

    2017-01-01

    Many structural variations (SVs) detection methods have been proposed due to the popularization of next-generation sequencing (NGS). These SV calling methods use different SV-property-dependent features; however, they all suffer from poor accuracy when running on low coverage sequences. The union of results from these tools achieves fairly high sensitivity but still produces low accuracy on low coverage sequence data. That is, these methods contain many false positives. In this paper, we present CNNdel, an approach for calling deletions from paired-end reads. CNNdel gathers SV candidates reported by multiple tools and then extracts features from aligned BAM files at the positions of candidates. With labeled feature-expressed candidates as a training set, CNNdel trains convolutional neural networks (CNNs) to distinguish true unlabeled candidates from false ones. Results show that CNNdel works well with NGS reads from 26 low coverage genomes of the 1000 Genomes Project. The paper demonstrates that convolutional neural networks can automatically assign the priority of SV features and reduce the false positives efficaciously. PMID:28630866

  8. Development of Diagnostic Biomarkers for Detecting Diabetic Retinopathy at Early Stages Using Quantitative Proteomics

    PubMed Central

    Min, Hophil; Kim, Sang Jin; Oh, Sohee; Kim, Kyunggon; Yu, Hyeong Gon; Park, Taesung; Kim, Youngsoo

    2016-01-01

    Diabetic retinopathy (DR) is a common microvascular complication caused by diabetes mellitus (DM) and is a leading cause of vision impairment and loss among adults. Here, we performed a comprehensive proteomic analysis to discover biomarkers for DR. First, to identify biomarker candidates that are specifically expressed in human vitreous, we performed data-mining on both previously published DR-related studies and our experimental data; 96 proteins were then selected. To confirm and validate the selected biomarker candidates, candidates were selected, confirmed, and validated using plasma from diabetic patients without DR (No DR) and diabetics with mild or moderate nonproliferative diabetic retinopathy (Mi or Mo NPDR) using semiquantitative multiple reaction monitoring (SQ-MRM) and stable-isotope dilution multiple reaction monitoring (SID-MRM). Additionally, we performed a multiplex assay using 15 biomarker candidates identified in the SID-MRM analysis, which resulted in merged AUC values of 0.99 (No DR versus Mo NPDR) and 0.93 (No DR versus Mi and Mo NPDR). Although further validation with a larger sample size is needed, the 4-protein marker panel (APO4, C7, CLU, and ITIH2) could represent a useful multibiomarker model for detecting the early stages of DR. PMID:26665153

  9. TESTING OF TMR SAND MANTIS FINAL REPORT

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

    Krementz, D; William Daugherty, W

    2007-06-12

    Screening tests of Sand Mantis candidate materials selected for erosion resistance have been completed. The results of this testing identified that over a relatively short period of operation (<1 hour), measurable erosion will occur in each of the candidate zoom tube materials given equal operating exposure. Additionally, this testing has shown that erosion of the rubber discharge hose directly downstream of the vehicle could be expected to limit the service life of the discharge hose. On the basis of these test results, SRNL recommends the following; {lg_bullet} redesign of critical system components (e.g., zoom tube, discharge hose) should be conductedmore » to improve system characteristics relative to erosion and capitalize on the results of this testing, {lg_bullet} continued efforts to deploy the Sand Mantis should include testing to better define and optimize operating parameters, and gain an understanding of system dynamics, {lg_bullet} discontinue wear testing with the selected materials pending redesign of critical system components (1st recommendation) and inclusion of other candidate materials. The final selection of additional candidate materials should be made following design changes, but might include a Stellite alloy or zirconia.« less

  10. ATCA follow-up of blazar candidates in the H-ATLAS fields

    NASA Astrophysics Data System (ADS)

    Massardi, Marcella; Ricci, Roberto; de Zotti, Gianfranco; White, Glenn; Michalowski, Michal; Ivison, Rob; Baes, Maarten; Lapi, Andrea; Temi, Pasquale; Lopez-Caniego, Marcos; Herranz, Diego; Seymour, Nick; Gonzalez-Nuevo, Joaquin; Bonavera, Laura; Negrello, Mattia

    2012-04-01

    The Herschel-ATLAS (H-ATLAS) survey that is covering 550 sq.deg. in 5 bands from 100 to 500 micron, allows for the first time a flux limited selection of blazars at sub-mm wavelengths. This wavelength range is particularly interesting because it is where the most luminous blazars are expected to show the synchrotron peak. The peak frequency and luminosity carry key information on the blazar physics. However, blazars constitute a tiny fraction of H-ATLAS sources and therefore picking them up isn't easy. A criterion to efficiently select candidate blazars exploiting the roughly flat blazar continuum spectrum from radio to sub-mm wavelengths has been devised by Lopez-Caniego et al. (in prep.). Multifrequency radio follow-up is however a necessary step to assess the nature of candidates. We propose to complete the validation of candidates in the H-ATLAS equatorial fields (partly done during few hours of ATCA DDT allocated time and with Medicina radiotelescope observations) and to extend the investigation to the Southern (SGP) fields reconstructing the blazars SED between 1.1 and 40 GHz. This will provide the first statistically significant blazar sample selected at sub-mm wavelengths.

  11. Space use of a dominant Arctic vertebrate: Effects of prey, sea ice, and land on Pacific walrus resource selection

    USGS Publications Warehouse

    Beatty, William; Jay, Chadwick V.; Fischbach, Anthony S.; Grebmeier, Jacqueline M.; Taylor, Rebecca L.; Blanchard, Arny L.; Jewett, Stephen C.

    2016-01-01

    Sea ice dominates marine ecosystems in the Arctic, and recent reductions in sea ice may alter food webs throughout the region. Sea ice loss may also stress Pacific walruses (Odobenus rosmarus divergens), which feed on benthic macroinvertebrates in the Bering and Chukchi seas. However, no studies have examined the effects of sea ice on foraging Pacific walrus space use patterns. We tested a series of hypotheses that examined walrus foraging resource selection as a function of proximity to resting substrates and prey biomass. We quantified walrus prey biomass with 17 benthic invertebrate families, which included bivalves, polychaetes, amphipods, tunicates, and sipunculids. We included covariates for distance to sea ice and distance to land, and systematically developed a series of candidate models to examine interactions among benthic prey biomass and resting substrates. We ranked candidate models with Bayesian Information Criterion and made inferences on walrus resource selection based on the top-ranked model. Based on the top model, biomass of the bivalve family Tellinidae, distance to ice, distance to land, and the interaction of distances to ice and land all positively influenced walrus foraging resource selection. Standardized model coefficients indicated that distance to ice explained the most variation in walrus foraging resource selection followed by Tellinidae biomass. Distance to land and the interaction of distances to ice and land accounted for similar levels of variation. Tellinidae biomass likely represented an index of overall bivalve biomass, indicating walruses focused foraging in areas with elevated levels of bivalve and tellinid biomass. Our results also emphasize the importance of sea ice to walruses. Projected sea ice loss will increase the duration of the open water season in the Chukchi Sea, altering the spatial distribution of resting sites relative to current foraging areas and possibly affecting the spatial structure of benthic communities.

  12. Ensemble candidate classification for the LOTAAS pulsar survey

    NASA Astrophysics Data System (ADS)

    Tan, C. M.; Lyon, R. J.; Stappers, B. W.; Cooper, S.; Hessels, J. W. T.; Kondratiev, V. I.; Michilli, D.; Sanidas, S.

    2018-03-01

    One of the biggest challenges arising from modern large-scale pulsar surveys is the number of candidates generated. Here, we implemented several improvements to the machine learning (ML) classifier previously used by the LOFAR Tied-Array All-Sky Survey (LOTAAS) to look for new pulsars via filtering the candidates obtained during periodicity searches. To assist the ML algorithm, we have introduced new features which capture the frequency and time evolution of the signal and improved the signal-to-noise calculation accounting for broad profiles. We enhanced the ML classifier by including a third class characterizing RFI instances, allowing candidates arising from RFI to be isolated, reducing the false positive return rate. We also introduced a new training data set used by the ML algorithm that includes a large sample of pulsars misclassified by the previous classifier. Lastly, we developed an ensemble classifier comprised of five different Decision Trees. Taken together these updates improve the pulsar recall rate by 2.5 per cent, while also improving the ability to identify pulsars with wide pulse profiles, often misclassified by the previous classifier. The new ensemble classifier is also able to reduce the percentage of false positive candidates identified from each LOTAAS pointing from 2.5 per cent (˜500 candidates) to 1.1 per cent (˜220 candidates).

  13. DNA sequence variation and selection of tag single-nucleotide polymorphisms at candidate genes for drought-stress response in Pinus taeda L.

    PubMed

    González-Martínez, Santiago C; Ersoz, Elhan; Brown, Garth R; Wheeler, Nicholas C; Neale, David B

    2006-03-01

    Genetic association studies are rapidly becoming the experimental approach of choice to dissect complex traits, including tolerance to drought stress, which is the most common cause of mortality and yield losses in forest trees. Optimization of association mapping requires knowledge of the patterns of nucleotide diversity and linkage disequilibrium and the selection of suitable polymorphisms for genotyping. Moreover, standard neutrality tests applied to DNA sequence variation data can be used to select candidate genes or amino acid sites that are putatively under selection for association mapping. In this article, we study the pattern of polymorphism of 18 candidate genes for drought-stress response in Pinus taeda L., an important tree crop. Data analyses based on a set of 21 putatively neutral nuclear microsatellites did not show population genetic structure or genomewide departures from neutrality. Candidate genes had moderate average nucleotide diversity at silent sites (pi(sil) = 0.00853), varying 100-fold among single genes. The level of within-gene LD was low, with an average pairwise r2 of 0.30, decaying rapidly from approximately 0.50 to approximately 0.20 at 800 bp. No apparent LD among genes was found. A selective sweep may have occurred at the early-response-to-drought-3 (erd3) gene, although population expansion can also explain our results and evidence for selection was not conclusive. One other gene, ccoaomt-1, a methylating enzyme involved in lignification, showed dimorphism (i.e., two highly divergent haplotype lineages at equal frequency), which is commonly associated with the long-term action of balancing selection. Finally, a set of haplotype-tagging SNPs (htSNPs) was selected. Using htSNPs, a reduction of genotyping effort of approximately 30-40%, while sampling most common allelic variants, can be gained in our ongoing association studies for drought tolerance in pine.

  14. Lepidopteran HMG-CoA reductase is a potential selective target for pest control

    PubMed Central

    Li, Yuan-mei; Huang, Juan; Tobe, Stephen S.

    2017-01-01

    As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR) revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta, whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata. The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins) could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide  targets. PMID:28133568

  15. Lepidopteran HMG-CoA reductase is a potential selective target for pest control.

    PubMed

    Li, Yuan-Mei; Kai, Zhen-Peng; Huang, Juan; Tobe, Stephen S

    2017-01-01

    As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR) revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta , whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata . The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins) could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide  targets.

  16. Estrogen receptor agonists/antagonists in breast cancer therapy: A critical review.

    PubMed

    Jameera Begam, A; Jubie, S; Nanjan, M J

    2017-04-01

    Estrogens display intriguing tissue selective action that is of great biomedical importance in the development of optimal therapeutics for the prevention and treatment of breast cancer. There are also strong evidences to show that both endogenous and exogenous estrogens are involved in the pathogenesis of breast cancer. Tamoxifen has been the only drug of choice for more than 30years to treat patients with estrogen related (ER) positive breast tumors. There is a need therefore, for identifying newer, potential and novel candidates for breast cancer. Keeping this in view, the present review focuses on selective estrogen receptor modulators and estrogen antagonists such as sulfatase and aromatase inhibitors involved in breast cancer therapy. A succinct and critical overview of the structure of estrogen receptors, their signaling and involvement in breast carcinogenesis are herein described. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Free-Energy-Based Design Policy for Robust Network Control against Environmental Fluctuation.

    PubMed

    Iwai, Takuya; Kominami, Daichi; Murata, Masayuki; Yomo, Tetsuya

    2015-01-01

    Bioinspired network control is a promising approach for realizing robust network controls. It relies on a probabilistic mechanism composed of positive and negative feedback that allows the system to eventually stabilize on the best solution. When the best solution fails due to environmental fluctuation, the system cannot keep its function until the system finds another solution again. To prevent the temporal loss of the function, the system should prepare some solution candidates and stochastically select available one from them. However, most bioinspired network controls are not designed with this issue in mind. In this paper, we propose a thermodynamics-based design policy that allows systems to retain an appropriate degree of randomness depending on the degree of environmental fluctuation, which prepares the system for the occurrence of environmental fluctuation. Furthermore, we verify the design policy by using an attractor selection model-based multipath routing to run simulation experiments.

  18. Selection of specific interactors from phage display library based on sea lamprey variable lymphocyte receptor sequences.

    PubMed

    Wezner-Ptasinska, Magdalena; Otlewski, Jacek

    2015-12-01

    Variable lymphocyte receptors (VLRs) are non-immunoglobulin components of adaptive immunity in jawless vertebrates. These proteins composed of leucine-rich repeat modules offer some advantages over antibodies in target binding and therefore are attractive candidates for biotechnological applications. In this paper we report the design and characterization of a phage display library based on a previously proposed dVLR scaffold containing six LRR modules [Wezner-Ptasinska et al., 2011]. Our library was designed based on a consensus approach in which the randomization scheme reflects the frequencies of amino acids naturally occurring in respective positions responsible for antigen recognition. We demonstrate general applicability of the scaffold by selecting dVLRs specific for lysozyme and S100A7 protein with KD values in the micromolar range. The dVLR library could be used as a convenient alternative to antibodies for effective isolation of high affinity binders.

  19. In silico selection of therapeutic antibodies for development: Viscosity, clearance, and chemical stability

    PubMed Central

    Sharma, Vikas K.; Patapoff, Thomas W.; Kabakoff, Bruce; Pai, Satyan; Hilario, Eric; Zhang, Boyan; Li, Charlene; Borisov, Oleg; Kelley, Robert F.; Chorny, Ilya; Zhou, Joe Z.; Dill, Ken A.; Swartz, Trevor E.

    2014-01-01

    For mAbs to be viable therapeutics, they must be formulated to have low viscosity, be chemically stable, and have normal in vivo clearance rates. We explored these properties by observing correlations of up to 60 different antibodies of the IgG1 isotype. Unexpectedly, we observe significant correlations with simple physical properties obtainable from antibody sequences and by molecular dynamics simulations of individual antibody molecules. mAbs viscosities increase strongly with hydrophobicity and charge dipole distribution and decrease with net charge. Fast clearance correlates with high hydrophobicities of certain complementarity determining regions and with high positive or high negative net charge. Chemical degradation from tryptophan oxidation correlates with the average solvent exposure time of tryptophan residues. Aspartic acid isomerization rates can be predicted from solvent exposure and flexibility as determined by molecular dynamics simulations. These studies should aid in more rapid screening and selection of mAb candidates during early discovery. PMID:25512516

  20. Constellation Pharmacology: A new paradigm for drug discovery

    PubMed Central

    Schmidt, Eric W.; Olivera, Baldomero M.

    2015-01-01

    Constellation Pharmacology is a cell-based high-content phenotypic-screening platform that utilizes subtype-selective pharmacological agents to elucidate the cell-specific combinations (“constellations”) of key signaling proteins that define specific cell types. Heterogeneous populations of native cells, in which the different individual cell types have been identified and characterized, are the foundation for this screening platform. Constellation Pharmacology is useful for screening small molecules or for deconvoluting complex mixtures of biologically-active natural products. This platform has been used to purify natural products and discover their molecular mechanisms. In the on-going development of Constellation Pharmacology, there is a positive-feedback loop between the pharmacological characterization of cell types and screening for new drug candidates. As Constellation Pharmacology is used to discover compounds with novel targeting-selectivity profiles, those new compounds then further help to elucidate the constellations of specific cell types, thereby increasing the content of this high-content platform. PMID:25562646

  1. A Review of Tribological Coatings for Control Drive Mechanisms in Space Reactors

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

    CJ Larkin; JD Edington; BJ Close

    2006-02-21

    Tribological coatings must provide lubrication for moving components of the control drive mechanism for a space reactor and prevent seizing due to friction or diffusion welding to provide highly reliable and precise control of reflector position over the mission lifetime. Several coatings were evaluated based on tribological performance at elevated temperatures and in ultrahigh vacuum environments. Candidates with proven performance in the anticipated environment are limited primarily to disulfide materials. Irradiation data for these coatings is nonexistent. Compatibility issues between coating materials and structural components may require the use of barrier layers between the solid lubricant and structural components tomore » prevent deleterious interactions. It would be advisable to consider possible lubricant interactions prior to down-selection of structural materials. A battery of tests was proposed to provide the necessary data for eventual solid lubricant/coating selection.« less

  2. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M.

    2012-01-01

    Two therapeutic HPV vaccine candidates successful in phase 1 Flu shot may prevent heart attacks and stroke CDX-1401 combined with TLR agonist: Positive phase 1 results Three MRSA vaccines in early clincial trials Ovarian cancer vaccine candidate DPX-Survivac: Positive interim results from phase 1 Chinese biotech partnership brings first hepatitis E vaccine to the market Therapeutic vaccine for treatment of genital herpes enters phase 2 Visionary concept: Printable vaccines PMID:23817319

  3. Oxygen electrodes for rechargeable alkaline fuel cells

    NASA Technical Reports Server (NTRS)

    Swette, L.; Kackley, N.

    1989-01-01

    Electrocatalysts and supports for the positive electrode of moderate temperature single-unit rechargeable alkaline fuel cells are being investigated and developed. Candidate support materials were drawn from transition metal carbides, borides, nitrides and oxides which have high conductivity (greater than 1 ohm/cm). Candidate catalyst materials were selected largely from metal oxides of the form ABO sub x (where A = Pb, Cd, Mn, Ti, Zr, La, Sr, Na, and B = Pt, Pd, Ir, Ru, Ni (Co) which were investigated and/or developed for one function only, O2 reduction or O2 evolution. The electrical conductivity requirement for catalysts may be lower, especially if integrated with a higher conductivity support. All candidate materials of acceptable conductivity are subjected to corrosion testing. Materials that survive chemical testing are examined for electrochemical corrosion activity. For more stringent corrosion testing, and for further evaluation of electrocatalysts (which generally show significant O2 evolution at at 1.4 V), samples are held at 1.6 V or 0.6 V for about 100 hours. The surviving materials are then physically and chemically analyzed for signs of degradation. To evaluate the bifunctional oxygen activity of candidate catalysts, Teflon-bonded electrodes are fabricated and tested in a floating electrode configuration. Many of the experimental materials being studied have required development of a customized electrode fabrication procedure. In advanced development, the goal is to reduce the polarization to about 300 to 350 mV. Approximately six support materials and five catalyst materials were identified to date for further development. The test results will be described.

  4. Evaluation of the influence of blood glucose level on oral candidal colonization in complete denture wearers with Type-II Diabetes Mellitus: An in vivo Study.

    PubMed

    Ganapathy, Dhanraj Muthuveera; Joseph, Sajeesh; Ariga, Padma; Selvaraj, Anand

    2013-01-01

    Candidal colonization in complete denture wearers is a commonly encountered condition that worsens in the presence of untreated Diabetes Mellitus. The aim of this study was to evaluate the correlation between oral candidiasis in denture-bearing mucosa and elevated blood glucose levels in complete denture wearers and to evaluate the effect of oral hypoglycemic drug therapy in controlling oral candidal colonization in denture-bearing mucosa of complete denture wearers with Type II Diabetes Mellitus. This prospective observational study involved the participation of 15 complete denture wearers with Type II Diabetes Mellitus. The sample collection was made prior and after oral hypoglycaemic drug intervention, by swabbing the rugal surfaces of palatal mucosa, cultured and the density of the candidal colony formed was analyzed and interpreted as colony forming units (CFU) per mL. The candidal samples CFU and corresponding pre- and post-prandial blood glucose levels were estimated, analyzed and compared using Karl Pearson correlation analysis and paired t-test (α = 0.05). The Karl Pearson correlation analysis showed that there was a positive correlation between the blood glucose levels (PPS and FBS) and the candidal colonization (CFU) (P < 0.05). The mean values of all the variables were analyzed using the paired t-test. There was significant reduction in the mean values of blood glucose levels (P < 0.001) and the mean values of the CFU (P < 0.001) following oral hypoglycemic drug therapy. Positive correlation was observed between oral candidiasis in complete denture-bearing mucosa and elevated blood glucose levels and oral hypoglycemic drug therapy has a positive effect in controlling oral candidal colonization in complete denture wearers with Type II Diabetes Mellitus.

  5. [The key parameters of design research and analysis of the Chinese reading visual acuity chart].

    PubMed

    Wang, Chen-xiao; Liu, Zhi-hui; Gao, Ji-tuo; Guo, Ying-xuan; He, Ji-cang; Qu, Jia; Lü, Fan

    2013-06-01

    Reading is a visual function human being used to understand environmental events based on writing materials. This study investigated the feasibility of reading visual acuity chart in assessment of reading ability by analysis of the key factors involved in the design of the visual acuity chart. The reading level was determined as grade 3 primary school with Song as the font and 30 characters included in the sentences. Each of the sentences consisted of 27 commonly-used Chinese characters (9 characters between any two punctuations) and 3 punctuations. There were no contextual clues between the 80 sentences selected. The characters had 13 different sizes with an increment of 0.1 log unit (e.g.1.2589) and 2.5 pt was determined as the critical threshold. Readable test for visual target was followed as (1) 29 candidates with a raw or corrected visual acuity (VA)of at least 1.0 were selected to read 80 selected sentences with the size of characters of 2.5 pt at a distance of 40 cm, (2) the time used for reading with the number of characters wrongly read was recorded, (3) 39 sentences were selected as visual targets based on reading speed, effective reading position and total number of character strokes, (4) The 39 selected sentences were then randomly divided into 3 groups with no significant difference among the groups in the 3 factors listed at (3) with paired t-test. This reading visual chart was at level of Grade 3 primary school with a total stroke number of 165-210(Mean 185 ± 10), 13 font sizes a 0.1 log unit increment, a song pattern and 2.5 pt as the critical threshold. All candidates achieved 100% correct in reading test under 2.5 pt with an effective reading speed as 120.65-162 wpm (Mean 142.93 ± 11.80) and effective reading position as 36.03-61.48(Mean 48.85 ± 6.81). The reading test for the 3 groups of sentences showed effective reading speed as (142.49 ± 12.14) wpm,(142.86 ± 12.55) wpm and (143.44 ± 11.63) wpm respectively(t1-2 = -0.899, t2-3 = -1.295, t1-3 = -1.435). The reading position was 48.55 ± 6.69, 48.99 ± 7.49 and 49.00 ± 6.76, respectively(t1-2 = -1.019, t2-3 = -0.019, t1-3 = -0.816). The total number of character strokes was 185.54 ± 7.55, 187.69 ± 13.76 and 182.62 ± 8.17, respectively(t1-2 = 0.191, t2-3 = 1.385, t1-3 = 1.686). A practical design of the Chinese reading visual chart should consider size, increment, legibility in selection of reading sentences. Reading visual acuity, critical threshold and effective reading speed could be used to express the reading visual function.

  6. Program for the medical examination (consultation) of cosmonauts

    NASA Technical Reports Server (NTRS)

    1980-01-01

    The medical selection process used to screen cosmonaut candidates is outlined. The various stages of selection are discussed, and the specific types of medical examinations are described. Various criteria used for selection are presented.

  7. Discriminative exemplar coding for sign language recognition with Kinect.

    PubMed

    Sun, Chao; Zhang, Tianzhu; Bao, Bing-Kun; Xu, Changsheng; Mei, Tao

    2013-10-01

    Sign language recognition is a growing research area in the field of computer vision. A challenge within it is to model various signs, varying with time resolution, visual manual appearance, and so on. In this paper, we propose a discriminative exemplar coding (DEC) approach, as well as utilizing Kinect sensor, to model various signs. The proposed DEC method can be summarized as three steps. First, a quantity of class-specific candidate exemplars are learned from sign language videos in each sign category by considering their discrimination. Then, every video of all signs is described as a set of similarities between frames within it and the candidate exemplars. Instead of simply using a heuristic distance measure, the similarities are decided by a set of exemplar-based classifiers through the multiple instance learning, in which a positive (or negative) video is treated as a positive (or negative) bag and those frames similar to the given exemplar in Euclidean space as instances. Finally, we formulate the selection of the most discriminative exemplars into a framework and simultaneously produce a sign video classifier to recognize sign. To evaluate our method, we collect an American sign language dataset, which includes approximately 2000 phrases, while each phrase is captured by Kinect sensor with color, depth, and skeleton information. Experimental results on our dataset demonstrate the feasibility and effectiveness of the proposed approach for sign language recognition.

  8. Distant clusters of galaxies in the 2XMM/SDSS footprint: follow-up observations with the LBT

    NASA Astrophysics Data System (ADS)

    Rabitz, A.; Lamer, G.; Schwope, A.; Takey, A.

    2017-11-01

    Context. Galaxy clusters at high redshift are important to test cosmological models and models for the growth of structure. They are difficult to find in wide-angle optical surveys, however, leaving dedicated follow-up of X-ray selected candidates as one promising identification route. Aims: We aim to increase the number of galaxy clusters beyond the SDSS-limit, z 0.75. Methods: We compiled a list of extended X-ray sources from the 2XMMp catalogue within the footprint of the Sloan Digital Sky Survey. Fields without optical counterpart were selected for further investigation. Deep optical imaging and follow-up spectroscopy were obtained with the Large Binocular Telescope, Arizona (LBT), of those candidates not known to the literature. Results: From initially 19 candidates, selected by visually screening X-ray images of 478 XMM-Newton observations and the corresponding SDSS images, 6 clusters were found in the literature. Imaging data through r,z filters were obtained for the remaining candidates, and 7 were chosen for multi-object (MOS) spectroscopy. Spectroscopic redshifts, optical magnitudes, and X-ray parameters (flux, temperature, and luminosity) are presented for the clusters with spectroscopic redshifts. The distant clusters studied here constitute one additional redshift bin for studies of the LX-T relation, which does not seem to evolve from high to low redshifts. Conclusions: The selection method of distant galaxy clusters presented here was highly successful. It is based solely on archival optical (SDSS) and X-ray (XMM-Newton) data. Out of 19 selected candidates, 6 of the 7 candidates selected for spectroscopic follow-up were verified as distant clusters, a further candidate is most likely a group of galaxies at z 1.21. Out of the remaining 12 candidates, 6 were known previously as galaxy clusters, one object is a likely X-ray emission from an AGN radio jet, and for 5 we see no clear evidence for them to be high-redshift galaxy clusters. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA.The LBT is an international collaboration among institutions in the United States, Italy and Germany. LBT Corporation partners are: the University of Arizona on behalf of the Arizona Board of Regents; Istituto Nazionale di Astrofisica, Italy; LBT Beteiligungsgesellschaft, Germany, representing the Max-Planck Society, The Leibniz Institute for Astrophysics Potsdam, and Heidelberg University; The Ohio State University, and The Research Corporation, on behalf of The University of Notre Dame, University of Minnesota and University of Virginia - http://www.lbto.org/for-investigators.htmlThe catalogue, similar to Table A.1, is also available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/607/A56

  9. 16 CFR 1018.16 - Membership selection.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Membership selection. 1018.16 Section 1018... Establishment of Advisory Committees § 1018.16 Membership selection. (a) Whenever new applicants are required... Candidate Evaluation Panel, using selection criteria established by the Commission, shall evaluate all...

  10. 16 CFR 1018.16 - Membership selection.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Membership selection. 1018.16 Section 1018... Establishment of Advisory Committees § 1018.16 Membership selection. (a) Whenever new applicants are required... Candidate Evaluation Panel, using selection criteria established by the Commission, shall evaluate all...

  11. 16 CFR 1018.16 - Membership selection.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Membership selection. 1018.16 Section 1018... Establishment of Advisory Committees § 1018.16 Membership selection. (a) Whenever new applicants are required... Candidate Evaluation Panel, using selection criteria established by the Commission, shall evaluate all...

  12. 16 CFR 1018.16 - Membership selection.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Membership selection. 1018.16 Section 1018... Establishment of Advisory Committees § 1018.16 Membership selection. (a) Whenever new applicants are required... Candidate Evaluation Panel, using selection criteria established by the Commission, shall evaluate all...

  13. Fusible heat sink materials - An identification of alternate candidates. [for astronaut thermoregulation in EVA portable life support systems

    NASA Technical Reports Server (NTRS)

    Selvaduray, Guna; Lomax, Curtis

    1991-01-01

    Fusible heat sinks are a possible source for thermal regulation of space suited astronauts. An extensive database search was undertaken to identify candidate materials with liquid solid transformations over the temperature range of -18 C to 5 C; and 1215 candidates were identified. Based on available data, 59 candidate materials with thermal storage capability, DeltaH values higher than that of water were identified. This paper presents the methodology utilized in the study, including the decision process used for materials selection.

  14. Teacher Behaviours Observed by Teacher Candidates throughout Their Primary and Secondary School Years

    ERIC Educational Resources Information Center

    Güven, Semra

    2015-01-01

    The aim of this study is to determine the positive/negative teacher behaviours which teacher candidates observed during their primary and secondary school years and the effects of these behaviours on themselves. The research was conducted in the spring term of 2012-2013 academic year with 88 teacher candidates (52 females and 36 males), studying…

  15. Satellite Data Transmission (SDT) requirement

    NASA Technical Reports Server (NTRS)

    Chie, C. M.; White, M.; Lindsey, W. C.

    1984-01-01

    An 85 Mb/s modem/codec to operate in a 34 MHz C-band domestic satellite transponder at a system carrier to noise power ratio of 19.5 dB is discussed. Characteristics of a satellite channel and the approach adopted for the satellite data transmission modem/codec selection are discussed. Measured data and simulation results of the existing 50 Mbps link are compared and used to verify the simulation techniques. Various modulation schemes that were screened for the SDT are discussed and the simulated performance of two prime candidates, the 8 PSK and the SMSK/2 are given. The selection process that leads to the candidate codec techniques are documented and the technology of the modem/codec candidates is assessed. Costs of the modems and codecs are estimated.

  16. 45 CFR 1217.4 - Selection procedure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Selection procedure. 1217.4 Section 1217.4 Public... VISTA VOLUNTEER LEADER § 1217.4 Selection procedure. (a) Nomination. Candidates may be nominated in... Director's review. (b) Selection. VISTA volunteer leaders will be selected by the Regional Director (or his...

  17. R. A. Fisher, Lancelot Hogben, and the ‘Competition’ for the Chair of Social Biology at the London School of Economics in 1930: Correcting the Legend

    PubMed Central

    Tabery, James; Sarkar, Sahotra

    2015-01-01

    From 1930 to 1937 Lancelot Hogben FRS occupied the Chair of Social Biology at the London School of Economics and Political Science. According to standard histories of this appointment, he and R. A. Fisher FRS both applied for the position, but Hogben was selected over Fisher. The episode has received attention in large part because of the later prominence of the two figures involved. The surviving archival records, however, tell a remarkably different story. Neither Fisher nor Hogben was ever an official candidate for the chair. Indeed, Fisher seems not to have applied for the position at all, and Hogben was approached only behind the scenes of the official search. The purpose of this paper is to correct and complete the history of this episode. PMID:26665489

  18. Quantifying Traversability of Terrain for a Mobile Robot

    NASA Technical Reports Server (NTRS)

    Howard, Ayanna; Seraji, Homayoun; Werger, Barry

    2005-01-01

    A document presents an updated discussion on a method of autonomous navigation for a robotic vehicle navigating across rough terrain. The method involves, among other things, the use of a measure of traversability, denoted the fuzzy traversability index, which embodies the information about the slope and roughness of terrain obtained from analysis of images acquired by cameras mounted on the robot. The improvements presented in the report focus on the use of the fuzzy traversability index to generate a traversability map and a grid map for planning the safest path for the robot. Once grid traversability values have been computed, they are utilized for rejecting unsafe path segments and for computing a traversalcost function for ranking candidate paths, selected by a search algorithm, from a specified initial position to a specified final position. The output of the algorithm is a set of waypoints designating a path having a minimal-traversal cost.

  19. Automatic Summarization as a Combinatorial Optimization Problem

    NASA Astrophysics Data System (ADS)

    Hirao, Tsutomu; Suzuki, Jun; Isozaki, Hideki

    We derived the oracle summary with the highest ROUGE score that can be achieved by integrating sentence extraction with sentence compression from the reference abstract. The analysis results of the oracle revealed that summarization systems have to assign an appropriate compression rate for each sentence in the document. In accordance with this observation, this paper proposes a summarization method as a combinatorial optimization: selecting the set of sentences that maximize the sum of the sentence scores from the pool which consists of the sentences with various compression rates, subject to length constrains. The score of the sentence is defined by its compression rate, content words and positional information. The parameters for the compression rates and positional information are optimized by minimizing the loss between score of oracles and that of candidates. The results obtained from TSC-2 corpus showed that our method outperformed the previous systems with statistical significance.

  20. A feasibility study of orbiter flight control experiments

    NASA Technical Reports Server (NTRS)

    Geissler, W. H.

    1978-01-01

    The results of a feasibility study of orbiter flight control experiments performed are summarized. Feasibility studies were performed on a group of 14 experiments selected from a candidate list of 35 submitted to the study contractor by the flight control community. Concepts and requirements were developed for the 14 selected experiments and they were ranked on a basis of technical value, feasibility, and cost. It was concluded that all the selected experiments can be considered as potential candidates for the Orbiter Experiment program, which is being formulated for the Orbiter Flight Tests and subsequent operational flights, regardless of the relative ranking established during the study. None of the selected experiments has significant safety implications and the cost of most was estimated to be less than $200K.

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