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Sample records for positive selection acting

  1. Population genetic evidence for positive and purifying selection acting at the human IFN-γ locus in Africa.

    Science.gov (United States)

    Campbell, Michael C; Smith, Lunden T; Harvey, Jayla

    2018-03-29

    Despite its critical role in the defense against microbial infection and tumor development, little is known about the range of nucleotide and haplotype variation at IFN-γ, or the evolutionary forces that have shaped patterns of diversity at this locus. To address this gap in knowledge, we examined sequence data from the IFN-γ gene in 1461 individuals from 15 worldwide populations. Our analyses uncovered novel patterns of variation in distinct African populations, including an excess of high frequency-derived alleles, unusually long haplotype structure surrounding the IFN-γ gene, and a "star-like" genealogy of African-specific haplotypes carrying variants previously associated with infectious disease. We also inferred a deep time to coalescence of variation at IFN-γ (~ 0.8 million years ago) and ancient ages for common polymorphisms predating the evolution of modern humans. Taken together, these results are congruent with a model of positive selection on standing variation in African populations. Furthermore, we inferred that common variants in intron 3 of IFN-γ are the likely targets of selection. In addition, we observed a paucity of non-synonymous substitutions relative to synonymous changes in the exons of IFN-γ in African and non-African populations, suggestive of strong purifying selection. Therefore, we contend that positive and purifying selection have influenced levels of diversity in different regions of IFN-γ, implying that these distinct genic regions are, or have been, functionally important. Overall, this study provides additional insights into the evolutionary events that have contributed to the frequency and distribution of alleles having a role in human health and disease.

  2. Genes under positive selection in Escherichia coli

    DEFF Research Database (Denmark)

    Petersen, Lise; Bollback, Jonathan P; Dimmic, Matt

    2007-01-01

    We used a comparative genomics approach to identify genes that are under positive selection in six strains of Escherichia coli and Shigella flexneri, including five strains that are human pathogens. We find that positive selection targets a wide range of different functions in the E. coli genome......, including cell surface proteins such as beta barrel porins, presumably because of the involvement of these genes in evolutionary arms races with other bacteria, phages, and/or the host immune system. Structural mapping of positively selected sites on trans-membrane beta barrel porins reveals...... that the residues under positive selection occur almost exclusively in the extracellular region of the proteins that are enriched with sites known to be targets of phages, colicins, or the host immune system. More surprisingly, we also find a number of other categories of genes that show very strong evidence...

  3. Positive selection on the killer whale mitogenome

    DEFF Research Database (Denmark)

    Foote, Andrew David; Morin, Phillip A.; Durban, John W.

    2011-01-01

    Mitochondria produce up to 95 per cent of the eukaryotic cell's energy. The coding genes of the mitochondrial DNA may therefore evolve under selection owing to metabolic requirements. The killer whale, Orcinus orca, is polymorphic, has a global distribution and occupies a range of ecological niches....... It is therefore a suitable organism for testing this hypothesis. We compared a global dataset of the complete mitochondrial genomes of 139 individuals for amino acid changes that were associated with radical physico-chemical property changes and were influenced by positive selection. Two such selected non...

  4. Positively selected sites in cetacean myoglobins contribute to protein stability

    DEFF Research Database (Denmark)

    Dasmeh, Pouria; Serohijos, Adrian W R; Kepp, Kasper P

    2013-01-01

    Since divergence ∼50 Ma ago from their terrestrial ancestors, cetaceans underwent a series of adaptations such as a ∼10-20 fold increase in myoglobin (Mb) concentration in skeletal muscle, critical for increasing oxygen storage capacity and prolonging dive time. Whereas the O2-binding affinity...... between Mb folding stability and protein abundance, suggesting that a selection pressure for stability acts proportionally to higher expression. We also identify a major divergence event leading to the common ancestor of whales, during which major stabilization occurred. Most of the positively selected...

  5. The Animal Welfare Act and the zoo: A positive approach

    Science.gov (United States)

    Olsen, Glenn H.

    1989-01-01

    Interpretations of the Animal Welfare Act and other regulations governing use of research animals in the United States are changing. Recent amendments to the Act have resulted in the inclusion of more species under the umbrella of regulation. The role of the zoo and wildlife veterinarian should be that of leading his or her institution into a positive endorsement of these regulations and their application. Recent additions to the Code of Federal Regulations spell out the roles of the veterinarian and the Animal Care and Use Committee at an institution.

  6. Positive Selection Linked with Generation of Novel Mammalian Dentition Patterns.

    Science.gov (United States)

    Machado, João Paulo; Philip, Siby; Maldonado, Emanuel; O'Brien, Stephen J; Johnson, Warren E; Antunes, Agostinho

    2016-09-11

    A diverse group of genes are involved in the tooth development of mammals. Several studies, focused mainly on mice and rats, have provided a detailed depiction of the processes coordinating tooth formation and shape. Here we surveyed 236 tooth-associated genes in 39 mammalian genomes and tested for signatures of selection to assess patterns of molecular adaptation in genes regulating mammalian dentition. Of the 236 genes, 31 (∼13.1%) showed strong signatures of positive selection that may be responsible for the phenotypic diversity observed in mammalian dentition. Mammalian-specific tooth-associated genes had accelerated mutation rates compared with older genes found across all vertebrates. More recently evolved genes had fewer interactions (either genetic or physical), were associated with fewer Gene Ontology terms and had faster evolutionary rates compared with older genes. The introns of these positively selected genes also exhibited accelerated evolutionary rates, which may reflect additional adaptive pressure in the intronic regions that are associated with regulatory processes that influence tooth-gene networks. The positively selected genes were mainly involved in processes like mineralization and structural organization of tooth specific tissues such as enamel and dentin. Of the 236 analyzed genes, 12 mammalian-specific genes (younger genes) provided insights on diversification of mammalian teeth as they have higher evolutionary rates and exhibit different expression profiles compared with older genes. Our results suggest that the evolution and development of mammalian dentition occurred in part through positive selection acting on genes that previously had other functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Physicochemical evolution and positive selection of the ...

    Indian Academy of Sciences (India)

    2010-04-08

    Apr 8, 2010 ... It is not clear whether matK evolves under Darwinian selection. In this study, the gymnosperm Taxaceae, Cephalotaxaceae and Pinaceae were used to illustrate the physicochemical evolution, molecular adaptation and evolutionary dynamics of gene divergence in matKs. matK sequences were amplified ...

  8. Jasmonates act positively in adventitious root formation in petunia cuttings.

    Science.gov (United States)

    Lischweski, Sandra; Muchow, Anne; Guthörl, Daniela; Hause, Bettina

    2015-09-22

    Petunia is a model to study the process of adventitious root (AR) formation on leafy cuttings. Excision of cuttings leads to a transient increase in jasmonates, which is regarded as an early, transient and critical event for rooting. Here, the role of jasmonates in AR formation on petunia cuttings has been studied by a reverse genetic approach. To reduce the endogenous levels of jasmonates, transgenic plants were generated expressing a Petunia hybrida ALLENE OXIDE CYCLASE (PhAOC)-RNAi construct. The transgenic plants exhibited strongly reduced PhAOC transcript and protein levels as well as diminished accumulation of cis-12-oxo-phytodienoic acid, jasmonic acid and jasmonoyl-isoleucine after wounding in comparison to wild type and empty vector expressing plants. Reduced levels of endogenous jasmonates resulted in formation of lower numbers of ARs. However, this effect was not accompanied by altered levels of auxin and aminocyclopropane carboxylate (ACC, precursor of ethylene) or by impaired auxin and ethylene-induced gene expression. Neither activity of cell-wall invertases nor accumulation of soluble sugars was altered by jasmonate deficiency. Diminished numbers of AR in JA-deficient cuttings suggest that jasmonates act as positive regulators of AR formation in petunia wild type. However, wound-induced rise in jasmonate levels in petunia wild type cuttings seems not to be causal for increased auxin and ethylene levels and for sink establishment.

  9. Directional Positive Selection on an Allele of Arbitrary Dominance

    OpenAIRE

    Teshima, Kosuke M.; Przeworski, Molly

    2006-01-01

    Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.

  10. Position paper - peer review and design verification of selected activities

    International Nuclear Information System (INIS)

    Stine, M.D.

    1994-09-01

    Position Paper to develop and document a position on the performance of independent peer reviews on selected design and analysis components of the Title I (preliminary) and Title II (detailed) design phases of the Multi-Function Waste Tank Facility project

  11. Selective control of attention supports the positivity effect in aging.

    Directory of Open Access Journals (Sweden)

    Laura K Sasse

    Full Text Available There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

  12. Selective control of attention supports the positivity effect in aging.

    Science.gov (United States)

    Sasse, Laura K; Gamer, Matthias; Büchel, Christian; Brassen, Stefanie

    2014-01-01

    There is emerging evidence for a positivity effect in healthy aging, which describes an age-specific increased focus on positive compared to negative information. Life-span researchers have attributed this effect to the selective allocation of cognitive resources in the service of prioritized emotional goals. We explored the basic principles of this assumption by assessing selective attention and memory for visual stimuli, differing in emotional content and self-relevance, in young and old participants. To specifically address the impact of cognitive control, voluntary attentional selection during the presentation of multiple-item displays was analyzed and linked to participants' general ability of cognitive control. Results revealed a positivity effect in older adults' selective attention and memory, which was particularly pronounced for self-relevant stimuli. Focusing on positive and ignoring negative information was most evident in older participants with a generally higher ability to exert top-down control during visual search. Our findings highlight the role of controlled selectivity in the occurrence of a positivity effect in aging. Since the effect has been related to well-being in later life, we suggest that the ability to selectively allocate top-down control might represent a resilience factor for emotional health in aging.

  13. Positive Selection and Centrality in the Yeast and Fly Protein-Protein Interaction Networks

    Directory of Open Access Journals (Sweden)

    Sandip Chakraborty

    2016-01-01

    Full Text Available Proteins within a molecular network are expected to be subject to different selective pressures depending on their relative hierarchical positions. However, it is not obvious what genes within a network should be more likely to evolve under positive selection. On one hand, only mutations at genes with a relatively high degree of control over adaptive phenotypes (such as those encoding highly connected proteins are expected to be “seen” by natural selection. On the other hand, a high degree of pleiotropy at these genes is expected to hinder adaptation. Previous analyses of the human protein-protein interaction network have shown that genes under long-term, recurrent positive selection (as inferred from interspecific comparisons tend to act at the periphery of the network. It is unknown, however, whether these trends apply to other organisms. Here, we show that long-term positive selection has preferentially targeted the periphery of the yeast interactome. Conversely, in flies, genes under positive selection encode significantly more connected and central proteins. These observations are not due to covariation of genes’ adaptability and centrality with confounding factors. Therefore, the distribution of proteins encoded by genes under recurrent positive selection across protein-protein interaction networks varies from one species to another.

  14. A map of recent positive selection in the human genome.

    Directory of Open Access Journals (Sweden)

    Benjamin F Voight

    2006-03-01

    Full Text Available The identification of signals of very recent positive selection provides information about the adaptation of modern humans to local conditions. We report here on a genome-wide scan for signals of very recent positive selection in favor of variants that have not yet reached fixation. We describe a new analytical method for scanning single nucleotide polymorphism (SNP data for signals of recent selection, and apply this to data from the International HapMap Project. In all three continental groups we find widespread signals of recent positive selection. Most signals are region-specific, though a significant excess are shared across groups. Contrary to some earlier low resolution studies that suggested a paucity of recent selection in sub-Saharan Africans, we find that by some measures our strongest signals of selection are from the Yoruba population. Finally, since these signals indicate the existence of genetic variants that have substantially different fitnesses, they must indicate loci that are the source of significant phenotypic variation. Though the relevant phenotypes are generally not known, such loci should be of particular interest in mapping studies of complex traits. For this purpose we have developed a set of SNPs that can be used to tag the strongest approximately 250 signals of recent selection in each population.

  15. Patterns of positive selection in six Mammalian genomes

    DEFF Research Database (Denmark)

    Kosiol, Carolin; Vinar, Tomás; da Fonseca, Rute R

    2008-01-01

    Genome-wide scans for positively selected genes (PSGs) in mammals have provided insight into the dynamics of genome evolution, the genetic basis of differences between species, and the functions of individual genes. However, previous scans have been limited in power and accuracy owing to small...... several new lineage- and clade-specific tests to be applied. Of approximately 16,500 human genes with high-confidence orthologs in at least two other species, 400 genes showed significant evidence of positive selection (FDR... showed evidence of positive selection on particular lineages or clades. As in previous studies, the identified PSGs were enriched for roles in defense/immunity, chemosensory perception, and reproduction, but enrichments were also evident for more specific functions, such as complement-mediated immunity...

  16. Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

    LENUS (Irish Health Repository)

    Li, Wenfu

    2011-04-21

    Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

  17. The signature of positive selection at randomly chosen loci.

    OpenAIRE

    Przeworski, Molly

    2002-01-01

    In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequ...

  18. The multilevel analysis of surface acting and mental health: A moderation of positive group affective tone

    Science.gov (United States)

    Lee, Meng-Shiu; Huang, Jui-Chan; Wu, Tzu-Jung

    2017-06-01

    The purpose of this study is to investigate the relationship among surface acting, mental health, and positive group affective tone. According to the prior theory, this study attempts to establish a comprehensive research framework among these variables, and furthermore tests the moderating effect of positive group affective tone. Data were collected from 435 employees in 52 service industrial companies by questionnaire, and this study conducted multilevel analysis. The results showed that surface acting will negatively affect the mental health. In addition, the positive group affective tone have significant moderating effect on the relationship among surface acting and mental health. Finally, this study discusses managerial implications and highlights future research suggestions.

  19. Signatures of positive selection: from selective sweeps at individual loci to subtle allele frequency changes in polygenic adaptation.

    Science.gov (United States)

    Stephan, Wolfgang

    2016-01-01

    In the past 15 years, numerous methods have been developed to detect selective sweeps underlying adaptations. These methods are based on relatively simple population genetic models, including one or two loci at which positive directional selection occurs, and one or two marker loci at which the impact of selection on linked neutral variation is quantified. Information about the phenotype under selection is not included in these models (except for fitness). In contrast, in the quantitative genetic models of adaptation, selection acts on one or more phenotypic traits, such that a genotype-phenotype map is required to bridge the gap to population genetics theory. Here I describe the range of population genetic models from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and I also consider the case of polygenic selection characterized by subtle allele frequency shifts at many loci. Furthermore, I present an overview of the statistical tests that have been proposed based on these population genetics models to detect evidence for positive selection in the genome. © 2015 John Wiley & Sons Ltd.

  20. The location selection act or 'the Emperor's new clothes'

    International Nuclear Information System (INIS)

    Feldmann, Ulrike

    2013-01-01

    As is generally known, the governing parties CDU/CSU and FDP agreed a few weeks ago in the 17 th legislative period of the German Bundestag in a rare show of unanimity, together with the parties SPD and Buendnis 90/Die Gruenen, as well as with the Laender, on a 'law to search and select a location for a permanent disposal site for heat-generating radioactive waste products and to change other laws', in brief a location selection act also called StandAG. The law was received with animated approval from the ranks of the parties - with the exception of the (left-wing) party Die Linke. This praise is a tad bewildering, since the Bundesumweltministerium (Federal Department of the Environment) named solving the task within a single generation as one of the principles for the StandAG, and it was emphasised again and again in the debates about the StandAG that the problem of permanent disposal must not be shifted to the next generation. Conclusion: - The StandAG leads to a postponement of solving the permanent disposal site issue by a least several generations with its predictable, long-winded selection method. - The decision not to explore Gorleben conclusively could lead to the site being permanently ('wasted' or) 'burned'. - The de-central, interim disposal site Gorleben is likewise 'burned' without having a resilient alternative solution for the glass coquilles that must be taken back. - The people's protest is exponentiated by the number of the potential sites for the StandAG. - The costs for the alternative site search will not be shifted to the producers of the waste that are obliged by law to deliver the waste because of the financial provisions of the constitution. - The third party protection dogma has not been broken up, which will at least lead to delays in the procedure and will have effects on other major projects in the long run. (orig.)

  1. A Demonstration of Regression False Positive Selection in Data Mining

    Science.gov (United States)

    Pinder, Jonathan P.

    2014-01-01

    Business analytics courses, such as marketing research, data mining, forecasting, and advanced financial modeling, have substantial predictive modeling components. The predictive modeling in these courses requires students to estimate and test many linear regressions. As a result, false positive variable selection ("type I errors") is…

  2. Evidence for Very Recent Positive Selection in Mongolians.

    Science.gov (United States)

    Nakayama, Kazuhiro; Ohashi, Jun; Watanabe, Kazuhisa; Munkhtulga, Lkagvasuren; Iwamoto, Sadahiko

    2017-08-01

    Mongols, the founders of the largest continental empire in history, successfully adapted to the harsh environments of Inner Asia through nomadic pastoralism. Considerable interest exists in ascertaining whether genetic adaptation also contributed to the Mongols' success, and dissecting the genome diversity of present-day populations in Mongolia can help address this question. To this end, we determined the genotypes of nearly 2.4 million single nucleotide polymorphisms (SNPs) of 96 unrelated Mongolian individuals in Ulaanbaatar city, and performed genome-wide scans for population-specific positive selection. We discovered signatures of Mongolian-specific positive selection at the chromosomal region 3p12.1, in which hits in genome-wide association studies were reported for medical and biological traits related to energy metabolism and reproduction. The top SNP, rs117799927, showed a distinctive geographic distribution: the frequency of the derived allele, rs117799927 G, was extremely low among worldwide populations (0.005) but exceptionally high in Mongolians (0.247). Approximate Bayesian computation-based age estimation showed that the rs117799927 G allele emerged or positive selection began to operate 50 generations before the present, near the age of the climate anomaly named Late Antique Little Ice Age. Furthermore, rs117799927 showed significant associations with multiple adiposity-related traits in Mongolians and allelic difference in enhancer activity in cells of adipocyte lineage, suggesting that positive selection at 3p12.1 might be related to adaptation in the energy metabolism system. These findings provide novel evidence for a very recent positive-selection event in Homo sapiens and offer insights into the roles of genes in 3p12.1 in the adaptive evolution of our species. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Evaluation of an Improved Branch-Site Likelihood Method for Detecting Positive Selection at the Molecular Level

    DEFF Research Database (Denmark)

    Zhang, Jianzhi; Nielsen, Rasmus; Yang, Ziheng

    2005-01-01

    of interest, while test 2 had acceptable false-positive rates and appeared robust against violations of model assumptions. As test 2 is a direct test of positive selection on the lineages of interest, it is referred to as the branch-site test of positive selection and is recommended for use in real data......Detecting positive Darwinian selection at the DNA sequence level has been a subject of considerable interest. However, positive selection is difficult to detect because it often operates episodically on a few amino acid sites, and the signal may be masked by negative selection. Several methods have...... been developed to test positive selection that acts on given branches (branch methods) or on a subset of sites (site methods). Recently, Yang, Z., and R. Nielsen (2002. Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol. Biol. Evol. 19...

  4. Positive selection for unpreferred codon usage in eukaryotic genomes

    Directory of Open Access Journals (Sweden)

    Galagan James E

    2007-07-01

    Full Text Available Abstract Background Natural selection has traditionally been understood as a force responsible for pushing genes to states of higher translational efficiency, whereas lower translational efficiency has been explained by neutral mutation and genetic drift. We looked for evidence of directional selection resulting in increased unpreferred codon usage (and presumably reduced translational efficiency in three divergent clusters of eukaryotic genomes using a simple optimal-codon-based metric (Kp/Ku. Results Here we show that for some genes natural selection is indeed responsible for causing accelerated unpreferred codon substitution, and document the scope of this selection. In Cryptococcus and to a lesser extent Drosophila, we find many genes showing a statistically significant signal of selection for unpreferred codon usage in one or more lineages. We did not find evidence for this type of selection in Saccharomyces. The signal of positive selection observed from unpreferred synonymous codon substitutions is coincident in Cryptococcus and Drosophila with the distribution of upstream open reading frames (uORFs, another genic feature known to reduce translational efficiency. Functional enrichment analysis of genes exhibiting low Kp/Ku ratios reveals that genes in regulatory roles are particularly subject to this type of selection. Conclusion Through genome-wide scans, we find recent selection for unpreferred codon usage at approximately 1% of genetic loci in a Cryptococcus and several genes in Drosophila. Unpreferred codons can impede translation efficiency, and we find that genes with translation-impeding uORFs are enriched for this selection signal. We find that regulatory genes are particularly likely to be subject to selection for unpreferred codon usage. Given that expression noise can propagate through regulatory cascades, and that low translational efficiency can reduce expression noise, this finding supports the hypothesis that translational

  5. 76 FR 26948 - Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting

    Science.gov (United States)

    2011-05-10

    ...] Small Business Jobs Act Tour: Selected Provisions Having an Effect on Government Contracting AGENCY: U.S... INFORMATION CONTACT: Richard L. Miller, Small Business Job's Act Tour-Office of Government Contracting and..., concerning the Small Business Act Tour: Selected Provisions Having an Effect on Government that announced a...

  6. Telling tails: selective pressures acting on investment in lizard tails.

    Science.gov (United States)

    Fleming, Patricia A; Valentine, Leonie E; Bateman, Philip W

    2013-01-01

    Caudal autotomy is a common defense mechanism in lizards, where the animal may lose part or all of its tail to escape entrapment. Lizards show an immense variety in the degree of investment in a tail (i.e., length) across species, with tails of some species up to three or four times body length (snout-vent length [SVL]). Additionally, body size and form also vary dramatically, including variation in leg development and robustness and length of the body and tail. Autotomy is therefore likely to have fundamentally different effects on the overall body form and function in different species, which may be reflected directly in the incidence of lost/regenerating tails within populations or, over a longer period, in terms of relative tail length for different species. We recorded data (literature, museum specimens, field data) for relative tail length (n=350 species) and the incidence of lost/regenerating tails (n=246 species). We compared these (taking phylogeny into account) with intrinsic factors that have been proposed to influence selective pressures acting on caudal autotomy, including body form (robustness, body length, leg development, and tail specialization) and ecology (foraging behavior, physical and temporal niches), in an attempt to identify patterns that might reflect adaptive responses to these different factors. More gracile species have relatively longer tails (all 350 spp., P lost/regenerating tails for nocturnal lizards (all 246 spp., P pressure.

  7. Positive Selection on Loci Associated with Drug and Alcohol Dependence.

    Directory of Open Access Journals (Sweden)

    Brooke Sadler

    Full Text Available Much of the evolution of human behavior remains a mystery, including how certain disadvantageous behaviors are so prevalent. Nicotine addiction is one such phenotype. Several loci have been implicated in nicotine related phenotypes including the nicotinic receptor gene clusters (CHRNs on chromosomes 8 and 15. Here we use 1000 Genomes sequence data from 3 populations (Africans, Asians and Europeans to examine whether natural selection has occurred at these loci. We used Tajima's D and the integrated haplotype score (iHS to test for evidence of natural selection. Our results provide evidence for strong selection in the nicotinic receptor gene cluster on chromosome 8, previously found to be significantly associated with both nicotine and cocaine dependence, as well as evidence selection acting on the region containing the CHRNA5 nicotinic receptor gene on chromosome 15, that is genome wide significant for risk for nicotine dependence. To examine the possibility that this selection is related to memory and learning, we utilized genetic data from the Collaborative Studies on the Genetics of Alcoholism (COGA to test variants within these regions with three tests of memory and learning, the Wechsler Adult Intelligence Scale (WAIS Block Design, WAIS Digit Symbol and WAIS Information tests. Of the 17 SNPs genotyped in COGA in this region, we find one significantly associated with WAIS digit symbol test results. This test captures aspects of reaction time and memory, suggesting that a phenotype relating to memory and learning may have been the driving force behind selection at these loci. This study could begin to explain why these seemingly deleterious SNPs are present at their current frequencies.

  8. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  9. The signature of positive selection at randomly chosen loci.

    Science.gov (United States)

    Przeworski, Molly

    2002-03-01

    In Drosophila and humans, there are accumulating examples of loci with a significant excess of high-frequency-derived alleles or high levels of linkage disequilibrium, relative to a neutral model of a random-mating population of constant size. These are features expected after a recent selective sweep. Their prevalence suggests that positive directional selection may be widespread in both species. However, as I show here, these features do not persist long after the sweep ends: The high-frequency alleles drift to fixation and no longer contribute to polymorphism, while linkage disequilibrium is broken down by recombination. As a result, loci chosen without independent evidence of recent selection are not expected to exhibit either of these features, even if they have been affected by numerous sweeps in their genealogical history. How then can we explain the patterns in the data? One possibility is population structure, with unequal sampling from different subpopulations. Alternatively, positive selection may not operate as is commonly modeled. In particular, the rate of fixation of advantageous mutations may have increased in the recent past.

  10. Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies.

    Science.gov (United States)

    Fetterman, Christina D; Rannala, Bruce; Walter, Michael A

    2008-09-24

    Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. Consideration of selection pressures observed in conjunction with known functional information allowed prediction of residue function and

  11. Identification and analysis of evolutionary selection pressures acting at the molecular level in five forkhead subfamilies

    Directory of Open Access Journals (Sweden)

    Rannala Bruce

    2008-09-01

    Full Text Available Abstract Background Members of the forkhead gene family act as transcription regulators in biological processes including development and metabolism. The evolution of forkhead genes has not been widely examined and selection pressures at the molecular level influencing subfamily evolution and differentiation have not been explored. Here, in silico methods were used to examine selection pressures acting on the coding sequence of five multi-species FOX protein subfamily clusters; FoxA, FoxD, FoxI, FoxO and FoxP. Results Application of site models, which estimate overall selection pressures on individual codons throughout the phylogeny, showed that the amino acid changes observed were either neutral or under negative selection. Branch-site models, which allow estimated selection pressures along specified lineages to vary as compared to the remaining phylogeny, identified positive selection along branches leading to the FoxA3 and Protostomia clades in the FoxA cluster and the branch leading to the FoxO3 clade in the FoxO cluster. Residues that may differentiate paralogs were identified in the FoxA and FoxO clusters and residues that differentiate orthologs were identified in the FoxA cluster. Neutral amino acid changes were identified in the forkhead domain of the FoxA, FoxD and FoxP clusters while positive selection was identified in the forkhead domain of the Protostomia lineage of the FoxA cluster. A series of residues under strong negative selection adjacent to the N- and C-termini of the forkhead domain were identified in all clusters analyzed suggesting a new method for refinement of domain boundaries. Extrapolation of domains among cluster members in conjunction with selection pressure information allowed prediction of residue function in the FoxA, FoxO and FoxP clusters and exclusion of known domain function in residues of the FoxA and FoxI clusters. Conclusion Consideration of selection pressures observed in conjunction with known

  12. A genome scan for positive selection in thoroughbred horses.

    Science.gov (United States)

    Gu, Jingjing; Orr, Nick; Park, Stephen D; Katz, Lisa M; Sulimova, Galina; MacHugh, David E; Hill, Emmeline W

    2009-06-02

    Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1) deviations from expected heterozygosity (Ewens-Watterson test) in Thoroughbred (n = 112) and (2) global differentiation among four geographically diverse horse populations (F(ST)). We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; PThoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1), ACTA1 (actin, alpha 1, skeletal muscle), ACTN2 (actinin, alpha 2), ADHFE1 (alcohol dehydrogenase, iron containing, 1), MTFR1 (mitochondrial fission regulator 1), PDK4 (pyruvate dehydrogenase kinase, isozyme 4) and TNC (tenascin C). Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes within the complex molecular networks underlying obesity and its consequential pathologies, such as type 2 diabetes. Therefore, we propose Thoroughbred as a novel in vivo large animal model for understanding molecular protection against metabolic disease.

  13. America COMPETES Act: Programs, Funding, and Selected Issues

    National Research Council Canada - National Science Library

    Stine, Deborah D

    2008-01-01

    .... The act responds to concerns that the United States may not be able to compete economically with other nations in the future due to insufficient investment today in science and technology research...

  14. Positive selection on a bacterial oncoprotein associated with gastric cancer

    Directory of Open Access Journals (Sweden)

    Delgado-Rosado Gisela

    2011-11-01

    Full Text Available Background Helicobacter pylori is a vertically inherited gut commensal that is carcinogenic if it possesses the cag pathogenicity island (cag PaI; infection with H.pylori is the major risk factor for gastric cancer, the second leading cause of death from cancer worldwide (WHO. The cag PaI locus encodes the cagA gene, whose protein product is injected into stomach epithelial cells via a Type IV secretion system, also encoded by the cag PaI. Once there, the cagA protein binds to various cellular proteins, resulting in dysregulation of cell division and carcinogenesis. For this reason, cagA may be described as an oncoprotein. A clear understanding of the mechanism of action of cagA and its benefit to the bacteria is lacking. Results Here, we reveal that the cagA gene displays strong signatures of positive selection in bacteria isolated from amerindian populations, using the Ka/Ks ratio. Weaker signatures are also detected in the gene from bacteria isolated from asian populations, using the Ka/Ks ratio and the more sensitive branches-sites model of the PAML package. When the cagA gene isolated from amerindian populations was examined in more detail it was found that the region under positive selection contains the EPIYA domains, which are known to modulate the carcinogenicity of the gene. This means that the carcinogenicity modulating region of the gene is undergoing adaptation. The results are discussed in relation to the high incidences of stomach cancer in some latin american and asian populations. Conclusion Positive selection on cagA indicates antagonistic coevolution between host and bacteria, which appears paradoxical given that cagA is detrimental to the human host upon which the bacteria depends. This suggests several non-exclusive possibilities; that gastric cancer has not been a major selective pressure on human populations, that cagA has an undetermined benefit to the human host, or that horizontal transmission of H.pylori between hosts

  15. A genome scan for positive selection in thoroughbred horses.

    Directory of Open Access Journals (Sweden)

    Jingjing Gu

    2009-06-01

    Full Text Available Thoroughbred horses have been selected for exceptional racing performance resulting in system-wide structural and functional adaptations contributing to elite athletic phenotypes. Because selection has been recent and intense in a closed population that stems from a small number of founder animals Thoroughbreds represent a unique population within which to identify genomic contributions to exercise-related traits. Employing a population genetics-based hitchhiking mapping approach we performed a genome scan using 394 autosomal and X chromosome microsatellite loci and identified positively selected loci in the extreme tail-ends of the empirical distributions for (1 deviations from expected heterozygosity (Ewens-Watterson test in Thoroughbred (n = 112 and (2 global differentiation among four geographically diverse horse populations (F(ST. We found positively selected genomic regions in Thoroughbred enriched for phosphoinositide-mediated signalling (3.2-fold enrichment; P<0.01, insulin receptor signalling (5.0-fold enrichment; P<0.01 and lipid transport (2.2-fold enrichment; P<0.05 genes. We found a significant overrepresentation of sarcoglycan complex (11.1-fold enrichment; P<0.05 and focal adhesion pathway (1.9-fold enrichment; P<0.01 genes highlighting the role for muscle strength and integrity in the Thoroughbred athletic phenotype. We report for the first time candidate athletic-performance genes within regions targeted by selection in Thoroughbred horses that are principally responsible for fatty acid oxidation, increased insulin sensitivity and muscle strength: ACSS1 (acyl-CoA synthetase short-chain family member 1, ACTA1 (actin, alpha 1, skeletal muscle, ACTN2 (actinin, alpha 2, ADHFE1 (alcohol dehydrogenase, iron containing, 1, MTFR1 (mitochondrial fission regulator 1, PDK4 (pyruvate dehydrogenase kinase, isozyme 4 and TNC (tenascin C. Understanding the genetic basis for exercise adaptation will be crucial for the identification of genes

  16. Positive allometry and the prehistory of sexual selection.

    Science.gov (United States)

    Tomkins, Joseph L; LeBas, Natasha R; Witton, Mark P; Martill, David M; Humphries, Stuart

    2010-08-01

    The function of the exaggerated structures that adorn many fossil vertebrates remains largely unresolved. One recurrent hypothesis is that these elaborated traits had a role in thermoregulation. This orthodoxy persists despite the observation that traits exaggerated to the point of impracticality in extant organisms are almost invariably sexually selected. We use allometric scaling to investigate the role of sexual selection and thermoregulation in the evolution of exaggerated traits of the crested pterosaur Pteranodon longiceps and the sail-backed eupelycosaurs Dimetrodon and Edaphosaurus. The extraordinarily steep positive allometry of the head crest of Pteranodon rules out all of the current hypotheses for this trait's main function other than sexual signaling. We also find interspecific patterns of allometry and sexual dimorphism in the sails of Dimetrodon and patterns of elaboration in Edaphosaurus consistent with a sexually selected function. Furthermore, small ancestral, sail-backed pelycosaurs would have been too small to need adaptations to thermoregulation. Our results question the popular view that the elaborated structures of these fossil species evolved as thermoregulatory organs and provide evidence in support of the hypothesis that Pteranodon crests and eupelycosaur sails are among the earliest and most extreme examples of elaborate sexual signals in the evolution of terrestrial vertebrates.

  17. The role of positive selection in hepatitis C virus.

    Science.gov (United States)

    Cuevas, José M; Gonzalez, Michael; Torres-Puente, Manuela; Jiménez-Hernández, Nuria; Bracho, María A; García-Robles, Inmaculada; González-Candelas, Fernando; Moya, Andrés

    2009-09-01

    Hepatitis C virus (HCV) is a major health problem worldwide, infecting an estimated 170 million people. In this study, we have employed a large data set of sequences (14,654 sequences from between 25 and 100 clone sequences per analyzed region and per patient) from 67 patients infected with HCV genotype 1 (23 subtype 1a and 44 subtype 1b). For all patients, a sample prior to combined therapy with alpha interferon plus ribavirin was available, whereas for some patients additional samples after 6 or 12 months of treatment were also available. Twenty-seven patients responded to treatment (12 subtype 1a and 15 subtype 1b) and forty patients did not respond to treatment (11 subtype 1a vs. 29 subtype 1b). Two regions of the HCV genome were analyzed, one compressing the hypervariable regions (HVR1, HVR2 and HVR3) of the envelope 2 glycoprotein and another one including the interferon sensitive determining region (ISDR) and the V3 domain of the NS5A protein. Previously (Cuevas, J.M., Torres-Puente, M., Jiménez-Hernández, N., Bracho, M.A., García-Robles, I., Wrobel, B., Carnicer, F., del Olmo, J., Ortega, E., Moya, A., González-Candelas, F., 2008b. Genetic variability of hepatitis C virus before and after combined therapy of interferon plus ribavirin. Plos One 3 (8), e3058), several amino acid positions in both regions analyzed were detected to be under positive selection. Here, we have compared the amino acid composition of each positively selected position between responder and non-responder patients for both subtypes. If we exclude some non-conclusive cases, no clear differences were detected in any case. In conclusion, identifying specific positions as completely discriminatory of treatment response seems to be a difficult task. Our results, in concordance with previous studies, suggest that HCV evasion strategies are more likely based on a global increased variability, which would yield combinations of mutations with an increased resistance, than on the fixation of

  18. The Patient Protection and Affordable Care Act: The Role of the School Nurse. Position Statement

    Science.gov (United States)

    Combe, Laurie G.; Sharpe, Susan; Feeser, Cynthia Jo; Ondeck, Lynnette; Fekaris, Nina

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that the registered professional school nurse (hereinafter referred to as school nurse) serves a vital role in the delivery of health care to our nation's students within the healthcare system reshaped by the Patient Protection and Affordable Care Act of 2010, commonly known as…

  19. Evidence of recombination and positive selection in cetacean papillomaviruses

    International Nuclear Information System (INIS)

    Robles-Sikisaka, Refugio; Rivera, Rebecca; Nollens, Hendrik H.; St Leger, Judy; Durden, Wendy N.; Stolen, Megan; Burchell, Jennifer; Wellehan, James F.X.

    2012-01-01

    Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.

  20. Positive-negative-selection-mediated gene targeting in rice

    Directory of Open Access Journals (Sweden)

    Zenpei eShimatani

    2015-01-01

    Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

  1. Evidence of recombination and positive selection in cetacean papillomaviruses

    Energy Technology Data Exchange (ETDEWEB)

    Robles-Sikisaka, Refugio, E-mail: refugio.robles1@gmail.com [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Rivera, Rebecca, E-mail: RRivera@hswri.org [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Nollens, Hendrik H., E-mail: Hendrik.Nollens@SeaWorld.com [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); College of Veterinary Medicine, University of Florida, PO Box 110885, Gainesville, FL 32611 (United States); SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); St Leger, Judy, E-mail: Judy.St.Leger@SeaWorld.com [SeaWorld San Diego, 500 SeaWorld Drive, San Diego, CA 92109 (United States); Durden, Wendy N., E-mail: WNoke@hswri.org [Hubbs-SeaWorld Research Institute, 3830 South Highway A1A 4-181, Melbourne Beach, FL 32951 (United States); Stolen, Megan, E-mail: MStolen@hswri.org [Hubbs-SeaWorld Research Institute, 3830 South Highway A1A 4-181, Melbourne Beach, FL 32951 (United States); Burchell, Jennifer, E-mail: JBurchell@hswri.org [Hubbs-SeaWorld Research Institute, Center for Marine Veterinary Virology, 2595 Ingraham Street, San Diego, CA 92109 (United States); Wellehan, James F.X., E-mail: WellehanJ@ufl.edu [College of Veterinary Medicine, University of Florida, PO Box 110885, Gainesville, FL 32611 (United States)

    2012-06-05

    Papillomaviruses (PVs) are small DNA viruses that have been associated with increased epithelial proliferation. Over one hundred PV types have been identified in humans; however, only three have been identified in bottlenose dolphins (Tursiops truncatus) to date. Using rolling circle amplification and degenerate PCR, we identified four novel PV genomes of bottlenose dolphins. TtPV4, TtPV5 and TtPV6 were identified in genital lesions while TtPV7 was identified in normal genital mucosa. Bayesian analysis of the full-length L1 genes found that TtPV4 and TtPV7 group within the Upsilonpapillomavirus genus while TtPV5 and TtPV6 group with Omikronpapillomavirus. However, analysis of the E1 gene did not distinguish these genera, implying that these genes may not share a common history, consistent with recombination. Recombination analyses identified several probable events. Signals of positive selection were found mostly in the E1 and E2 genes. Recombination and diversifying selection pressures constitute important driving forces of cetacean PV evolution.

  2. Selective bowel decontamination results in gram-positive translocation.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Rowe, M I

    1990-05-01

    Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

  3. FY2017 National Defense Authorization Act: Selected Military Personnel Issues

    Science.gov (United States)

    2017-01-23

    Service ........................................................................................................................... 28 *Military Sexual ...Assault and Sexual Harassment ......................................................................... 29 Child Abuse and Domestic Violence...requires most males between the ages of 18 and 26 who are citizens or residents of the United States to register with Selective Service. Women in the

  4. Evidence of Positive Selection of Aquaporins Genes from Pontoporia blainvillei during the Evolutionary Process of Cetaceans.

    Directory of Open Access Journals (Sweden)

    Simone Lima São Pedro

    Full Text Available Marine mammals are well adapted to their hyperosmotic environment. Several morphological and physiological adaptations for water conservation and salt excretion are known to be present in cetaceans, being responsible for regulating salt balance. However, most previous studies have focused on the unique renal physiology of marine mammals, but the molecular bases of these mechanisms remain poorly explored. Many genes have been identified to be involved in osmotic regulation, including the aquaporins. Considering that aquaporin genes were potentially subject to strong selective pressure, the aim of this study was to analyze the molecular evolution of seven aquaporin genes (AQP1, AQP2, AQP3, AQP4, AQP6, AQP7, and AQP9 comparing the lineages of cetaceans and terrestrial mammals.Our results demonstrated strong positive selection in cetacean-specific lineages acting only in the gene for AQP2 (amino acids 23, 83, 107,179, 180, 181, 182, whereas no selection was observed in terrestrial mammalian lineages. We also analyzed the changes in the 3D structure of the aquaporin 2 protein. Signs of strong positive selection in AQP2 sites 179, 180, 181, and 182 were unexpectedly identified only in the baiji lineage, which was the only river dolphin examined in this study. Positive selection in aquaporins AQP1 (45, AQP4 (74, AQP7 (342, 343, 356 was detected in cetaceans and artiodactyls, suggesting that these events are not related to maintaining water and electrolyte homeostasis in seawater.Our results suggest that the AQP2 gene might reflect different selective pressures in maintaining water balance in cetaceans, contributing to the passage from the terrestrial environment to the aquatic. Further studies are necessary, especially those including other freshwater dolphins, who exhibit osmoregulatory mechanisms different from those of marine cetaceans for the same essential task of maintaining serum electrolyte balance.

  5. Transcriptome sequencing and positive selected genes analysis of Bombyx mandarina.

    Directory of Open Access Journals (Sweden)

    Tingcai Cheng

    Full Text Available The wild silkworm Bombyx mandarina is widely believed to be an ancestor of the domesticated silkworm, Bombyx mori. Silkworms are often used as a model for studying the mechanism of species domestication. Here, we performed transcriptome sequencing of the wild silkworm using an Illumina HiSeq2000 platform. We produced 100,004,078 high-quality reads and assembled them into 50,773 contigs with an N50 length of 1764 bp and a mean length of 941.62 bp. A total of 33,759 unigenes were identified, with 12,805 annotated in the Nr database, 8273 in the Pfam database, and 9093 in the Swiss-Prot database. Expression profile analysis found significant differential expression of 1308 unigenes between the middle silk gland (MSG and posterior silk gland (PSG. Three sericin genes (sericin 1, sericin 2, and sericin 3 were expressed specifically in the MSG and three fibroin genes (fibroin-H, fibroin-L, and fibroin/P25 were expressed specifically in the PSG. In addition, 32,297 Single-nucleotide polymorphisms (SNPs and 361 insertion-deletions (INDELs were detected. Comparison with the domesticated silkworm p50/Dazao identified 5,295 orthologous genes, among which 400 might have experienced or to be experiencing positive selection by Ka/Ks analysis. These data and analyses presented here provide insights into silkworm domestication and an invaluable resource for wild silkworm genomics research.

  6. Identification of ligand-selective peptidic ActRIIB-antagonists using phage display technology

    Directory of Open Access Journals (Sweden)

    Kotaro Sakamoto

    2017-09-01

    Full Text Available ActRIIB (activin receptor type-2B is an activin receptor subtype constitutively expressed in the whole body, playing a role in cellular proliferation, differentiation, and metabolism. For its various physiological activities, ActRIIB interacts with activin and multiple other ligands including myostatin (MSTN, growth differentiation factor 11 (GDF11, and bone morphogenetic protein 9 (BMP9. Notably, the protein-protein interaction (PPI between ActRIIB and MSTN negatively controls muscular development. Therefore, this PPI has been targeted for effective treatment of muscle degenerative diseases such as muscular dystrophy and sarcopenia. Here, we report the identification of ligand-selective peptidic ActRIIB-antagonists by phage display technology. Our peptides bound to the extracellular domain of ActRIIB, inhibited PPIs between ActRIIB expressed on the cell surface and its ligands, and subsequently suppressed activation of Smad that serves as the downstream signal of the ActRIIB pathway. Interestingly, these peptidic antagonists displayed different ligand selectivities; the AR2mini peptide inhibited multiple ligands (activin A, MSTN, GDF11, and BMP9, AR9 inhibited MSTN and GDF11, while AR8 selectively inhibited MSTN. This is the first report of artificial peptidic ActRIIB-antagonists possessing ligand-selectivity.

  7. Impact of selected troposphere models on Precise Point Positioning convergence

    Science.gov (United States)

    Kalita, Jakub; Rzepecka, Zofia

    2016-04-01

    The Precise Point Positioning (PPP) absolute method is currently intensively investigated in order to reach fast convergence time. Among various sources that influence the convergence of the PPP, the tropospheric delay is one of the most important. Numerous models of tropospheric delay are developed and applied to PPP processing. However, with rare exceptions, the quality of those models does not allow fixing the zenith path delay tropospheric parameter, leaving difference between nominal and final value to the estimation process. Here we present comparison of several PPP result sets, each of which based on different troposphere model. The respective nominal values are adopted from models: VMF1, GPT2w, MOPS and ZERO-WET. The PPP solution admitted as reference is based on the final troposphere product from the International GNSS Service (IGS). The VMF1 mapping function was used for all processing variants in order to provide capability to compare impact of applied nominal values. The worst case initiates zenith wet delay with zero value (ZERO-WET). Impact from all possible models for tropospheric nominal values should fit inside both IGS and ZERO-WET border variants. The analysis is based on data from seven IGS stations located in mid-latitude European region from year 2014. For the purpose of this study several days with the most active troposphere were selected for each of the station. All the PPP solutions were determined using gLAB open-source software, with the Kalman filter implemented independently by the authors of this work. The processing was performed on 1 hour slices of observation data. In addition to the analysis of the output processing files, the presented study contains detailed analysis of the tropospheric conditions for the selected data. The overall results show that for the height component the VMF1 model outperforms GPT2w and MOPS by 35-40% and ZERO-WET variant by 150%. In most of the cases all solutions converge to the same values during first

  8. Autonomous site selection and instrument positioning for sample acquisition

    Science.gov (United States)

    Shaw, A.; Barnes, D.; Pugh, S.

    The European Space Agency Aurora Exploration Program aims to establish a European long-term programme for the exploration of Space, culminating in a human mission to space in the 2030 timeframe. Two flagship missions, namely Mars Sample Return and ExoMars, have been proposed as recognised steps along the way. The Exomars Rover is the first of these flagship missions and includes a rover carrying the Pasteur Payload, a mobile exobiology instrumentation package, and the Beagle 2 arm. The primary objective is the search for evidence of past or present life on mars, but the payload will also study the evolution of the planet and the atmosphere, look for evidence of seismological activity and survey the environment in preparation for future missions. The operation of rovers in unknown environments is complicated, and requires large resources not only on the planet but also in ground based operations. Currently, this can be very labour intensive, and costly, if large teams of scientists and engineers are required to assess mission progress, plan mission scenarios, and construct a sequence of events or goals for uplink. Furthermore, the constraints in communication imposed by the time delay involved over such large distances, and line-of-sight required, make autonomy paramount to mission success, affording the ability to operate in the event of communications outages and be opportunistic with respect to scientific discovery. As part of this drive to reduce mission costs and increase autonomy the Space Robotics group at the University of Wales, Aberystwyth is researching methods of autonomous site selection and instrument positioning, directly applicable to the ExoMars mission. The site selection technique used builds on the geometric reasoning algorithms used previously for localisation and navigation [Shaw 03]. It is proposed that a digital elevation model (DEM) of the local surface, generated during traverse and without interaction from ground based operators, can be

  9. The Patient Protection and Affordable Care Act - The Role of the School Nurse: Position Statement.

    Science.gov (United States)

    2015-07-01

    It is the position of the National Association of School Nurses that the registered professional school nurse (hereinafter referred to as the school nurse) serves a vital role in the delivery of health care to our nation’s students within the health care system reshaped by the Patient Protection and Affordable Care Act of 2010, commonly known as the Affordable Care Act (ACA). This law presents an opportunity to transform the health care system through three primary goals: expanding access, improving quality, and reducing cost (U.S. Government Printing Office, 2010). School nurses stand at the forefront of this system change and continue to provide evidence-based, quality interventions and preventive care that, according to recent studies, actually save health care dollars (Wang et al., 2014). NASN supports the concept that school nursing services receive the same financial parity as other health care providers to improve overall health outcomes, including insurance reimbursement for services provided to students.

  10. Whole genome detection of signature of positive selection in African cattle reveals selection for thermotolerance.

    Science.gov (United States)

    Taye, Mengistie; Lee, Wonseok; Caetano-Anolles, Kelsey; Dessie, Tadelle; Hanotte, Olivier; Mwai, Okeyo Ally; Kemp, Stephen; Cho, Seoae; Oh, Sung Jong; Lee, Hak-Kyo; Kim, Heebal

    2017-12-01

    As African indigenous cattle evolved in a hot tropical climate, they have developed an inherent thermotolerance; survival mechanisms include a light-colored and shiny coat, increased sweating, and cellular and molecular mechanisms to cope with high environmental temperature. Here, we report the positive selection signature of genes in African cattle breeds which contribute for their heat tolerance mechanisms. We compared the genomes of five indigenous African cattle breeds with the genomes of four commercial cattle breeds using cross-population composite likelihood ratio (XP-CLR) and cross-population extended haplotype homozygosity (XP-EHH) statistical methods. We identified 296 (XP-EHH) and 327 (XP-CLR) positively selected genes. Gene ontology analysis resulted in 41 biological process terms and six Kyoto Encyclopedia of Genes and Genomes pathways. Several genes and pathways were found to be involved in oxidative stress response, osmotic stress response, heat shock response, hair and skin properties, sweat gland development and sweating, feed intake and metabolism, and reproduction functions. The genes and pathways identified directly or indirectly contribute to the superior heat tolerance mechanisms in African cattle populations. The result will improve our understanding of the biological mechanisms of heat tolerance in African cattle breeds and opens an avenue for further study. © 2017 Japanese Society of Animal Science.

  11. Positive allometry and the prehistory of sexual selection

    OpenAIRE

    Tomkins, Joseph L.; LeBas, Natasha R.; Witton, Mark P.; Martill, David M.; Humphries, Stuart

    2010-01-01

    The function of the exaggerated structures that adorn many fossil vertebrates remains largely unresolved. One recurrent hypothesis is that these elaborated traits had a role in thermoregulation. This orthodoxy persists despite the observation that traits exaggerated to the point of impracticality in extant organisms are almost invariably sexually selected. We use allometric scaling to investigate the role of sexual selection and thermoregulation in the evolution of exaggerated traits of the c...

  12. Enteric Micromotor Can Selectively Position and Spontaneously Propel in the Gastrointestinal Tract.

    Science.gov (United States)

    Li, Jinxing; Thamphiwatana, Soracha; Liu, Wenjuan; Esteban-Fernández de Ávila, Berta; Angsantikul, Pavimol; Sandraz, Elodie; Wang, Jianxing; Xu, Tailin; Soto, Fernando; Ramez, Valentin; Wang, Xiaolei; Gao, Weiwei; Zhang, Liangfang; Wang, Joseph

    2016-09-22

    The gastrointestinal (GI) tract, which hosts hundreds of bacteria species, becomes the most exciting organ for the emerging microbiome research. Some of these GI microbes are hostile and cause a variety of diseases. These bacteria colonize in different segments of the GI tract dependent on the local physicochemical and biological factors. Therefore, selectively locating therapeutic or imaging agents to specific GI segments is of significant importance for studying gut microbiome and treating various GI-related diseases. Herein, we demonstrate an enteric micromotor system capable of precise positioning and controllable retention in desired segments of the GI tract. These motors, consisting of magnesium-based tubular micromotors coated with an enteric polymer layer, act as a robust nanobiotechnology tool for site-specific GI delivery. The micromotors can deliver payload to a particular location via dissolution of their enteric coating to activate their propulsion at the target site toward localized tissue penetration and retention.

  13. Positional Differences in Elite Basketball: Selecting Appropriate Training - Load Measures.

    Science.gov (United States)

    Svilar, Luka; Castellano, Julen; Jukic, Igor; Casamichana, David

    2018-01-18

    The purpose of this paper was to study the structure of interrelationships among external training load measures and how these vary among different positions in elite basketball. Eight external variables of jumping (JUMP), acceleration (ACC), deceleration (DEC) and change of direction (COD), and two internal load variables (RPE and sRPE) were collected from 13 professional players with 300 session records. Three playing positions were considered: guards (n=4), forwards (n=4) and centers (n=5). High and total external variables (hJUMP and tJUMP, hACC and tACC, hDEC and tDEC, hCOD and tCOD) were used for the principal component analysis. Extraction criteria were set at the eigenvalue of greater than one. Varimax rotation mode was used to extract multiple principal components. The analysis showed that all positions had two or three principal components (explaining almost all of the variance), but the configuration of each factor was different: tACC, tDEC, tCOD and hJUMP for centers, hACC, tACC, tCOD and hJUMP for guards, and tACC, hDEC, tDEC, hCOD, and tCOD for forwards are specifically demanded in training sessions and, therefore, these variables must be prioritized in load monitoring. Furthermore, for all playing positions, RPE and sRPE have high correlation with the total amount of ACC, DEC and COD. This would suggest that, although players perform the same training tasks, the demands of each position can vary. A particular combination of external load measures is required to describe training load of each playing position, especially to better understand internal responses among players.

  14. A method for selecting cis-acting regulatory sequences that respond to small molecule effectors

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    Allas Ülar

    2010-08-01

    Full Text Available Abstract Background Several cis-acting regulatory sequences functioning at the level of mRNA or nascent peptide and specifically influencing transcription or translation have been described. These regulatory elements often respond to specific chemicals. Results We have developed a method that allows us to select cis-acting regulatory sequences that respond to diverse chemicals. The method is based on the β-lactamase gene containing a random sequence inserted into the beginning of the ORF. Several rounds of selection are used to isolate sequences that suppress β-lactamase expression in response to the compound under study. We have isolated sequences that respond to erythromycin, troleandomycin, chloramphenicol, meta-toluate and homoserine lactone. By introducing synonymous and non-synonymous mutations we have shown that at least in the case of erythromycin the sequences act at the peptide level. We have also tested the cross-activities of the constructs and found that in most cases the sequences respond most strongly to the compound on which they were isolated. Conclusions Several selected peptides showed ligand-specific changes in amino acid frequencies, but no consensus motif could be identified. This is consistent with previous observations on natural cis-acting peptides, showing that it is often impossible to demonstrate a consensus. Applying the currently developed method on a larger scale, by selecting and comparing an extended set of sequences, might allow the sequence rules underlying the activity of cis-acting regulatory peptides to be identified.

  15. Evidence for positive selection and recombination hotspots in Deformed wing virus (DWV).

    Science.gov (United States)

    Dalmon, A; Desbiez, C; Coulon, M; Thomasson, M; Le Conte, Y; Alaux, C; Vallon, J; Moury, B

    2017-01-25

    Deformed wing virus (DWV) is considered one of the most damaging pests in honey bees since the spread of its vector, Varroa destructor. In this study, we sequenced the whole genomes of two virus isolates and studied the evolutionary forces that act on DWV genomes. The isolate from a Varroa-tolerant bee colony was characterized by three recombination breakpoints between DWV and the closely related Varroa destructor virus-1 (VDV-1), whereas the variant from the colony using conventional Varroa management was similar to the originally described DWV. From the complete sequence dataset, nine independent DWV-VDV-1 recombination breakpoints were detected, and recombination hotspots were found in the 5' untranslated region (5' UTR) and the conserved region encoding the helicase. Partial sequencing of the 5' UTR and helicase-encoding region in 41 virus isolates suggested that most of the French isolates were recombinants. By applying different methods based on the ratio between non-synonymous (dN) and synonymous (dS) substitution rates, we identified four positions that showed evidence of positive selection. Three of these positions were in the putative leader protein (Lp), and one was in the polymerase. These findings raise the question of the putative role of the Lp in viral evolution.

  16. A strategy for position-selective epoxidation of polyprenols.

    Science.gov (United States)

    Gnanadesikan, Vijay; Corey, E J

    2008-06-25

    An effective strategy has been developed for the efficient site-selective epoxidation of poylolefinic isoprenoid alcohols, based on the use of an internal control element for intramolecular reaction. The approach is illustrated by application to a series of polyisoprenoid alcohols (polyprenols) at substrate concentration of 0.5 mM. With polyprenol substrates having the hydroxyl function at one terminus, the internal epoxidation can be directed at the double bond of the polyprenol, which is either four or five away from the terminal hydroxyprenyl subunit.

  17. 75 FR 44724 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

    Science.gov (United States)

    2010-07-29

    ... statutory mandate, PPQ and VS each convene separate interagency working groups in order to review the lists... responsibility for implementing the provisions of the Act within the Department of Agriculture (USDA). Veterinary Services (VS) select agents and toxins, listed in 9 CFR 121.3, are those that have been determined to have...

  18. A scan for positively selected genes in the genomes of humans and chimpanzees.

    Directory of Open Access Journals (Sweden)

    Rasmus Nielsen

    2005-06-01

    Full Text Available Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

  19. Reference satellite selection method for GNSS high-precision relative positioning

    Directory of Open Access Journals (Sweden)

    Xiao Gao

    2017-03-01

    Full Text Available Selecting the optimal reference satellite is an important component of high-precision relative positioning because the reference satellite directly influences the strength of the normal equation. The reference satellite selection methods based on elevation and positional dilution of precision (PDOP value were compared. Results show that all the above methods cannot select the optimal reference satellite. We introduce condition number of the design matrix in the reference satellite selection method to improve structure of the normal equation, because condition number can indicate the ill condition of the normal equation. The experimental results show that the new method can improve positioning accuracy and reliability in precise relative positioning.

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

    Science.gov (United States)

    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.

  1. Macular hole surgery with short-acting gas and short-duration face-down positioning

    Directory of Open Access Journals (Sweden)

    Xirou T

    2012-07-01

    Full Text Available Tina Xirou,1 Panagiotis G Theodossiadis,2 Michael Apostolopoulos,3 A Stamatina Kabanarou,1 Elias Feretis,1 Ioannis D Ladas,3 Chrysanthi Koutsandrea31Vitreoretinal Unit, Red Cross Hospital, 2B Department of Ophthalmology, University of Athens, Greece; 3A Department of Ophthalmology, University of Athens, GreecePurpose: To report on the outcomes of vitrectomy and sulfur hexafluoride (SF6 gas tamponade for idiopathic macular holes with 2 days of face-down positioning.Patients and methods: This was a prospective, nonrandomized, observational sequential case-series study on 23 consecutive patients receiving macular hole surgery using 20% SF6 and advised to stay in a face-down position for 2 days postoperatively (SF6 group. These patients were compared to 23 consecutive patients who had previously undergone macular hole surgery, had received 14% C3F8, and were advised to maintain a face-down position for 2 days (C3F8 group. Patients in both groups underwent vitrectomy, internal limiting membrane peeling, and fluid gas exchange using either SF6 or C3F8. Preoperative and postoperative data included best corrected visual acuity recorded in LogMAR units, slit-lamp biomicroscopy, and optical coherence tomography.Results: At a 6-month follow-up, macular hole closure was noted in 23/23 eyes (100% and in 22/23 eyes (96% in the SF6 and C3F8 groups, respectively. The improvement in visual acuity (measured through Snellen acuity lines both preoperatively until 6 months postoperatively was 4.08 ± 2.31 (95% confidence interval [CI]: 3.08–5.08 for the SF6 group and 2.87 ± 2.30 (95% CI: 1.87–3.86 for the C3F8 group; this difference was not statistically significant (P = 0.06.Conclusion: Vitrectomy with internal limiting membrane peeling and a short-acting gas tamponade using SF6 with posture limitation for 2 days may give a high success rate in macular hole surgery.Keywords: idiopathic macular holes, SF6 gas tamponade, C3F8 gas tamponade

  2. Recent adaptive events in human brain revealed by meta-analysis of positively selected genes.

    Directory of Open Access Journals (Sweden)

    Yue Huang

    Full Text Available BACKGROUND AND OBJECTIVES: Analysis of positively-selected genes can help us understand how human evolved, especially the evolution of highly developed cognitive functions. However, previous works have reached conflicting conclusions regarding whether human neuronal genes are over-represented among genes under positive selection. METHODS AND RESULTS: We divided positively-selected genes into four groups according to the identification approaches, compiling a comprehensive list from 27 previous studies. We showed that genes that are highly expressed in the central nervous system are enriched in recent positive selection events in human history identified by intra-species genomic scan, especially in brain regions related to cognitive functions. This pattern holds when different datasets, parameters and analysis pipelines were used. Functional category enrichment analysis supported these findings, showing that synapse-related functions are enriched in genes under recent positive selection. In contrast, immune-related functions, for instance, are enriched in genes under ancient positive selection revealed by inter-species coding region comparison. We further demonstrated that most of these patterns still hold even after controlling for genomic characteristics that might bias genome-wide identification of positively-selected genes including gene length, gene density, GC composition, and intensity of negative selection. CONCLUSION: Our rigorous analysis resolved previous conflicting conclusions and revealed recent adaptation of human brain functions.

  3. 20 CFR 670.420 - Are there any special requirements for enrollment related to the Military Selective Service Act?

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Are there any special requirements for enrollment related to the Military Selective Service Act? 670.420 Section 670.420 Employees' Benefits... INVESTMENT ACT Recruitment, Eligibility, Screening, Selection and Assignment, and Enrollment § 670.420 Are...

  4. Positive selection in octopus haemocyanin indicates functional links to temperature adaptation.

    Science.gov (United States)

    Oellermann, Michael; Strugnell, Jan M; Lieb, Bernhard; Mark, Felix C

    2015-07-05

    Octopods have successfully colonised the world's oceans from the tropics to the poles. Yet, successful persistence in these habitats has required adaptations of their advanced physiological apparatus to compensate impaired oxygen supply. Their oxygen transporter haemocyanin plays a major role in cold tolerance and accordingly has undergone functional modifications to sustain oxygen release at sub-zero temperatures. However, it remains unknown how molecular properties evolved to explain the observed functional adaptations. We thus aimed to assess whether natural selection affected molecular and structural properties of haemocyanin that explains temperature adaptation in octopods. Analysis of 239 partial sequences of the haemocyanin functional units (FU) f and g of 28 octopod species of polar, temperate, subtropical and tropical origin revealed natural selection was acting primarily on charge properties of surface residues. Polar octopods contained haemocyanins with higher net surface charge due to decreased glutamic acid content and higher numbers of basic amino acids. Within the analysed partial sequences, positive selection was present at site 2545, positioned between the active copper binding centre and the FU g surface. At this site, methionine was the dominant amino acid in polar octopods and leucine was dominant in tropical octopods. Sites directly involved in oxygen binding or quaternary interactions were highly conserved within the analysed sequence. This study has provided the first insight into molecular and structural mechanisms that have enabled octopods to sustain oxygen supply from polar to tropical conditions. Our findings imply modulation of oxygen binding via charge-charge interaction at the protein surface, which stabilize quaternary interactions among functional units to reduce detrimental effects of high pH on venous oxygen release. Of the observed partial haemocyanin sequence, residue 2545 formed a close link between the FU g surface and the

  5. PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes.

    Science.gov (United States)

    Su, Fei; Ou, Hong-Yu; Tao, Fei; Tang, Hongzhi; Xu, Ping

    2013-12-27

    With genomic sequences of many closely related bacterial strains made available by deep sequencing, it is now possible to investigate trends in prokaryotic microevolution. Positive selection is a sub-process of microevolution, in which a particular mutation is favored, causing the allele frequency to continuously shift in one direction. Wide scanning of prokaryotic genomes has shown that positive selection at the molecular level is much more frequent than expected. Genes with significant positive selection may play key roles in bacterial adaption to different environmental pressures. However, selection pressure analyses are computationally intensive and awkward to configure. Here we describe an open access web server, which is designated as PSP (Positive Selection analysis for Prokaryotic genomes) for performing evolutionary analysis on orthologous coding genes, specially designed for rapid comparison of dozens of closely related prokaryotic genomes. Remarkably, PSP facilitates functional exploration at the multiple levels by assignments and enrichments of KO, GO or COG terms. To illustrate this user-friendly tool, we analyzed Escherichia coli and Bacillus cereus genomes and found that several genes, which play key roles in human infection and antibiotic resistance, show significant evidence of positive selection. PSP is freely available to all users without any login requirement at: http://db-mml.sjtu.edu.cn/PSP/. PSP ultimately allows researchers to do genome-scale analysis for evolutionary selection across multiple prokaryotic genomes rapidly and easily, and identify the genes undergoing positive selection, which may play key roles in the interactions of host-pathogen and/or environmental adaptation.

  6. Reciprocity is not give and take: asymmetric reciprocity to positive and negative acts.

    Science.gov (United States)

    Keysar, Boaz; Converse, Benjamin A; Wang, Jiunwen; Epley, Nicholas

    2008-12-01

    Unlike economic exchange, social exchange has no well-defined "value." It is based on the norm of reciprocity, in which giving and taking are to be repaid in equivalent measure. Although giving and taking are colloquially assumed to be equivalent actions, we demonstrate that they produce different patterns of reciprocity. In five experiments utilizing a dictator game, people reciprocated in like measure to apparently prosocial acts of giving, but reciprocated more selfishly to apparently antisocial acts of taking, even when the objective outcomes of the acts of giving and taking were identical. Additional results demonstrate that acts of giving in social exchanges are perceived as more generous than objectively identical acts of taking, that taking tends to escalate, and that the asymmetry in reciprocity is not due to gaining versus losing resources. Reciprocity appears to operate on an exchange rate that assigns value to the meaning of events, in a fashion that encourages prosocial exchanges.

  7. How to Make a Dolphin: Molecular Signature of Positive Selection in Cetacean Genome.

    Directory of Open Access Journals (Sweden)

    Mariana F Nery

    Full Text Available Cetaceans are unique in being the only mammals completely adapted to an aquatic environment. This adaptation has required complex changes and sometimes a complete restructuring of physiology, behavior and morphology. Identifying genes that have been subjected to selection pressure during cetacean evolution would greatly enhance our knowledge of the ways in which genetic variation in this mammalian order has been shaped by natural selection. Here, we performed a genome-wide scan for positive selection in the dolphin lineage. We employed models of codon substitution that account for variation of selective pressure over branches on the tree and across sites in a sequence. We analyzed 7,859 nuclear-coding ortholog genes and using a series of likelihood ratio tests (LRTs, we identified 376 genes (4.8% with molecular signatures of positive selection in the dolphin lineage. We used the cow as the sister group and compared estimates of selection in the cetacean genome to this using the same methods. This allowed us to define which genes have been exclusively under positive selection in the dolphin lineage. The enrichment analysis found that the identified positively selected genes are significantly over-represented for three exclusive functional categories only in the dolphin lineage: segment specification, mesoderm development and system development. Of particular interest for cetacean adaptation to an aquatic life are the following GeneOntology targets under positive selection: genes related to kidney, heart, lung, eye, ear and nervous system development.

  8. On the redshift distribution and physical properties of ACT-selected DSFGs

    Science.gov (United States)

    Su, T.; Marriage, T. A.; Asboth, V.; Baker, A. J.; Bond, J. R.; Crichton, D.; Devlin, M. J.; Dünner, R.; Farrah, D.; Frayer, D. T.; Gralla, M. B.; Hall, K.; Halpern, M.; Harris, A. I.; Hilton, M.; Hincks, A. D.; Hughes, J. P.; Niemack, M. D.; Page, L. A.; Partridge, B.; Rivera, J.; Scott, D.; Sievers, J. L.; Thornton, R. J.; Viero, M. P.; Wang, L.; Wollack, E. J.; Zemcov, M.

    2017-01-01

    We present multi-wavelength detections of nine candidate gravitationally lensed dusty star-forming galaxies (DSFGs) selected at 218 GHz (1.4 mm) from the Atacama Cosmology Telescope (ACT) equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in Herschel SPIRE fields, and all nine of the 218 GHz detections were found to have bright Herschel counterparts. By fitting their spectral energy distributions (SEDs) with a modified blackbody model with power-law temperature distribution, we find the sample has a median redshift of z=4.1^{+1.1}_{-1.0} (68 per cent confidence interval), as expected for 218 GHz selection, and an apparent total infrared luminosity of log _{10}(μ L_IR/L_{odot }) = 13.86^{+0.33}_{-0.30}, which suggests that they are either strongly lensed sources or unresolved collections of unlensed DSFGs. The effective apparent diameter of the sample is sqrt{μ }d= 4.2^{+1.7}_{-1.0} kpc, further evidence of strong lensing or multiplicity, since the typical diameter of DSFGs is 1.0-2.5 kpc. We emphasize that the effective apparent diameter derives from SED modelling without the assumption of optically thin dust (as opposed to image morphology). We find that the sources have substantial optical depth (tau = 4.2^{+3.7}_{-1.9}) to dust around the peak in the modified blackbody spectrum (λobs ≤ 500 μm), a result that is robust to model choice.

  9. Genome-wide analysis of positively selected genes in seasonal and non-seasonal breeding species.

    Directory of Open Access Journals (Sweden)

    Yuhuan Meng

    Full Text Available Some mammals breed throughout the year, while others breed only at certain times of year. These differences in reproductive behavior can be explained by evolution. We identified positively-selected genes in two sets of species with different degrees of relatedness including seasonal and non-seasonal breeding species, using branch-site models. After stringent filtering by sum of pairs scoring, we revealed that more genes underwent positive selection in seasonal compared with non-seasonal breeding species. Positively-selected genes were verified by cDNA mapping of the positive sites with the corresponding cDNA sequences. The design of the evolutionary analysis can effectively lower the false-positive rate and thus identify valid positive genes. Validated, positively-selected genes, including CGA, DNAH1, INVS, and CD151, were related to reproductive behaviors such as spermatogenesis and cell proliferation in non-seasonal breeding species. Genes in seasonal breeding species, including THRAP3, TH1L, and CMTM6, may be related to the evolution of sperm and the circadian rhythm system. Identification of these positively-selected genes might help to identify the molecular mechanisms underlying seasonal and non-seasonal reproductive behaviors.

  10. The Rehabilitation Act of 1973--its impact on employee selection practices.

    Science.gov (United States)

    Guy, J H

    1978-01-01

    The employee selection practices of private and public enterprises that contract with the federal government or receive federal financial assistance have been subjected to extensive regulation by the agencies administering sections 503 and 504 of the 1973 Rehabilitation Act, which provide protection to qualified handicapped individuals. The author discusses the nature and significance of these restrictions and gives practical guidance on compliance. She cautions that the enforcement powers of the agencies administering the Act--the power to cut off federal funds, debar from future contracts, award back pay, and provide equitable relief--make it necessary for employers to show good faith and proper justification when a decision is made to reject a handicapped person for a job or a promotion.

  11. β-Catenin acts in a position-independent regeneration response in the simple eumetazoan Hydra.

    Science.gov (United States)

    Gufler, S; Artes, B; Bielen, H; Krainer, I; Eder, M-K; Falschlunger, J; Bollmann, A; Ostermann, T; Valovka, T; Hartl, M; Bister, K; Technau, U; Hobmayer, B

    2018-01-15

    Wnt/β-Catenin signaling plays crucial roles in regenerative processes in eumetazoans. It also acts in regeneration and axial patterning in the simple freshwater polyp Hydra, whose morphallactic regenerative capacity is unparalleled in the animal kingdom. Previous studies have identified β-catenin as an early response gene activated within the first 30min in Hydra head regeneration. Here, we have studied the role of β-Catenin in more detail. First, we show that nuclear β-Catenin signaling is required for head and foot regeneration. Loss of nuclear β-Catenin function blocks head and foot regeneration. Transgenic Hydra tissue, in which β-Catenin is over-expressed, regenerates more heads and feet. In addition, we have identified a set of putative β-Catenin target genes by transcriptional profiling, and these genes exhibit distinct expression patterns in the hypostome, in the tentacles, or in an apical gradient in the body column. All of them are transcriptionally up-regulated in the tips of early head and foot regenerates. In foot regenerates, this is a transient response, and expression starts to disappear after 12-36h. ChIP experiments using an anti-HydraTcf antibody show Tcf binding at promoters of these targets. We propose that gene regulatory β-Catenin activity in the pre-patterning phase is generally required as an early regeneration response. When regenerates are blocked with iCRT14, initial local transcriptional activation of β-catenin and the target genes occurs, and all these genes remain upregulated at the site of both head and foot regeneration for the following 2-3 days. This indicates that the initial regulatory network is followed by position-specific programs that inactivate fractions of this network in order to proceed to differentiation of head or foot structures. brachyury1 (hybra1) has previously been described as early response gene in head and foot regeneration. The HyBra1 protein, however, appears in head regenerating tips not earlier

  12. Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins.

    LENUS (Irish Health Repository)

    Morgan, Claire C

    2010-01-01

    ABSTRACT: BACKGROUND: Reproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, the mammalia are a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety of mammalia. RESULTS: We show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality. CONCLUSION: Our in silico analyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across the mammalia and specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.

  13. A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera.

    Science.gov (United States)

    Zayed, Amro; Whitfield, Charles W

    2008-03-04

    Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating "Africanized" honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive selection, detected by contrasting genetic differentiation estimates (F(ST)) between coding and noncoding SNPs. In native populations, SNPs in protein-coding regions had significantly higher F(ST) estimates than those in noncoding regions, indicating adaptive evolution in the genome driven by positive selection. This signal of selection was associated with the expansion of honey bees from Africa into Western and Northern Europe, perhaps reflecting adaptation to temperate environments. We estimate that positive selection acted on a minimum of 852-1,371 genes or approximately 10% of the bee's coding genome. We also detected positive selection associated with the invasion of African-derived honey bees in the New World. We found that introgression of European-derived alleles into Africanized bees was significantly greater for coding than noncoding regions. Our findings demonstrate that Africanized bees exploited the genetic diversity present from preexisting introductions in an adaptive way. Finally, we found a significant negative correlation between F(ST) estimates and the local GC content surrounding coding SNPs, suggesting that AT-rich genes play an important role in adaptive evolution in the honey bee.

  14. Inference of purifying and positive selection in three subspecies of chimpanzees (Pan troglodytes) from exome sequencing

    DEFF Research Database (Denmark)

    Bataillon, Thomas; Duan, Jinjie; Hvilsom, Christina

    2015-01-01

    of recent gene flow from Western into Eastern chimpanzees. The striking contrast in X-linked vs. autosomal polymorphism and divergence previously reported in Central chimpanzees is also found in Eastern and Western chimpanzees. We show that the direction of selection (DoS) statistic exhibits a strong non......-monotonic relationship with the strength of purifying selection S, making it inappropriate for estimating S. We instead use counts in synonymous vs. non-synonymous frequency classes to infer the distribution of S coefficients acting on non-synonymous mutations in each subspecies. The strength of purifying selection we...... infer is congruent with the differences in effective sizes of each subspecies: Central chimpanzees are undergoing the strongest purifying selection followed by Eastern and Western chimpanzees. Coding indels show stronger selection against indels changing the reading frame than observed in human...

  15. Continental-scale footprint of balancing and positive selection in a small rodent (Microtus arvalis.

    Directory of Open Access Journals (Sweden)

    Martin C Fischer

    Full Text Available Genetic adaptation to different environmental conditions is expected to lead to large differences between populations at selected loci, thus providing a signature of positive selection. Whereas balancing selection can maintain polymorphisms over long evolutionary periods and even geographic scale, thus leads to low levels of divergence between populations at selected loci. However, little is known about the relative importance of these two selective forces in shaping genomic diversity, partly due to difficulties in recognizing balancing selection in species showing low levels of differentiation. Here we address this problem by studying genomic diversity in the European common vole (Microtus arvalis presenting high levels of differentiation between populations (average F ST = 0.31. We studied 3,839 Amplified Fragment Length Polymorphism (AFLP markers genotyped in 444 individuals from 21 populations distributed across the European continent and hence over different environmental conditions. Our statistical approach to detect markers under selection is based on a Bayesian method specifically developed for AFLP markers, which treats AFLPs as a nearly codominant marker system, and therefore has increased power to detect selection. The high number of screened populations allowed us to detect the signature of balancing selection across a large geographic area. We detected 33 markers potentially under balancing selection, hence strong evidence of stabilizing selection in 21 populations across Europe. However, our analyses identified four-times more markers (138 being under positive selection, and geographical patterns suggest that some of these markers are probably associated with alpine regions, which seem to have environmental conditions that favour adaptation. We conclude that despite favourable conditions in this study for the detection of balancing selection, this evolutionary force seems to play a relatively minor role in shaping the genomic

  16.  Molecular evolution and positive selection of the symbiotic gene NORK in Medicago truncatula

    DEFF Research Database (Denmark)

    De Mita, Stephane; Santoni, Sylvain; Hochu, Isabelle

    2006-01-01

     Understanding the selective constraints of partner specificity in mutually beneficial symbiosis is a significant, yet largely unexplored, prospect of evolutionary biology. These selective constraints can be explored through the study of nucleotide polymorphism at loci controlling specificity...... domain of the protein, evolved under the regime of positive selection. Further research should focus on the rate and direction of molecular coevolution between microorganisms' signaling molecules and legumes' receptors....

  17. The role of positive selection in determining the molecular cause of species differences in disease

    Directory of Open Access Journals (Sweden)

    Foord Steven M

    2008-10-01

    Full Text Available Abstract Background Related species, such as humans and chimpanzees, often experience the same disease with varying degrees of pathology, as seen in the cases of Alzheimer's disease, or differing symptomatology as in AIDS. Furthermore, certain diseases such as schizophrenia, epithelial cancers and autoimmune disorders are far more frequent in humans than in other species for reasons not associated with lifestyle. Genes that have undergone positive selection during species evolution are indicative of functional adaptations that drive species differences. Thus we investigate whether biomedical disease differences between species can be attributed to positively selected genes. Results We identified genes that putatively underwent positive selection during the evolution of humans and four mammals which are often used to model human diseases (mouse, rat, chimpanzee and dog. We show that genes predicted to have been subject to positive selection pressure during human evolution are implicated in diseases such as epithelial cancers, schizophrenia, autoimmune diseases and Alzheimer's disease, all of which differ in prevalence and symptomatology between humans and their mammalian relatives. In agreement with previous studies, the chimpanzee lineage was found to have more genes under positive selection than any of the other lineages. In addition, we found new evidence to support the hypothesis that genes that have undergone positive selection tend to interact with each other. This is the first such evidence to be detected widely among mammalian genes and may be important in identifying molecular pathways causative of species differences. Conclusion Our dataset of genes predicted to have been subject to positive selection in five species serves as an informative resource that can be consulted prior to selecting appropriate animal models during drug target validation. We conclude that studying the evolution of functional and biomedical disease differences

  18. Likelihood analysis of the chalcone synthase genes suggests the role of positive selection in morning glories (Ipomoea).

    Science.gov (United States)

    Yang, Ji; Gu, Hongya; Yang, Ziheng

    2004-01-01

    Chalcone synthase (CHS) is a key enzyme in the biosynthesis of flavonoides, which are important for the pigmentation of flowers and act as attractants to pollinators. Genes encoding CHS constitute a multigene family in which the copy number varies among plant species and functional divergence appears to have occurred repeatedly. In morning glories (Ipomoea), five functional CHS genes (A-E) have been described. Phylogenetic analysis of the Ipomoea CHS gene family revealed that CHS A, B, and C experienced accelerated rates of amino acid substitution relative to CHS D and E. To examine whether the CHS genes of the morning glories underwent adaptive evolution, maximum-likelihood models of codon substitution were used to analyze the functional sequences in the Ipomoea CHS gene family. These models used the nonsynonymous/synonymous rate ratio (omega = d(N)/ d(S)) as an indicator of selective pressure and allowed the ratio to vary among lineages or sites. Likelihood ratio test suggested significant variation in selection pressure among amino acid sites, with a small proportion of them detected to be under positive selection along the branches ancestral to CHS A, B, and C. Positive Darwinian selection appears to have promoted the divergence of subfamily ABC and subfamily DE and is at least partially responsible for a rate increase following gene duplication.

  19. POSITIVE EXPRESSIVE SPEECH ACTS COMPLIMENTING AND SELF - COMPLI MENTING IN THE NOVEL CIOCOII VECHI Ș I NOI

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    Roxana - Florentina FLUERAȘU

    2015-11-01

    Full Text Available The present paper aims at analysing some specific aspects regarding the functioning of compliment and self - compliment - speec h acts belonging to the category of positively perceived expressives - in a literary text, Nicolae Filimon‟s novel “ Ciocoii vechi şi noi ” 1 . The purpose of the paper is to highlight the role of these subtypes of speech acts in contouring a human typology cha racterized by a specific relational system. The following parameters are taken into account: the environment in which the speech acts are produced, the target addressees, the object of the speech acts (concrete or abstract, moral or physical features of th e addressee and the value ( inherently positive or attributed by the speaker of the elements that mark the illocutionary force as positive. In the novel under consideration, there is a dichotomy between the characters with high moral qualities and the par venus – a social type definitory for the Phanariot times. Author‟s intention is to emphasize the victory of good and healthy moral principles.

  20. Positive diversifying selection is a pervasive adaptive force throughout the Drosophila radiation

    DEFF Research Database (Denmark)

    Cicconardi, Francesco; Marcatili, Paolo; Arthofer, Wolfgang

    2017-01-01

    The growing genomic information on non-model organisms eases exploring the evolutionary history of biodiversity. This is particularly true for Drosophila flies, in which the number of sequenced species doubled recently. Because of its outstanding diversity of species, Drosophila has become one....... grimshawi, a strong putative signal of positive diversifying selection was found related to cell, morphological, neuronal, and sensorial development and function. A recurrent signal of positive diversifying selection was found on genes related to aging and lifespan, suggesting that selection had shaped...

  1. Genome-scale detection of positive selection in nine primates predicts human-virus evolutionary conflicts.

    Science.gov (United States)

    van der Lee, Robin; Wiel, Laurens; van Dam, Teunis J P; Huynen, Martijn A

    2017-10-13

    Hotspots of rapid genome evolution hold clues about human adaptation. We present a comparative analysis of nine whole-genome sequenced primates to identify high-confidence targets of positive selection. We find strong statistical evidence for positive selection in 331 protein-coding genes (3%), pinpointing 934 adaptively evolving codons (0.014%). Our new procedure is stringent and reveals substantial artefacts (20% of initial predictions) that have inflated previous estimates. The final 331 positively selected genes (PSG) are strongly enriched for innate and adaptive immunity, secreted and cell membrane proteins (e.g. pattern recognition, complement, cytokines, immune receptors, MHC, Siglecs). We also find evidence for positive selection in reproduction and chromosome segregation (e.g. centromere-associated CENPO, CENPT), apolipoproteins, smell/taste receptors and mitochondrial proteins. Focusing on the virus-host interaction, we retrieve most evolutionary conflicts known to influence antiviral activity (e.g. TRIM5, MAVS, SAMHD1, tetherin) and predict 70 novel cases through integration with virus-human interaction data. Protein structure analysis further identifies positive selection in the interaction interfaces between viruses and their cellular receptors (CD4-HIV; CD46-measles, adenoviruses; CD55-picornaviruses). Finally, primate PSG consistently show high sequence variation in human exomes, suggesting ongoing evolution. Our curated dataset of positive selection is a rich source for studying the genetics underlying human (antiviral) phenotypes. Procedures and data are available at https://github.com/robinvanderlee/positive-selection. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. On the Redshift Distribution and Physical Properties of ACT-Selected DSFGs

    Science.gov (United States)

    Su, T.; Marriage, T. A.; Asboth, V.; Baker, A. J.; Bond, J. R.; Crichton, D.; Devlin, M. J.; Dunner, R.; Farrah, D.; Frayer, D. T.; hide

    2016-01-01

    We present multi-wavelength detections of nine candidate gravitationally-lensed dusty starforming galaxies (DSFGs) selected at 218 GHz (1.4 mm) from the ACT equatorial survey. Among the brightest ACT sources, these represent the subset of the total ACT sample lying in Herschel SPIRE fields, and all nine of the 218 GHz detections were found to have bright Herschel counterparts. By fitting their spectral energy distributions (SEDs) with a modified blackbody model with power-law temperature distribution, we find the sample has a median redshift of 4.1 (+ 1.1, -10) (68 percent confidence interval), as expected for 218 GHz selection and an apparent total infrared luminosity of log 10(uL(sub IR)/solar luminosity) = 13.86(+0.33, -0.30), which suggests that they are either strongly lensed sources or unresolved collections of unlensed DSFGs. The effective apparent diameter of the sample is square root of mu d = 4.2 (+ 1.7, -1.0) kpc, further evidence of strong lensing of multiplicity, since the typical diameter of dusty star-forming galaxies is 1.0-2.5 kpc. We emphasize that the effective apparent diameter derives from SED modeling without the assumption of opticaly thin dust (as opposed to image morphology). We find that the sources have substantial optical depth (tau = (4.2+, -1.9) of dust around the peak in the modified blackbody spectrum (lambda obs is less than 500 micrometers), a result that is robust to model choice.

  3. Widespread signatures of positive selection in common risk alleles associated to autism spectrum disorder.

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    Renato Polimanti

    2017-02-01

    Full Text Available The human brain is the outcome of innumerable evolutionary processes; the systems genetics of psychiatric disorders could bear their signatures. On this basis, we analyzed five psychiatric disorders, attention deficit hyperactivity disorder, autism spectrum disorder (ASD, bipolar disorder, major depressive disorder, and schizophrenia (SCZ, using GWAS summary statistics from the Psychiatric Genomics Consortium. Machine learning-derived scores were used to investigate two natural-selection scenarios: complete selection (loci where a selected allele reached fixation and incomplete selection (loci where a selected allele has not yet reached fixation. ASD GWAS results positively correlated with incomplete-selection (p = 3.53*10-4. Variants with ASD GWAS p<0.1 were shown to have a 19%-increased probability to be in the top-5% for incomplete-selection score (OR = 1.19, 95%CI = 1.11-1.8, p = 9.56*10-7. Investigating the effect directions of minor alleles, we observed an enrichment for positive associations in SNPs with ASD GWAS p<0.1 and top-5% incomplete-selection score (permutation p<10-4. Considering the set of these ASD-positive-associated variants, we observed gene-expression enrichments for brain and pituitary tissues (p = 2.3*10-5 and p = 3*10-5, respectively and 53 gene ontology (GO enrichments, such as nervous system development (GO:0007399, p = 7.57*10-12, synapse organization (GO:0050808, p = 8.29*10-7, and axon guidance (GO:0007411, p = 1.81*10-7. Previous genetic studies demonstrated that ASD positively correlates with childhood intelligence, college completion, and years of schooling. Accordingly, we hypothesize that certain ASD risk alleles were under positive selection during human evolution due to their involvement in neurogenesis and cognitive ability.

  4. Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents.

    Science.gov (United States)

    Tschirren, B; Råberg, L; Westerdahl, H

    2011-06-01

    Patterns of selection acting on immune defence genes have recently been the focus of considerable interest. Yet, when it comes to vertebrates, studies have mainly focused on the acquired branch of the immune system. Consequently, the direction and strength of selection acting on genes of the vertebrate innate immune defence remain poorly understood. Here, we present a molecular analysis of selection on an important receptor of the innate immune system of vertebrates, the Toll-like receptor 2 (TLR2), across 17 rodent species. Although purifying selection was the prevalent evolutionary force acting on most parts of the rodent TLR2, we found that codons in close proximity to pathogen-binding and TLR2-TLR1 heterodimerization sites have been subject to positive selection. This indicates that parasite-mediated selection is not restricted to acquired immune system genes like the major histocompatibility complex, but also affects innate defence genes. To obtain a comprehensive understanding of evolutionary processes in host-parasite systems, both innate and acquired immunity thus need to be considered. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  5. Absence of positive selection on CenH3 in Luzula suggests that holokinetic chromosomes may suppress centromere drive.

    Science.gov (United States)

    Zedek, František; Bureš, Petr

    2016-12-01

    The centromere drive theory explains diversity of eukaryotic centromeres as a consequence of the recurrent conflict between centromeric repeats and centromeric histone H3 (CenH3), in which selfish centromeres exploit meiotic asymmetry and CenH3 evolves adaptively to counterbalance deleterious consequences of driving centromeres. Accordingly, adaptively evolving CenH3 has so far been observed only in eukaryotes with asymmetric meiosis. However, if such evolution is a consequence of centromere drive, it should depend not only on meiotic asymmetry but also on monocentric or holokinetic chromosomal structure. Selective pressures acting on CenH3 have never been investigated in organisms with holokinetic meiosis despite the fact that holokinetic chromosomes have been hypothesized to suppress centromere drive. Therefore, the present study evaluates selective pressures acting on the CenH3 gene in holokinetic organisms for the first time, specifically in the representatives of the plant genus Luzula (Juncaceae), in which the kinetochore formation is not co-localized with any type of centromeric repeat. PCR, cloning and sequencing, and database searches were used to obtain coding CenH3 sequences from Luzula species. Codon substitution models were employed to infer selective regimes acting on CenH3 in Luzula KEY RESULTS: In addition to the two previously published CenH3 sequences from L. nivea, 16 new CenH3 sequences have been isolated from 12 Luzula species. Two CenH3 isoforms in Luzula that originated by a duplication event prior to the divergence of analysed species were found. No signs of positive selection acting on CenH3 in Luzula were detected. Instead, evidence was found that selection on CenH3 of Luzula might have been relaxed. The results indicate that holokinetism itself may suppress centromere drive and, therefore, holokinetic chromosomes might have evolved as a defence against centromere drive. © The Author 2016. Published by Oxford University Press on behalf of

  6. Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

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    Daniel R Matute

    Full Text Available Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27 show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

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

    Science.gov (United States)

    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.

  8. Positive selection within the Schizophrenia-associated GABA(A receptor beta(2 gene.

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    Wing-Sze Lo

    Full Text Available The gamma-aminobutyric acid type-A (GABA(A receptor plays a major role in inhibitory neurotransmissions. Intronic SNPs and haplotypes in GABRB2, the gene for GABA(A receptor beta(2 subunit, are associated with schizophrenia and correlated with the expression of two alternatively spliced beta(2 isoforms. In the present study, using chimpanzee as an ancestral reference, high frequencies were observed for the derived (D alleles of the four SNPs rs6556547, rs187269, rs1816071 and rs1816072 in GABRB2, suggesting the occurrence of positive selection for these derived alleles. Coalescence-based simulation showed that the population frequency spectra and the frequencies of H56, the haplotype having all four D alleles, significantly deviated from neutral-evolution expectation in various demographic models. Haplotypes containing the derived allele of rs1816072 displayed significantly less diversity compared to haplotypes containing its ancestral allele, further supporting positive selection. The variations in DD-genotype frequencies in five human populations provided a snapshot of the evolutionary history, which suggested that the positive selections of the D alleles are recent and likely ongoing. The divergence between the DD-genotype profiles of schizophrenic and control samples pointed to the schizophrenia-relevance of positive selections, with the schizophrenic samples showing weakened selections compared to the controls. These DD-genotypes were previously found to increase the expression of beta(2, especially its long isoform. Electrophysiological analysis showed that this long beta(2 isoform favored by the positive selections is more sensitive than the short isoform to the inhibition of GABA(A receptor function by energy depletion. These findings represent the first demonstration of positive selection in a schizophrenia-associated gene.

  9. Positive Selection or Free to Vary? Assessing the Functional Significance of Sequence Change Using Molecular Dynamics.

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    Jane R Allison

    Full Text Available Evolutionary arms races between pathogens and their hosts may be manifested as selection for rapid evolutionary change of key genes, and are sometimes detectable through sequence-level analyses. In the case of protein-coding genes, such analyses frequently predict that specific codons are under positive selection. However, detecting positive selection can be non-trivial, and false positive predictions are a common concern in such analyses. It is therefore helpful to place such predictions within a structural and functional context. Here, we focus on the p19 protein from tombusviruses. P19 is a homodimer that sequesters siRNAs, thereby preventing the host RNAi machinery from shutting down viral infection. Sequence analysis of the p19 gene is complicated by the fact that it is constrained at the sequence level by overprinting of a viral movement protein gene. Using homology modeling, in silico mutation and molecular dynamics simulations, we assess how non-synonymous changes to two residues involved in forming the dimer interface-one invariant, and one predicted to be under positive selection-impact molecular function. Interestingly, we find that both observed variation and potential variation (where a non-synonymous change to p19 would be synonymous for the overprinted movement protein does not significantly impact protein structure or RNA binding. Consequently, while several methods identify residues at the dimer interface as being under positive selection, MD results suggest they are functionally indistinguishable from a site that is free to vary. Our analyses serve as a caveat to using sequence-level analyses in isolation to detect and assess positive selection, and emphasize the importance of also accounting for how non-synonymous changes impact structure and function.

  10. Positive selection on MHC class II DRB and DQB genes in the bank vole (Myodes glareolus).

    Science.gov (United States)

    Scherman, Kristin; Råberg, Lars; Westerdahl, Helena

    2014-05-01

    The major histocompatibility complex (MHC) class IIB genes show considerable sequence similarity between loci. The MHC class II DQB and DRB genes are known to exhibit a high level of polymorphism, most likely maintained by parasite-mediated selection. Studies of the MHC in wild rodents have focused on DRB, whilst DQB has been given much less attention. Here, we characterised DQB genes in Swedish bank voles Myodes glareolus, using full-length transcripts. We then designed primers that specifically amplify exon 2 from DRB (202 bp) and DQB (205 bp) and investigated molecular signatures of natural selection on DRB and DQB alleles. The presence of two separate gene clusters was confirmed using BLASTN and phylogenetic analysis, where our seven transcripts clustered according to either DQB or DRB homologues. These gene clusters were again confirmed on exon 2 data from 454-amplicon sequencing. Our DRB primers amplify a similar number of alleles per individual as previously published DRB primers, though our reads are longer. Traditional d N/d S analyses of DRB sequences in the bank vole have not found a conclusive signal of positive selection. Using a more advanced substitution model (the Kumar method) we found positive selection in the peptide binding region (PBR) of both DRB and DQB genes. Maximum likelihood models of codon substitutions detected positively selected sites located in the PBR of both DQB and DRB. Interestingly, these analyses detected at least twice as many positively selected sites in DQB than DRB, suggesting that DQB has been under stronger positive selection than DRB over evolutionary time.

  11. Evidence of positive selection at codon sites localized in extracellular domains of mammalian CC motif chemokine receptor proteins

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    Metzger Kelsey J

    2010-05-01

    Full Text Available Abstract Background CC chemokine receptor proteins (CCR1 through CCR10 are seven-transmembrane G-protein coupled receptors whose signaling pathways are known for their important roles coordinating immune system responses through targeted trafficking of white blood cells. In addition, some of these receptors have been identified as fusion proteins for viral pathogens: for example, HIV-1 strains utilize CCR5, CCR2 and CCR3 proteins to obtain cellular entry in humans. The extracellular domains of these receptor proteins are involved in ligand-binding specificity as well as pathogen recognition interactions. In mammals, the majority of chemokine receptor genes are clustered together; in humans, seven of the ten genes are clustered in the 3p21-24 chromosome region. Gene conversion events, or exchange of DNA sequence between genes, have been reported in chemokine receptor paralogs in various mammalian lineages, especially between the cytogenetically closely located pairs CCR2/5 and CCR1/3. Datasets of mammalian orthologs for each gene were analyzed separately to minimize the potential confounding impact of analyzing highly similar sequences resulting from gene conversion events. Molecular evolution approaches and the software package Phylogenetic Analyses by Maximum Likelihood (PAML were utilized to investigate the signature of selection that has acted on the mammalian CC chemokine receptor (CCR gene family. The results of neutral vs. adaptive evolution (positive selection hypothesis testing using Site Models are reported. In general, positive selection is defined by a ratio of nonsynonymous/synonymous nucleotide changes (dN/dS, or ω >1. Results Of the ten mammalian CC motif chemokine receptor sequence datasets analyzed, only CCR2 and CCR3 contain amino acid codon sites that exhibit evidence of positive selection using site based hypothesis testing in PAML. Nineteen of the twenty codon sites putatively indentified as likely to be under positive

  12. A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Bustamente, Carlos; Clark, Andrew G.

    2005-01-01

    Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect...... such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved...

  13. Recruitment and selection for the packer position in a supermarket network

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    Lucila Moraes Cardoso

    2013-06-01

    Full Text Available The method of personnel recruitment and selection is a common practice to hire people in organizations. The goal of this study is to report and to reflect about this process in a supermarket chain, which operates in food and non-food retail in the state of Sao Paulo. The purpose of the present intervention was to facilitate the recruitment and selection process for the packer position. After the intervention, we noticed an improvement on the hiring process, on the working conditions and a turnover reduction in this position.

  14. Positive and purifying selection influence the evolution of doublesex in the Anastrepha fraterculus species group.

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    Iderval S Sobrinho

    Full Text Available The gene doublesex (dsx is considered to be under strong selective constraint along its evolutionary history because of its central role in somatic sex differentiation in insects. However, previous studies of dsx used global estimates of evolutionary rates to investigate its molecular evolution, which potentially miss signals of adaptive changes in generally conserved genes. In this work, we investigated the molecular evolution of dsx in the Anastrepha fraterculus species group (Diptera, Tephritidae, and test the hypothesis that this gene evolved solely by purifying selection using divergence-based and population-based methods. In the first approach, we compared sequences from Anastrepha and other Tephritidae with other Muscomorpha species, analyzed variation in nonsynonymous to synonymous rate ratios (dN/dS in the Tephritidae, and investigated radical and conservative changes in amino acid physicochemical properties. We show a general selective constraint on dsx, but with signs of positive selection mainly in the common region. Such changes were localized in alpha-helices previously reported to be involved in dimer formation in the OD2 domain and near the C-terminal of the OD1 domain. In the population-based approach, we amplified a region of 540 bp that spanned almost all of the region common to both sexes from 32 different sites in Brazil. We investigated patterns of selection using neutrality tests based on the frequency spectrum and locations of synonymous and nonsynonymous mutations in a haplotype network. As in the divergence-based approach, these analyses showed that dsx has evolved under an overall selective constraint, but with some events of positive selection. In contrast to previous studies, our analyses indicate that even though dsx has indeed evolved as a conserved gene, the common region of dsx has also experienced bouts of positive selection, perhaps driven by sexual selection, during its evolution.

  15. Flexible selection process based on skills applied to the communication manager position

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    Rita Jácome López

    2016-03-01

    Full Text Available The Communication Manager position is relevant to the reputation of an organization, because it influences through its own personal image and reputation; therefore, the selection of this manager has to be painstaking. In this paper we propose a flexible selection process based on fuzzy logic, to fit the skills of candidates for the job and to support decision making. We present two techniques:one that selects the best applicant and another one that compares candidates with an ideal constructed with information provided by Spanish managers.

  16. Genetic signature of strong recent positive selection at interleukin-32 gene in goat

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    Akhtar Rasool Asif

    2017-07-01

    Full Text Available Objective Identification of the candidate genes that play key roles in phenotypic variations can provide new information about evolution and positive selection. Interleukin (IL-32 is involved in many biological processes, however, its role for the immune response against various diseases in mammals is poorly understood. Therefore, the current investigation was performed for the better understanding of the molecular evolution and the positive selection of single nucleotide polymorphisms in IL-32 gene. Methods By using fixation index (FST based method, IL-32 (9375 gene was found to be outlier and under significant positive selection with the provisional combined allocation of mean heterozygosity and FST. Using nucleotide sequences of 11 mammalian species from National Center for Biotechnology Information database, the evolutionary selection of IL-32 gene was determined using Maximum likelihood model method, through four models (M1a, M2a, M7, and M8 in Codeml program of phylogenetic analysis by maximum liklihood. Results IL-32 is detected under positive selection using the FST simulations method. The phylogenetic tree revealed that goat IL-32 was in close resemblance with sheep IL-32. The coding nucleotide sequences were compared among 11 species and it was found that the goat IL-32 gene shared identity with sheep (96.54%, bison (91.97%, camel (58.39%, cat (56.59%, buffalo (56.50%, human (56.13%, dog (50.97%, horse (54.04%, and rabbit (53.41% respectively. Conclusion This study provides evidence for IL-32 gene as under significant positive selection in goat.

  17. Superoxide dismutase 1 is positively selected to minimize protein aggregation in great apes

    DEFF Research Database (Denmark)

    Dasmeh, Pouria; Kepp, Kasper Planeta

    2017-01-01

    Positive (adaptive) selection has recently been implied in human superoxide dismutase 1 (SOD1), a highly abundant antioxidant protein with energy signaling and antiaging functions, one of very few examples of direct selection on a human protein product (exon); the molecular drivers...... and SOD1 aggregates and triggered by aging. Our study thus marks an example of direct selection for a particular chemical phenotype (high net charge and stability) in a single human protein with possible implications for the evolution of aging....... of this selection are unknown. We mapped 30 extant SOD1 sequences to the recently established mammalian species tree and inferred ancestors, key substitutions, and signatures of selection during the protein's evolution. We detected elevated substitution rates leading to great apes (Hominidae) at ~1 per 2 million...

  18. MDEP Common Position CP-DICWG-07. Common position on selection and use of industrial digital devices of limited functionality

    International Nuclear Information System (INIS)

    2014-01-01

    The nuclear power industry is increasingly interested in using industrial digital devices of limited functionality in systems important to safety, but that have not been developed specifically for use in nuclear power applications. These devices should meet certain specific requirements in order to be selected and used in systems important to safety at nuclear power plants. Typically, some of these devices are found embedded in plant components and actuating devices, e.g. sensing instrumentation, motors, pumps, actuators, breakers. The Digital Instrumentation and Controls Working Group (DICWG) has agreed that a common position on this topic is warranted given the increase of use of Digital I and C in new reactor designs, its safety implications, and the need to develop a common understanding from the perspectives of regulatory authorities. This action follows the DICWG examination of the regulatory requirements of the participating members and of relevant industry standards and IAEA documents. The DICWG proposes a common position based on its recent experience with the new reactor application reviews and operating plant issues

  19. Positive selection rather than relaxation of functional constraint drives the evolution of vision during chicken domestication.

    Science.gov (United States)

    Wang, Ming-Shan; Zhang, Rong-Wei; Su, Ling-Yan; Li, Yan; Peng, Min-Sheng; Liu, He-Qun; Zeng, Lin; Irwin, David M; Du, Jiu-Lin; Yao, Yong-Gang; Wu, Dong-Dong; Zhang, Ya-Ping

    2016-05-01

    As noted by Darwin, chickens have the greatest phenotypic diversity of all birds, but an interesting evolutionary difference between domestic chickens and their wild ancestor, the Red Junglefowl, is their comparatively weaker vision. Existing theories suggest that diminished visual prowess among domestic chickens reflect changes driven by the relaxation of functional constraints on vision, but the evidence identifying the underlying genetic mechanisms responsible for this change has not been definitively characterized. Here, a genome-wide analysis of the domestic chicken and Red Junglefowl genomes showed significant enrichment for positively selected genes involved in the development of vision. There were significant differences between domestic chickens and their wild ancestors regarding the level of mRNA expression for these genes in the retina. Numerous additional genes involved in the development of vision also showed significant differences in mRNA expression between domestic chickens and their wild ancestors, particularly for genes associated with phototransduction and photoreceptor development, such as RHO (rhodopsin), GUCA1A, PDE6B and NR2E3. Finally, we characterized the potential role of the VIT gene in vision, which experienced positive selection and downregulated expression in the retina of the village chicken. Overall, our results suggest that positive selection, rather than relaxation of purifying selection, contributed to the evolution of vision in domestic chickens. The progenitors of domestic chickens harboring weaker vision may have showed a reduced fear response and vigilance, making them easier to be unconsciously selected and/or domesticated.

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

    Science.gov (United States)

    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.

  1. Mode Selection Rules for a Two-Delay System with Positive and Negative Feedback Loops

    Science.gov (United States)

    Takahashi, Kin'ya; Kobayashi, Taizo

    2018-04-01

    The mode selection rules for a two-delay system, which has negative feedback with a short delay time t1 and positive feedback with a long delay time t2, are studied numerically and theoretically. We find two types of mode selection rules depending on the strength of the negative feedback. When the strength of the negative feedback |α1| (α1 0), 2m + 1-th harmonic oscillation is well sustained in a neighborhood of t1/t2 = even/odd, i.e., relevant condition. In a neighborhood of the irrelevant condition given by t1/t2 = odd/even or t1/t2 = odd/odd, higher harmonic oscillations are observed. However, if |α1| is slightly less than α2, a different mode selection rule works, where the condition t1/t2 = odd/even is relevant and the conditions t1/t2 = odd/odd and t1/t2 = even/odd are irrelevant. These mode selection rules are different from the mode selection rule of the normal two-delay system with two positive feedback loops, where t1/t2 = odd/odd is relevant and the others are irrelevant. The two types of mode selection rules are induced by individually different mechanisms controlling the Hopf bifurcation, i.e., the Hopf bifurcation controlled by the "boosted bifurcation process" and by the "anomalous bifurcation process", which occur for |α1| below and above the threshold value αth, respectively.

  2. Determining loads acting on the pelvis in upright and recumbent birthing positions: A case study.

    Science.gov (United States)

    Hemmerich, Andrea; Geens, Emily; Diesbourg, Tara; Dumas, Geneviève A

    2018-05-24

    The biomechanics of mothers' birthing positions and their impact on maternal and newborn health outcomes are poorly understood. Our objectives were to determine the loads applied to the female pelvis during dynamic movement that may occur during childbirth; findings are intended to inform clinical understanding and further research on birth positioning mechanics. An optical motion capture system and force platforms were used to collect upright and supine movement data from two pregnant and three non-pregnant participants. Using an inverse dynamics approach, normalized three-dimensional hip and sagittal plane lumbosacral joint moments were estimated during squatting, all-fours, and supine activities. During squatting, peak hip abduction moments were greater for our pregnant (compared with non-pregnant) participants and lumbosacral extension moments substantially exceeded those during walking. The all-fours activity, conversely, generated flexion moments at the L5/S1 joint throughout most of the cycle. In supine, the magnitude of the ground reaction force reached 100% body weight with legs and upper body raised (McRoberts' position); the centre of pressure remained cranial to the sacrum. Squatting generated appreciable moments at the hip and lumbosacral joints that could potentially affect pelvic motion during childbirth. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Signatures of positive selection in Toll-like receptor (TLR genes in mammals

    Directory of Open Access Journals (Sweden)

    Areal Helena

    2011-12-01

    Full Text Available Abstract Background Toll-like receptors (TLRs are a major class of pattern recognition receptors (PRRs expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are encoded by a multigene family and represent the first line of defense against pathogens by detecting foreigner microbial molecular motifs, the pathogen-associated molecular patterns (PAMPs. TLRs are also important by triggering the adaptive immunity in vertebrates. They are characterized by the presence of leucine-rich repeats (LRRs in the ectodomain, which are associated with the PAMPs recognition. The direct recognition of different pathogens by TLRs might result in different evolutionary adaptations important to understand the dynamics of the host-pathogen interplay. Ten mammal TLR genes, viral (TLR3, 7, 8, 9 and non-viral (TLR1-6, 10, were selected to identify signatures of positive selection that might have been imposed by interacting pathogens and to clarify if viral and non-viral TLRs might display different patterns of molecular evolution. Results By using Maximum Likelihood approaches, evidence of positive selection was found in all the TLRs studied. The number of positively selected codons (PSC ranged between 2-26 codons (0.25%-2.65% with the non-viral TLR4 as the receptor with higher percentage of positively selected codons (2.65%, followed by the viral TLR8 (2.50%. The results indicated that viral and non-viral TLRs are similarly under positive selection. Almost all TLRs have at least one PSC located in the LRR ectodomain which underlies the importance of the pathogen recognition by this region. Conclusions Our results are not in line with previous studies on primates and birds that identified more codons under positive selection in non-viral TLRs. This might be explained by the fact that both primates and birds are homogeneous groups probably being affected by only a restricted number of related viruses with equivalent motifs to be

  4. Sardinians genetic background explained by runs of homozygosity and genomic regions under positive selection.

    Directory of Open Access Journals (Sweden)

    Cornelia Di Gaetano

    Full Text Available The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods--fixation index, inflation factor, principal component analysis and ancestry estimation--we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (F(RoH%0.5 when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces.

  5. Gene transfer preferentially selects MHC class I positive tumour cells and enhances tumour immunogenicity.

    Science.gov (United States)

    Hacker, Ulrich T; Schildhauer, Ines; Barroso, Margarita Céspedes; Kofler, David M; Gerner, Franz M; Mysliwietz, Josef; Buening, Hildegard; Hallek, Michael; King, Susan B S

    2006-05-01

    The modulated expression of MHC class I on tumour tissue is well documented. Although the effect of MHC class I expression on the tumorigenicity and immunogenicity of MHC class I negative tumour cell lines has been rigorously studied, less is known about the validity of gene transfer and selection in cell lines with a mixed MHC class I phenotype. To address this issue we identified a C26 cell subline that consists of distinct populations of MHC class I (H-2D/K) positive and negative cells. Transient transfection experiments using liposome-based transfer showed a lower transgene expression in MHC class I negative cells. In addition, MHC class I negative cells were more sensitive to antibiotic selection. This led to the generation of fully MHC class I positive cell lines. In contrast to C26 cells, all transfectants were rejected in vivo and induced protection against the parental tumour cells in rechallenge experiments. Tumour cell specificity of the immune response was demonstrated in in vitro cytokine secretion and cytotoxicity assays. Transfectants expressing CD40 ligand and hygromycin phosphotransferase were not more immunogenic than cells expressing hygromycin resistance alone. We suggest that the MHC class I positive phenotype of the C26 transfectants had a bearing on their immunogenicity, because selected MHC class I positive cells were more immunogenic than parental C26 cells and could induce specific anti-tumour immune responses. These data demonstrate that the generation of tumour cell transfectants can lead to the selection of subpopulations that show an altered phenotype compared to the parental cell line and display altered immunogenicity independent of selection marker genes or other immune modulatory genes. Our results show the importance of monitoring gene transfer in the whole tumour cell population, especially for the evaluation of in vivo therapies targeted to heterogeneous tumour cell populations.

  6. Evidence for positive selection on the leptin gene in Cetacea and Pinnipedia.

    Directory of Open Access Journals (Sweden)

    Li Yu

    Full Text Available The leptin gene has received intensive attention and scientific investigation for its importance in energy homeostasis and reproductive regulation in mammals. Furthermore, study of the leptin gene is of crucial importance for public health, particularly for its role in obesity, as well as for other numerous physiological roles that it plays in mammals. In the present work, we report the identification of novel leptin genes in 4 species of Cetacea, and a comparison with 55 publicly available leptin sequences from mammalian genome assemblies and previous studies. Our study provides evidence for positive selection in the suborder Odontoceti (toothed whales of the Cetacea and the family Phocidae (earless seals of the Pinnipedia. We also detected positive selection in several leptin gene residues in these two lineages. To test whether leptin and its receptor evolved in a coordinated manner, we analyzed 24 leptin receptor gene (LPR sequences from available mammalian genome assemblies and other published data. Unlike the case of leptin, our analyses did not find evidence of positive selection for LPR across the Cetacea and Pinnipedia lineages. In line with this, positively selected sites identified in the leptin genes of these two lineages were located outside of leptin receptor binding sites, which at least partially explains why co-evolution of leptin and its receptor was not observed in the present study. Our study provides interesting insights into current understanding of the evolution of mammalian leptin genes in response to selective pressures from life in an aquatic environment, and leads to a hypothesis that new tissue specificity or novel physiologic functions of leptin genes may have arisen in both odontocetes and phocids. Additional data from other species encompassing varying life histories and functional tests of the adaptive role of the amino acid changes identified in this study will help determine the factors that promote the adaptive

  7. Positing a difference between acts and omissions: the principle of justice, Rachels' cases and moral weakness.

    Science.gov (United States)

    Mohindra, R

    2009-05-01

    The difficulty in discovering a difference between killing and letting die has led many philosophers to deny the distinction. This paper seeks to develop an argument defending the distinction between killing and letting die. In relation to Rachels' cases, the argument is that (a) even accepting that Smith and Jones may select equally heinous options from the choices they have available to them, (b) the fact that the choices available to them are different is morally relevant, and (c) this difference in available choices can be used to distinguish between the agents in certain circumstances. It is the principle of justice, as espoused by Aristotle, which requires that equal things are treated equally and that unequal things are treated unequally that creates a presumption that Smith and Jones should be treated differently. The magnitude of this difference can be amplified by other premises, making the distinction morally relevant in practical reality.

  8. Positive selection in the SLC11A1 gene in the family Equidae.

    Science.gov (United States)

    Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan; Orlando, Ludovic; Horin, Petr

    2016-05-01

    Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed.

  9. Design Modification of Double Acting Positioning Mechanism Inside a Research Reactor Pool

    International Nuclear Information System (INIS)

    El-Bahrawy, A.H.A.

    2002-01-01

    One of the major problems that can face the designers of long actuators is the blocking due to high friction and severe wear of sliding parts, when the case become metal to metal in contact. The present work is an optimum solution for a typical blocking problem that had been raised during the commissioning test of the fission counter three positioning mechanisms inside MPR research reactor at Inshas. A detailed technical investigation had been made in order to define precisely the main reasons behind the problem. High misalignment values of piston and piston rod assembly inside the hydraulic cylinders due to poor design has been discovered to be the main source of the problem. The author has introduced a new design idea, and other mechanisms have been manufactured based on the new design to replace the old ones. The system was tested and found to function with good performance

  10. The Hourglass Model: Are There Structural Problems with the Scarcity of Positive Results for Flexible ACT?

    Science.gov (United States)

    Norlander, Torsten; Nordén, Tommy

    2015-01-01

    The aim of the present article was to discuss the commentary by van Veldhuizen, Delespaul and Mulder (2015) regarding the review by Nordén and Norlander (2014) based on five empirical articles about Flexible Assertive Community Treatment (FACT). Veldhuizen et al. agree on that there is insufficient evidence for the effectiveness of FACT. However, van Veldhuizen et al. avoid a discussion of the lack of positive results despite extensive research during several years and therefore an analysis of why FACT did not fare better is missing. According to FACT it is an advantage that one single team spans the entire chain of care and rehabilitation, but no evidence is given for such an opinion. Instead there may be difficulties for the staff to shift between psychiatric care and psychiatric rehabilitation and the clients perhaps don't want to encounter the same professional team during all phases of care and rehabilitation.

  11. Nitric oxide acts as a positive regulator to induce metamorphosis of the ascidian Herdmania momus.

    Science.gov (United States)

    Ueda, Nobuo; Degnan, Sandie M

    2013-01-01

    Marine invertebrates commonly have a biphasic life cycle in which the metamorphic transition from a pelagic larva to a benthic post-larva is mediated by the nitric oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide synthase (NOS), which is a client protein of the molecular chaperon heat shock protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been implicated in regulating metamorphosis in marine invertebrates as diverse as urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the suppression of NOS activity by the application of either NOS- or HSP90-inhibiting pharmacological agents has been shown consistently to induce the initiation of metamorphosis, leading to the hypothesis that a negative regulatory role of NO is widely conserved in biphasic life cycles. Further, the induction of metamorphosis by heat-shock has been demonstrated for multiple species. Here, we investigate the regulatory role of NO in induction of metamorphosis of the solitary tropical ascidian, Herdmania momus. By coupling pharmacological treatments with analysis of HmNOS and HmHSP90 gene expression, we present compelling evidence of a positive regulatory role for NO in metamorphosis of this species, in contrast to all existing ascidian data that supports the hypothesis of NO as a conserved negative regulator of metamorphosis. The exposure of competent H. momus larvae to a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90 genes. Heat shock of competent larvae induces metamorphosis in a temperature dependent manner, up to a thermal tolerance that approaches 35°C. Both larval/post-larval survival and the appearance of abnormal morphologies in H. momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in response to heat-shock. The demonstrated role of NO as a positive metamorphic regulator in H. momus suggests the existence of inter-specific adaptations of NO regulation in ascidian

  12. Purifying selection acts on coding and non-coding sequences of paralogous genes in Arabidopsis thaliana.

    Science.gov (United States)

    Hoffmann, Robert D; Palmgren, Michael

    2016-06-13

    Whole-genome duplications in the ancestors of many diverse species provided the genetic material for evolutionary novelty. Several models explain the retention of paralogous genes. However, how these models are reflected in the evolution of coding and non-coding sequences of paralogous genes is unknown. Here, we analyzed the coding and non-coding sequences of paralogous genes in Arabidopsis thaliana and compared these sequences with those of orthologous genes in Arabidopsis lyrata. Paralogs with lower expression than their duplicate had more nonsynonymous substitutions, were more likely to fractionate, and exhibited less similar expression patterns with their orthologs in the other species. Also, lower-expressed genes had greater tissue specificity. Orthologous conserved non-coding sequences in the promoters, introns, and 3' untranslated regions were less abundant at lower-expressed genes compared to their higher-expressed paralogs. A gene ontology (GO) term enrichment analysis showed that paralogs with similar expression levels were enriched in GO terms related to ribosomes, whereas paralogs with different expression levels were enriched in terms associated with stress responses. Loss of conserved non-coding sequences in one gene of a paralogous gene pair correlates with reduced expression levels that are more tissue specific. Together with increased mutation rates in the coding sequences, this suggests that similar forces of purifying selection act on coding and non-coding sequences. We propose that coding and non-coding sequences evolve concurrently following gene duplication.

  13. Exocellular extract of Fusarium oxysporum, fungus free, is able to permeate and act selectively in skin.

    Science.gov (United States)

    Sibin Melo, Katia C; Correia, Marcelo H; Svidzinski, Terezinha I E; Hernandes, Luzmarina

    2018-05-01

    The skin is an important gateway for Fusarium infection in humans. Our hypothesis is that metabolites produced by Fusarium oxysporum should change the barrier structure to permeate the skin. Male Wistar rats received a topical application of a solution (0.05 mg/mL) of Fusarium metabolites. The animals were euthanized 3, 6, 12, 24 h after and the skin was processed for immunostaining by laminin and E-cadherin to investigate whether the Fusarium metabolites can break the barrier of healthy skin. Other techniques were employed: H&E to study the morphology; metalloproteinase-9 (MMP-9), TUNEL, and PCNA immunostaining to evaluate the inflammation, cell death, and proliferation, respectively. There was an inflammatory response mainly centered in the dermis. Qualitatively, the skin of the experimental group showed reduced E-cadherin and laminin immunostaining at 3, 12, and 24 h. Higher intensity staining by TUNEL at 3 h, and PCNA at 6, 12, and 24 h. There was intense MMP-9 activity at 6, 12, and 24 h. None of analyses revealed any changes in the epidermis. It was concluded that the fraction was able to permeate the skin and act selectively in dermis, inducing inflammatory response, increasing MMP-9 immunostaining, inducing apoptosis, and reducing E-cadherin and laminin immunostaining. © 2018 APMIS. Published by John Wiley & Sons Ltd.

  14. VizieR Online Data Catalog: 44 SZ-selected galaxy clusters ACT observations (Sifon+, 2016)

    Science.gov (United States)

    Sifon, C.; Battaglia, N.; Hasselfield, M.; Menanteau, F.; Barrientos, L. F.; Bond, J. R.; Crichton, D.; Devlin, M. J.; Dunner, R.; Hilton, M.; Hincks, A. D.; Hlozek, R.; Huffenberger, K. M.; Hughes, J. P.; Infante, L.; Kosowsky, A.; Marsden, D.; Marriage, T. A.; Moodley, K.; Niemack, M. D.; Page, L. A.; Spergel, D. N.; Staggs, S. T.; Trac, H.; Wollack, E. J.

    2017-11-01

    ACT is a 6-metre off-axis Gregorian telescope located at an altitude of 5200um in the Atacama desert in Chile, designed to observe the CMB at arcminute resolution. Galaxy clusters were detected in the 148GHz band by matched-filtering the maps with the pressure profile suggested by Arnaud et al. (2010A&A...517A..92A), fit to X-ray selected local (zGMOS) on the Gemini-South telescope, split in semesters 2011B (ObsID:GS-2011B-C-1, PI:Barrientos/Menanteau) and 2012A (ObsID:GS-2012A-C-1, PI:Menanteau), prioritizing clusters in the cosmological sample at 0.3

  15. Barley disease susceptibility factor RACB acts in epidermal cell polarity and positioning of the nucleus.

    Science.gov (United States)

    Scheler, Björn; Schnepf, Vera; Galgenmüller, Carolina; Ranf, Stefanie; Hückelhoven, Ralph

    2016-05-01

    RHO GTPases are regulators of cell polarity and immunity in eukaryotes. In plants, RHO-like RAC/ROP GTPases are regulators of cell shaping, hormone responses, and responses to microbial pathogens. The barley (Hordeum vulgare L.) RAC/ROP protein RACB is required for full susceptibility to penetration by Blumeria graminis f.sp. hordei (Bgh), the barley powdery mildew fungus. Disease susceptibility factors often control host immune responses. Here we show that RACB does not interfere with early microbe-associated molecular pattern-triggered immune responses such as the oxidative burst or activation of mitogen-activated protein kinases. RACB also supports rather than restricts expression of defence-related genes in barley. Instead, silencing of RACB expression by RNAi leads to defects in cell polarity. In particular, initiation and maintenance of root hair growth and development of stomatal subsidiary cells by asymmetric cell division is affected by silencing expression of RACB. Nucleus migration is a common factor of developmental cell polarity and cell-autonomous interaction with Bgh RACB is required for positioning of the nucleus near the site of attack from Bgh We therefore suggest that Bgh profits from RACB's function in cell polarity rather than from immunity-regulating functions of RACB. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  16. Effect of antiviral treatment and host susceptibility on positive selection in hepatitis C virus (HCV).

    Science.gov (United States)

    Jiménez-Hernández, Nuria; Sentandreu, Vicente; Castro, José A; Torres-Puente, Manuela; Bracho, Alma; García-Robles, Inmaculada; Ortega, Enrique; Del Olmo, Juan; Carnicer, Fernando; González-Candelas, Fernando; Moya, Andrés

    2008-02-01

    We have conducted a large sequence study of the E1-E2 and NS5A regions of the HCV, subtypes 1a and b, both in patients previously treated with interferon, and untreated patients, who later responded, or not, to a combination therapy based on interferon plus ribavirin. We have examined the role played by the number of positively selected sites on disease progression and its relationship with several variables such as patients' age, sex and their risk of acquiring the disease. We have detected three groups of patients that respond or not to combination therapy: responders of intermediate age, older non-responders and young non-responders, they possess an increasing average number of positively selected sites in the E1-E2 region, respectively. We conclude that the host's genetic factors play an important role in whether the disease is contained or becomes chronic.

  17. A synbio approach for selection of highly expressed gene variants in Gram-positive bacteria

    DEFF Research Database (Denmark)

    Ferro, Roberto; Rennig, Maja; Hernández Rollán, Cristina

    2018-01-01

    with a long history in food fermentation. We have developed a synbio approach for increasing gene expression in two Gram-positive bacteria. First of all, the gene of interest was coupled to an antibiotic resistance gene to create a growth-based selection system. We then randomised the translation initiation...... region (TIR) preceding the gene of interest and selected clones that produced high protein titres, as judged by their ability to survive on high concentrations of antibiotic. Using this approach, we were able to significantly increase production of two industrially relevant proteins; sialidase in B....... subtilis and tyrosine ammonia lyase in L. lactis. Gram-positive bacteria are widely used to produce industrial enzymes. High titres are necessary to make the production economically feasible. The synbio approach presented here is a simple and inexpensive way to increase protein titres, which can be carried...

  18. De novo transcriptome assembly and positive selection analysis of an individual deep-sea fish.

    Science.gov (United States)

    Lan, Yi; Sun, Jin; Xu, Ting; Chen, Chong; Tian, Renmao; Qiu, Jian-Wen; Qian, Pei-Yuan

    2018-05-24

    High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives. We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod. Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies.

  19. Growth of non-Campylobacter, oxidase-positive bacteria on selective Campylobacter agar.

    OpenAIRE

    Moskowitz, L B; Chester, B

    1982-01-01

    A total of 67 oxidase-positive, gram-negative bacteria were tested for growth on selective Campylobacter agar (Blaser formulation, BBL Microbiology Systems, Cockeysville, Md.) at 42 degrees C under microaerophilic conditions. Although the growth of most of these bacteria was prevented, all strains of Achromobacter xylosoxidans, Pseudomonas aeruginosa, Pseudomonas putrefaciens, Pseudomonas alcaligenes, and Pseudomonas pseudoalcaligenes grew as well as Campylobacter fetus subsp. jejuni.

  20. DISCRIMINATIVE MODEL OF CERTAIN MOTOR INDICATORS OF FOOTBALL PLAYERS AS SELECTION CRITERIA FOR TEAM POSITION

    Directory of Open Access Journals (Sweden)

    Goran Vučković

    2013-07-01

    Full Text Available Well-designed and implemented selection is one of the important prerequisites for achieving the expected results in the modern competitive sport at all levels. The aim of this work was to determine how the selection was made for Serbian League players, on the basis of their certain motor parameters and the positions in the team. A sample of 25 senior players of a football team competing in the Serbian League is divided into four sub-samples, based on team positions. For assessment of motor characteristics following tests were used: long jump (LJ, Abalac test (AT; 10 seconds push-ups (PU, 30 seconds trunk bends (TB, 20 meter flying start running (20FSR, 20 meter high start running (20HSR, 50 meter high start running (50HSR and Cooper test (CT . Based on the obtained results it can be concluded that there are significant differences for variable 20FSR and variable CT (F = 3754, 9835, p = .027, .000, respectively. Three canonical discriminant functions were singled out, where the first explained even 84.6%, the second 14.5% and the third only 1% of the total variance, or in summary first two functions explained 99.0% of the variance. It can be concluded that the selected players, in terms of the position in the team, distinguished first by performing on the Cooper test, followed by the result of 20 meter flying start running, 20 meter high start running, 50 meter high start running, trunk bends, and finally by Abalac test, push-ups and long jump. Observed as a function of certain motor characteristics, it could be concluded that in the selection of players in terms of the playing position confidence level was 72.0% in general level, with the most reliable for goalkeepers (100%, midfielders (71.4% and defensive players (70.0%, while the smallest was at strikers (50%.

  1. High amino acid diversity and positive selection at a putative coral immunity gene (tachylectin-2

    Directory of Open Access Journals (Sweden)

    Hellberg Michael E

    2010-05-01

    Full Text Available Abstract Background Genes involved in immune functions, including pathogen recognition and the activation of innate defense pathways, are among the most genetically variable known, and the proteins that they encode are often characterized by high rates of amino acid substitutions, a hallmark of positive selection. The high levels of variation characteristic of immunity genes make them useful tools for conservation genetics. To date, highly variable immunity genes have yet to be found in corals, keystone organisms of the world's most diverse marine ecosystem, the coral reef. Here, we examine variation in and selection on a putative innate immunity gene from Oculina, a coral genus previously used as a model for studies of coral disease and bleaching. Results In a survey of 244 Oculina alleles, we find high nonsynonymous variation and a signature of positive selection, consistent with a putative role in immunity. Using computational protein structure prediction, we generate a structural model of the Oculina protein that closely matches the known structure of tachylectin-2 from the Japanese horseshoe crab (Tachypleus tridentatus, a protein with demonstrated function in microbial recognition and agglutination. We also demonstrate that at least three other genera of anthozoan cnidarians (Acropora, Montastrea and Nematostella possess proteins structurally similar to tachylectin-2. Conclusions Taken together, the evidence of high amino acid diversity, positive selection and structural correspondence to the horseshoe crab tachylectin-2 suggests that this protein is 1 part of Oculina's innate immunity repertoire, and 2 evolving adaptively, possibly under selective pressure from coral-associated microorganisms. Tachylectin-2 may serve as a candidate locus to screen coral populations for their capacity to respond adaptively to future environmental change.

  2. Young Adults’ Selection and Use of Dependent Coverage under the Affordable Care Act

    Directory of Open Access Journals (Sweden)

    Weiwei Chen

    2018-01-01

    Full Text Available The dependent coverage expansion under the Affordable Care Act (ACA required health insurance policies that cover dependents to offer coverage for policyholder’ children up to age 26. It has been well documented that the provision successfully reduced the uninsured rate among the young adults. However, less is known about whether dependent coverage crowded out other insurance types and whether young adults used dependent coverage as a fill-in-the-gap short-term option. Using data from the Survey of Income and Program Participation 2008 Panel, the paper assesses dependent coverage uptake and duration before and after the ACA provision among young adults aged 19–26 versus those aged 27–30. Regressions for additional coverage outcomes were also performed to estimate the crowd-out rate. It was found that the ACA provision had a significant positive impact on dependent coverage uptake and duration. The estimated crowd-out rate ranges from 27 to 42%, depending on the definition. Most dependent coverage enrollees used the coverage for 1 or 2 years. Differences in dependent coverage uptake and duration remained among racial groups. Less healthy individuals were also less likely to make use of dependent coverage.

  3. Positive selection and propeptide repeats promote rapid interspecific divergence of a gastropod sperm protein.

    Science.gov (United States)

    Hellberg, M E; Moy, G W; Vacquier, V D

    2000-03-01

    Male-specific proteins have increasingly been reported as targets of positive selection and are of special interest because of the role they may play in the evolution of reproductive isolation. We report the rapid interspecific divergence of cDNA encoding a major acrosomal protein of unknown function (TMAP) of sperm from five species of teguline gastropods. A mitochondrial DNA clock (calibrated by congeneric species divided by the Isthmus of Panama) estimates that these five species diverged 2-10 MYA. Inferred amino acid sequences reveal a propeptide that has diverged rapidly between species. The mature protein has diverged faster still due to high nonsynonymous substitution rates (> 25 nonsynonymous substitutions per site per 10(9) years). cDNA encoding the mature protein (89-100 residues) shows evidence of positive selection (Dn/Ds > 1) for 4 of 10 pairwise species comparisons. cDNA and predicted secondary-structure comparisons suggest that TMAP is neither orthologous nor paralogous to abalone lysin, and thus marks a second, phylogenetically independent, protein subject to strong positive selection in free-spawning marine gastropods. In addition, an internal repeat in one species (Tegula aureotincta) produces a duplicated cleavage site which results in two alternatively processed mature proteins differing by nine amino acid residues. Such alternative processing may provide a mechanism for introducing novel amino acid sequence variation at the amino-termini of proteins. Highly divergent TMAP N-termini from two other tegulines (Tegula regina and Norrisia norrisii) may have originated by such a mechanism.

  4. Positive Selection Driving Cytoplasmic Genome Evolution of the Medicinally Important Ginseng Plant Genus Panax.

    Science.gov (United States)

    Jiang, Peng; Shi, Feng-Xue; Li, Ming-Rui; Liu, Bao; Wen, Jun; Xiao, Hong-Xing; Li, Lin-Feng

    2018-01-01

    Panax L. (the ginseng genus) is a shade-demanding group within the family Araliaceae and all of its species are of crucial significance in traditional Chinese medicine. Phylogenetic and biogeographic analyses demonstrated that two rounds of whole genome duplications accompanying with geographic and ecological isolations promoted the diversification of Panax species. However, contributions of the cytoplasmic genomes to the adaptive evolution of Panax species remained largely uninvestigated. In this study, we sequenced the chloroplast and mitochondrial genomes of 11 accessions belonging to seven Panax species. Our results show that heterogeneity in nucleotide substitution rate is abundant in both of the two cytoplasmic genomes, with the mitochondrial genome possessing more variants at the total level but the chloroplast showing higher sequence polymorphisms at the genic regions. Genome-wide scanning of positive selection identified five and 12 genes from the chloroplast and mitochondrial genomes, respectively. Functional analyses further revealed that these selected genes play important roles in plant development, cellular metabolism and adaptation. We therefore conclude that positive selection might be one of the potential evolutionary forces that shaped nucleotide variation pattern of these Panax species. In particular, the mitochondrial genes evolved under stronger selective pressure compared to the chloroplast genes.

  5. Red Queen Processes Drive Positive Selection on Major Histocompatibility Complex (MHC Genes.

    Directory of Open Access Journals (Sweden)

    Maciej Jan Ejsmond

    2015-11-01

    Full Text Available Major Histocompatibility Complex (MHC genes code for proteins involved in the incitation of the adaptive immune response in vertebrates, which is achieved through binding oligopeptides (antigens of pathogenic origin. Across vertebrate species, substitutions of amino acids at sites responsible for the specificity of antigen binding (ABS are positively selected. This is attributed to pathogen-driven balancing selection, which is also thought to maintain the high polymorphism of MHC genes, and to cause the sharing of allelic lineages between species. However, the nature of this selection remains controversial. We used individual-based computer simulations to investigate the roles of two phenomena capable of maintaining MHC polymorphism: heterozygote advantage and host-pathogen arms race (Red Queen process. Our simulations revealed that levels of MHC polymorphism were high and driven mostly by the Red Queen process at a high pathogen mutation rate, but were low and driven mostly by heterozygote advantage when the pathogen mutation rate was low. We found that novel mutations at ABSs are strongly favored by the Red Queen process, but not by heterozygote advantage, regardless of the pathogen mutation rate. However, while the strong advantage of novel alleles increased the allele turnover rate, under a high pathogen mutation rate, allelic lineages persisted for a comparable length of time under Red Queen and under heterozygote advantage. Thus, when pathogens evolve quickly, the Red Queen is capable of explaining both positive selection and long coalescence times, but the tension between the novel allele advantage and persistence of alleles deserves further investigation.

  6. Positive selection on D-lactate dehydrogenases of Lactobacillus delbrueckii subspecies bulgaricus.

    Science.gov (United States)

    Zhang, Jifeng; Gong, Guangyu; Wang, Xiao; Zhang, Hao; Tian, Weidong

    2015-08-01

    Lactobacillus delbrueckii has been widely used for yogurt fermentation. It has genes encoding both D- and L-type lactate dehydrogenases (LDHs) that catalyse the production of L(+) or D(-) stereoisomer of lactic acid. D-lactic acid is the primary lactate product by L. delbrueckii, yet it cannot be metabolised by human intestine. Since it has been domesticated for long time, an interesting question arises regarding to whether the selection pressure has affected the evolution of both L-LDH and D-LDH genes in the genome. To answer this question, in this study the authors first investigated the evolution of these two genes by constructing phylogenetic trees. They found that D-LDH-based phylogenetic tree could better represent the phylogenetic relationship in the acidophilus complex than L-LDH-based tree. They next investigated the evolutions of LDH genes of L. delbrueckii at amino acid level, and found that D-LDH gene in L. delbrueckii is positively selected, possibly a consequence of long-term domestication. They further identified four amino acids that are under positive selection. One of them, V261, is located at the centre of three catalytic active sites, indicating likely functional effects on the enzyme activity. The selection from the domestication process thus provides direction for future engineering of D-LDH.

  7. Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene.

    Directory of Open Access Journals (Sweden)

    Per Erixon

    Full Text Available BACKGROUND: Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. METHODOLOGY/PRINCIPLE FINDINGS: We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family. Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. CONCLUSIONS/SIGNIFICANCE: We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the

  8. Ancient and recent positive selection transformed opioid cis-regulation in humans.

    Directory of Open Access Journals (Sweden)

    Matthew V Rockman

    2005-12-01

    Full Text Available Changes in the cis-regulation of neural genes likely contributed to the evolution of our species' unique attributes, but evidence of a role for natural selection has been lacking. We found that positive natural selection altered the cis-regulation of human prodynorphin, the precursor molecule for a suite of endogenous opioids and neuropeptides with critical roles in regulating perception, behavior, and memory. Independent lines of phylogenetic and population genetic evidence support a history of selective sweeps driving the evolution of the human prodynorphin promoter. In experimental assays of chimpanzee-human hybrid promoters, the selected sequence increases transcriptional inducibility. The evidence for a change in the response of the brain's natural opioids to inductive stimuli points to potential human-specific characteristics favored during evolution. In addition, the pattern of linked nucleotide and microsatellite variation among and within modern human populations suggests that recent selection, subsequent to the fixation of the human-specific mutations and the peopling of the globe, has favored different prodynorphin cis-regulatory alleles in different parts of the world.

  9. General Labour Code (Act No. 2 of 1986), 5 April 1986. [Selected provisions].

    Science.gov (United States)

    1989-01-01

    Guinea-Bissau's General Labor Code, Act No. 2 of 1986, requires that employers adopt non-discriminatory procedures in dealing with their employees, disallowing discrimination based on gender, race, national origin, religion, political ideology or inclination, or on whether or not an employee is affiliated to a worker's union. Women are guaranteed equality with men in work opportunity and employment treatment; they are assured access to any type of job, profession, or position which does not pose any potential or actual threat to their genetic functioning. Additional legislation shall establish the conditions and prohibitions for contracting woman for heavy labor, for jobs performed under insalubrious conditions, for underground work, and for other types of jobs which might endanger a woman's genetic functioning. Job offers must not discriminate, unless the restrictions or specifications are essential to the nature of the job, rendering the job qualitatively differentiable when performed by a man or a woman. The employer must ensure that female workers have the same job opportunity and treatment for professional training and career development. Different specific job categories may not be created for men and women if a woman's salary is inferior to that of a man performing equivalent work in a corresponding professional category. Protection during pregnancy and delivery guarantees a woman the right to decline medically inadvisable tasks without loss of wages; to decline overtime work; to be absent from work when necessary for maternal medical care without loss of wages; to interrupt daily work to nurse her children for 1 hour or 2 for half-hour periods for up to 1 year without the loss of wages. Every female employee has the right to 60 days pregnancy and maternity leave, without loss of wages, for whatever clinical type of delivery, including for still births and for births where the infant died shortly thereafter.

  10. Widespread Positive Selection Drives Differentiation of Centromeric Proteins in the Drosophila melanogaster subgroup.

    Science.gov (United States)

    Beck, Emily A; Llopart, Ana

    2015-11-25

    Rapid evolution of centromeric satellite repeats is thought to cause compensatory amino acid evolution in interacting centromere-associated kinetochore proteins. Cid, a protein that mediates kinetochore/centromere interactions, displays particularly high amino acid turnover. Rapid evolution of both Cid and centromeric satellite repeats led us to hypothesize that the apparent compensatory evolution may extend to interacting partners in the Condensin I complex (i.e., SMC2, SMC4, Cap-H, Cap-D2, and Cap-G) and HP1s. Missense mutations in these proteins often result in improper centromere formation and aberrant chromosome segregation, thus selection for maintained function and coevolution among proteins of the complex is likely strong. Here, we report evidence of rapid evolution and recurrent positive selection in seven centromere-associated proteins in species of the Drosophila melanogaster subgroup, and further postulate that positive selection on these proteins could be a result of centromere drive and compensatory changes, with kinetochore proteins competing for optimal spindle attachment.

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

    Science.gov (United States)

    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.

  12. A synbio approach for selection of highly expressed gene variants in Gram-positive bacteria.

    Science.gov (United States)

    Ferro, Roberto; Rennig, Maja; Hernández-Rollán, Cristina; Daley, Daniel O; Nørholm, Morten H H

    2018-03-08

    The market for recombinant proteins is on the rise, and Gram-positive strains are widely exploited for this purpose. Bacillus subtilis is a profitable host for protein production thanks to its ability to secrete large amounts of proteins, and Lactococcus lactis is an attractive production organism with a long history in food fermentation. We have developed a synbio approach for increasing gene expression in two Gram-positive bacteria. First of all, the gene of interest was coupled to an antibiotic resistance gene to create a growth-based selection system. We then randomised the translation initiation region (TIR) preceding the gene of interest and selected clones that produced high protein titres, as judged by their ability to survive on high concentrations of antibiotic. Using this approach, we were able to significantly increase production of two industrially relevant proteins; sialidase in B. subtilis and tyrosine ammonia lyase in L. lactis. Gram-positive bacteria are widely used to produce industrial enzymes. High titres are necessary to make the production economically feasible. The synbio approach presented here is a simple and inexpensive way to increase protein titres, which can be carried out in any laboratory within a few days. It could also be implemented as a tool for applications beyond TIR libraries, such as screening of synthetic, homologous or domain-shuffled genes.

  13. Bayes Empirical Bayes Inference of Amino Acid Sites Under Positive Selection

    DEFF Research Database (Denmark)

    Yang, Ziheng; Wong, Wendy Shuk Wan; Nielsen, Rasmus

    2005-01-01

    , with > 1 indicating positive selection. Statistical distributions are used to model the variation in among sites, allowing a subset of sites to have > 1 while the rest of the sequence may be under purifying selection with ... probabilities that a site comes from the site class with > 1. Current implementations, however, use the naive EB (NEB) approach and fail to account for sampling errors in maximum likelihood estimates of model parameters, such as the proportions and ratios for the site classes. In small data sets lacking...... information, this approach may lead to unreliable posterior probability calculations. In this paper, we develop a Bayes empirical Bayes (BEB) approach to the problem, which assigns a prior to the model parameters and integrates over their uncertainties. We compare the new and old methods on real and simulated...

  14. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Foreign Intelligence Surveillance Act: Selected Legislation from the 108th Congress

    National Research Council Canada - National Science Library

    Bazan, Elizabeth B

    2005-01-01

    The Foreign Intelligence Surveillance Act, 50 U.S.C. 1801 (FISA) as passed in 1978, provided a statutory framework for the use of electronic surveillance in the context of foreign intelligence gathering...

  16. Positive selection on the nonhomologous end-joining factor Cernunnos-XLF in the human lineage

    Directory of Open Access Journals (Sweden)

    Jurka Jerzy

    2006-06-01

    Full Text Available Abstract Background Cernunnos-XLF is a nonhomologous end-joining factor that is mutated in patients with a rare immunodeficiency with microcephaly. Several other microcephaly-associated genes such as ASPM and microcephalin experienced recent adaptive evolution apparently linked to brain size expansion in humans. In this study we investigated whether Cernunnos-XLF experienced similar positive selection during human evolution. Results We obtained or reconstructed full-length coding sequences of chimpanzee, rhesus macaque, canine, and bovine Cernunnos-XLF orthologs from sequence databases and sequence trace archives. Comparison of coding sequences revealed an excess of nonsynonymous substitutions consistent with positive selection on Cernunnos-XLF in the human lineage. The hotspots of adaptive evolution are concentrated around a specific structural domain, whose analogue in the structurally similar XRCC4 protein is involved in binding of another nonhomologous end-joining factor, DNA ligase IV. Conclusion Cernunnos-XLF is a microcephaly-associated locus newly identified to be under adaptive evolution in humans, and possibly played a role in human brain expansion. We speculate that Cernunnos-XLF may have contributed to the increased number of brain cells in humans by efficient double strand break repair, which helps to prevent frequent apoptosis of neuronal progenitors and aids mitotic cell cycle progression. Reviewers This article was reviewed by Chris Ponting and Richard Emes (nominated by Chris Ponting, Kateryna Makova, Gáspár Jékely and Eugene V. Koonin.

  17. Transcriptome profile and unique genetic evolution of positively selected genes in yak lungs.

    Science.gov (United States)

    Lan, DaoLiang; Xiong, XianRong; Ji, WenHui; Li, Jian; Mipam, Tserang-Donko; Ai, Yi; Chai, ZhiXin

    2018-04-01

    The yak (Bos grunniens), which is a unique bovine breed that is distributed mainly in the Qinghai-Tibetan Plateau, is considered a good model for studying plateau adaptability in mammals. The lungs are important functional organs that enable animals to adapt to their external environment. However, the genetic mechanism underlying the adaptability of yak lungs to harsh plateau environments remains unknown. To explore the unique evolutionary process and genetic mechanism of yak adaptation to plateau environments, we performed transcriptome sequencing of yak and cattle (Bos taurus) lungs using RNA-Seq technology and a subsequent comparison analysis to identify the positively selected genes in the yak. After deep sequencing, a normal transcriptome profile of yak lung that containing a total of 16,815 expressed genes was obtained, and the characteristics of yak lungs transcriptome was described by functional analysis. Furthermore, Ka/Ks comparison statistics result showed that 39 strong positively selected genes are identified from yak lungs. Further GO and KEGG analysis was conducted for the functional annotation of these genes. The results of this study provide valuable data for further explorations of the unique evolutionary process of high-altitude hypoxia adaptation in yaks in the Tibetan Plateau and the genetic mechanism at the molecular level.

  18. Evidence of positive selection associated with placental loss in tiger sharks.

    Science.gov (United States)

    Swift, Dominic G; Dunning, Luke T; Igea, Javier; Brooks, Edward J; Jones, Catherine S; Noble, Leslie R; Ciezarek, Adam; Humble, Emily; Savolainen, Vincent

    2016-06-14

    All vertebrates initially feed their offspring using yolk reserves. In some live-bearing species these yolk reserves may be supplemented with extra nutrition via a placenta. Sharks belonging to the Carcharhinidae family are all live-bearing, and with the exception of the tiger shark (Galeocerdo cuvier), develop placental connections after exhausting yolk reserves. Phylogenetic relationships suggest the lack of placenta in tiger sharks is due to secondary loss. This represents a dramatic shift in reproductive strategy, and is likely to have left a molecular footprint of positive selection within the genome. We sequenced the transcriptome of the tiger shark and eight other live-bearing shark species. From this data we constructed a time-calibrated phylogenetic tree estimating the tiger shark lineage diverged from the placental carcharhinids approximately 94 million years ago. Along the tiger shark lineage, we identified five genes exhibiting a signature of positive selection. Four of these genes have functions likely associated with brain development (YWHAE and ARL6IP5) and sexual reproduction (VAMP4 and TCTEX1D2). Our results indicate the loss of placenta in tiger sharks may be associated with subsequent adaptive changes in brain development and sperm production.

  19. Influence of needle position on lumbar segmental nerve root block selectivity.

    Science.gov (United States)

    Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

    2006-01-01

    In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

  20. Examination of Signatures of Recent Positive Selection on Genes Involved in Human Sialic Acid Biology.

    Science.gov (United States)

    Moon, Jiyun M; Aronoff, David M; Capra, John A; Abbot, Patrick; Rokas, Antonis

    2018-03-28

    Sialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that

  1. Device for the selective positioning of a component on a tube plate

    International Nuclear Information System (INIS)

    1974-01-01

    The invention relates to a device for the selective positioning of a component on a tube plate. It particularly applies to the positioning of a guide tube head successively opposite all the tubes of the tube bundle of a nuclear reactor steam generator. The large number of tubes in the tube bundle of the steam generator in a pressure water nuclear power station must be checked periodically for any likely corrosion. This check is effected with a Foucault current probe which is inserted in each tube in turn and is connected to a probe signal processing unit. The probe is placed in a flexible guide tube brought in turn in front of each tube of the bundle to be checked. The invention concerns a device to move the opening of a tube guide for a Foucault current detector over the entire surface of the tube plate, thereby providing access to all the tubes whilst limiting the interventions to a single positioning and a single withdrawal of the apparatus for testing all the bundle. Between the two interventions at the beginning and end of the operation, all displacements are remote controlled from outside the dangerous radioacive area [fr

  2. Discovery and characterization of ACT-335827, an orally available, brain penetrant orexin receptor type 1 selective antagonist.

    Science.gov (United States)

    Steiner, Michel A; Gatfield, John; Brisbare-Roch, Catherine; Dietrich, Hendrik; Treiber, Alexander; Jenck, Francois; Boss, Christoph

    2013-06-01

    Stress relief: Orexin neuropeptides regulate arousal and stress processing through orexin receptor type 1 (OXR-1) and 2 (OXR-2) signaling. A selective OXR-1 antagonist, represented by a phenylglycine-amide substituted tetrahydropapaverine derivative (ACT-335827), is described that is orally available, penetrates the brain, and decreases fear, compulsive behaviors and autonomic stress reactions in rats. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Augmenting the Genetic Toolbox for Sulfolobus islandicus with a Stringent Positive Selectable Marker for Agmatine Prototrophy

    Science.gov (United States)

    Cooper, Tara E.; Krause, David J.

    2013-01-01

    Sulfolobus species have become the model organisms for studying the unique biology of the crenarchaeal division of the archaeal domain. In particular, Sulfolobus islandicus provides a powerful opportunity to explore natural variation via experimental functional genomics. To support these efforts, we further expanded genetic tools for S. islandicus by developing a stringent positive selection for agmatine prototrophs in strains in which the argD gene, encoding arginine decarboxylase, has been deleted. Strains with deletions in argD were shown to be auxotrophic for agmatine even in nutrient-rich medium, but growth could be restored by either supplementation of exogenous agmatine or reintroduction of a functional copy of the argD gene from S. solfataricus P2 into the ΔargD host. Using this stringent selection, a robust targeted gene knockout system was established via an improved next generation of the MID (marker insertion and unmarked target gene deletion) method. Application of this novel system was validated by targeted knockout of the upsEF genes involved in UV-inducible cell aggregation formation. PMID:23835176

  4. Genes under positive selection in a model plant pathogenic fungus, Botrytis.

    Science.gov (United States)

    Aguileta, Gabriela; Lengelle, Juliette; Chiapello, Hélène; Giraud, Tatiana; Viaud, Muriel; Fournier, Elisabeth; Rodolphe, François; Marthey, Sylvain; Ducasse, Aurélie; Gendrault, Annie; Poulain, Julie; Wincker, Patrick; Gout, Lilian

    2012-07-01

    The rapid evolution of particular genes is essential for the adaptation of pathogens to new hosts and new environments. Powerful methods have been developed for detecting targets of selection in the genome. Here we used divergence data to compare genes among four closely related fungal pathogens adapted to different hosts to elucidate the functions putatively involved in adaptive processes. For this goal, ESTs were sequenced in the specialist fungal pathogens Botrytis tulipae and Botrytis ficariarum, and compared with genome sequences of Botrytis cinerea and Sclerotinia sclerotiorum, responsible for diseases on over 200 plant species. A maximum likelihood-based analysis of 642 predicted orthologs detected 21 genes showing footprints of positive selection. These results were validated by resequencing nine of these genes in additional Botrytis species, showing they have also been rapidly evolving in other related species. Twenty of the 21 genes had not previously been identified as pathogenicity factors in B. cinerea, but some had functions related to plant-fungus interactions. The putative functions were involved in respiratory and energy metabolism, protein and RNA metabolism, signal transduction or virulence, similarly to what was detected in previous studies using the same approach in other pathogens. Mutants of B. cinerea were generated for four of these genes as a first attempt to elucidate their functions. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Kinetics and selectivity of permanganate chemiluminescence: a study of hydroxyl and amino disubstituted benzene positional isomers.

    Science.gov (United States)

    Slezak, Teo; Smith, Zoe M; Adcock, Jacqui L; Hindson, Christopher M; Barnett, Neil W; Nesterenko, Pavel N; Francis, Paul S

    2011-11-30

    Examination of the chemiluminescence reactions of dihydroxybenzenes, aminophenols and phenylenediamines with acidic potassium permanganate has provided a new understanding of the relationships between analyte structure, reaction conditions, kinetics of the light-producing pathway and emission intensity, with broad implications for this widely utilised chemiluminescence detection system. Using a permanganate reagent prepared in a polyphosphate solution and adjusted to pH 2.5, large differences in the rate of reaction with different positional isomers were observed, with the meta-substituted forms reacting far slower and therefore exhibiting much lower chemiluminescence intensities in flow analysis systems. The preliminary partial reduction of permanganate to form significant concentrations of Mn(III) increased the rate of reaction with all analytes tested, resulting in comparable or (in the case of aminophenol and phenylenediamine) even greater emission intensities for the meta-isomers, demonstrating the opportunity to tune the selectivity of the reagent towards certain classes of compound or even specific positional isomers of the same compound. Using more acidic permanganate reagents, in which polyphosphates are not required, the discrepancy between the chemiluminescence intensities was still observed, but was less prominent due to the generally faster rates of reaction. The enhancement of these chemiluminescence reactions by on-line addition of formic acid or formaldehyde can in part also be attributed to the generation of significant pools of the key Mn(III) precursor to the emitting species. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Positive evolutionary selection of an HD motif on Alzheimer precursor protein orthologues suggests a functional role.

    Science.gov (United States)

    Miklós, István; Zádori, Zoltán

    2012-02-01

    HD amino acid duplex has been found in the active center of many different enzymes. The dyad plays remarkably different roles in their catalytic processes that usually involve metal coordination. An HD motif is positioned directly on the amyloid beta fragment (Aβ) and on the carboxy-terminal region of the extracellular domain (CAED) of the human amyloid precursor protein (APP) and a taxonomically well defined group of APP orthologues (APPOs). In human Aβ HD is part of a presumed, RGD-like integrin-binding motif RHD; however, neither RHD nor RXD demonstrates reasonable conservation in APPOs. The sequences of CAEDs and the position of the HD are not particularly conserved either, yet we show with a novel statistical method using evolutionary modeling that the presence of HD on CAEDs cannot be the result of neutral evolutionary forces (pHD motif is underrepresented in the proteomes of all species of the animal kingdom. Position migration can be explained by high probability occurrence of multiple copies of HD on intermediate sequences, from which only one is kept by selective evolutionary forces, in a similar way as in the case of the "transcription binding site turnover." CAED of all APP orthologues and homologues are predicted to bind metal ions including Amyloid-like protein 1 (APLP1) and Amyloid-like protein 2 (APLP2). Our results suggest that HDs on the CAEDs are most probably key components of metal-binding domains, which facilitate and/or regulate inter- or intra-molecular interactions in a metal ion-dependent or metal ion concentration-dependent manner. The involvement of naturally occurring mutations of HD (Tottori (D7N) and English (H6R) mutations) in early onset Alzheimer's disease gives additional support to our finding that HD has an evolutionary preserved function on APPOs.

  7. Pharmacological stimuli decreasing nucleus accumbens dopamine can act as positive reinforcers but have a low addictive potential.

    Science.gov (United States)

    Marinelli, M; Barrot, M; Simon, H; Oberlander, C; Dekeyne, A; Le Moal, M; Piazza, P V

    1998-10-01

    Opioid peptides, through mu and delta receptors, play an important part in reward. In contrast, the role of kappa receptors is more controversial. We examined the possible positive reinforcing effects of a selective kappa agonist, RU 51599, by studying intravenous self-administration in the rat. The effect of RU 51599 on dopamine release in the nucleus accumbens was also studied, as opioids and dopamine seem to interact in the mediation of reward. The behavioural and dopaminergic effects of RU 51599 were compared with those of the mu agonist heroin. Rats self-administered both RU 51599 (6.5, 20 and 60 microg/inj) and heroin (30 microg/inj) at low ratio requirement. When the ratio requirement, i.e. the number of responses necessary to receive one drug infusion, was increased, self-administration of RU 51599 rapidly extinguished, whereas self-administration of heroin was maintained. Intravenous infusion of RU 51599 (100, 200 and 400 microg) dose-dependently decreased (25, 30 and 40%, respectively) extracellular concentrations of dopamine, as measured by means of microdialysis in freely moving rats. In contrast, heroin increased accumbens dopamine (130% over baseline). These results indicate that kappa receptors, similarly to mu ones, can mediate positive reinforcing effects of opioid peptides. However, the strength of the reinforcement is very low for kappa receptors. This suggests that changes in accumbens dopamine do not correlate with the capacity of a stimulus to induce reward or aversion. In contrast, a parallel seems to exist between an increase in accumbens dopamine and the drive to reach or obtain a positive reinforcer.

  8. The roles of gene duplication, gene conversion and positive selection in rodent Esp and Mup pheromone gene families with comparison to the Abp family.

    Science.gov (United States)

    Karn, Robert C; Laukaitis, Christina M

    2012-01-01

    Three proteinaceous pheromone families, the androgen-binding proteins (ABPs), the exocrine-gland secreting peptides (ESPs) and the major urinary proteins (MUPs) are encoded by large gene families in the genomes of Mus musculus and Rattus norvegicus. We studied the evolutionary histories of the Mup and Esp genes and compared them with what is known about the Abp genes. Apparently gene conversion has played little if any role in the expansion of the mouse Class A and Class B Mup genes and pseudogenes, and the rat Mups. By contrast, we found evidence of extensive gene conversion in many Esp genes although not in all of them. Our studies of selection identified at least two amino acid sites in β-sheets as having evolved under positive selection in the mouse Class A and Class B MUPs and in rat MUPs. We show that selection may have acted on the ESPs by determining K(a)/K(s) for Exon 3 sequences with and without the converted sequence segment. While it appears that purifying selection acted on the ESP signal peptides, the secreted portions of the ESPs probably have undergone much more rapid evolution. When the inner gene converted fragment sequences were removed, eleven Esp paralogs were present in two or more pairs with K(a)/K(s) >1.0 and thus we propose that positive selection is detectable by this means in at least some mouse Esp paralogs. We compare and contrast the evolutionary histories of all three mouse pheromone gene families in light of their proposed functions in mouse communication.

  9. Thinking about a Limited Future Enhances the Positivity of Younger and Older Adults’ Recall: Support for Socioemotional Selectivity Theory

    OpenAIRE

    Barber, Sarah J.; Opitz, Philipp C.; Martins, Bruna; Sakaki, Michiko; Mather, Mara

    2016-01-01

    Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus...

  10. Comparative Genomics of Smut Pathogens: Insights From Orphans and Positively Selected Genes Into Host Specialization

    Directory of Open Access Journals (Sweden)

    Juliana Benevenuto

    2018-04-01

    Full Text Available Host specialization is a key evolutionary process for the diversification and emergence of new pathogens. However, the molecular determinants of host range are poorly understood. Smut fungi are biotrophic pathogens that have distinct and narrow host ranges based on largely unknown genetic determinants. Hence, we aimed to expand comparative genomics analyses of smut fungi by including more species infecting different hosts and to define orphans and positively selected genes to gain further insights into the genetics basis of host specialization. We analyzed nine lineages of smut fungi isolated from eight crop and non-crop hosts: maize, barley, sugarcane, wheat, oats, Zizania latifolia (Manchurian rice, Echinochloa colona (a wild grass, and Persicaria sp. (a wild dicot plant. We assembled two new genomes: Ustilago hordei (strain Uhor01 isolated from oats and U. tritici (strain CBS 119.19 isolated from wheat. The smut genomes were of small sizes, ranging from 18.38 to 24.63 Mb. U. hordei species experienced genome expansions due to the proliferation of transposable elements and the amount of these elements varied among the two strains. Phylogenetic analysis confirmed that Ustilago is not a monophyletic genus and, furthermore, detected misclassification of the U. tritici specimen. The comparison between smut pathogens of crop and non-crop hosts did not reveal distinct signatures, suggesting that host domestication did not play a dominant role in shaping the evolution of smuts. We found that host specialization in smut fungi likely has a complex genetic basis: different functional categories were enriched in orphans and lineage-specific selected genes. The diversification and gain/loss of effector genes are probably the most important determinants of host specificity.

  11. Functional divergence caused by ancient positive selection of a Drosophila hybrid incompatibility locus.

    Directory of Open Access Journals (Sweden)

    Daniel A Barbash

    2004-06-01

    Full Text Available Interspecific hybrid lethality and sterility are a consequence of divergent evolution between species and serve to maintain the discrete identities of species. The evolution of hybrid incompatibilities has been described in widely accepted models by Dobzhansky and Muller where lineage-specific functional divergence is the essential characteristic of hybrid incompatibility genes. Experimentally tractable models are required to identify and test candidate hybrid incompatibility genes. Several Drosophila melanogaster genes involved in hybrid incompatibility have been identified but none has yet been shown to have functionally diverged in accordance with the Dobzhansky-Muller model. By introducing transgenic copies of the X-linked Hybrid male rescue (Hmr gene into D. melanogaster from its sibling species D. simulans and D. mauritiana, we demonstrate that Hmr has functionally diverged to cause F1 hybrid incompatibility between these species. Consistent with the Dobzhansky-Muller model, we find that Hmr has diverged extensively in the D. melanogaster lineage, but we also find extensive divergence in the sibling-species lineage. Together, these findings implicate over 13% of the amino acids encoded by Hmr as candidates for causing hybrid incompatibility. The exceptional level of divergence at Hmr cannot be explained by neutral processes because we use phylogenetic methods and population genetic analyses to show that the elevated amino-acid divergence in both lineages is due to positive selection in the distant past-at least one million generations ago. Our findings suggest that multiple substitutions driven by natural selection may be a general phenomenon required to generate hybrid incompatibility alleles.

  12. New evidence for positive selection helps explain the paternal age effect observed in achondroplasia

    Science.gov (United States)

    Shinde, Deepali N.; Elmer, Dominik P.; Calabrese, Peter; Boulanger, Jérôme; Arnheim, Norman; Tiemann-Boege, Irene

    2013-01-01

    There are certain de novo germline mutations associated with genetic disorders whose mutation rates per generation are orders of magnitude higher than the genome average. Moreover, these mutations occur exclusively in the male germ line and older men have a higher probability of having an affected child than younger ones, known as the paternal age effect (PAE). The classic example of a genetic disorder exhibiting a PAE is achondroplasia, caused predominantly by a single-nucleotide substitution (c.1138G>A) in FGFR3. To elucidate what mechanisms might be driving the high frequency of this mutation in the male germline, we examined the spatial distribution of the c.1138G>A substitution in a testis from an 80-year-old unaffected man. Using a technology based on bead-emulsion amplification, we were able to measure mutation frequencies in 192 individual pieces of the dissected testis with a false-positive rate lower than 2.7 × 10−6. We observed that most mutations are clustered in a few pieces with 95% of all mutations occurring in 27% of the total testis. Using computational simulations, we rejected the model proposing an elevated mutation rate per cell division at this nucleotide site. Instead, we determined that the observed mutation distribution fits a germline selection model, where mutant spermatogonial stem cells have a proliferative advantage over unmutated cells. Combined with data on several other PAE mutations, our results support the idea that the PAE, associated with a number of Mendelian disorders, may be explained primarily by a selective mechanism. PMID:23740942

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

    Science.gov (United States)

    2016-10-14

    start or continue a profitable growth pattern and boost morale and motivation, a poor decision may bring the company to the brink of financial...HON Frank Kendall issued a memorandum titled “Key Leadership Positions and Qualification Criteria” (Kendall, 2013). This memorandum provides a...Chief Developmental Tester • Program Lead, Business Financial Manager SELECTING CANDIDATES FOR KEY LEADERSHIP POSITIONS 4

  14. Antibacterial properties of biosurfactants against selected Gram-positive and -negative bacteria.

    Science.gov (United States)

    Díaz De Rienzo, Mayri A; Stevenson, Paul; Marchant, Roger; Banat, Ibrahim M

    2016-01-01

    The antibacterial properties and ability to disrupt biofilms of biosurfactants (rhamnolipids, sophorolipids) and sodium dodecyl sulphate (SDS) in the presence and absence of selected organic acids were investigated. Pseudomonas aeruginosa PAO1 was inhibited by sophorolipids and SDS at concentrations >5% v/v, and the growth of Escherichia coli NCTC 10418 was also inhibited by sophorolipids and SDS at concentrations >5% and 0.1% v/v, respectively. Bacillus subtilis NCTC 10400 was inhibited by rhamnolipids, sophorolipids and SDS at concentrations >0.5% v/v of all three; the same effect was observed with Staphylococcus aureus ATCC 9144. The ability to attach to surfaces and biofilm formation of P. aeruginosa PAO1, E. coli NCTC 10418 and B. subtilis NCTC 10400 was inhibited by sophorolipids (1% v/v) in the presence of caprylic acid (0.8% v/v). In the case of S. aureus ATCC 9144, the best results were obtained using caprylic acid on its own. It was concluded that sophorolipids are promising compounds for the inhibition/disruption of biofilms formed by Gram-positive and Gram-negative microorganisms and this activity can be enhanced by the presence of booster compounds such as caprylic acid. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Differential positive selection of malaria resistance genes in three indigenous populations of Peninsular Malaysia.

    Science.gov (United States)

    Liu, Xuanyao; Yunus, Yushimah; Lu, Dongsheng; Aghakhanian, Farhang; Saw, Woei-Yuh; Deng, Lian; Ali, Mohammad; Wang, Xu; Nor, Fadzilah Mohd; Ghazali, Fadzilah; Rahman, Thuhairah Abdul; Shaari, Shahrul Azlin; Salleh, Mohd Zaki; Phipps, Maude E; Ong, Rick Twee-Hee; Xu, Shuhua; Teo, Yik-Ying; Hoh, Boon-Peng

    2015-04-01

    The indigenous populations from Peninsular Malaysia, locally known as Orang Asli, continue to adopt an agro-subsistence nomadic lifestyle, residing primarily within natural jungle habitats. Leading a hunter-gatherer lifestyle in a tropical jungle environment, the Orang Asli are routinely exposed to malaria. Here we surveyed the genetic architecture of individuals from four Orang Asli tribes with high-density genotyping across more than 2.5 million polymorphisms. These tribes reside in different geographical locations in Peninsular Malaysia and belong to three main ethno-linguistic groups, where there is minimal interaction between the tribes. We first dissect the genetic diversity and admixture between the tribes and with neighboring urban populations. Later, by implementing five metrics, we investigated the genome-wide signatures for positive natural selection of these Orang Asli, respectively. Finally, we searched for evidence of genomic adaptation to the pressure of malaria infection. We observed that different evolutionary responses might have emerged in the different Orang Asli communities to mitigate malaria infection.

  16. Source apportionment and location by selective wind sampling and Positive Matrix Factorization.

    Science.gov (United States)

    Venturini, Elisa; Vassura, Ivano; Raffo, Simona; Ferroni, Laura; Bernardi, Elena; Passarini, Fabrizio

    2014-10-01

    In order to determine the pollution sources in a suburban area and identify the main direction of their origin, PM2.5 was collected with samplers coupled with a wind select sensor and then subjected to Positive Matrix Factorization (PMF) analysis. In each sample, soluble ions, organic carbon, elemental carbon, levoglucosan, metals, and Polycyclic Aromatic Hydrocarbons (PAHs) were determined. PMF results identified six main sources affecting the area: natural gas home appliances, motor vehicles, regional transport, biomass combustion, manufacturing activities, and secondary aerosol. The connection of factor temporal trends with other parameters (i.e., temperature, PM2.5 concentration, and photochemical processes) confirms factor attributions. PMF analysis indicated that the main source of PM2.5 in the area is secondary aerosol. This should be mainly due to regional contributions, owing to both the secondary nature of the source itself and the higher concentration registered in inland air masses. The motor vehicle emission source contribution is also important. This source likely has a prevalent local origin. The most toxic determined components, i.e., PAHs, Cd, Pb, and Ni, are mainly due to vehicular traffic. Even if this is not the main source in the study area, it is the one of greatest concern. The application of PMF analysis to PM2.5 collected with this new sampling technique made it possible to obtain more detailed results on the sources affecting the area compared to a classical PMF analysis.

  17. Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

    Science.gov (United States)

    Pierron, Denis; Opazo, Juan C; Heiske, Margit; Papper, Zack; Uddin, Monica; Chand, Gopi; Wildman, Derek E; Romero, Roberto; Goodman, Morris; Grossman, Lawrence I

    2011-01-01

    Cytochrome c (cyt c) participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i) loss of the paralogous testis isoform, (ii) an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii) atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection) occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

  18. 77 FR 61055 - Agricultural Bioterrorism Protection Act of 2002; Biennial Review and Republication of the Select...

    Science.gov (United States)

    2012-10-05

    ... be modified genetically to become harmful are not included on the select agent list because of this... oryzae has been modified for use as a biological weapon in the past, it has been retained on the list of... disease virus is used by vaccine manufacturers as the challenge organism to verify the potency of...

  19. Transcriptome-based phylogeny of endemic Lake Baikal amphipod species flock: fast speciation accompanied by frequent episodes of positive selection.

    Science.gov (United States)

    Naumenko, Sergey A; Logacheva, Maria D; Popova, Nina V; Klepikova, Anna V; Penin, Aleksey A; Bazykin, Georgii A; Etingova, Anna E; Mugue, Nikolai S; Kondrashov, Alexey S; Yampolsky, Lev Y

    2017-01-01

    Endemic species flocks inhabiting ancient lakes, oceanic islands and other long-lived isolated habitats are often interpreted as adaptive radiations. Yet molecular evidence for directional selection during species flocks radiation is scarce. Using partial transcriptomes of 64 species of Lake Baikal (Siberia, Russia) endemic amphipods and two nonendemic outgroups, we report a revised phylogeny of this species flock and analyse evidence for positive selection within the endemic lineages. We confirm two independent invasions of amphipods into Baikal and demonstrate that several morphological features of Baikal amphipods, such as body armour and reduction in appendages and sensory organs, evolved in several lineages in parallel. Radiation of Baikal amphipods has been characterized by short phylogenetic branches and frequent episodes of positive selection which tended to be more frequent in the early phase of the second invasion of amphipods into Baikal when the most intensive diversification occurred. Notably, signatures of positive selection are frequent in genes encoding mitochondrial membrane proteins with electron transfer chain and ATP synthesis functionality. In particular, subunits of both the membrane and substrate-level ATP synthases show evidence of positive selection in the plankton species Macrohectopus branickii, possibly indicating adaptation to active plankton lifestyle and to survival under conditions of low temperature and high hydrostatic pressures known to affect membranes functioning. Other functional categories represented among genes likely to be under positive selection include Ca-binding muscle-related proteins, possibly indicating adaptation to Ca-deficient low mineralization Baikal waters. © 2016 John Wiley & Sons Ltd.

  20. Systematic detection of positive selection in the human-pathogen interactome and lasting effects on infectious disease susceptibility.

    Directory of Open Access Journals (Sweden)

    Erik Corona

    Full Text Available Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS, providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.

  1. Mathematical Optimization Algorithm for Minimizing the Cost Function of GHG Emission in AS/RS Using Positive Selection Based Clonal Selection Principle

    Science.gov (United States)

    Mahalakshmi; Murugesan, R.

    2018-04-01

    This paper regards with the minimization of total cost of Greenhouse Gas (GHG) efficiency in Automated Storage and Retrieval System (AS/RS). A mathematical model is constructed based on tax cost, penalty cost and discount cost of GHG emission of AS/RS. A two stage algorithm namely positive selection based clonal selection principle (PSBCSP) is used to find the optimal solution of the constructed model. In the first stage positive selection principle is used to reduce the search space of the optimal solution by fixing a threshold value. In the later stage clonal selection principle is used to generate best solutions. The obtained results are compared with other existing algorithms in the literature, which shows that the proposed algorithm yields a better result compared to others.

  2. Intraocular lens power selection and positioning with and without intraoperative aberrometry.

    Science.gov (United States)

    Hatch, Kathryn M; Woodcock, Emily C; Talamo, Jonathan H

    2015-04-01

    To determine the value of intraoperative aberrometry in cases of toric intraocular lens (IOL) implantation and positioning. In this non-randomized retrospective comparative trial, two groups of eyes underwent cataract extraction with toric IOL implantation: the aberrometry group (n = 37 eyes), where toric IOL power and alignment were determined before surgery with automated keratometry, standard optical biometry, and an online calculator and then refined using intraoperative aberrometry, and the toric calculator group (n = 27 eyes), where IOL selection was performed in a similar manner but without intraoperative aberrometry. The primary outcome measure was mean postoperative residual refractive astigmatism (RRA). Mean RRA measured at follow-up after surgery was 0.46 ± 0.42 and 0.68 ± 0.34 diopters (D) in the aberrometry and toric calculator groups, respectively (P = .0153). A 75% and 57% reduction in cylinder was noted between preoperative keratometric astigmatism and postoperative RRA in the aberrometry and toric calculator groups, respectively (P = .0027). RRA of 0.25 D or less, 0.50 D or less, 0.75 D or less, and 1.00 D or less was seen 38%, 78%, 86%, and 95% of the time, respectively, in the aberrometry group and 22%, 33%, 74%, and 89% of the time, respectively, in the toric calculator group. These data show that the chance of a patient being in a lower postoperative RRA range increased when intraoperative aberrometry was used (P = .0130). Patients undergoing cataract extraction with toric IOL placement aided by intraoperative aberrometry were 2.4 times more likely to have less than 0.50 D of RRA compared to standard methods. Copyright 2015, SLACK Incorporated.

  3. Silencing, positive selection and parallel evolution: busy history of primate cytochromes C.

    Directory of Open Access Journals (Sweden)

    Denis Pierron

    Full Text Available Cytochrome c (cyt c participates in two crucial cellular processes, energy production and apoptosis, and unsurprisingly is a highly conserved protein. However, previous studies have reported for the primate lineage (i loss of the paralogous testis isoform, (ii an acceleration and then a deceleration of the amino acid replacement rate of the cyt c somatic isoform, and (iii atypical biochemical behavior of human cyt c. To gain insight into the cause of these major evolutionary events, we have retraced the history of cyt c loci among primates. For testis cyt c, all primate sequences examined carry the same nonsense mutation, which suggests that silencing occurred before the primates diversified. For somatic cyt c, maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses yielded the same tree topology. The evolutionary analyses show that a fast accumulation of non-synonymous mutations (suggesting positive selection occurred specifically on the anthropoid lineage root and then continued in parallel on the early catarrhini and platyrrhini stems. Analysis of evolutionary changes using the 3D structure suggests they are focused on the respiratory chain rather than on apoptosis or other cyt c functions. In agreement with previous biochemical studies, our results suggest that silencing of the cyt c testis isoform could be linked with the decrease of primate reproduction rate. Finally, the evolution of cyt c in the two sister anthropoid groups leads us to propose that somatic cyt c evolution may be related both to COX evolution and to the convergent brain and body mass enlargement in these two anthropoid clades.

  4. Potent and long-acting corticotropin releasing factor (CRF) receptor 2 selective peptide competitive antagonists.

    Science.gov (United States)

    Rivier, J; Gulyas, J; Kirby, D; Low, W; Perrin, M H; Kunitake, K; DiGruccio, M; Vaughan, J; Reubi, J C; Waser, B; Koerber, S C; Martinez, V; Wang, L; Taché, Y; Vale, W

    2002-10-10

    We present evidence that members of the corticotropin releasing factor (CRF) family assume distinct structures when interacting with the CRF(1) and CRF(2) receptors. Predictive methods, physicochemical measurements, and structure-activity relationship studies have suggested that CRF, its family members, and competitive antagonists such as astressin [cyclo(30-33)[DPhe(12),Nle(21),Glu(30),Lys(33),Nle(38)]hCRF((12-41))] assume an alpha-helical conformation when interacting with their receptors. We had shown that alpha-helical CRF((9-41)) and sauvagine showed some selectivity for CRF receptors other than that responsible for ACTH secretion(1) and later for CRF2.(2) More recently, we suggested the possibility of a helix-turn-helix motif around a turn encompassing residues 30-33(3) that would confer high affinity for both CRF(1) and CRF(2)(2,4) in agonists and antagonists of all members of the CRF family.(3) On the other hand, the substitutions that conferred ca. 100-fold CRF(2) selectivity to the antagonist antisauvagine-30 [[DPhe(11),His(12)]sauvagine((11-40))] did not confer such property to the corresponding N-terminally extended agonists. We find here that a Glu(32)-Lys(35) side chain to side chain covalent lactam constraint in hCRF and the corresponding Glu(31)-Lys(34) side chain to side chain covalent lactam constraint in sauvagine yield potent ligands that are selective for CRF(2). Additionally, we introduced deletions and substitutions known to increase duration of action to yield antagonists such as cyclo(31-34)[DPhe(11),His(12),C(alpha)MeLeu(13,39),Nle(17),Glu(31),Lys(34)]Ac-sauvagine((8-40)) (astressin(2)-B) with CRF(2) selectivities greater than 100-fold. CRF receptor autoradiography was performed in rat tissue known to express CRF(2) and CRF(1) in order to confirm that astressin(2)-B could indeed bind to established CRF(2) but not CRF(1) receptor-expressing tissues. Extended duration of action of astressin(2)-B vs that of antisauvagine-30 is demonstrated in

  5. The Hrs/Stam complex acts as a positive and negative regulator of RTK signaling during Drosophila development.

    Directory of Open Access Journals (Sweden)

    Hélène Chanut-Delalande

    Full Text Available BACKGROUND: Endocytosis is a key regulatory step of diverse signalling pathways, including receptor tyrosine kinase (RTK signalling. Hrs and Stam constitute the ESCRT-0 complex that controls the initial selection of ubiquitinated proteins, which will subsequently be degraded in lysosomes. It has been well established ex vivo and during Drosophila embryogenesis that Hrs promotes EGFR down regulation. We have recently isolated the first mutations of stam in flies and shown that Stam is required for air sac morphogenesis, a larval respiratory structure whose formation critically depends on finely tuned levels of FGFR activity. This suggest that Stam, putatively within the ESCRT-0 complex, modulates FGF signalling, a possibility that has not been examined in Drosophila yet. PRINCIPAL FINDINGS: Here, we assessed the role of the Hrs/Stam complex in the regulation of signalling activity during Drosophila development. We show that stam and hrs are required for efficient FGFR signalling in the tracheal system, both during cell migration in the air sac primordium and during the formation of fine cytoplasmic extensions in terminal cells. We find that stam and hrs mutant cells display altered FGFR/Btl localisation, likely contributing to impaired signalling levels. Electron microscopy analyses indicate that endosome maturation is impaired at distinct steps by hrs and stam mutations. These somewhat unexpected results prompted us to further explore the function of stam and hrs in EGFR signalling. We show that while stam and hrs together downregulate EGFR signalling in the embryo, they are required for full activation of EGFR signalling during wing development. CONCLUSIONS/SIGNIFICANCE: Our study shows that the ESCRT-0 complex differentially regulates RTK signalling, either positively or negatively depending on tissues and developmental stages, further highlighting the importance of endocytosis in modulating signalling pathways during development.

  6. Evidence of natural selection acting on a polymorphic hybrid incompatibility locus in Mimulus.

    Science.gov (United States)

    Sweigart, Andrea L; Flagel, Lex E

    2015-02-01

    As a common cause of reproductive isolation in diverse taxa, hybrid incompatibilities are fundamentally important to speciation. A key question is which evolutionary forces drive the initial substitutions within species that lead to hybrid dysfunction. Previously, we discovered a simple genetic incompatibility that causes nearly complete male sterility and partial female sterility in hybrids between the two closely related yellow monkeyflower species Mimulus guttatus and M. nasutus. In this report, we fine map the two major incompatibility loci-hybrid male sterility 1 (hms1) and hybrid male sterility 2 (hms2)-to small nuclear genomic regions (each <70 kb) that include strong candidate genes. With this improved genetic resolution, we also investigate the evolutionary dynamics of hms1 in a natural population of M. guttatus known to be polymorphic at this locus. Using classical genetic crosses and population genomics, we show that a 320-kb region containing the hms1 incompatibility allele has risen to intermediate frequency in this population by strong natural selection. This finding provides direct evidence that natural selection within plant species can lead to hybrid dysfunction between species. Copyright © 2015 by the Genetics Society of America.

  7. Adaptive evolution of the spike gene of SARS coronavirus: changes in positively selected sites in different epidemic groups

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    He Shao-Heng

    2006-10-01

    Full Text Available Abstract Background It is believed that animal-to-human transmission of severe acute respiratory syndrome (SARS coronavirus (CoV is the cause of the SARS outbreak worldwide. The spike (S protein is one of the best characterized proteins of SARS-CoV, which plays a key role in SARS-CoV overcoming species barrier and accomplishing interspecies transmission from animals to humans, suggesting that it may be the major target of selective pressure. However, the process of adaptive evolution of S protein and the exact positively selected sites associated with this process remain unknown. Results By investigating the adaptive evolution of S protein, we identified twelve amino acid sites (75, 239, 244, 311, 479, 609, 613, 743, 765, 778, 1148, and 1163 in the S protein under positive selective pressure. Based on phylogenetic tree and epidemiological investigation, SARS outbreak was divided into three epidemic groups: 02–04 interspecies, 03-early-mid, and 03-late epidemic groups in the present study. Positive selection was detected in the first two groups, which represent the course of SARS-CoV interspecies transmission and of viral adaptation to human host, respectively. In contrast, purifying selection was detected in 03-late group. These indicate that S protein experiences variable positive selective pressures before reaching stabilization. A total of 25 sites in 02–04 interspecies epidemic group and 16 sites in 03-early-mid epidemic group were identified under positive selection. The identified sites were different between these two groups except for site 239, which suggests that positively selected sites are changeable between groups. Moreover, it was showed that a larger proportion (24% of positively selected sites was located in receptor-binding domain (RBD than in heptad repeat (HR1-HR2 region in 02–04 interspecies epidemic group (p = 0.0208, and a greater percentage (25% of these sites occurred in HR1–HR2 region than in RBD in 03-early

  8. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-09-16

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  9. Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

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    Leo Heyndrickx

    Full Text Available BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01. Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. RESULTS: It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model

  10. Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

    Science.gov (United States)

    Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne; Schuitemaker, Hanneke; Bowles, Emma; Buonaguro, Luigi; Grevstad, Berit; Vinner, Lasse; Vereecken, Katleen; Parker, Joe; Ramaswamy, Meghna; Biswas, Priscilla; Vanham, Guido; Scarlatti, Gabriella; Fomsgaard, Anders

    2013-01-01

    Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies.

  11. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

    Science.gov (United States)

    Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

    2015-05-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  12. Prediction of Genes Related to Positive Selection Using Whole-Genome Resequencing in Three Commercial Pig Breeds

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    HyoYoung Kim

    2015-12-01

    Full Text Available Selective sweep can cause genetic differentiation across populations, which allows for the identification of possible causative regions/genes underlying important traits. The pig has experienced a long history of allele frequency changes through artificial selection in the domestication process. We obtained an average of 329,482,871 sequence reads for 24 pigs from three pig breeds: Yorkshire (n = 5, Landrace (n = 13, and Duroc (n = 6. An average read depth of 11.7 was obtained using whole-genome resequencing on an Illumina HiSeq2000 platform. In this study, cross-population extended haplotype homozygosity and cross-population composite likelihood ratio tests were implemented to detect genes experiencing positive selection for the genome-wide resequencing data generated from three commercial pig breeds. In our results, 26, 7, and 14 genes from Yorkshire, Landrace, and Duroc, respectively were detected by two kinds of statistical tests. Significant evidence for positive selection was identified on genes ST6GALNAC2 and EPHX1 in Yorkshire, PARK2 in Landrace, and BMP6, SLA-DQA1, and PRKG1 in Duroc.These genes are reportedly relevant to lactation, reproduction, meat quality, and growth traits. To understand how these single nucleotide polymorphisms (SNPs related positive selection affect protein function, we analyzed the effect of non-synonymous SNPs. Three SNPs (rs324509622, rs80931851, and rs80937718 in the SLA-DQA1 gene were significant in the enrichment tests, indicating strong evidence for positive selection in Duroc. Our analyses identified genes under positive selection for lactation, reproduction, and meat-quality and growth traits in Yorkshire, Landrace, and Duroc, respectively.

  13. "Accentuate the Positive; Eliminate the Negative": Hegemonic Interest Convergence, Racialization of Latino Poverty, and the 1968 Bilingual Education Act

    Science.gov (United States)

    Sung, Kenzo K.

    2017-01-01

    Derrick Bell's interest convergence thesis is a seminal framework to analyze social change within critical race theory. While interest convergence's influence has grown, two foundational questions have been raised: do interest groups act rationally; does interest convergence also offer a change prescription or only an explanation of prior events.…

  14. Positive Selection of γδ CTL by TL Antigen Expressed in the Thymus

    Science.gov (United States)

    Tsujimura, Kunio; Takahashi, Toshitada; Morita, Akimichi; Hasegawa-Nishiwaki, Hitomi; Iwase, Shigeru; Obata, Yuichi

    1996-01-01

    the 14 clones. Taken together, these results suggest that Tlaa-3-TL antigen expressed in the thymus engages in positive selection of a sizable population of γδ T cells. PMID:8976173

  15. Pearl millet transformation system using the positive selectable marker gene phosphomannose isomerase

    CSIR Research Space (South Africa)

    O'Kennedy, MM

    2004-04-01

    Full Text Available of the transgene. Similar to results obtained from previous studies with maize and wheat, the manA gene was shown to be a superior selectable marker gene for improving transformation efficiencies when compared to antibiotic or herbicide selectable marker genes....

  16. The Evaluation and Selection of a Fifth Ground Antenna Site for the Global Positioning System.

    Science.gov (United States)

    1987-12-07

    selection was the region between Australia and South America and north of the Antartic . Using the performance results of this study, further study...indicated that the best region for selection was between Australia and South America and north of the Antartic . Using the performance results of this

  17. Can a Selective Serotonin Reuptake Inhibitor Act as a Glutamatergic Modulator?

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    Marcos Emilio Frizzo, PhD

    2017-01-01

    Full Text Available Sertraline (Zoloft and fluoxetine (Prozac are selective serotonin reuptake inhibitors whose antidepressant mechanism of action is classically attributed to an elevation of the extracellular levels of serotonin in the synaptic cleft. However, the biological effects of these drugs seem to be more complex than their traditionally described mechanism of action. Among their actions is the inhibition of different types of Na+ and K+ channels, as well as of glutamate uptake activity. The clearance of extracellular glutamate is essential to maintain the central nervous system within physiological conditions, and this excitatory neurotransmitter is removed from the synaptic cleft by astrocyte transporters. This transport depends upon a hyperpolarized membrane potential in astrocytes that is mainly maintained by Kir4.1 K+ channels. The impairment of the Kir4.1 channel activity reduces driving force for the glutamate transporter, resulting in an accumulation of extracellular glutamate. It has been shown that sertraline and fluoxetine inhibit Kir4.1 K+ channels. Recently, we demonstrated that sertraline reduces glutamate uptake in human platelets, which contain a high-affinity Na+-dependent glutamate uptake system, with kinetic and pharmacological properties similar to astrocytes in the central nervous system. Considering these similarities between human platelets and astrocytes, one might ask if sertraline could potentially reduce glutamate clearance in the synaptic cleft and consequently modulate glutamatergic transmission. This possibility merits investigation, since it may provide additional information regarding the mechanism of action and perhaps the side effects of these antidepressants.

  18. A distant cis acting intronic element induces site-selective RNA editing

    DEFF Research Database (Denmark)

    Daniel, Chammiran; Venø, Morten Trillingsgaard; Ekdahl, Ylva

    2012-01-01

    Transcripts have been found to be site selectively edited from adenosine-to-inosine (A-to-I) in the mammalian brain, mostly in genes involved in neurotransmission. While A-to-I editing occurs at double-stranded structures, other structural requirements are largely unknown. We have investigated...... shown to be important for A-to-I editing. We demonstrate that the element also can induce editing in related but normally not edited RNA sequences. In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce...... the requirements for editing at the I/M site in the Gabra-3 transcript of the GABA(A) receptor. We identify an evolutionarily conserved intronic duplex, 150 nt downstream of the exonic hairpin where the I/M site resides, which is required for its editing. This is the first time a distant RNA structure has been...

  19. The 3'-terminal 55 nucleotides of bovine coronavirus defective interfering RNA harbor cis-acting elements required for both negative- and positive-strand RNA synthesis.

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    Wei-Yu Liao

    Full Text Available The synthesis of the negative-strand [(--strand] complement of the ∼30 kilobase, positive-strand [(+-strand] coronaviral genome is a necessary early step for genome replication. The identification of cis-acting elements required for (--strand RNA synthesis in coronaviruses, however, has been hampered due to insufficiencies in the techniques used to detect the (--strand RNA species. Here, we employed a method of head-to-tail ligation and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR to detect and quantitate the synthesis of bovine coronavirus (BCoV defective interfering (DI RNA (- strands. Furthermore, using the aforementioned techniques along with Northern blot assay, we specifically defined the cis-acting RNA elements within the 3'-terminal 55 nucleotides (nts which function in the synthesis of (-- or (+-strand BCoV DI RNA. The major findings are as follows: (i nts from -5 to -39 within the 3'-terminal 55 nts are the cis-acting elements responsible for (--strand BCoV DI RNA synthesis, (ii nts from -3 to -34 within the 3'-terminal 55 nts are cis-acting elements required for (+-strand BCoV DI RNA synthesis, and (iii the nucleotide species at the 3'-most position (-1 is important, but not critical, for both (-- and (+-strand BCoV DI RNA synthesis. These results demonstrate that the 3'-terminal 55 nts in BCoV DI RNA harbor cis-acting RNA elements required for both (-- and (+-strand DI RNA synthesis and extend our knowledge on the mechanisms of coronavirus replication. The method of head-to-tail ligation and qRT-PCR employed in the study may also be applied to identify other cis-acting elements required for (--strand RNA synthesis in coronaviruses.

  20. Positive selection in the chromosome 16 VKORC1 genomic region has contributed to the variability of anticoagulant response in humans.

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    Blandine Patillon

    Full Text Available VKORC1 (vitamin K epoxide reductase complex subunit 1, 16p11.2 is the main genetic determinant of human response to oral anticoagulants of antivitamin K type (AVK. This gene was recently suggested to be a putative target of positive selection in East Asian populations. In this study, we genotyped the HGDP-CEPH Panel for six VKORC1 SNPs and downloaded chromosome 16 genotypes from the HGDP-CEPH database in order to characterize the geographic distribution of footprints of positive selection within and around this locus. A unique VKORC1 haplotype carrying the promoter mutation associated with AVK sensitivity showed especially high frequencies in all the 17 HGDP-CEPH East Asian population samples. VKORC1 and 24 neighboring genes were found to lie in a 505 kb region of strong linkage disequilibrium in these populations. Patterns of allele frequency differentiation and haplotype structure suggest that this genomic region has been submitted to a near complete selective sweep in all East Asian populations and only in this geographic area. The most extreme scores of the different selection tests are found within a smaller 45 kb region that contains VKORC1 and three other genes (BCKDK, MYST1 (KAT8, and PRSS8 with different functions. Because of the strong linkage disequilibrium, it is not possible to determine if VKORC1 or one of the three other genes is the target of this strong positive selection that could explain present-day differences among human populations in AVK dose requirement. Our results show that the extended region surrounding a presumable single target of positive selection should be analyzed for genetic variation in a wide range of genetically diverse populations in order to account for other neighboring and confounding selective events and the hitchhiking effect.

  1. Act on Numbers: Numerical Magnitude Influences Selection and Kinematics of Finger Movement

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    Rosa Rugani

    2017-08-01

    Full Text Available In the past decade hand kinematics has been reliably adopted for investigating cognitive processes and disentangling debated topics. One of the most controversial issues in numerical cognition literature regards the origin – cultural vs. genetically driven – of the mental number line (MNL, oriented from left (small numbers to right (large numbers. To date, the majority of studies have investigated this effect by means of response times, whereas studies considering more culturally unbiased measures such as kinematic parameters are rare. Here, we present a new paradigm that combines a “free response” task with the kinematic analysis of movement. Participants were seated in front of two little soccer goals placed on a table, one on the left and one on the right side. They were presented with left- or right-directed arrows and they were instructed to kick a small ball with their right index toward the goal indicated by the arrow. In a few test trials participants were presented also with a small (2 or a large (8 number, and they were allowed to choose the kicking direction. Participants performed more left responses with the small number and more right responses with the large number. The whole kicking movement was segmented in two temporal phases in order to make a hand kinematics’ fine-grained analysis. The Kick Preparation and Kick Finalization phases were selected on the basis of peak trajectory deviation from the virtual midline between the two goals. Results show an effect of both small and large numbers on action execution timing. Participants were faster to finalize the action when responding to small numbers toward the left and to large number toward the right. Here, we provide the first experimental demonstration which highlights how numerical processing affects action execution in a new and not-overlearned context. The employment of this innovative and unbiased paradigm will permit to disentangle the role of nature and culture

  2. Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

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    Kawai Satoru

    2010-02-01

    Full Text Available Abstract Background The 200 kDa merozoite surface protein 1 (MSP-1 of malaria parasites, a strong vaccine candidate, plays a key role during erythrocyte invasion and is a target of host protective immune response. Plasmodium vivax, the most widespread human malaria parasite, is closely related to parasites that infect Asian Old World monkeys, and has been considered to have become a parasite of man by host switch from a macaque malaria parasite. Several Asian monkey parasites have a range of natural hosts. The same parasite species shows different disease manifestations among host species. This suggests that host immune responses to P. vivax-related malaria parasites greatly differ among host species (albeit other factors. It is thus tempting to invoke that a major immune target parasite protein such as MSP-1 underwent unique evolution, depending on parasite species that exhibit difference in host range and host specificity. Results We performed comparative phylogenetic and population genetic analyses of the gene encoding MSP-1 (msp1 from P. vivax and nine P. vivax-related simian malaria parasites. The inferred phylogenetic tree of msp1 significantly differed from that of the mitochondrial genome, with a striking displacement of P. vivax from a position close to P. cynomolgi in the mitochondrial genome tree to an outlier of Asian monkey parasites. Importantly, positive selection was inferred for two ancestral branches, one leading to P. inui and P. hylobati and the other leading to P. vivax, P. fieldi and P. cynomolgi. This ancestral positive selection was estimated to have occurred three to six million years ago, coinciding with the period of radiation of Asian macaques. Comparisons of msp1 polymorphisms between P. vivax, P. inui and P. cynomolgi revealed that while some positively selected amino acid sites or regions are shared by these parasites, amino acid changes greatly differ, suggesting that diversifying selection is acting species

  3. Positive selection in the SLC11A1 gene in the family Equidae

    DEFF Research Database (Denmark)

    Bayerova, Zuzana; Janova, Eva; Matiasovic, Jan

    2016-01-01

    Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes...... a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans...... and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence...

  4. Selection of permanent pacing position of cardiac ventricle in patients with complete right bundle branch block

    International Nuclear Information System (INIS)

    Yang Minquan; Zhou Jun; Zhu Yan; Wang Jin; Rong Xin; Zhang Xiaoyi

    2005-01-01

    Objective: To find out the optimal pacing localization by comparing different pacing positions of the right ventricle in brady-cardiacarrhythmia patients with complete right bundle branch block. Methods: DDD type of double lumen permanent pacemaker was implanted in each of the 8 cases of sick sinus syndrome (SSS) and/or III degree atrioventricular block (III degree AVB) with complete right bundle branch block in normal heart function or class I. For each patient, four pacing positions in right ventricle were compared and the QRS pacing durations were recorded. The position with the shortest the QRS duration was chosen as the permanent pacing position. Heart function, chest X-rays and left ventricle ejection fraction (LVEF) were followed up after the operation. Results: In all the 8 cases, the posterior septum of the right ventricle were chosen as the permanent pacing position, with the shorter pacing QRS duration than that of pre-operation (P<0.05) and other pacing positions of the right ventricle. All parameters of this permanent pacing position were within the normal range. During the follow-up of 6-36 months, no abnormity was found in cardiac functions. Conclusion: In brady-cardiacarrhythmia patients with complete right bundle branch block, the implantation of permanent pacemaker should be at the junction region of inlet and outlet tracts, of the posterior septum of the right ventricle with ideal physiological function. (authors)

  5. Thinking about a limited future enhances the positivity of younger and older adults' recall: Support for socioemotional selectivity theory.

    Science.gov (United States)

    Barber, Sarah J; Opitz, Philipp C; Martins, Bruna; Sakaki, Michiko; Mather, Mara

    2016-08-01

    Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the "positivity effect," and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants' recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults' recall is typically more positive than younger adults' recall may index naturally shifting time horizons and goals with age.

  6. Thinking about a Limited Future Enhances the Positivity of Younger and Older Adults’ Recall: Support for Socioemotional Selectivity Theory

    Science.gov (United States)

    Barber, Sarah J.; Opitz, Philipp C.; Martins, Bruna; Sakaki, Michiko; Mather, Mara

    2016-01-01

    Compared with younger adults, older adults have a relative preference to attend to and remember positive over negative information. This is known as the “positivity effect,” and researchers have typically evoked socioemotional selectivity theory to explain it. According to socioemotional selectivity theory, as people get older they begin to perceive their time left in life as more limited. These reduced time horizons prompt older adults to prioritize achieving emotional gratification and thus exhibit increased positivity in attention and recall. Although this is the most commonly cited explanation of the positivity effect, there is currently a lack of clear experimental evidence demonstrating a link between time horizons and positivity. The goal of the current research was to address this issue. In two separate experiments, we asked participants to complete a writing activity, which directed them to think of time as being either limited or expansive (Experiments 1 and 2) or did not orient them to think about time in a particular manner (Experiment 2). Participants were then shown a series of emotional pictures, which they subsequently tried to recall. Results from both studies showed that regardless of chronological age, thinking about a limited future enhanced the relative positivity of participants’ recall. Furthermore, the results of Experiment 2 showed that this effect was not driven by changes in mood. Thus, the fact that older adults’ recall is typically more positive than younger adults’ recall may index naturally shifting time horizons and goals with age. PMID:27112461

  7. Role of maturity timing in selection procedures and in the specialisation of playing positions in youth basketball

    NARCIS (Netherlands)

    te Wierike, Sanne Cornelia Maria; Elferink-Gemser, Marije Titia; Tromp, Eveline Jenny Yvonne; Vaeyens, Roel; Visscher, Chris

    2015-01-01

    This study investigated the role of maturity timing in selection procedures and in the specialisation of playing positions in youth male basketball. Forty-three talented Dutch players (14.66 +/- 1.09years) participated in this study. Maturity timing (age at peak height velocity), anthropometric,

  8. Evolution of species-specific major seminal fluid proteins in placental mammals by gene death and positive selection

    NARCIS (Netherlands)

    Meslin, C.; Laurin, M.; Callebaut, I.; Druart, X.; Monget, P.

    2015-01-01

    The seminal fluid is a complex substance composed of a variety of secreted proteins and has been shown to play an important role in the fertilisation process in mammals and also in Drosophila. Several genes under positive selection have been documented in some rodents and primates. Our study

  9. Positive selection and ancient duplications in the evolution of class B floral homeotic genes of orchids and grasses

    Directory of Open Access Journals (Sweden)

    Koch Marcus A

    2009-04-01

    Full Text Available Abstract Background Positive selection is recognized as the prevalence of nonsynonymous over synonymous substitutions in a gene. Models of the functional evolution of duplicated genes consider neofunctionalization as key to the retention of paralogues. For instance, duplicate transcription factors are specifically retained in plant and animal genomes and both positive selection and transcriptional divergence appear to have played a role in their diversification. However, the relative impact of these two factors has not been systematically evaluated. Class B MADS-box genes, comprising DEF-like and GLO-like genes, encode developmental transcription factors essential for establishment of perianth and male organ identity in the flowers of angiosperms. Here, we contrast the role of positive selection and the known divergence in expression patterns of genes encoding class B-like MADS-box transcription factors from monocots, with emphasis on the family Orchidaceae and the order Poales. Although in the monocots these two groups are highly diverse and have a strongly canalized floral morphology, there is no information on the role of positive selection in the evolution of their distinctive flower morphologies. Published research shows that in Poales, class B-like genes are expressed in stamens and in lodicules, the perianth organs whose identity might also be specified by class B-like genes, like the identity of the inner tepals of their lily-like relatives. In orchids, however, the number and pattern of expression of class B-like genes have greatly diverged. Results The DEF-like genes from Orchidaceae form four well-supported, ancient clades of orthologues. In contrast, orchid GLO-like genes form a single clade of ancient orthologues and recent paralogues. DEF-like genes from orchid clade 2 (OMADS3-like genes are under less stringent purifying selection than the other orchid DEF-like and GLO-like genes. In comparison with orchids, purifying selection

  10. Identification of cis-acting elements on positive-strand subgenomic mRNA required for the synthesis of negative-strand counterpart in bovine coronavirus.

    Science.gov (United States)

    Yeh, Po-Yuan; Wu, Hung-Yi

    2014-07-30

    It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(-)-strand] complement. However, the cis-acting elements on the positive-strand [(+)-strand] sgmRNA required for (-)-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV) sgmRNA 7 required for the synthesis of its (-)-strand counterpart by deletion mutagenesis. The major findings are as follows. (1) Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (-)-strand sgmRNA complement. (2) Deletions of the 3' untranslated region (UTR) bulged stem-loop showed no effect on (-)-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (-)-strand sgmRNA. (3) Nucleotides positioned from -15 to -34 of the sgmRNA 7 3'-terminal region are required for efficient (-)-strand sgmRNA synthesis. (4) Nucleotide species at the 3'-most position (-1) of sgmRNA 7 is correlated to the efficiency of (-)-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (-)-strand sgmRNA synthesis in BCoV.

  11. Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation

    Directory of Open Access Journals (Sweden)

    Dall’Olio Giovanni

    2012-06-01

    Full Text Available Abstract Background Asparagine N-Glycosylation is one of the most important forms of protein post-translational modification in eukaryotes. This metabolic pathway can be subdivided into two parts: an upstream sub-pathway required for achieving proper folding for most of the proteins synthesized in the secretory pathway, and a downstream sub-pathway required to give variability to trans-membrane proteins, and involved in adaptation to the environment and innate immunity. Here we analyze the nucleotide variability of the genes of this pathway in human populations, identifying which genes show greater population differentiation and which genes show signatures of recent positive selection. We also compare how these signals are distributed between the upstream and the downstream parts of the pathway, with the aim of exploring how forces of population differentiation and positive selection vary among genes involved in the same metabolic pathway but subject to different functional constraints. Results Our results show that genes in the downstream part of the pathway are more likely to show a signature of population differentiation, while events of positive selection are equally distributed among the two parts of the pathway. Moreover, events of positive selection are frequent on genes that are known to be at bifurcation points, and that are identified as being in key position by a network-level analysis such as MGAT3 and GCS1. Conclusions These findings indicate that the upstream part of the Asparagine N-Glycosylation pathway has lower diversity among populations, while the downstream part is freer to tolerate diversity among populations. Moreover, the distribution of signatures of population differentiation and positive selection can change between parts of a pathway, especially between parts that are exposed to different functional constraints. Our results support the hypothesis that genes involved in constitutive processes can be expected to show

  12. Exposure to selected fragrance materials. A case study of fragrance-mix-positive eczema patients

    DEFF Research Database (Denmark)

    Johansen, J D; Rastogi, Suresh Chandra; Menné, T

    1996-01-01

    . In all cases, the use of these cosmetics completely or partly explained present or past episodes of eczema. Between 1 to 6 constituents of the fragrance mix were found in 22 out of 23 products. The cosmetics of all the patients sensitive to hydroxycitronellal, eugenol, cinnamic alcohol and alpha......The aim of the present study was to assess exposure to constituents of the fragrance mix from cosmetic products used by fragrance-mix-positive eczema patients. 23 products, which had either given a positive patch and/or use test in a total of 11 fragrance-mix-positive patients, were analyzed....... It is concluded that exposure to constituents of the fragrance mix is common in fragrance-allergic patients with cosmetic eczema, and that the fragrance mix is a good reflection of actual exposure....

  13. Response to Comment on "Positive Selection of Tyrosine Loss in Metazoan Evolution"

    DEFF Research Database (Denmark)

    Tan, Chris Soon Heng; Schoof, Erwin; Creixell, Pau

    2011-01-01

    Su et al. claim guanine-cytosine (GC) content variation can largely explain the observed tyrosine frequency variation, independent of adaptive evolution of cell-signaling complexity. We found that GC content variation, in the absence of selection for amino acid changes, can only maximally account...

  14. Detecting Positive Selection of Korean Native Goat Populations Using Next-Generation Sequencing

    Science.gov (United States)

    Lee, Wonseok; Ahn, Sojin; Taye, Mengistie; Sung, Samsun; Lee, Hyun-Jeong; Cho, Seoae; Kim, Heebal

    2016-01-01

    Goats (Capra hircus) are one of the oldest species of domesticated animals. Native Korean goats are a particularly interesting group, as they are indigenous to the area and were raised in the Korean peninsula almost 2,000 years ago. Although they have a small body size and produce low volumes of milk and meat, they are quite resistant to lumbar paralysis. Our study aimed to reveal the distinct genetic features and patterns of selection in native Korean goats by comparing the genomes of native Korean goat and crossbred goat populations. We sequenced the whole genome of 15 native Korean goats and 11 crossbred goats using next-generation sequencing (Illumina platform) to compare the genomes of the two populations. We found decreased nucleotide diversity in the native Korean goats compared to the crossbred goats. Genetic structural analysis demonstrated that the native Korean goat and crossbred goat populations shared a common ancestry, but were clearly distinct. Finally, to reveal the native Korean goat’s selective sweep region, selective sweep signals were identified in the native Korean goat genome using cross-population extended haplotype homozygosity (XP-EHH) and a cross-population composite likelihood ratio test (XP-CLR). As a result, we were able to identify candidate genes for recent selection, such as the CCR3 gene, which is related to lumbar paralysis resistance. Combined with future studies and recent goat genome information, this study will contribute to a thorough understanding of the native Korean goat genome. PMID:27989103

  15. Site suitability, selection and characterization: Branch technical position--Low-Level Waste Licensing Branch

    International Nuclear Information System (INIS)

    Siefken, D.; Pangburn, G.; Pennifill, R.; Starmer, R.J.

    1982-04-01

    The staff provides an expanded interpretation of the site suitability requirements in the proposed rule 10 CFR Part 61, a description of the anticipated site selection process, and a detailed discussion of the site characterization program needed to support a license application and environmental report. The paper provides early-on guidance to prospective applicants in these three subject areas

  16. Enrollees are positive about selective contracting, but not if it limits their freedom of choice.

    NARCIS (Netherlands)

    Bes, R.E.; Brabers, A.E.M.; Reitsma-van Rooijen, P.M.; Jong, J.D. de

    2013-01-01

    Background: In the last decades, health care systems in several European countries changed from a supply-oriented system to a demand-oriented system based on managed competition. In The Netherlands managed competition was introduced in 2006. Health insurers are allowed to selectively contract care

  17. Detecting Positive Selection of Korean Native Goat Populations Using Next-Generation Sequencing.

    Science.gov (United States)

    Lee, Wonseok; Ahn, Sojin; Taye, Mengistie; Sung, Samsun; Lee, Hyun-Jeong; Cho, Seoae; Kim, Heebal

    2016-12-01

    Goats ( Capra hircus ) are one of the oldest species of domesticated animals. Native Korean goats are a particularly interesting group, as they are indigenous to the area and were raised in the Korean peninsula almost 2,000 years ago. Although they have a small body size and produce low volumes of milk and meat, they are quite resistant to lumbar paralysis. Our study aimed to reveal the distinct genetic features and patterns of selection in native Korean goats by comparing the genomes of native Korean goat and crossbred goat populations. We sequenced the whole genome of 15 native Korean goats and 11 crossbred goats using next-generation sequencing (Illumina platform) to compare the genomes of the two populations. We found decreased nucleotide diversity in the native Korean goats compared to the crossbred goats. Genetic structural analysis demonstrated that the native Korean goat and crossbred goat populations shared a common ancestry, but were clearly distinct. Finally, to reveal the native Korean goat's selective sweep region, selective sweep signals were identified in the native Korean goat genome using cross-population extended haplotype homozygosity (XP-EHH) and a cross-population composite likelihood ratio test (XP-CLR). As a result, we were able to identify candidate genes for recent selection, such as the CCR3 gene, which is related to lumbar paralysis resistance. Combined with future studies and recent goat genome information, this study will contribute to a thorough understanding of the native Korean goat genome.

  18. Differential selection on carotenoid biosynthesis genes as a function of gene position in the metabolic pathway: a study on the carrot and dicots.

    Directory of Open Access Journals (Sweden)

    Jérémy Clotault

    Full Text Available Selection of genes involved in metabolic pathways could target them differently depending on the position of genes in the pathway and on their role in controlling metabolic fluxes. This hypothesis was tested in the carotenoid biosynthesis pathway using population genetics and phylogenetics.Evolutionary rates of seven genes distributed along the carotenoid biosynthesis pathway, IPI, PDS, CRTISO, LCYB, LCYE, CHXE and ZEP, were compared in seven dicot taxa. A survey of deviations from neutrality expectations at these genes was also undertaken in cultivated carrot (Daucus carota subsp. sativus, a species that has been intensely bred for carotenoid pattern diversification in its root during its cultivation history. Parts of sequences of these genes were obtained from 46 individuals representing a wide diversity of cultivated carrots. Downstream genes exhibited higher deviations from neutral expectations than upstream genes. Comparisons of synonymous and nonsynonymous substitution rates between genes among dicots revealed greater constraints on upstream genes than on downstream genes. An excess of intermediate frequency polymorphisms, high nucleotide diversity and/or high differentiation of CRTISO, LCYB1 and LCYE in cultivated carrot suggest that balancing selection may have targeted genes acting centrally in the pathway.Our results are consistent with relaxed constraints on downstream genes and selection targeting the central enzymes of the carotenoid biosynthesis pathway during carrot breeding history.

  19. [Long-acting insulins in the treatment of type 2 diabetes and their position in the current treatment algorithm].

    Science.gov (United States)

    Haluzík, Martin

    Insulin therapy has been for many years an inseparable part of the treatment of patients with type 2 diabetes, in particular those with longer diabetes duration. Current national and international guidelines list insulin treatment as a possible second choice therapy in patient with unsatisfactory glucose control on monotherapy with metformin. In reality, insulin therapy is often initiated later than it optimally should be. The reasons include among others the fear of patients and sometimes also of physicians from the side effects of insulin. Even though the options of antidiabetic treatment has been diversified by the addition of novel groups of antidiabetics with good efficacy and low risk of hypoglycemia, long acting insulin therapy still remains the most effective way of decreasing fasting hyperglycemia with the effect lasting further throughout the day. In this paper we summarize the current knowledge concerning long-acting insulins available on the Czech market or the ones that should be available in the near future. We discuss the differences among available long-acting insulins and their clinical consequences with respect to the selection of particular insulin for particular patient.Key words: biosimilar insulins - body weight - diabetes mellitus - hypoglycemia - long acting insulin.

  20. Ground Receiving Station Reference Pair Selection Technique for a Minimum Configuration 3D Emitter Position Estimation Multilateration System

    Directory of Open Access Journals (Sweden)

    Abdulmalik Shehu Yaro

    2017-01-01

    Full Text Available Multilateration estimates aircraft position using the Time Difference Of Arrival (TDOA with a lateration algorithm. The Position Estimation (PE accuracy of the lateration algorithm depends on several factors which are the TDOA estimation error, the lateration algorithm approach, the number of deployed GRSs and the selection of the GRS reference used for the PE process. Using the minimum number of GRSs for 3D emitter PE, a technique based on the condition number calculation is proposed to select the suitable GRS reference pair for improving the accuracy of the PE using the lateration algorithm. Validation of the proposed technique was performed with the GRSs in the square and triangular GRS configuration. For the selected emitter positions, the result shows that the proposed technique can be used to select the suitable GRS reference pair for the PE process. A unity condition number is achieved for GRS pair most suitable for the PE process. Monte Carlo simulation result, in comparison with the fixed GRS reference pair lateration algorithm, shows a reduction in PE error of at least 70% for both GRS in the square and triangular configuration.

  1. Sexual Orientation and Spatial Position Effects on Selective Forms of Object Location Memory

    Science.gov (United States)

    Rahman, Qazi; Newland, Cherie; Smyth, Beatrice Mary

    2011-01-01

    Prior research has demonstrated robust sex and sexual orientation-related differences in object location memory in humans. Here we show that this sexual variation may depend on the spatial position of target objects and the task-specific nature of the spatial array. We tested the recovery of object locations in three object arrays (object…

  2. Positive selection in the leucine-rich repeat domain of Gro1 genes in ...

    Indian Academy of Sciences (India)

    history during which the main structure of the domain has been conserved such that ... from the column using 100 μL of distilled water. The LRR fragments from the ... ture of the domain and to obtain the best PDB template for mapping positive ...

  3. Can neurological evidence refute free will? The failure of a phenomenological analysis of acts in Libet’s denial of «positive free will»

    Directory of Open Access Journals (Sweden)

    Josef Seifert

    2013-07-01

    Full Text Available In a first part of this paper I expound briefly the essential characteristics of free will. The second part deals with the objections of Benjamin Libet, allegedly based on brain-scientific foundations, against «positive free will». The third and main part shows that Libet’s anti-positive-free-will-position is due to an almost complete failure of a phenomenology of the conscious acts that precede, accompany and follow voluntary movement. The fourth part defends the thesis that Libet’s experimental results, far from supporting his philosophical stance, contain strong empirical confirmations of human free will, which, apart from a phenomenology of human acts, becomes further clear upon noticing striking philosophical deficiencies and contradictions in his distinction between ‘positive’ and ‘negative’ free will. The conclusions summarize the results, according to which positive free will and causality through freedom exist and are confirmed by Libet’s and other test results. Free will is the primary and model case of an efficient cause, instead of contradicting or challenging the principles of causality and of sufficient reason

  4. The positive impact of women's employment on divorce: Context, selection, or anticipation?

    Directory of Open Access Journals (Sweden)

    Daniele Vignoli

    2018-03-01

    Full Text Available Background: Empirical findings regarding the impact of women's employment on divorce are mixed. One explanation is that the effects are moderated by the country context. Another is that previous studies have failed to account for unobserved factors that introduce bias into the estimated effects. Studies also rarely consider possible anticipatory employment behavior on the part of women who are thinking of divorce. Objective: The aim of this study is to deepen our understanding of the nexus between women's employment and divorce in a comparative perspective. Methods: We adopt an analytical strategy that allows us to account for selection and anticipation mechanisms. Namely, we estimate marital disruption and employment jointly, and monitor the timing of divorce after employment entry. This approach is implemented using micro-level data for Germany, Hungary, Italy, and Poland. Results: We find that women's employment facilitates marital disruption in Italy and Poland, but not in Germany and Hungary. We also show that selection effects play out differently in different contexts. Finally, we notice traces of anticipatory behavior in Italy. Contribution: We conclude that women's employment is less likely to be linked to divorce in countries with easier access to divorce and in countries with more generous financial support for families and single mothers, which in turn makes women less reliant on the market. With this study we hope to encourage future researchers to consider the potentially distorting effects of selection and anticipation strategies in (comparative divorce research.

  5. Soft sweeps III: the signature of positive selection from recurrent mutation.

    Directory of Open Access Journals (Sweden)

    Pleuni S Pennings

    2006-12-01

    Full Text Available Polymorphism data can be used to identify loci at which a beneficial allele has recently gone to fixation, given that an accurate description of the signature of selection is available. In the classical model that is used, a favored allele derives from a single mutational origin. This ignores the fact that beneficial alleles can enter a population recurrently by mutation during the selective phase. In this study, we present a combination of analytical and simulation results to demonstrate the effect of adaptation from recurrent mutation on summary statistics for polymorphism data from a linked neutral locus. We also analyze the power of standard neutrality tests based on the frequency spectrum or on linkage disequilibrium (LD under this scenario. For recurrent beneficial mutation at biologically realistic rates, we find substantial deviations from the classical pattern of a selective sweep from a single new mutation. Deviations from neutrality in the level of polymorphism and in the frequency spectrum are much less pronounced than in the classical sweep pattern. In contrast, for levels of LD, the signature is even stronger if recurrent beneficial mutation plays a role. We suggest a variant of existing LD tests that increases their power to detect this signature.

  6. Probing of RNA structures in a positive sense RNA virus reveals selection pressures for structural elements

    Science.gov (United States)

    Watters, Kyle E; Choudhary, Krishna; Aviran, Sharon; Perry, Keith L

    2018-01-01

    Abstract In single stranded (+)-sense RNA viruses, RNA structural elements (SEs) play essential roles in the infection process from replication to encapsidation. Using selective 2′-hydroxyl acylation analyzed by primer extension sequencing (SHAPE-Seq) and covariation analysis, we explore the structural features of the third genome segment of cucumber mosaic virus (CMV), RNA3 (2216 nt), both in vitro and in plant cell lysates. Comparing SHAPE-Seq and covariation analysis results revealed multiple SEs in the coat protein open reading frame and 3′ untranslated region. Four of these SEs were mutated and serially passaged in Nicotiana tabacum plants to identify biologically selected changes to the original mutated sequences. After passaging, loop mutants showed partial reversion to their wild-type sequence and SEs that were structurally disrupted by mutations were restored to wild-type-like structures via synonymous mutations in planta. These results support the existence and selection of virus open reading frame SEs in the host organism and provide a framework for further studies on the role of RNA structure in viral infection. Additionally, this work demonstrates the applicability of high-throughput chemical probing in plant cell lysates and presents a new method for calculating SHAPE reactivities from overlapping reverse transcriptase priming sites. PMID:29294088

  7. [Selection of access and positioning for operative treatment of pelvic injuries. Decision-making strategies].

    Science.gov (United States)

    Ossendorf, C; Hofmann, A; Rommens, P M

    2013-03-01

    Surgical treatment of pelvic ring injuries requires in-depth knowledge of the topographic anatomy of the pelvic bones, joints and soft tissue structures. A wide range of stabilizing techniques is available including bridging plate osteosynthesis, iliosacral compression screw osteosynthesis and transpubic positioning screws. In this article the different treatment strategies with the respective surgical approaches and patient positioning for pelvic ring fractures and combined lesions of the pelvic ring and acetabulum are presented. Pelvic ring lesions with rotational instability are approached from the anterior and occasionally from both the anterior and posterior based on the amount and localization of the instability. In vertically unstable lesions the most unstable part must be addressed first by reduction and fixation of the dislocated part to the axial skeleton. In combined fractures of the pelvis and acetabulum dorsal stabilization is carried out first.

  8. 78 FR 32257 - Privacy Act of 1974; Report of a New Routine Use for Selected CMS Systems of Records

    Science.gov (United States)

    2013-05-29

    ... systems of records to assist in preventing and detecting fraud, waste and abuse. The new routine use will... for the purpose of preventing and detecting fraud, waste and abuse, pursuant to section 1128C(a)(2) of the Social Security Act (``the Act''). At section 1128C(c) of the Act, a health plan is defined as a...

  9. Is self-selection the main driver of positive interpretations of general health checks?

    DEFF Research Database (Denmark)

    Bender, Anne Mette; Jørgensen, Torben; Pisinger, Charlotta

    2015-01-01

    OBJECTIVE: To investigate if the lower mortality among participants of a health check followed by lifestyle intervention of high risk persons is explained by self-selection. METHODS: All persons residing in the study area (Copenhagen; Denmark) were randomized to intervention (n=11,629) or control...... group (n=47,987). Persons in the intervention group were invited for a health check and individual lifestyle counselling. At baseline, 52.5% participated. Differences between participants and control group in 10-year all-cause and disease specific mortality was assessed. In survival analyses we...... was seen both for lifestyle related and non-lifestyle related diseases....

  10. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Science.gov (United States)

    Botosso, Viviane F; Zanotto, Paolo M de A; Ueda, Mirthes; Arruda, Eurico; Gilio, Alfredo E; Vieira, Sandra E; Stewien, Klaus E; Peret, Teresa C T; Jamal, Leda F; Pardini, Maria I de M C; Pinho, João R R; Massad, Eduardo; Sant'anna, Osvaldo A; Holmes, Eddie C; Durigon, Edison L

    2009-01-01

    Human respiratory syncytial virus (HRSV) is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  11. Positive selection results in frequent reversible amino acid replacements in the G protein gene of human respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Viviane F Botosso

    2009-01-01

    Full Text Available Human respiratory syncytial virus (HRSV is the major cause of lower respiratory tract infections in children under 5 years of age and the elderly, causing annual disease outbreaks during the fall and winter. Multiple lineages of the HRSVA and HRSVB serotypes co-circulate within a single outbreak and display a strongly temporal pattern of genetic variation, with a replacement of dominant genotypes occurring during consecutive years. In the present study we utilized phylogenetic methods to detect and map sites subject to adaptive evolution in the G protein of HRSVA and HRSVB. A total of 29 and 23 amino acid sites were found to be putatively positively selected in HRSVA and HRSVB, respectively. Several of these sites defined genotypes and lineages within genotypes in both groups, and correlated well with epitopes previously described in group A. Remarkably, 18 of these positively selected tended to revert in time to a previous codon state, producing a "flip-flop" phylogenetic pattern. Such frequent evolutionary reversals in HRSV are indicative of a combination of frequent positive selection, reflecting the changing immune status of the human population, and a limited repertoire of functionally viable amino acids at specific amino acid sites.

  12. Human apolipoprotein CIII gene expression is regulated by positive and negative cis-acting elements and tissue-specific protein factors

    International Nuclear Information System (INIS)

    Reue, K.; Leff, T.; Breslow, J.L.

    1988-01-01

    Apolipoprotein CIII (apoCIII) is a major protein constituent of triglyceride-rich lipoproteins and is synthesized primarily in the liver. Cis-acting DNA elements required for liver-specific apoCIII gene transcription were identified with transient expression assays in the human hepatoma (HepG2) and epithelial carcinoma (HeLa) cell lines. In liver cells, 821 nucleotides of the human apoCIII gene 5'-flanking sequence were required for maximum levels of gene expression, while the proximal 110 nucleotides alone were sufficient. No expression was observed in similar studies with HeLa cells. The level of expression was modulated by a combination of positive and negative cis-acting sequences, which interact with distinct sets of proteins from liver and HeLa cell nuclear extracts. The proximal positive regulatory region shares homology with similarly located sequences of other genes strongly expressed in the liver, including α 1 -antitrypsin and other apolipoprotein genes. The negative regulatory region is striking homologous to the human β-interferon gene regulatory element. The distal positive region shares homology with some viral enhancers and has properties of a tissue-specific enhancer. The regulation of the apoCIII gene is complex but shares features with other genes, suggesting shuffling of regulatory elements as a common mechanism for cell type-specific gene expression

  13. Plant operator selection system for evaluating employment candidates' potential for success in electric power plant operations positions

    International Nuclear Information System (INIS)

    Dunnette, M.D.

    1982-01-01

    The Plant Operator Selection System is a battery of tests and questionnaires that can be administered to job candidates in less than three hours. Various components of the battery measure what a job candidate has accomplished in previous educational and work situations, how well a candidate compares with others on a number of important aptitudes or abilities, and whether or not a candidate possesses the kind of personal stability required in power plant operations positions. A job candidate's answers to the tests and questionnaires of the Plant Operator Selection System are scored and converted to an OVERALL POTENTIAL INDEX. Values of the OVERALL POTENTIAL INDEX [OPI] range between 0 and 15. Candidates with high OPI values are much more likely to become effective and successful plant operators than candidates with low OPI values. It is possible to estimate the financial advantages to a company of using the Plant Operator Selection System in evaluating candidates for plant operations jobs

  14. Sexual orientation and spatial position effects on selective forms of object location memory.

    Science.gov (United States)

    Rahman, Qazi; Newland, Cherie; Smyth, Beatrice Mary

    2011-04-01

    Prior research has demonstrated robust sex and sexual orientation-related differences in object location memory in humans. Here we show that this sexual variation may depend on the spatial position of target objects and the task-specific nature of the spatial array. We tested the recovery of object locations in three object arrays (object exchanges, object shifts, and novel objects) relative to veridical center (left compared to right side of the arrays) in a sample of 35 heterosexual men, 35 heterosexual women, and 35 homosexual men. Relative to heterosexual men, heterosexual women showed better location recovery in the right side of the array during object exchanges and homosexual men performed better in the right side during novel objects. However, the difference between heterosexual and homosexual men disappeared after controlling for IQ. Heterosexual women and homosexual men did not differ significantly from each other in location change detection with respect to task or side of array. These data suggest that visual space biases in processing categorical spatial positions may enhance aspects of object location memory in heterosexual women. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Religiousness, well-being and ageing – selected explanations of positive relationships

    Directory of Open Access Journals (Sweden)

    Woźniak Barbara

    2015-12-01

    Full Text Available According to research that have been conducted in the field of gerontology, sociology and psychology of ageing, there is a relationship between the level of religious involvement and health status/ well-being/quality of life in older age. How does religiousness influence aging process and health status? The aim of the article is to review explanations of a positive relationship between religiousness and health that are discussed in the literature. Those explanations may be grouped in three broad categories reflecting three functions of religion that play a role for well-being in older age. Those functions are: (1 religiousness as a source of coherence and the role of religious coping and provision of meaning in dealing with stressful life events (including ageing losses (2 religiousness as a source of positive self-perception and a sense of personal control, (3 provision of social resources (i.e. social ties and social support within religious community and emphasis on interpersonal relations (with special focus on forgiveness as a norm in interpersonal relations. Those functions of religion are discussed in the context of their potential role in successful ageing, as determined by - among others - active engagement in life.

  16. Positive affect, meaning in life, and future time perspective: an application of socioemotional selectivity theory.

    Science.gov (United States)

    Hicks, Joshua A; Trent, Jason; Davis, William E; King, Laura A

    2012-03-01

    Four studies tested the prediction that positive affect (PA) would relate more strongly to meaning in life (MIL) as a function of perceived time limitations. In Study 1 (N = 360), adults completed measures of PA and MIL. As predicted, PA related more strongly to MIL for older, compared to younger, participants. In Studies 2 and 3, adults (N = 514) indicated their current position in their life span, and rated their MIL. PA, whether naturally occurring (Study 2) or induced (Study 3), was a stronger predictor of MIL for individuals who perceived themselves as having a limited amount of time left to live. Finally, in Study 4 (N = 98) students completed a measure of PA, MIL, and future time perspective (FTP). Results showed that PA was more strongly linked to MIL for those who believed they had fewer opportunities left to pursue their goals. Overall, these findings suggest that the experience of PA becomes increasingly associated with the experience of MIL as the perception of future time becomes limited. The contribution of age related processes to judgments of well-being are discussed.

  17. Position of the Mental Foramen in Panoramic Radiography and Its Relationship to Age in a Selected Iranian Population

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    Dehghani

    2016-02-01

    Full Text Available Background The position of the mental foramen is critical for surgery and local anesthesia. Objectives This study was conducted to assess the position of the mental foramen and its relationship to age in a selected Iranian population. Materials and Methods This was a cross-sectional descriptive study. Three hundred panoramic radiographs were assessed. Three variables were assessed for each radiograph: anterior-posterior position, superior-inferior position, and radiographic appearance. The position and appearance of the mental foramen were recorded according to gender and age. The results were analyzed using Chi-square and Fisher’s exact tests. Results Considering the anterior-posterior position, the mental foramina were located in the following positions: between premolars (41.5%, at the apex of the second premolars (31.7%, in the posterior area of the second premolars (19.2%, in the anterior area of the first premolars (4.3%, and at the apex of the first premolars (3.3%.The superior-inferior position of the mental foramina were below, above, and at the level of the apices of the premolars in 78.8%, 2.5%, and 18.7% of cases, respectively. The appearance of the mental foramen was continuous in relation to the mandibular canal in 55.9% of cases, while it was separated, diffuse, and unidentified in 29.5%, 9.7%, and 5% of cases, respectively. Age was found to affect the position and appearance of mental foramen. Conclusions The mental foramina were most commonly located between the first and second premolars and below the apex. A continuous appearance was the most common appearance for the mental foramen, which was similar in males and females.

  18. Does positive selection drive transcription factor binding site turnover? A test with Drosophila cis-regulatory modules.

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    Bin Z He

    2011-04-01

    Full Text Available Transcription factor binding site(s (TFBS gain and loss (i.e., turnover is a well-documented feature of cis-regulatory module (CRM evolution, yet little attention has been paid to the evolutionary force(s driving this turnover process. The predominant view, motivated by its widespread occurrence, emphasizes the importance of compensatory mutation and genetic drift. Positive selection, in contrast, although it has been invoked in specific instances of adaptive gene expression evolution, has not been considered as a general alternative to neutral compensatory evolution. In this study we evaluate the two hypotheses by analyzing patterns of single nucleotide polymorphism in the TFBS of well-characterized CRM in two closely related Drosophila species, Drosophila melanogaster and Drosophila simulans. An important feature of the analysis is classification of TFBS mutations according to the direction of their predicted effect on binding affinity, which allows gains and losses to be evaluated independently along the two phylogenetic lineages. The observed patterns of polymorphism and divergence are not compatible with neutral evolution for either class of mutations. Instead, multiple lines of evidence are consistent with contributions of positive selection to TFBS gain and loss as well as purifying selection in its maintenance. In discussion, we propose a model to reconcile the finding of selection driving TFBS turnover with constrained CRM function over long evolutionary time.

  19. Detecting loci under recent positive selection in dairy and beef cattle by combining different genome-wide scan methods.

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    Yuri Tani Utsunomiya

    Full Text Available As the methodologies available for the detection of positive selection from genomic data vary in terms of assumptions and execution, weak correlations are expected among them. However, if there is any given signal that is consistently supported across different methodologies, it is strong evidence that the locus has been under past selection. In this paper, a straightforward frequentist approach based on the Stouffer Method to combine P-values across different tests for evidence of recent positive selection in common variations, as well as strategies for extracting biological information from the detected signals, were described and applied to high density single nucleotide polymorphism (SNP data generated from dairy and beef cattle (taurine and indicine. The ancestral Bovinae allele state of over 440,000 SNP is also reported. Using this combination of methods, highly significant (P<3.17×10(-7 population-specific sweeps pointing out to candidate genes and pathways that may be involved in beef and dairy production were identified. The most significant signal was found in the Cornichon homolog 3 gene (CNIH3 in Brown Swiss (P = 3.82×10(-12, and may be involved in the regulation of pre-ovulatory luteinizing hormone surge. Other putative pathways under selection are the glucolysis/gluconeogenesis, transcription machinery and chemokine/cytokine activity in Angus; calpain-calpastatin system and ribosome biogenesis in Brown Swiss; and gangliosides deposition in milk fat globules in Gyr. The composite method, combined with the strategies applied to retrieve functional information, may be a useful tool for surveying genome-wide selective sweeps and providing insights in to the source of selection.

  20. Depression and selection of positive and negative social feedback: motivated preference or cognitive balance?

    Science.gov (United States)

    Alloy, L B; Lipman, A J

    1992-05-01

    In this commentary we examine Swann, Wenzlaff, Krull, and Pelham's (1992) findings with respect to each of 5 central propositions in self-verification theory. We conclude that although the data are consistent with self-verification theory, none of the 5 components of the theory have been demonstrated convincingly as yet. Specifically, we argue that depressed subjects' selection of social feedback appears to be balanced or evenhanded rather than biased toward negative feedback and that there is little evidence to indicate that depressives actively seek negative appraisals. Furthermore, we suggest that the studies are silent with respect to the motivational postulates of self-verification theory and that a variety of competing cognitive and motivational models can explain Swann et al.'s findings as well as self-verification theory.

  1. Identification of Cis-Acting Elements on Positive-Strand Subgenomic mRNA Required for the Synthesis of Negative-Strand Counterpart in Bovine Coronavirus

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    Po-Yuan Yeh

    2014-07-01

    Full Text Available It has been demonstrated that, in addition to genomic RNA, sgmRNA is able to serve as a template for the synthesis of the negative-strand [(−-strand] complement. However, the cis-acting elements on the positive-strand [(+-strand] sgmRNA required for (−-strand sgmRNA synthesis have not yet been systematically identified. In this study, we employed real-time quantitative reverse transcription polymerase chain reaction to analyze the cis-acting elements on bovine coronavirus (BCoV sgmRNA 7 required for the synthesis of its (−-strand counterpart by deletion mutagenesis. The major findings are as follows. (1 Deletion of the 5'-terminal leader sequence on sgmRNA 7 decreased the synthesis of the (−-strand sgmRNA complement. (2 Deletions of the 3' untranslated region (UTR bulged stem-loop showed no effect on (−-strand sgmRNA synthesis; however, deletion of the 3' UTR pseudoknot decreased the yield of (−-strand sgmRNA. (3 Nucleotides positioned from −15 to −34 of the sgmRNA 7 3'-terminal region are required for efficient (−-strand sgmRNA synthesis. (4 Nucleotide species at the 3'-most position (−1 of sgmRNA 7 is correlated to the efficiency of (−-strand sgmRNA synthesis. These results together suggest, in principle, that the 5'- and 3'-terminal sequences on sgmRNA 7 harbor cis-acting elements are critical for efficient (−-strand sgmRNA synthesis in BCoV.

  2. Impact of low-energy CT imaging on selection of positive oral contrast media concentration.

    Science.gov (United States)

    Patino, Manuel; Murcia, Diana J; Iamurri, Andrea Prochowski; Kambadakone, Avinash R; Hahn, Peter F; Sahani, Dushyant V

    2017-05-01

    To determine to what extent low-energy CT imaging affects attenuation of gastrointestinal tract (GIT) opacified with positive oral contrast media (OCM). Second, to establish optimal OCM concentrations for low-energy diagnostic CT exams. One hundred patients (38 men and 62 women; age 62 ± 11 years; BMI 26 ± 5) with positive OCM-enhanced 120-kVp single-energy CT (SECT), and follow-up 100-kVp acquisitions (group A; n = 50), or 40-70-keV reconstructions from rapid kV switching-single-source dual-energy CT (ssDECT) (group B; n = 50) were included. Luminal attenuation from different GIT segments was compared between exams. Standard dose of three OCM and diluted solutions (75%, 50%, and 25% concentrations) were introduced serially in a gastrointestinal phantom and scanned using SECT (120, 100, and 80 kVp) and DECT (80/140 kVp) acquisitions on a ssDECT scanner. Luminal attenuation was obtained on SECT and DECT images (40-70 keV), and compared to 120-kVp scans with standard OCM concentrations. Luminal attenuation was higher on 100-kVp (328 HU) and on 40-60-keV images (410-924 HU) in comparison to 120-kVp scans (298 HU) in groups A and B (p < 0.05). Phantom: There was an inverse correlation between luminal attenuation and X-ray energy, increasing up to 527 HU on low-kVp and 999 HU on low-keV images (p < 0.05). 25% and 50% diluted OCM solutions provided similar or higher attenuation than 120 kVp, at low kVp and keV, respectively. Low-energy CT imaging increases the attenuation of GIT opacified with positive OCM, permitting reduction of 25%-75% OCM concentration.

  3. Structure refinement and membrane positioning of selectively labeled OmpX in phospholipid nanodiscs

    Energy Technology Data Exchange (ETDEWEB)

    Hagn, Franz, E-mail: franz.hagn@tum.de; Wagner, Gerhard, E-mail: gerhard-wagner@hms.harvard.edu [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States)

    2015-04-15

    NMR structural studies on membrane proteins are often complicated by their large size, taking into account the contribution of the membrane mimetic. Therefore, classical resonance assignment approaches often fail. The large size of phospholipid nanodiscs, a detergent-free phospholipid bilayer mimetic, prevented their use in high-resolution solution-state NMR spectroscopy so far. We recently introduced smaller nanodiscs that are suitable for NMR structure determination. However, side-chain assignments of a membrane protein in nanodiscs still remain elusive. Here, we utilized a NOE-based approach to assign (stereo-) specifically labeled Ile, Leu, Val and Ala methyl labeled and uniformly {sup 15}N-Phe and {sup 15}N-Tyr labeled OmpX and calculated a refined high-resolution structure. In addition, we were able to obtain residual dipolar couplings (RDCs) of OmpX in nanodiscs using Pf1 phage medium for the induction of weak alignment. Back-calculated NOESY spectra of the obtained NMR structures were compared to experimental NOESYs in order to validate the quality of these structures. We further used NOE information between protonated lipid head groups and side-chain methyls to determine the position of OmpX in the phospholipid bilayer. These data were verified by paramagnetic relaxation enhancement (PRE) experiments obtained with Gd{sup 3+}-modified lipids. Taken together, this study emphasizes the need for the (stereo-) specific labeling of membrane proteins in a highly deuterated background for high-resolution structure determination, particularly in large membrane mimicking systems like phospholipid nanodiscs. Structure validation by NOESY back-calculation will be helpful for the structure determination and validation of membrane proteins where NOE assignment is often difficult. The use of protein to lipid NOEs will be beneficial for the positioning of a membrane protein in the lipid bilayer without the need for preparing multiple protein samples.

  4. James Cook University's rurally orientated medical school selection process: quality graduates and positive workforce outcomes.

    Science.gov (United States)

    Ray, Robin A; Woolley, Torres; Sen Gupta, Tarun

    2015-01-01

    The regionally based James Cook University (JCU) College of Medicine and Dentistry aims to meet its mission to address the health needs of the region by using a selection policy favouring rural origin applicants and providing students with early and repeated exposure to rural experiences during training. This study seeks to determine if the JCU medical school's policy of preferentially selecting rural and remote background students is associated with differing patterns of undergraduate performance or graduate practice location. Data at application to medical school and during the undergraduate years was retrieved from administrative databases held by the university and the medical school. Postgraduate location data were obtained either from personal contact via email, telephone or Facebook or electronically from the Australian Health Practitioner Regulation Authority website. Practice location was described across Australian Standard Geographical Classification Remoteness Area (ASGC-RA) categories, with 1 being a major city and 5 being a very remote location. The 856 Australian-based students accepted into the JCU medical program between 2000 and 2008 came from all geographical regions across Australia: 20% metropolitan (ASGC-RA 1), 20% inner regional (ASGC-RA 2), 56% outer regional (ASGC-RA 3), and 5% from remote or very remote locations (ASGC-RA 4 and 5). Having a rural or remote hometown at application (ASGC-RA 3-5) was significantly associated with a lower tertiary entrance score (pacademic achievement across years 1 to 3 (p=0.002, p=0.005 and p=0.025, respectively). Graduates having either a rural or a remote home town at application were more likely to practise in rural (RA 3-5) towns than graduates from metropolitan/inner regional centre across all postgraduate years. For example, the prevalence odds ratios (POR) for graduates practising in a rural town at postgraduate year 1 (PGY 1) having either a rural or remote hometown were 2.6 and 1.8, respectively

  5. Negative and positive components of psychological masculinity and femininity and their relationships to self-reports of neurotic and acting out behaviors.

    Science.gov (United States)

    Spence, J T; Helmreich, R L; Holahan, C K

    1979-10-01

    Negatively valued masculinity (M-) and femininity (F-) personality scales were developed to supplement the positively valued Masculinity (M+) and Femininity (F+) scales of the Personal Attributes Questionnaire (PAQ; Spence & Helmreich). M- consisted of traits that had been judged to be (a) more typical of males than females, (b) undesirable in both sexes, and (c ) agentic or instrumental in content. Two F- scales were developed, both containing stereotypically feminine, undesirable traits, one set of traits referring to communionlike characteristics (Fc-) and the other to verbal passive-aggressive qualities (FVA-). Significant sex differences in the predicted direction were found on all scales. In both sexes, low and typically nonsignificant correlations were found between parallel positive and negative scales, but highly significant negative correlations were found between positive and negative cross-sex scales. These findings provide additional evidence for the multidimentionslity of masculinity and femininity. Scores on a self-esteem measure were positively correlated with M+ and F+, uncorrelated with M-, and negatively correlated with the F- scales. Different patterns of scores were associated with two types of problem behaviors. In both sexes, neuroticism was most highly correlated (in a negative direction) with M+, and acting out behavoir was most strongly correlated (in a positive direction) with M-. The next highest correlation in both instances was with FVA-.

  6. Effect of repetitive yogic squats with specific hand position (Thoppukaranam) on selective attention and psychological states.

    Science.gov (United States)

    Chandrasekeran, Angelica; Rajesh, Sasidharan K; Srinivasan, Tm

    2014-01-01

    Research on the effect of Thoppukaranam is limited despite it being practiced as a form of worship to the elephant-headed deity Lord Ganapati and punishment in schools. The purpose of this study was to examine the effect of Thoppukaranam on selective attention and psychological states in a sample of young adults. A randomized self-as-control within subjects design was employed. Thirty undergraduate students (4 females and 26 males) from a residential Yoga University in Southern India were recruited for this study (group mean age ± standard deviation, 20.17 ± 2.92). The d2 test, State Anxiety Inventory-Short Form and State Mindful Attention Awareness Scale (SMAAS) were used to measure cognitive performance and psychological states. Assessments were made in three sessions: Baseline, control (squats), and experimental (Thoppukaranam) on 3 separate days. Data were analyzed using one-way repeated measures analyses of variance between three sessions, that is, baseline, squat, and Thoppukaranam. There was a significant improvement in all measures of the d2 test of attention (TN, E, TN-E, E%, and concentration performance) and state mindfulness after Thoppukaranam. Further state anxiety reduced significantly after the experimental session. These findings indicate Thoppukaranam results in enhancement of cognitive functioning and psychological states.

  7. Selective internalization of self-assembled artificial oil bodies by HER2/neu-positive cells

    International Nuclear Information System (INIS)

    Chiang, Chung-Jen; Lin, Che-Chin; Lin, Li-Jen; Chang, Chih-Hsiang; Chao, Yun-Peng

    2011-01-01

    A novel delivery carrier was developed using artificial oil bodies (AOBs). Plant seed oil bodies (OBs) consist of a triacylglycerol matrix surrounded by a monolayer of phospholipids embedded with the storage protein oleosin (Ole). Ole consists of a central hydrophobic domain with two amphiphatic arms that extrude from the surface of OBs. In this study, a bivalent anti-HER2/neu affibody domain (ZH2) was fused with Ole at the C terminus. After overproduction in Escherichia coli, the fusion protein (Ole-ZH2) was recovered to assemble AOBs. The size of self-assembled AOBs was tailored by varying the oil/Ole-ZH2 ratio and pH to reach a nanoscale. Upon co-incubation with tumor cells, the nanoscale AOBs encapsulated with a hydrophobic fluorescence dye were selectively internalized by HER2/neu-overexpressing cells and displayed biocompatibility with the cells. In addition, the ZH2-mediated endosomal entry of AOBs occurred in a time- and AOB dose-dependent manner. The internalization efficiency was as high as 90%. The internalized AOBs disintegrated at the non-permissive pH (e.g. in acidic endosomes) and the cargo dye was released. Results of in vitro study revealed a sustained and prolonged release profile. Taken together, our findings indicate the potential of AOBs as a delivery carrier.

  8. Multi-scale textural feature extraction and particle swarm optimization based model selection for false positive reduction in mammography.

    Science.gov (United States)

    Zyout, Imad; Czajkowska, Joanna; Grzegorzek, Marcin

    2015-12-01

    The high number of false positives and the resulting number of avoidable breast biopsies are the major problems faced by current mammography Computer Aided Detection (CAD) systems. False positive reduction is not only a requirement for mass but also for calcification CAD systems which are currently deployed for clinical use. This paper tackles two problems related to reducing the number of false positives in the detection of all lesions and masses, respectively. Firstly, textural patterns of breast tissue have been analyzed using several multi-scale textural descriptors based on wavelet and gray level co-occurrence matrix. The second problem addressed in this paper is the parameter selection and performance optimization. For this, we adopt a model selection procedure based on Particle Swarm Optimization (PSO) for selecting the most discriminative textural features and for strengthening the generalization capacity of the supervised learning stage based on a Support Vector Machine (SVM) classifier. For evaluating the proposed methods, two sets of suspicious mammogram regions have been used. The first one, obtained from Digital Database for Screening Mammography (DDSM), contains 1494 regions (1000 normal and 494 abnormal samples). The second set of suspicious regions was obtained from database of Mammographic Image Analysis Society (mini-MIAS) and contains 315 (207 normal and 108 abnormal) samples. Results from both datasets demonstrate the efficiency of using PSO based model selection for optimizing both classifier hyper-parameters and parameters, respectively. Furthermore, the obtained results indicate the promising performance of the proposed textural features and more specifically, those based on co-occurrence matrix of wavelet image representation technique. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Novel HER2 Aptamer Selectively Delivers Cytotoxic Drug to HER2-positive Breast Cancer Cells in Vitro

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    Liu Zhe

    2012-07-01

    Full Text Available Abstract Background Aptamer-based tumor targeted drug delivery system is a promising approach that may increase the efficacy of chemotherapy and reduce the related toxicity. HER2 protein is an attractive target for tumor-specific drug delivery because of its overexpression in multiple malignancies, including breast, gastric, ovarian, and lung cancers. Methods In this paper, we developed a new HER2 aptamer (HB5 by using systematic evolution of ligands by exponential enrichment technology (SELEX and exploited its role as a targeting ligand for delivering doxorubicin (Dox to breast cancer cells in vitro. Results The selected aptamer was an 86-nucleotide DNA molecule that bound to an epitope peptide of HER2 with a Kd of 18.9 nM. The aptamer also bound to the extracellular domain (ECD of HER2 protein with a Kdof 316 nM, and had minimal cross reactivity to albumin or trypsin. In addition, the aptamer was found to preferentially bind to HER2-positive but not HER2-negative breast cancer cells. An aptamer-doxorubicin complex (Apt-Dox was formulated by intercalating Dox into the DNA structure of HB5. The Apt-Dox complex could selectively deliver Dox to HER2-positive breast cancer cells while reducing the drug intake by HER2-negative cells in vitro. Moreover, Apt-Dox retained the cytotoxicity of Dox against HER2-positive breast cancer cells, but reduced the cytotoxicity to HER2-negative cells. Conclusions The results suggest that the selected HER2 aptamer may have application potentials in targeted therapy against HER2-positive breast cancer cells.

  10. Identifying selectively important amino acid positions associated with alternative habitat environments in fish mitochondrial genomes.

    Science.gov (United States)

    Xia, Jun Hong; Li, Hong Lian; Zhang, Yong; Meng, Zi Ning; Lin, Hao Ran

    2018-05-01

    Fish species inhabitating seawater (SW) or freshwater (FW) habitats have to develop genetic adaptations to alternative environment factors, especially salinity. Functional consequences of the protein variations associated with habitat environments in fish mitochondrial genomes have not yet received much attention. We analyzed 829 complete fish mitochondrial genomes and compared the amino acid differences of 13 mitochondrial protein families between FW and SW fish groups. We identified 47 specificity determining sites (SDS) that associated with FW or SW environments from 12 mitochondrial protein families. Thirty-two (68%) of the SDS sites are hydrophobic, 13 (28%) are neutral, and the remaining sites are acidic or basic. Seven of those SDS from ND1, ND2 and ND5 were scored as probably damaging to the protein structures. Furthermore, phylogenetic tree based Bayes Empirical Bayes analysis also detected 63 positive sites associated with alternative habitat environments across ten mtDNA proteins. These signatures could be important for studying mitochondrial genetic variation relevant to fish physiology and ecology.

  11. A design of a valid signal selecting and position decoding ASIC for PET using silicon photomultipliers

    International Nuclear Information System (INIS)

    Cho, M.; Lim, K.-T.; Kim, J.; Lee, C.; Cho, G.; Kim, H.; Yeom, J.-Y.; Choi, H.

    2017-01-01

    In most cases, a PET system has numerous electrical components and channel circuits and thus it would rather be a bulky product. Also, most existing systems receive analog signals from detectors which make them vulnerable to signal distortions. For these reasons, channel reduction techniques are important. In this work, an ASIC for PET module is being proposed. An ASIC chip for 16 PET detector channels, VSSPDC, has been designed and simulated. The main function of the chip is 16-to-1 channel reduction, i.e., finding the position of only the valid signals, signal timing, and magnitudes in all 16 channels at every recorded event. The ASIC comprises four of 4-channel modules and a 2 nd 4-to-1 router. A single channel module comprises a transimpedance amplifier for the silicon photomultipliers, dual comparators with high and low level references, and a logic circuitry. While the high level reference was used to test the validity of the signal, the low level reference was used for the timing. The 1-channel module of the ASIC produced an energy pulse by time-over-threshold method and it also produced a time pulse with a fixed delayed time. Since the ASIC chip outputs only a few digital pulses and does not require an external clock, it has an advantage over noise properties. The cadence simulation showed the good performance of the chip as designed.

  12. Positive selection of a duplicated UV-sensitive visual pigment coincides with wing pigment evolution in Heliconius butterflies

    Science.gov (United States)

    Briscoe, Adriana D.; Bybee, Seth M.; Bernard, Gary D.; Yuan, Furong; Sison-Mangus, Marilou P.; Reed, Robert D.; Warren, Andrew D.; Llorente-Bousquets, Jorge; Chiao, Chuan-Chin

    2010-01-01

    The butterfly Heliconius erato can see from the UV to the red part of the light spectrum with color vision proven from 440 to 640 nm. Its eye is known to contain three visual pigments, rhodopsins, produced by an 11-cis-3-hydroxyretinal chromophore together with long wavelength (LWRh), blue (BRh) and UV (UVRh1) opsins. We now find that H. erato has a second UV opsin mRNA (UVRh2)—a previously undescribed duplication of this gene among Lepidoptera. To investigate its evolutionary origin, we screened eye cDNAs from 14 butterfly species in the subfamily Heliconiinae and found both copies only among Heliconius. Phylogeny-based tests of selection indicate positive selection of UVRh2 following duplication, and some of the positively selected sites correspond to vertebrate visual pigment spectral tuning residues. Epi-microspectrophotometry reveals two UV-absorbing rhodopsins in the H. erato eye with λmax = 355 nm and 398 nm. Along with the additional UV opsin, Heliconius have also evolved 3-hydroxy-DL-kynurenine (3-OHK)-based yellow wing pigments not found in close relatives. Visual models of how butterflies perceive wing color variation indicate this has resulted in an expansion of the number of distinguishable yellow colors on Heliconius wings. Functional diversification of the UV-sensitive visual pigments may help explain why the yellow wing pigments of Heliconius are so colorful in the UV range compared to the yellow pigments of close relatives lacking the UV opsin duplicate. PMID:20133601

  13. Micronutrient Availability in Relation to Selected Soil Properties and landscape Position in Calcareous Soils of Golpayegan

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    Mojtaba Fathi

    2017-02-01

    Full Text Available Introduction: Variety of soil reactions govern the distribution of metal micronutrients that includes complexation with organic and inorganic ligands, ion exchange, adsorption and desorption processes, precipitation and dissolution of solids and acid-based equilibria. The relative importance of these reactions depends on many factors such as soil physical, chemical, and mineralogical properties and the nature of metal ions. Environmental factors such as climate, physiographic position, and soil development may affect variability of some soil properties and thereby nutrient availability. The present research was conducted to find relationships between Iron, manganese, zinc, and copper availability and some major soil properties, physiographic condition and soil development. Materials and Methods: Golpayegan region is located in northwest of Isfahan province in central Iran. The mean elevation of the studied area is 1790 above sea level. Annual precipitation was about 244mm and mean monthly temperature ranges from -6 in January to 34°C in August. The soils were developed on different physiographic conditions including piedmont plains, alluvial-fan, plateaus, and flood plains belonging to Entisols and Aridisols. Soil samples (0–60 cm were collected from 98 grid points with 2000m distance in the agricultural area of Golpayegan. Particle size distribution, calcium carbonate, organic carbon, available potassium and phosphorus of the soils were measured by SWRI standard methods. Available Zn, Cu, Mn, and Fe were determined by addition of 10 g soil to 20mL 0.005M diethylentriaminepentacetic‏. The solutions were shaken for 2 h at 25°C, centrifuged, filtered, and Fe, Mn, Zn, and Cu concentrations were measured by an atomic absorption spectrophotometer. Results Discussion: Studied soils were developed on calcareous material and about 60% of samples have more than 20% of calcium carbonate. Available Fe ranged from 1.4 to 6.5 mg kg-1 (mean 15.8 mg kg-1

  14. A Radish Basic Helix-Loop-Helix Transcription Factor, RsTT8 Acts a Positive Regulator for Anthocyanin Biosynthesis

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    Sun-Hyung Lim

    2017-11-01

    Full Text Available The MYB-bHLH-WDR (MBW complex activates anthocyanin biosynthesis through the transcriptional regulation. RsMYB1 has been identified as a key player in anthocyanin biosynthesis in red radish (Raphanus sativus L., but its partner bHLH transcription factor (TF remains to be determined. In this study, we isolated a bHLH TF gene from red radish. Phylogenetic analysis indicated that this gene belongs to the TT8 clade of the IIIF subgroup of bHLH TFs, and we thus designated this gene RsTT8. Subcellular localization analysis showed that RsTT8-sGFP was localized to the nuclei of Arabidopsis thaliana protoplasts harboring the RsTT8-sGFP construct. We evaluated anthocyanin biosynthesis and RsTT8 expression levels in three radish varieties (N, C, and D that display different red phenotypes in the leaves, root flesh, and root skins. The root flesh of the C variety and the leaves and skins of the D variety exhibit intense red pigmentation; in these tissues, RsTT8 expression showed totally positive association with the expression of RsMYB1 TF and of five of eight tested anthocyanin biosynthesis genes (i.e., RsCHS, RsCHI, RsF3H, RsDFR, and RsANS. Heterologous co-expression of both RsTT8 and RsMYB1 in tobacco leaves dramatically increased the expression of endogenous anthocyanin biosynthesis genes and anthocyanin accumulation. Furthermore, a yeast two-hybrid assay showed that RsTT8 interacts with RsMYB1 at the MYB-interacting region (MIR, and a transient transactivation assay indicated that RsTT8 activates the RsCHS and RsDFR promoters when co-expressed with RsMYB1. Complementation of the Arabidopsis tt8-1 mutant, which lacks red pigmentation in the leaves and seeds, with RsTT8 restored red pigmentation, and resulted in high anthocyanin and proanthocyanidin contents in the leaves and seeds, respectively. Together, these results show that RsTT8 functions as a regulatory partner with RsMYB1 during anthocyanin biosynthesis.

  15. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Directory of Open Access Journals (Sweden)

    Michael R Garvin

    Full Text Available The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  16. Positive Darwinian selection in the piston that powers proton pumps in complex I of the mitochondria of Pacific salmon.

    Science.gov (United States)

    Garvin, Michael R; Bielawski, Joseph P; Gharrett, Anthony J

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm.

  17. Positive Darwinian Selection in the Piston That Powers Proton Pumps in Complex I of the Mitochondria of Pacific Salmon

    Science.gov (United States)

    Garvin, Michael R.; Bielawski, Joseph P.; Gharrett, Anthony J.

    2011-01-01

    The mechanism of oxidative phosphorylation is well understood, but evolution of the proteins involved is not. We combined phylogenetic, genomic, and structural biology analyses to examine the evolution of twelve mitochondrial encoded proteins of closely related, yet phenotypically diverse, Pacific salmon. Two separate analyses identified the same seven positively selected sites in ND5. A strong signal was also detected at three sites of ND2. An energetic coupling analysis revealed several structures in the ND5 protein that may have co-evolved with the selected sites. These data implicate Complex I, specifically the piston arm of ND5 where it connects the proton pumps, as important in the evolution of Pacific salmon. Lastly, the lineage to Chinook experienced rapid evolution at the piston arm. PMID:21969854

  18. Positive Selection Drives the Evolution of rhino, a Member of the Heterochromatin Protein 1 Family in Drosophila.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

  19. Positive selection drives the evolution of rhino, a member of the heterochromatin protein 1 family in Drosophila.

    Directory of Open Access Journals (Sweden)

    Danielle Vermaak

    2005-07-01

    Full Text Available Heterochromatin comprises a significant component of many eukaryotic genomes. In comparison to euchromatin, heterochromatin is gene poor, transposon rich, and late replicating. It serves many important biological roles, from gene silencing to accurate chromosome segregation, yet little is known about the evolutionary constraints that shape heterochromatin. A complementary approach to the traditional one of directly studying heterochromatic DNA sequence is to study the evolution of proteins that bind and define heterochromatin. One of the best markers for heterochromatin is the heterochromatin protein 1 (HP1, which is an essential, nonhistone chromosomal protein. Here we investigate the molecular evolution of five HP1 paralogs present in Drosophila melanogaster. Three of these paralogs have ubiquitous expression patterns in adult Drosophila tissues, whereas HP1D/rhino and HP1E are expressed predominantly in ovaries and testes respectively. The HP1 paralogs also have distinct localization preferences in Drosophila cells. Thus, Rhino localizes to the heterochromatic compartment in Drosophila tissue culture cells, but in a pattern distinct from HP1A and lysine-9 dimethylated H3. Using molecular evolution and population genetic analyses, we find that rhino has been subject to positive selection in all three domains of the protein: the N-terminal chromo domain, the C-terminal chromo-shadow domain, and the hinge region that connects these two modules. Maximum likelihood analysis of rhino sequences from 20 species of Drosophila reveals that a small number of residues of the chromo and shadow domains have been subject to repeated positive selection. The rapid and positive selection of rhino is highly unusual for a gene encoding a chromosomal protein and suggests that rhino is involved in a genetic conflict that affects the germline, belying the notion that heterochromatin is simply a passive recipient of "junk DNA" in eukaryotic genomes.

  20. Breast conservation therapy based on liberal selection criteria and less extensive surgery. Analysis of cases with positive margins

    International Nuclear Information System (INIS)

    Amemiya, Atsushi; Kondo, Makoto

    1999-01-01

    The relationship between the margin status and the risk of in-breast recurrence (IBR) is an important consideration in patients treated with breast conservation therapy but has not been defined adequately. To address this issue, 1533 clinical stage I and II patients who completed irradiation therapy between 1983 and 1998 were evaluated. Only selection criterion was whether she could be satisfied with cosmesis after lumpectomy. Size and location of the tumor, nodal status, histology and age were not primary consideration. The tumor was excised in such a way to obtain macroscopically clear margins. The breast was treated with 50 Gy of external irradiation but without boost. Margins were evaluated by serially sectioning of the specimen and the margin was judged positive only when cancer cells were present on the inked surface. Margins were also evaluated by scratch cytology. Seventy two IBR were experienced within 5 years. Only age and margin status were found to be independent risk factors. Five-year IBR rate with negative and positive margins was 3.7% and 10.0%, respectively. In patients with positive margins, number of positive site and positive cytology were independent risk factor for IBR. IBR rate among patients with focally involved margins by non-comedo, comedo and invasive ca, was 0.0%, 3.5%, and 8.7%, respectively. IBR rate in more than focal involvement by non-comedo, comedo, and invasive ca, was 4.0%, 33.0% and 30.0%, respectively. If histologically positive margin was also positive cytologically, IBR was 14.8%, whereas only 3.6% if negative cytologically. Even with liberal patient selection and less extensive local treatment, adequate local control can be obtained, provided that margins are histologically and/or cytologically negative. Focal margin involvement by DCIS or more than focal involvement by non-comedo type DCIS does not jeopardize local control. More than focal involvement by comedo DCIS or involvement by invasive ca results in high IBR rate

  1. Device to position selectively a tool carried by a vehicle moving on the perforated plate of a tube bundle

    International Nuclear Information System (INIS)

    Bernardin, M.

    1985-01-01

    The aim of the invention is an examination device for a tube bundle of an apparatus such as, but not restrictively, a steam generator, situated in a dangerous zone, e.g. radioactive and designed to be introduced into the water box of the said and placed against the perforated plate of the tube bundle by an operator working outside of the said apparatus and able to operate whatever the vertical or horizontal position of the tube plate. The device has a selectively positionable tool - carrying vehicle comprising pistons positioning fingers extendable into the tubes and mounted on extendable supports perpendicular to the pistons and to each other, and an articulated telescopic arm fixed at one end to a rotary mounting on the vehicle and at the other end to an access opening in the vessel containing the tube plate, to hold the vehicle against the plate [fr

  2. Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening.

    Directory of Open Access Journals (Sweden)

    Weihua Liu

    Full Text Available Overexpressed Human epidermal growth factor receptor 2 (HER2 drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.

  3. HIV-positive patients’ perceptions of care received at a selected antiretroviral therapy clinic in Vhembe district, South Africa

    Directory of Open Access Journals (Sweden)

    Tshifhiwa V. Ndou

    2016-04-01

    Full Text Available Background: Patients’ experiences are a reflection of what has happened during the care process and, therefore, provide information about the performance of health care professional workers. They refer to the process of care provision at the antiretroviral therapy (ART sites. Aim and setting: This article explored the perceptions of HIV-positive patients of care received at the Gateway Clinic of the regional hospital that provides antiretroviral treatment in the Vhembe district. Methods: A qualitative, explorative and descriptive design was used. A non-probability, convenient sampling method was used to select 20 HIV-positive patients who were above 18 years of age. In-depth individual interviews were used to collect data. Data were analysed through Tech’s open coding method. Results: One theme and two sub-themes emerged, namely positive experiences related to the environment and attitudes of health professionals, and negative experiences concerning the practices by health care providers. Conclusion: Patients’ perceptions of quality of, and satisfaction with, health care may affect health outcomes. Recommendations are made to consider, practice and strengthen the protocols, the standard operating procedures and the principles of infection control in the health facilities. Keywords: Human Immunodeficiecy Virus, Antiretroviral Treatment, HIV positive, Limpopo

  4. A genomic survey of positive selection in Burkholderia pseudomallei provides insights into the evolution of accidental virulence.

    Directory of Open Access Journals (Sweden)

    Tannistha Nandi

    2010-04-01

    Full Text Available Certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence". To understand this process, we compared eleven isolate genomes of Burkholderia pseudomallei (Bp, a tropical soil microbe and causative agent of the human and animal disease melioidosis. We found evidence for the existence of several new genes in the Bp reference genome, identifying 282 novel genes supported by at least two independent lines of supporting evidence (mRNA transcripts, database homologs, and presence of ribosomal binding sites and 81 novel genes supported by all three lines. Within the Bp core genome, 211 genes exhibited significant levels of positive selection (4.5%, distributed across many cellular pathways including carbohydrate and secondary metabolism. Functional experiments revealed that certain positively selected genes might enhance mammalian virulence by interacting with host cellular pathways or utilizing host nutrients. Evolutionary modifications improving Bp environmental fitness may thus have indirectly facilitated the ability of Bp to colonize and survive in mammalian hosts. These findings improve our understanding of the pathogenesis of melioidosis, and establish Bp as a model system for studying the genetics of accidental virulence.

  5. Natural resistance to experimental feline infectious peritonitis virus infection is decreased rather than increased by positive genetic selection.

    Science.gov (United States)

    Pedersen, Niels C; Liu, Hongwei; Durden, Monica; Lyons, Leslie A

    2016-03-01

    A previous study demonstrated the existence of a natural resistance to feline infectious peritonitis virus (FIPV) among 36% of randomly bred laboratory cats. A genome wide association study (GWAS) on this population suggested that resistance was polygenic but failed to identify any strong specific associations. In order to enhance the power of GWAS or whole genome sequencing to identify strong genetic associations, a decision was made to positively select for resistance over three generations. The inbreeding experiment began with a genetically related parental (P) population consisting of three toms and four queens identified from among the survivors of the earlier study and belonging to a closely related subgroup (B). The subsequent effects of inbreeding were measured using 42 genome-wide STR markers. P generation cats produced 57 first filial (F1) kittens, only five of which (9.0%) demonstrated a natural resistance to FIPV infection. One of these five F1 survivors was then used to produce six F1/P-backcrosses kittens, only one of which proved resistant to FIP. Six of eight of the F1 and F1/P survivors succumbed to a secondary exposure 4-12 months later. Therefore, survival after both primary and secondary infection was decreased rather than increased by positive selection for resistance. The common genetic factor associated with this diminished resistance was a loss of heterozygosity. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. A Novel Variant with Positive Natural Selection Influenced Hb A2 Levels in Chinese Individuals with β-Thalassemia.

    Science.gov (United States)

    Yu, Shanjuan; Chen, Yang; Lai, Ketong; Dewan, Roma Kajal; He, Yunyan

    2017-05-01

    β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A 2 is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A 2 levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A 2 levels. The presence of the C allele was associated with elevated Hb A 2 levels. Our results suggest that rs231841 on the KCNQ1 gene with positive natural selection is related to Hb A 2 levels in Chinese β-thal carriers, and KCNQ1 is probably associated with the expression of the β-like globin gene cluster.

  7. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium.

    Science.gov (United States)

    Gribble, Phillip A; Delahunt, Eamonn; Bleakley, Chris; Caulfield, Brian; Docherty, Carrie; Fourchet, François; Fong, Daniel Tik-Pui; Hertel, Jay; Hiller, Claire; Kaminski, Thomas; McKeon, Patrick; Refshauge, Kathryn; van der Wees, Philip; Vincenzino, Bill; Wikstrom, Erik

    2014-07-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly. This major gap within the literature limits the ability to generalise this evidence to the target patient population. Therefore, there is a need to provide standards for patient/participant selection criteria in research focused on CAI with justifications using the best available evidence. The International Ankle Consortium provides this position paper to present and discuss an endorsed set of selection criteria for patients with CAI based on the best available evidence to be used in future research and study designs. These recommendations will enhance the validity of research conducted in this clinical population with the end goal of bringing the research evidence to the clinician and patient. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Meta-analysis of age and skill effects on recalling chess positions and selecting the best move.

    Science.gov (United States)

    Moxley, Jerad H; Charness, Neil

    2013-10-01

    A meta-analysis was conducted of studies that measured the effects of both age and skill in chess on the tasks of selecting the best move for chess positions (the best move task) as well as recalling chess game positions (the recall task). Despite a small sample of studies, we demonstrated that there are age and skill effects on both tasks: age being negatively associated with performance on both tasks and skill being positively associated with performance on both tasks. On the best move task, we found that skill was the dominant effect, while on the recall task, skill and age were approximately equally strong effects. We also found that skill was best measured by the best move task. In the case of the best move task, this result is consistent with the argument that it accurately replicates expert performance (Ericsson & Smith, 1991). Results for the recall task argue that this task captures effects related to skill, but also effects likely due to a general aging process. Implications for our understanding of aging in skilled domains are also discussed.

  9. Optimization of Cognitive Radio Secondary Information Gathering Station Positioning and Operating Channel Selection for IoT Sensor Networks

    Directory of Open Access Journals (Sweden)

    Jinyi Wen

    2018-01-01

    Full Text Available The Internet of Things (IoT is the interconnection of different objects through the internet using different communication technologies. The objects are equipped with sensors and communications modules. The cognitive radio network is a key technique for the IoT and can effectively address spectrum-related issues for IoT applications. In our paper, a novel method for IoT sensor networks is proposed to obtain the optimal positions of secondary information gathering stations (SIGSs and to select the optimal operating channel. Our objective is to maximize secondary system capacity while protecting the primary system. In addition, we propose an appearance probability matrix for secondary IoT devices (SIDs to maximize the supportable number of SIDs that can be installed in a car, in wearable devices, or for other monitoring devices, based on optimal deployment and probability. We derive fitness functions based on the above objectives and also consider signal to interference-plus-noise ratio (SINR and position constraints. The particle swarm optimization (PSO technique is used to find the best position and operating channel for the SIGSs. In a simulation study, the performance of the proposed method is evaluated and compared with a random resources allocation algorithm (parts of this paper were presented at the ICTC2017 conference (Wen et al., 2017.

  10. Effect of process parameters and injector position on the efficiency of NOx reduction by selective non catalytic reduction technique

    International Nuclear Information System (INIS)

    Hamid, A.; Mehmood, M.A.; Irfan, N.; Javed, M.T.; Waheed, K.

    2009-01-01

    An experimental investigation has been performed to study the effect of atomizer pressure dilution of the reducing reagent and the injector position on the efficiency or the NOx reduction by a selective non-catalytic reduction technique using urea as a reducing agent. Experiments were performed with a flow reactor in which flue gas was generated by the combustion of methane in air at stoichiometric amount of oxygen and the desired levels of initial NOx (400-450 ppm) were achieved by doping the flame with ammonia. The work was directed to investigate the effect of atomizer pressure, dilution of urea reagent and the injector position. The atomizer pressure was varied from 1 to 3bar and 20-25% increase in efficiency was observed by decreasing the pressure. Effect of dilution of urea solution was investigated by varying the strength of the solution from the 8 to 32% and 40-45% increase in the efficiency was observed. Effects of injector position was investigated by injecting the urea solution both in co current and counter current direction of the flue gases and 20-25% increase in the efficiency was observed in counter current direction. (author)

  11. Analysis of seasonal position variation for selected GNSS sites in Poland using loading modelling and GRACE data

    Directory of Open Access Journals (Sweden)

    Marcin Rajner

    2017-07-01

    Full Text Available In this study we compared weekly GNSS position time series with modelled values of crustal deformations on the basis of Gravity Recovery and Climate Experiment (GRACE data. The Global Navigation Satellite Systems (GNSS time series were taken from homogeneously reprocessed global network solutions within the International GNSS Service (IGS Reprocessing 1 project and from regional solutions performed by Warsaw University of Technology (WUT European Permanent Network (EPN Local Analysis Center (LAC within the EPN reprocessing project. Eight GNSS sites from the territory of Poland with observation timespans between 2.5 and 13 years were selected for this study. The Total Water Equivalent (TWE estimation from GRACE data was used to compute deformations using the Green's function formalism. High frequency components were removed from GRACE data to avoid aliasing problems. Since GRACE observes mainly the mass transport in continental storage of water, we also compared GRACE deformations and the GNSS position time series, with the deformations computed on the basis of a hydrosphere model. We used the output of Water GAP Hydrology Model (WGHM to compute deformations in the same manner as for the GRACE data. The WGHM gave slightly larger amplitudes than GNSS and GRACE. The atmospheric non-tidal loading effect was removed from GNSS position time series before comparing them with modelled deformations. The results confirmed that the major part of observed seasonal variations for GNSS vertical components can be attributed to the hydrosphere loading. The results for these components agree very well both in the amplitude and phase. The decrease in standard deviation of the residual GNSS position time series for vertical components corrected for the hydrosphere loading reached maximally 36% and occurred for all but one stations for both global and regional solutions. For horizontal components the amplitudes are about three times smaller than for vertical

  12. Phylodynamic analysis of clinical and environmental Vibrio cholerae isolates from Haiti reveals diversification driven by positive selection.

    Science.gov (United States)

    Azarian, Taj; Ali, Afsar; Johnson, Judith A; Mohr, David; Prosperi, Mattia; Veras, Nazle M; Jubair, Mohammed; Strickland, Samantha L; Rashid, Mohammad H; Alam, Meer T; Weppelmann, Thomas A; Katz, Lee S; Tarr, Cheryl L; Colwell, Rita R; Morris, J Glenn; Salemi, Marco

    2014-12-23

    Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy. Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in

  13. [Selected problems in the forensic-psychiatric evaluation of persons posing a likelihood of repeating a criminal act].

    Science.gov (United States)

    Florkowski, Antoni; Zboralski, Krzysztof; Nowacka, Agata; Strójwas, Krzysztof; Flinik-Jankowska, Magdalena; Konopa, Aleksandra; Łacisz, Joanna; Wierzbiński, Piotr

    2014-09-01

    In the current penal code, compared to previous regulations, there have been alterations concerning medical security measures. These amendments have been prompted by socio-politic circumstances in Poland as well as implementation of Mental Health Act. According to the current law the court, on the request of expert psychiatrists, can pronounce a sentence of obligatory stay in psychiatric institution for perpetrator of criminal act who has been deemed not sane due to 31 subsection 1 of penal code and who is predictably able of recidivism. In legal-medical practice those less experienced expert psychiatrists may encounter difficulties producing expertise for the court, especially evaluating probability of recurrence of committing a criminal act and resulting request for psychiatric detention. In order to make this issue more acquainted we present a review of literature concerning it.

  14. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

    OpenAIRE

    Steiner, Michel A.; Sciarretta, Carla; Pasquali, Anne; Jenck, Francois

    2013-01-01

    The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS...

  15. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome.

    Science.gov (United States)

    Steiner, Michel A; Sciarretta, Carla; Pasquali, Anne; Jenck, Francois

    2013-01-01

    The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1) in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF) diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO) associated with metabolic syndrome (MetS). Rats were fed either standard chow (SC) or a cafeteria (CAF) diet comprised of intermittent human snacks and a constant free choice between a HF/sweet (HF/S) diet and SC for 13 weeks. Thereafter the SC group was treated with vehicle (for 4 weeks) and the CAF group was divided into a vehicle and an ACT-335827 treatment group. Energy and water intake, food preference, and indicators of MetS (abdominal obesity, glucose homeostasis, plasma lipids, and blood pressure) were monitored. Hippocampus-dependent memory, which can be impaired by DIO, was assessed. CAF diet fed rats treated with ACT-335827 consumed less of the HF/S diet and more of the SC, but did not change their snack or total kcal intake compared to vehicle-treated rats. ACT-335827 increased water intake and the high-density lipoprotein associated cholesterol proportion of total circulating cholesterol. ACT-335827 slightly increased body weight gain (4% vs. controls) and feed efficiency in the absence of hyperphagia. These effects were not associated with significant changes in the elevated fasting glucose and triglyceride (TG) plasma levels, glucose intolerance, elevated blood pressure, and adiposity due to CAF diet consumption. Neither CAF diet consumption alone nor ACT-335827 affected memory. In conclusion, the main metabolic characteristics associated with DIO and MetS in rats remained unaffected by chronic ACT-335827 treatment, suggesting that pharmacological OXR-1 blockade has minimal impact in this model.

  16. The selective orexin receptor 1 antagonist ACT-335827 in a rat model of diet-induced obesity associated with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Michel Alexander Steiner

    2013-12-01

    Full Text Available The orexin system regulates feeding, nutrient metabolism and energy homeostasis. Acute pharmacological blockade of orexin receptor 1 (OXR-1 in rodents induces satiety and reduces normal and palatable food intake. Genetic OXR-1 deletion in mice improves hyperglycemia under high-fat (HF diet conditions. Here we investigated the effects of chronic treatment with the novel selective OXR-1 antagonist ACT-335827 in a rat model of diet-induced obesity (DIO associated with metabolic syndrome (MetS. Rats were fed either standard chow (SC or a cafeteria (CAF diet comprised of intermittent human snacks and a constant free choice between a HF/sweet (HF/S diet and SC for 13 weeks. Thereafter the SC group was treated with vehicle (for 4 weeks and the CAF group was divided into a vehicle and an ACT-335827 treatment group. Energy and water intake, food preference, and indicators of MetS (abdominal obesity, glucose homeostasis, plasma lipids, and blood pressure were monitored. Hippocampus-dependent memory, which can be impaired by DIO, was assessed. CAF diet fed rats treated with ACT-335827 consumed less of the HF/S diet and more of the SC, but did not change their snack or total kcal intake compared to vehicle-treated rats. ACT-335827 increased water intake and the high-density lipoprotein associated cholesterol proportion of total circulating cholesterol. ACT-335827 slightly increased body weight gain (4% versus controls and feed efficiency in the absence of hyperphagia. These effects were not associated with significant changes in the elevated fasting glucose and triglyceride (TG plasma levels, glucose intolerance, elevated blood pressure, and adiposity due to CAF diet consumption. Neither CAF diet consumption alone nor ACT-335827 affected memory. In conclusion, the main metabolic characteristics associated with DIO and MetS in rats remained unaffected by chronic ACT-335827 treatment, suggesting that pharmacological OXR-1 blockade has minimal impact in this

  17. Shared and unique components of human population structure and genome-wide signals of positive selection in South Asia.

    Science.gov (United States)

    Metspalu, Mait; Romero, Irene Gallego; Yunusbayev, Bayazit; Chaubey, Gyaneshwer; Mallick, Chandana Basu; Hudjashov, Georgi; Nelis, Mari; Mägi, Reedik; Metspalu, Ene; Remm, Maido; Pitchappan, Ramasamy; Singh, Lalji; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

    2011-12-09

    South Asia harbors one of the highest levels genetic diversity in Eurasia, which could be interpreted as a result of its long-term large effective population size and of admixture during its complex demographic history. In contrast to Pakistani populations, populations of Indian origin have been underrepresented in previous genomic scans of positive selection and population structure. Here we report data for more than 600,000 SNP markers genotyped in 142 samples from 30 ethnic groups in India. Combining our results with other available genome-wide data, we show that Indian populations are characterized by two major ancestry components, one of which is spread at comparable frequency and haplotype diversity in populations of South and West Asia and the Caucasus. The second component is more restricted to South Asia and accounts for more than 50% of the ancestry in Indian populations. Haplotype diversity associated with these South Asian ancestry components is significantly higher than that of the components dominating the West Eurasian ancestry palette. Modeling of the observed haplotype diversities suggests that both Indian ancestry components are older than the purported Indo-Aryan invasion 3,500 YBP. Consistent with the results of pairwise genetic distances among world regions, Indians share more ancestry signals with West than with East Eurasians. However, compared to Pakistani populations, a higher proportion of their genes show regionally specific signals of high haplotype homozygosity. Among such candidates of positive selection in India are MSTN and DOK5, both of which have potential implications in lipid metabolism and the etiology of type 2 diabetes. Copyright © 2011 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  18. Positive- and negative-acting regulatory elements contribute to the tissue-specific expression of INNER NO OUTER, a YABBY-type transcription factor gene in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Simon Marissa K

    2012-11-01

    Full Text Available Abstract Background The INNER NO OUTER (INO gene, which encodes a YABBY-type transcription factor, specifies and promotes the growth of the outer integument of the ovule in Arabidopsis. INO expression is limited to the abaxial cell layer of the developing outer integument of the ovule and is regulated by multiple regions of the INO promoter, including POS9, a positive element that when present in quadruplicate can produce low-level expression in the normal INO pattern. Results Significant redundancy in activity between different regions of the INO promoter is demonstrated. For specific regulatory elements, multimerization or the addition of the cauliflower mosaic virus 35S general enhancer was able to activate expression of reporter gene constructs that were otherwise incapable of expression on their own. A new promoter element, POS6, is defined and is shown to include sufficient positive regulatory information to reproduce the endogenous pattern of expression in ovules, but other promoter regions are necessary to fully suppress expression outside of ovules. The full-length INO promoter, but not any of the INO promoter deletions tested, is able to act as an enhancer-blocking insulator to prevent the ectopic activation of expression by the 35S enhancer. Sequence conservation between the promoter regions of Arabidopsis thaliana, Brassica oleracea and Brassica rapa aligns closely with the functional definition of the POS6 and POS9 regions, and with a defined INO minimal promoter. The B. oleracea INO promoter is sufficient to promote a similar pattern and level of reporter gene expression in Arabidopsis to that observed for the Arabidopsis promoter. Conclusions At least two independent regions of the INO promoter contain sufficient regulatory information to direct the specific pattern but not the level of INO gene expression. These regulatory regions act in a partially redundant manner to promote the expression in a specific pattern in the ovule and

  19. Positive dielectrophoresis used for selective trapping of nanoparticles from flue gas in a gradient field electrodes device

    Energy Technology Data Exchange (ETDEWEB)

    Lungu, Mihail, E-mail: lmihai@physics.uvt.ro; Neculae, Adrian; Lungu, Antoanetta [West University of Timisoara, Faculty of Physics (Romania)

    2015-12-15

    This paper investigates the possibility to use positive dielectrophoresis (pDEP) for selective trapping of nanoparticle dispersed in flue gas in a vertical pDEP-based microfluidic system. The experimental gradient field electrodes device contains as main part a vertical deposition plate with parallel planar electrodes in single connection on an insulating substrate, parallel to the reference electrode—a dielectric plate with a metalized side. The performances of the device were described and analyzed by numerical simulations and experimental tests in terms of two new specific parameters, called Retention rate and Filtration, related to the trapping of nanoparticles in suspension inside the device and the consequent purification of flue gas. It is outlined, both numerically and experimentally, that the concentration of particles trapped inside the device decreases as they are moving away from the inlet zone. The experimental results also highlight the nanoparticle size distribution of the particles collected from the deposition plate, using a nanoparticle tracking analysis method, and their selective capture on the deposition plate, depending on the amplitude and shape of the applied voltage, in a good agreement with the numerical simulations results.

  20. A high efficiency gene disruption strategy using a positive-negative split selection marker and electroporation for Fusarium oxysporum.

    Science.gov (United States)

    Liang, Liqin; Li, Jianqiang; Cheng, Lin; Ling, Jian; Luo, Zhongqin; Bai, Miao; Xie, Bingyan

    2014-11-01

    The Fusarium oxysporum species complex consists of fungal pathogens that cause serial vascular wilt disease on more than 100 cultivated species throughout the world. Gene function analysis is rapidly becoming more and more important as the whole-genome sequences of various F. oxysporum strains are being completed. Gene-disruption techniques are a common molecular tool for studying gene function, yet are often a limiting step in gene function identification. In this study we have developed a F. oxysporum high-efficiency gene-disruption strategy based on split-marker homologous recombination cassettes with dual selection and electroporation transformation. The method was efficiently used to delete three RNA-dependent RNA polymerase (RdRP) genes. The gene-disruption cassettes of three genes can be constructed simultaneously within a short time using this technique. The optimal condition for electroporation is 10μF capacitance, 300Ω resistance, 4kV/cm field strength, with 1μg of DNA (gene-disruption cassettes). Under these optimal conditions, we were able to obtain 95 transformants per μg DNA. And after positive-negative selection, the transformants were efficiently screened by PCR, screening efficiency averaged 85%: 90% (RdRP1), 85% (RdRP2) and 77% (RdRP3). This gene-disruption strategy should pave the way for high throughout genetic analysis in F. oxysporum. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    Science.gov (United States)

    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.

  2. Selectivity improvement of positive photoionization ion mobility spectrometry for rapid detection of organophosphorus pesticides by switching dopant concentration.

    Science.gov (United States)

    Zhou, Qinghua; Li, Jia; Wang, Bin; Wang, Shuang; Li, Haiyang; Chen, Jinyuan

    2018-01-01

    Ion mobility spectrometry (IMS) opened a potential avenue for the rapid detection of organophosphorus pesticides (OPPs), though an improved selectivity of stand-alone IMS was still in high demand. In this study, a stand-alone positive photoionization ion mobility spectrometry (PP-IMS) apparatus was constructed for the rapid detection of OPPs with acetone as dopant. The photoionization of acetone molecules was induced by the ultraviolet irradiation to produce the reactant ions (Ac) 2 H + , which were employed to ionize the OPPs including fenthion, imidan, phosphamidon, dursban, dimethoate and isocarbophos via the proton transfer reaction. Due to the difference in proton affinity, the tested OPPs exhibited the different dopant-dependent manners. Based on this observation, the switching of dopant concentration was implemented to improve the selectivity of PP-IMS for OPPs detection. For instance, a mixture of fenthion, dursban and dimethoate was tested. By switching the concentration of doped acetone from 0.07 to 2.33 to 19.94mgL -1 , the ion peaks of fenthion and dursban were inhibited in succession, achieving the selective detection of dimethoate at last. In addition, another mixture of imidan and phosphamidon was initially detected by PP-IMS with a dose of 0.07mgL -1 acetone, indicating that their ion peaks were severely overlapped; when the concentration of doped acetone was switched to 19.94mgL -1 , the inhibition of imidan signals promised the accurate identification of phosphamidon in mixture. Finally, the PP-IMS in combination of switching dopant concentration was applied to detect the mixed fenthion, dursban and dimethoate in Chinese cabbage, demonstrating the applicability of proposed method to real samples. Copyright © 2017. Published by Elsevier B.V.

  3. 78 FR 23938 - Privacy Act of 1974; Report of a New Routine Use for Selected CMS Systems of Records

    Science.gov (United States)

    2013-04-23

    ... & Medicaid Services (CMS), Department of Health and Human Services (HHS). ACTION: Altered Systems Notice... the systems of records being modified; the new routine use is compatible with the health care purposes... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Medicare & Medicaid Services Privacy Act of...

  4. Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

    Directory of Open Access Journals (Sweden)

    Yoichiro Shibata

    2012-06-01

    Full Text Available Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

  5. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

    Science.gov (United States)

    Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

    2005-01-01

    The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

  6. Awareness and Perception of Housewives in Selected Municipalities of Palawan Regarding R.A. 9262 (Anti-Violence against Women and their Children Act of 2004

    Directory of Open Access Journals (Sweden)

    Dr. Cecilia S. Santiago

    2014-10-01

    Full Text Available This study was conducted to determine the level of awareness and perception of housewives in selected municipalities of Palawan regarding R.A. 9262. Specifically, it aimed to determine the demographic characteristics of the respondents; to identify the level of awareness of housewives regarding R.A. 9262; and to find out their perception regarding the Act. Seven municipalities which include Aborlan, Narra, Brooke’s Point, Quezon, Rizal, Bataraza and El Nido were the study sites. One hundred women from each municipality were purposely selected that served as respondents with a total of 700. Those considered were married, with husband at present and who has children. The survey questionnaire which was translated in Filipino was composed of two parts. Part one was about the demographic characteristics of the respondents while part two dealt on statements about acts of violence against women & their children as stated in RA 9262 that determined the level of awareness & perception on the provisions of the said Republic Act. Results revealed that the mean age of the respondents was 38.39 years old and the mean number of children was 3.63. In addition, most of the respondents were plain housewives has 3-4 children, high school graduates and within the PhP 5,000.00 and below bracket of monthly income. With regards to the level of awareness, majority of the respondents were moderately aware of the provisions of R.A. 9262. As to the perception of the respondents, they strongly agree that the provisions or statements are considered acts of violence against women and their children. Based on the results of the study, an Action Plan will be proposed which will focus on the enhancement of the housewives’ awareness regarding R.A. 9262 to provide information and make them fully aware of the provisions of the republic act and be safe from domestic violence.

  7. Improved methods in Agrobacterium-mediated transformation of almond using positive (mannose/pmi) or negative (kanamycin resistance) selection-based protocols.

    Science.gov (United States)

    Ramesh, Sunita A; Kaiser, Brent N; Franks, Tricia; Collins, Graham; Sedgley, Margaret

    2006-08-01

    A protocol for Agrobacterium-mediated transformation with either kanamycin or mannose selection was developed for leaf explants of the cultivar Prunus dulcis cv. Ne Plus Ultra. Regenerating shoots were selected on medium containing 15 muM kanamycin (negative selection), while in the positive selection strategy, shoots were selected on 2.5 g/l mannose supplemented with 15 g/l sucrose. Transformation efficiencies based on PCR analysis of individual putative transformed shoots from independent lines relative to the initial numbers of leaf explants tested were 5.6% for kanamycin/nptII and 6.8% for mannose/pmi selection, respectively. Southern blot analysis on six randomly chosen PCR-positive shoots confirmed the presence of the nptII transgene in each, and five randomly chosen lines identified to contain the pmi transgene by PCR showed positive hybridisation to a pmi DNA probe. The positive (mannose/pmi) and the negative (kanamycin) selection protocols used in this study have greatly improved transformation efficiency in almond, which were confirmed with PCR and Southern blot. This study also demonstrates that in almond the mannose/pmi selection protocol is appropriate and can result in higher transformation efficiencies over that of kanamycin/nptII selection protocols.

  8. Selective loss of Purkinje cells in a patient with anti-gliadin-antibody-positive autoimmune cerebellar ataxia

    Directory of Open Access Journals (Sweden)

    Hasegawa Akira

    2011-02-01

    Full Text Available Abstract The patient was an 84-year-old woman who had the onset of truncal ataxia at age 77 and a history of Basedow's disease. Her ataxic gait gradually deteriorated. She could not walk without support at age 81 and she was admitted to our hospital at age 83. Gaze-evoked nystagmus and dysarthria were observed. Mild ataxia was observed in all limbs. Her deep tendon reflex and sense of position were normal. IgA anti-gliadin antibody, IgG anti-gliadin antibody, anti-SS-A/Ro antibody, anti-SS-B/La antibody and anti-TPO antibody were positive. A conventional brain MRI did not show obvious cerebellar atrophy. However, MRI voxel based morphometry (VBM and SPECT-eZIS revealed cortical cerebellar atrophy and reduced cerebellar blood flow. IVIg treatment was performed and was moderately effective. After her death at age 85, the patient was autopsied. Neuropathological findings were as follows: selective loss of Purkinje cells; no apparent degenerative change in the efferent pathways, such as the dentate nuclei or vestibular nuclei; no prominent inflammatory reaction. From these findings, we diagnosed this case as autoimmune cerebellar atrophy associated with gluten ataxia. All 3 autopsies previously reported on gluten ataxia have noted infiltration of inflammatory cells in the cerebellum. In this case, we postulated that the infiltration of inflammatory cells was not found because the patient's condition was based on humoral immunity. The clinical conditions of gluten ataxia have not yet been properly elucidated, but are expected to be revealed as the number of autopsied cases increases.

  9. PRECONCEPTION AND PRENATAL DIAGNOSTIC TECHNIQUES ACT 1994 AND ITS MAIN ROLE TO CURB SEX DETERMINATION AND SEX SELECTION

    OpenAIRE

    Adv. Vaishali V. Waghmare; Dr. (Mrs) Hema Menon

    2016-01-01

    India has a male dominated culture where women are treated like a commodity and slave. Our Indian society gives preference only to the Son not to female because of which girls' child is not heartily welcomed and discrimination against girl child still prevails. Sex selective abortion is one of major issue in recent era in relation to violence against women under which the Ultrasonography machine plays an important role of sex detection. Main cause for sex selection are Patriarchal system, Do...

  10. The EG95 Antigen of Echinococcus spp. Contains Positively Selected Amino Acids, which May Influence Host Specificity and Vaccine Efficacy

    Science.gov (United States)

    Haag, Karen Luisa; Gottstein, Bruno; Ayala, Francisco Jose

    2009-01-01

    Echinococcosis is a worldwide zoonotic parasitic disease of humans and various herbivorous domestic animals (intermediate hosts) transmitted by the contact with wild and domestic carnivores (definitive hosts), mainly foxes and dogs. Recently, a vaccine was developed showing high levels of protection against one parasite haplotype (G1) of Echinococcus granulosus, and its potential efficacy against distinct parasite variants or species is still unclear. Interestingly, the EG95 vaccine antigen is a secreted glycosylphosphatydilinositol (GPI)-anchored protein containing a fibronectin type III domain, which is ubiquitous in modular proteins involved in cell adhesion. EG95 is highly expressed in oncospheres, the parasite life cycle stage which actively invades the intermediate hosts. After amplifying and sequencing the complete CDS of 57 Echinococcus isolates belonging to 7 distinct species, we uncovered a large amount of genetic variability, which may influence protein folding. Two positively selected sites are outside the vaccine epitopes, but are predicted to alter protein conformation. Moreover, phylogenetic analyses indicate that EG95 isoform evolution is convergent with regard to the number of beta-sheets and alpha-helices. We conclude that having a variety of EG95 isoforms is adaptive for Echinococcus parasites, in terms of their ability to invade different hosts, and we propose that a mixture of isoforms could possibly maximize vaccine efficacy. PMID:19401778

  11. AtSOFL1 and AtSOFL2 act redundantly as positive modulators of the endogenous content of specific cytokinins in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jingyu Zhang

    Full Text Available BACKGROUND: Although cytokinins have been known for decades to play important roles in the regulation of plant growth and development, our knowledge of the regulatory mechanism of endogenous content of specific cytokinins remains limited. METHODOLOGY/PRINCIPAL FINDINGS: Here, we characterized two SOB five-like (SOFL genes, AtSOFL1 and AtSOFL2, in Arabidopsis (Arabidopsis thaliana and showed that they acted redundantly in regulating specific cytokinin levels. Analysis of the translational fusion AtSOFL1:AtSOFL1-GUS and AtSOFL2:AtSOFL2-GUS indicated that AtSOFL1 and AtSOFL2 exhibited similar expression patterns. Both proteins were predominantly expressed in the vascular tissues of developing leaves, flowers and siliques, but barely detectable in roots and stems. Overexpression of either AtSOFL1 or AtSOFL2 led to increased cytokinin content and obvious corresponding mutant phenotypes for both transgenic seedlings and adult plants. In addition, overexpression and site-directed mutagenesis experiments demonstrated that the SOFL domains are necessary for AtSOFL2's overexpression phenotypes. Silencing or disrupting either AtSOFL1 or AtSOFL2 caused no obvious developmental defects. Endogenous cytokinin analysis, however, revealed that compared to the wild type control, the SOFL1-RNAi62 sofl2-1 double mutant accumulated lower levels of trans-zeatin riboside monophosphate (tZRMP and N(6-(Delta(2-isopentenyladenosine monophosphate (iPRMP, which are biosynthetic intermediates of bioactive cytokinins. The double mutant also displayed decreased response to exogenous cytokinin in both callus-formation and inhibition-of-hypocotyl-elongation assays. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that in plants AtSOFL1 and AtSOFL2 work redundantly as positive modulators in the fine-tuning of specific cytokinin levels as well as responsiveness.

  12. A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection.

    Directory of Open Access Journals (Sweden)

    George Nicholson

    2011-09-01

    Full Text Available We have performed a metabolite quantitative trait locus (mQTL study of the (1H nuclear magnetic resonance spectroscopy ((1H NMR metabolome in humans, building on recent targeted knowledge of genetic drivers of metabolic regulation. Urine and plasma samples were collected from two cohorts of individuals of European descent, with one cohort comprised of female twins donating samples longitudinally. Sample metabolite concentrations were quantified by (1H NMR and tested for association with genome-wide single-nucleotide polymorphisms (SNPs. Four metabolites' concentrations exhibited significant, replicable association with SNP variation (8.6×10(-11positive selection in European populations. Genes NAT8 and PYROXD2, both with relatively uncharacterized functional roles, are good candidates for mediating the corresponding mQTL associations. The study's longitudinal twin design allowed detailed variance-components analysis of the sources of population variation in metabolite levels. The mQTLs explained 40%-64% of biological population variation in the corresponding metabolites' concentrations. These effect sizes are stronger than those reported in a recent, targeted mQTL study of metabolites in serum using the targeted-metabolomics Biocrates platform. By re-analysing our plasma samples using the Biocrates platform, we replicated the mQTL findings of the previous study and discovered a previously uncharacterized yet substantial familial component of variation in metabolite levels in addition to the heritability contribution from

  13. Distinction of Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of water-soluble tetrazolium salts with a selection medium.

    Science.gov (United States)

    Tsukatani, Tadayuki; Suenaga, Hikaru; Higuchi, Tomoko; Shiga, Masanobu; Noguchi, Katsuya; Matsumoto, Kiyoshi

    2011-01-01

    Bacteria are fundamentally divided into two groups: Gram-positive and Gram-negative. Although the Gram stain and other techniques can be used to differentiate these groups, some issues exist with traditional approaches. In this study, we developed a method for differentiating Gram-positive and -negative bacteria using a colorimetric microbial viability assay based on the reduction of the tetrazolium salt {2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt} (WST-8) via 2-methyl-1,4-napthoquinone with a selection medium. We optimized the composition of the selection medium to allow the growth of Gram-negative bacteria while inhibiting the growth of Gram-positive bacteria. When the colorimetric viability assay was carried out in a selection medium containing 0.5µg/ml crystal violet, 5.0 µg/ml daptomycin, and 5.0µg/ml vancomycin, the reduction in WST-8 by Gram-positive bacteria was inhibited. On the other hand, Gram-negative bacteria produced WST-8-formazan in the selection medium. The proposed method was also applied to determine the Gram staining characteristics of bacteria isolated from various foodstuffs. There was good agreement between the results obtained using the present method and those obtained using a conventional staining method. These results suggest that the WST-8 colorimetric assay with selection medium is a useful technique for accurately differentiating Gram-positive and -negative bacteria.

  14. Enzyme-like specificity in zeolites: a unique site position in mordenite for selective carbonylation of methanol and dimethyl ether with CO.

    Science.gov (United States)

    Boronat, Mercedes; Martínez-Sánchez, Cristina; Law, David; Corma, Avelino

    2008-12-03

    The mechanism of methanol carbonylation at different positions of zeolite MOR is investigated by quantum-chemical methods in order to discover which are the active sites that can selectively catalyze the desired reaction. It is shown that when methanol carbonylation competes with hydrocarbon formation, the first reaction occurs preferentially within 8MR channels. However, the unique selectivity for the carbonylation of methanol and dimethyl ether in mordenite is not only due to the size of the 8MR channel: neither process occurs equally at the two T3-O31 and T3-O33 positions. We show that only the T3-O33 positions are selective and that this selectivity is due to the unusual orientation of the methoxy group in relation to the 8MR channel (parallel to the cylinder axis). Only in this situation does the transition state for the attack of CO fit perfectly in the 8MR channel, while the reaction with methanol or DME is sterically impeded. This result explains why T3-O31, while also located in the 8MR channel of mordenite, is not as selective as the T3-O33 position and why ferrierite, although it contains 8MR channels, is less selective than mordenite. The competing effect of water is explained at the molecular level, and the molecular microkinetic reaction model has been established.

  15. Cis-acting pathways selectively enforce the non-immunogenicity of shed placental antigen for maternal CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Chin-Siean Tay

    Full Text Available Maternal immune tolerance towards the fetus and placenta is thought to be established in part by pathways that attenuate T cell priming to antigens released from the placenta into maternal blood. These pathways remain largely undefined and their existence, at face value, seems incompatible with a mother's need to maintain a functional immune system during pregnancy. A particular conundrum is evident if we consider that maternal antigen presenting cells, activated in order to prime T cells to pathogen-derived antigens, would also have the capacity to prime T cells to co-ingested placental antigens. Here, we address this paradox using a transgenic system in which placental membranes are tagged with a strong surrogate antigen (ovalbumin. We find that although a remarkably large quantity of acellular ovalbumin-containing placental material is released into maternal blood, splenic CD8 T cells in pregnant mice bearing unmanipulated T cell repertoires are not primed to ovalbumin even if the mice are intravenously injected with adjuvants. This failure was largely independent of regulatory T cells, and instead was linked to the intrinsic characteristics of the released material that rendered it selectively non-immunogenic, potentially by sequestering it from CD8α(+ dendritic cells. The release of ovalbumin-containing placental material into maternal blood thus had no discernable impact on CD8 T cell priming to soluble ovalbumin injected intravenously during pregnancy, nor did it induce long-term tolerance to ovalbumin. Together, these results outline a major pathway governing the maternal immune response to the placenta, and suggest how tolerance to placental antigens can be maintained systemically without being detrimental to host defense.

  16. Cis-Acting Pathways Selectively Enforce the Non-Immunogenicity of Shed Placental Antigen for Maternal CD8 T Cells

    Science.gov (United States)

    Tay, Chin-Siean; Tagliani, Elisa; Collins, Mary K.; Erlebacher, Adrian

    2013-01-01

    Maternal immune tolerance towards the fetus and placenta is thought to be established in part by pathways that attenuate T cell priming to antigens released from the placenta into maternal blood. These pathways remain largely undefined and their existence, at face value, seems incompatible with a mother's need to maintain a functional immune system during pregnancy. A particular conundrum is evident if we consider that maternal antigen presenting cells, activated in order to prime T cells to pathogen-derived antigens, would also have the capacity to prime T cells to co-ingested placental antigens. Here, we address this paradox using a transgenic system in which placental membranes are tagged with a strong surrogate antigen (ovalbumin). We find that although a remarkably large quantity of acellular ovalbumin-containing placental material is released into maternal blood, splenic CD8 T cells in pregnant mice bearing unmanipulated T cell repertoires are not primed to ovalbumin even if the mice are intravenously injected with adjuvants. This failure was largely independent of regulatory T cells, and instead was linked to the intrinsic characteristics of the released material that rendered it selectively non-immunogenic, potentially by sequestering it from CD8α+ dendritic cells. The release of ovalbumin-containing placental material into maternal blood thus had no discernable impact on CD8 T cell priming to soluble ovalbumin injected intravenously during pregnancy, nor did it induce long-term tolerance to ovalbumin. Together, these results outline a major pathway governing the maternal immune response to the placenta, and suggest how tolerance to placental antigens can be maintained systemically without being detrimental to host defense. PMID:24391885

  17. Alpha-conotoxin analogs with additional positive charge show increased selectivity towards Torpedo californica and some neuronal subtypes of nicotinic acetylcholine receptors

    NARCIS (Netherlands)

    Kasheverov, I.E.; Zhmak, M.N.; Vulfius, C.A.; Corbacheva, E.V.; Mordvintsev, D.Y.; Utkin, Y.N.; van Elk, R.; Smit, A.B.; Tsetlin, V.I.

    2006-01-01

    α-Conotoxins from Conus snails are indispensable tools for distinguishing various subtypes of nicotinic acetylcholine receptors (nAChRs), and synthesis of α-conotoxin analogs may yield novel antagonists of higher potency and selectivity. We incorporated additional positive charges into α-conotoxins

  18. Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence.

    Science.gov (United States)

    Van Beeren, H C; Jong, W M C; Kaptein, E; Visser, T J; Bakker, O; Wiersinga, W M

    2003-02-01

    Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we investigate whether Dron and/or its metabolite debutyldronedarone inhibit T(3) binding to TRalpha(1) and TRbeta(1) in vitro and whether dronedarone behaves similarly to amiodarone in vivo. In vitro, Dron had a inhibitory effect of 14% on the binding of T(3) to TRalpha(1), but not on TRbeta(1). Desethylamiodarone inhibited T(3) binding to TRalpha(1) and TRbeta(1) equally. Debutyldronedarone inhibited T(3) binding to TRalpha(1) by 77%, but to TRbeta(1) by only 25%. In vivo, AM increased plasma TSH and rT(3), and decreased T(3). Dron decreased T(4) and T(3), rT(3) did not change, and TSH fell slightly. Plasma total cholesterol was increased by AM, but remained unchanged in Dron-treated animals. TRbeta(1)-dependent liver low density lipoprotein receptor protein and type 1 deiodinase activities decreased in AM-treated, but not in Dron-treated, animals. TRalpha(1)-mediated lengthening of the QTc interval was present in both AM- and Dron-treated animals. The in vitro and in vivo findings suggest that dronedarone via its metabolite debutyldronedarone acts as a TRalpha(1)-selective inhibitor.

  19. When the Americans with Disabilities Act Goes Online: Application of the ADA to the Internet and the Worldwide Web. Position Paper.

    Science.gov (United States)

    National Council on Disability, Washington, DC.

    This paper addresses the issue of how the Americans with Disabilities Act (ADA) applies to commercial and other private sector Web sites. Beginning with a brief discussion of the role electronic communication plays in our lives, the paper then considers the placement of the ADA in the context of current technology and of computer usage in the…

  20. Selection Of Employees In The Metal Industry Based On Competences, On The Example Of A Designer Position

    Directory of Open Access Journals (Sweden)

    Skrzypek Katarzyna

    2015-06-01

    Full Text Available The selection of an effective team of employees is crucial to proper management of the company. The success of the project often depends on the competencies of employees who carry out those projects. Therefore, the selection of the workers, whose competences complement each other in terms of subject matter, in terms of personality, and also in practical terms, is very important. This article presents the proposal of applying the FAHP (fuzzy analytic hierarchy process and TOPSIS (technique for order preference by similarity to an ideal solution methods as a tool to facilitate the management of human resources in the metal production factories based on the skills of employees.

  1. SU-G-BRC-13: Model Based Classification for Optimal Position Selection for Left-Sided Breast Radiotherapy: Free Breathing, DIBH, Or Prone

    Energy Technology Data Exchange (ETDEWEB)

    Lin, H; Liu, T; Xu, X [Rensselaer Polytechnic Institute, Troy, NY (United States); Shi, C [Saint Vincent Medical Center, Bridgeport, CT (United States); Petillion, S; Kindts, I [University Hospitals Leuven, Leuven, Vlaams-Brabant (Belgium); Tang, X [Memorial Sloan Kettering Cancer Center, West Harrison, NY (United States)

    2016-06-15

    Purpose: There are clinical decision challenges to select optimal treatment positions for left-sided breast cancer patients—supine free breathing (FB), supine Deep Inspiration Breath Hold (DIBH) and prone free breathing (prone). Physicians often make the decision based on experiences and trials, which might not always result optimal OAR doses. We herein propose a mathematical model to predict the lowest OAR doses among these three positions, providing a quantitative tool for corresponding clinical decision. Methods: Patients were scanned in FB, DIBH, and prone positions under an IRB approved protocol. Tangential beam plans were generated for each position, and OAR doses were calculated. The position with least OAR doses is defined as the optimal position. The following features were extracted from each scan to build the model: heart, ipsilateral lung, breast volume, in-field heart, ipsilateral lung volume, distance between heart and target, laterality of heart, and dose to heart and ipsilateral lung. Principal Components Analysis (PCA) was applied to remove the co-linearity of the input data and also to lower the data dimensionality. Feature selection, another method to reduce dimensionality, was applied as a comparison. Support Vector Machine (SVM) was then used for classification. Thirtyseven patient data were acquired; up to now, five patient plans were available. K-fold cross validation was used to validate the accuracy of the classifier model with small training size. Results: The classification results and K-fold cross validation demonstrated the model is capable of predicting the optimal position for patients. The accuracy of K-fold cross validations has reached 80%. Compared to PCA, feature selection allows causal features of dose to be determined. This provides more clinical insights. Conclusion: The proposed classification system appeared to be feasible. We are generating plans for the rest of the 37 patient images, and more statistically significant

  2. Testing the prediction from sexual selection of a positive genetic correlation between human mate preferences and corresponding traits

    NARCIS (Netherlands)

    Verweij, K.J.H.; Burri, A.V.; Zietsch, B.P.

    2014-01-01

    Sexual selection can cause evolution in traits that affect mating success, and it has thus been implicated in the evolution of human physical and behavioural traits that influence attractiveness. We use a large sample of identical and nonidentical female twins to test the prediction from mate choice

  3. Selecting Children's Picture Books with Positive Chinese, Japanese, and Other Asian and Asian-American Fathers and Father Figures.

    Science.gov (United States)

    Heller, Craig; Cunningham, Bruce; Lee, Ginny; Heller, Hannah M.

    2000-01-01

    Discusses distinctive children's picture books that depict Asian fathers and other men who play significant roles in the lives of children. Books are grouped by theme, such as fairly tale versus real life, Asian immigration to North America, and discipline. Includes guidelines for selecting and evaluating books and appropriate classroom teaching…

  4. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium

    NARCIS (Netherlands)

    Gribble, P.A.; Delahunt, E.; Bleakley, C.M.; Caulfield, B.; Docherty, C.L.; Fong, D.T.; Fourchet, F.; Hertel, J.; Hiller, C.E.; Kaminski, T.W.; McKeon, P.O.; Refshauge, K.M.; Wees, P.J. van der; Vicenzino, W.; Wikstrom, E.A.

    2014-01-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant or patient selection criteria across studies presents a potential obstacle to addressing the problem

  5. Selection criteria for patients with chronic ankle instability in controlled research: a position statement of the International Ankle Consortium

    NARCIS (Netherlands)

    Gribble, P.A.; Delahunt, E.; Bleakley, C.; Caulfield, B.; Docherty, C.; Fourchet, F.; Fong, D.T.; Hertel, J.; Hiller, C.; Kaminski, T.; McKeon, P.; Refshauge, K.; Wees, P.J. van der; Vincenzino, B.; Wikstrom, E.

    2014-01-01

    While research on chronic ankle instability (CAI) and awareness of its impact on society and health care systems has grown substantially in the last 2 decades, the inconsistency in participant/patient selection criteria across studies presents a potential obstacle to addressing the problem properly.

  6. Genomic selection strategies in breeding programs: Strong positive interaction between application of genotypic information and intensive use of young bulls on genetic gain

    DEFF Research Database (Denmark)

    Buch, Line Hjortø; Sørensen, Morten Kargo; Berg, Peer

    2012-01-01

    We tested the following hypotheses: (i) breeding schemes with genomic selection are superior to breeding schemes without genomic selection regarding annual genetic gain of the aggregate genotype (ΔGAG), annual genetic gain of the functional traits and rate of inbreeding per generation (ΔF), (ii......) a positive interaction exists between the use of genotypic information and a short generation interval on ΔGAG and (iii) the inclusion of an indicator trait in the selection index will only result in a negligible increase in ΔGAG if genotypic information about the breeding goal trait is known. We examined......, greater contributions of the functional trait to ΔGAG and lower ΔF than the two breeding schemes without genomic selection. Thus, the use of genotypic information may lead to more sustainable breeding schemes. In addition, a short generation interval increases the effect of using genotypic information...

  7. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

    International Nuclear Information System (INIS)

    Brown, Nicole; Nagarkatti, Mitzi; Nagarkatti, Prakash S.

    2006-01-01

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8 + T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8 + T cells. The density of expression of HY-TCR on CD8 + cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery

  8. Multi-criteria decision analysis to select the optimum position and proper field of view of a photosensor

    International Nuclear Information System (INIS)

    Doulos, L.; Tsangrassoulis, A.; Topalis, F.V.

    2014-01-01

    Highlights: • A new methodology for the determination of proper FOV and position of a photosensor is proposed. • Model takes into account illuminance ratio, energy savings and lighting adequacy. • A multiple criteria decision method (ELECTRE) is used to estimate best solution. • A number of simulations were performed in order to clarify the calculation procedure. • An experimental procedure was performed in order to verify the simulation procedure. - Abstract: The lack of knowledge concerning the commissioning of a daylight responsive system constitutes a serious impediment to their widespread use. Furthermore, installation details and tools regarding their photosensor position and field of view (FOV) are insufficient. This paper presents a decision making method capable to estimate the best position of a photosensor on the ceiling and its proper FOV based on multiple criteria analysis. The criteria used are (a) the correlation of the lighting levels between the working plane and the ceiling, (b) the corresponding energy savings and (c) the lighting adequacy which is defined as the percentage for occupied time with total illuminance exceeding design illuminance (i.e 500 lux EN 12464-1, 2011) and is strongly affected by the control algorithm. A number of simulations with variable FOV and position of photosensors were performed in order to clarify the calculation procedure of the proposed methodology. Three different typical room geometries have been used with variable window sizes and orientation. Furthermore a prototype photosensor with variable FOV through the use of a telescopic cylinder was constructed and placed in a scale room (1:10) in order to verify the results of simulations. The verification was based on a set of experimental procedures concerning measurements of the spatial response of the prototype photosensor (for various FOVs) and measurements of ceiling/workplane illuminance inside the scaled room for various combinations of position and

  9. Factors in selecting serum samples for use in determining the positive/negative threshold (cut-off) in ELISA

    International Nuclear Information System (INIS)

    Jacobson, R.H.

    1998-01-01

    The threshold (cut-off) that defines whether a test result is seropositive or seronegative is calculated by testing serum samples from a subpopulation of animals that is assumed to represent the target population in all aspects. For this proposition to be true, it is essential to consider the variables in the target population that must be represented in the subpopulation. Without representation of the variables in the subpopulation, it is likely that the cut-off selected for the test will be errant and will misclassify animals as to their infection status. The purpose of this paper is to identify a few of the principal variables that need to be taken into account when selecting a subpopulation of animals for test validation. (author)

  10. Using ArcMap, Google Earth, and Global Positioning Systems to select and locate random households in rural Haiti.

    Science.gov (United States)

    Wampler, Peter J; Rediske, Richard R; Molla, Azizur R

    2013-01-18

    A remote sensing technique was developed which combines a Geographic Information System (GIS); Google Earth, and Microsoft Excel to identify home locations for a random sample of households in rural Haiti. The method was used to select homes for ethnographic and water quality research in a region of rural Haiti located within 9 km of a local hospital and source of health education in Deschapelles, Haiti. The technique does not require access to governmental records or ground based surveys to collect household location data and can be performed in a rapid, cost-effective manner. The random selection of households and the location of these households during field surveys were accomplished using GIS, Google Earth, Microsoft Excel, and handheld Garmin GPSmap 76CSx GPS units. Homes were identified and mapped in Google Earth, exported to ArcMap 10.0, and a random list of homes was generated using Microsoft Excel which was then loaded onto handheld GPS units for field location. The development and use of a remote sensing method was essential to the selection and location of random households. A total of 537 homes initially were mapped and a randomized subset of 96 was identified as potential survey locations. Over 96% of the homes mapped using Google Earth imagery were correctly identified as occupied dwellings. Only 3.6% of the occupants of mapped homes visited declined to be interviewed. 16.4% of the homes visited were not occupied at the time of the visit due to work away from the home or market days. A total of 55 households were located using this method during the 10 days of fieldwork in May and June of 2012. The method used to generate and field locate random homes for surveys and water sampling was an effective means of selecting random households in a rural environment lacking geolocation infrastructure. The success rate for locating households using a handheld GPS was excellent and only rarely was local knowledge required to identify and locate households. This

  11. Using ArcMap, Google Earth, and Global Positioning Systems to select and locate random households in rural Haiti

    Directory of Open Access Journals (Sweden)

    Wampler Peter J

    2013-01-01

    Full Text Available Abstract Background A remote sensing technique was developed which combines a Geographic Information System (GIS; Google Earth, and Microsoft Excel to identify home locations for a random sample of households in rural Haiti. The method was used to select homes for ethnographic and water quality research in a region of rural Haiti located within 9 km of a local hospital and source of health education in Deschapelles, Haiti. The technique does not require access to governmental records or ground based surveys to collect household location data and can be performed in a rapid, cost-effective manner. Methods The random selection of households and the location of these households during field surveys were accomplished using GIS, Google Earth, Microsoft Excel, and handheld Garmin GPSmap 76CSx GPS units. Homes were identified and mapped in Google Earth, exported to ArcMap 10.0, and a random list of homes was generated using Microsoft Excel which was then loaded onto handheld GPS units for field location. The development and use of a remote sensing method was essential to the selection and location of random households. Results A total of 537 homes initially were mapped and a randomized subset of 96 was identified as potential survey locations. Over 96% of the homes mapped using Google Earth imagery were correctly identified as occupied dwellings. Only 3.6% of the occupants of mapped homes visited declined to be interviewed. 16.4% of the homes visited were not occupied at the time of the visit due to work away from the home or market days. A total of 55 households were located using this method during the 10 days of fieldwork in May and June of 2012. Conclusions The method used to generate and field locate random homes for surveys and water sampling was an effective means of selecting random households in a rural environment lacking geolocation infrastructure. The success rate for locating households using a handheld GPS was excellent and only

  12. A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera

    OpenAIRE

    Zayed, Amro; Whitfield, Charles W.

    2008-01-01

    Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating “Africanized” honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive sel...

  13. Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression.

    Science.gov (United States)

    de Vries, Y A; Roest, A M; Franzen, M; Munafò, M R; Bastiaansen, J A

    2016-10-01

    Caspi et al.'s 2003 report that 5-HTTLPR genotype moderates the influence of life stress on depression has been highly influential but remains contentious. We examined whether the evidence base for the 5-HTTLPR-stress interaction has been distorted by citation bias and a selective focus on positive findings. A total of 73 primary studies were coded for study outcomes and focus on positive findings in the abstract. Citation rates were compared between studies with positive and negative results, both within this network of primary studies and in Web of Science. In addition, the impact of focus on citation rates was examined. In all, 24 (33%) studies were coded as positive, but these received 48% of within-network and 68% of Web of Science citations. The 38 (52%) negative studies received 42 and 23% of citations, respectively, while the 11 (15%) unclear studies received 10 and 9%. Of the negative studies, the 16 studies without a positive focus (42%) received 47% of within-network citations and 32% of Web of Science citations, while the 13 (34%) studies with a positive focus received 39 and 51%, respectively, and the nine (24%) studies with a partially positive focus received 14 and 17%. Negative studies received fewer citations than positive studies. Furthermore, over half of the negative studies had a (partially) positive focus, and Web of Science citation rates were higher for these studies. Thus, discussion of the 5-HTTLPR-stress interaction is more positive than warranted. This study exemplifies how evidence-base-distorting mechanisms undermine the authenticity of research findings.

  14. BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

    International Nuclear Information System (INIS)

    Watanabe, Kenta; Hirata, Michiko; Tominari, Tsukasa; Matsumoto, Chiho; Endo, Yasuyuki; Murphy, Gillian; Nagase, Hideaki

    2016-01-01

    Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

  15. BA321, a novel carborane analog that binds to androgen and estrogen receptors, acts as a new selective androgen receptor modulator of bone in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenta [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Cooperative Major in Advanced Health Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Hirata, Michiko [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Tominari, Tsukasa [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Matsumoto, Chiho [Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Endo, Yasuyuki [Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, 981-8558 (Japan); Murphy, Gillian [Department of Oncology, University of Cambridge, Cancer Research UK, Cambridge Institute, Li Ka Shing Centre, Cambridge, CB2 0RE (United Kingdom); Nagase, Hideaki [Institute of Global Innovation Research, Tokyo University of Agriculture and Technology, 2-24-16 Nakamachi, Koganei, Tokyo 184-8588 (Japan); Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7FY (United Kingdom); and others

    2016-09-09

    Carboranes are a class of carbon-containing polyhedral boron cluster compounds with globular geometry and hydrophobic surface that interact with hormone receptors such as estrogen receptor (ER) and androgen receptor (AR). We have synthesized BA321, a novel carborane compound, which binds to AR. We found here that it also binds to ERs, ERα and ERβ. In orchidectomized (ORX) mice, femoral bone mass was markedly reduced due to androgen deficiency and BA321 restored bone loss in the male, whilst the decreased weight of seminal vesicle in ORX mice was not recovered by administration of BA321. In female mice, BA321 acts as a pure estrogen agonist, and restored both the loss of bone mass and uterine atrophy due to estrogen deficiency in ovariectomized (OVX) mice. In bone tissues, the trabecular bone loss occurred in both ORX and OVX mice, and BA321 completely restored the trabecular bone loss in both sexes. Cortical bone loss occurred in ORX mice but not in OVX mice, and BA321 clearly restored cortical bone loss due to androgen deficiency in ORX mice. Therefore, BA321 is a novel selective androgen receptor modulator (SARM) that may offer a new therapy option for osteoporosis in the male. - Highlights: • A novel carborane compound BA321 binds to both AR and ERs, ERα and ERβ. • BA321 restores bone loss in orchidectomized mice without effects on sex organ. • BA321 acts as an estrogen agonist in bone and uterus in ovariectomized mice. • BA321 may be a new SARM to prevent the loss of musculoskeletal mass in elder men.

  16. Whole-genome sequencing of two North American Drosophila melanogaster populations reveals genetic differentiation and positive selection.

    Science.gov (United States)

    Campo, D; Lehmann, K; Fjeldsted, C; Souaiaia, T; Kao, J; Nuzhdin, S V

    2013-10-01

    The prevailing demographic model for Drosophila melanogaster suggests that the colonization of North America occurred very recently from a subset of European flies that rapidly expanded across the continent. This model implies a sudden population growth and range expansion consistent with very low or no population subdivision. As flies adapt to new environments, local adaptation events may be expected. To describe demographic and selective events during North American colonization, we have generated a data set of 35 individual whole-genome sequences from inbred lines of D. melanogaster from a west coast US population (Winters, California, USA) and compared them with a public genome data set from Raleigh (Raleigh, North Carolina, USA). We analysed nuclear and mitochondrial genomes and described levels of variation and divergence within and between these two North American D. melanogaster populations. Both populations exhibit negative values of Tajima's D across the genome, a common signature of demographic expansion. We also detected a low but significant level of genome-wide differentiation between the two populations, as well as multiple allele surfing events, which can be the result of gene drift in local subpopulations on the edge of an expansion wave. In contrast to this genome-wide pattern, we uncovered a 50-kilobase segment in chromosome arm 3L that showed all the hallmarks of a soft selective sweep in both populations. A comparison of allele frequencies within this divergent region among six populations from three continents allowed us to cluster these populations in two differentiated groups, providing evidence for the action of natural selection on a global scale. © 2013 John Wiley & Sons Ltd.

  17. Selection of the new position for the instrumented fuel Flip type; Seleccion de la nueva posicion para el combustible instrumentado tipo Flip

    Energy Technology Data Exchange (ETDEWEB)

    Paredes G, L C

    1991-12-15

    It was selected and proved the new position for the instrumented fuel, in function of the smallest influence on the temperature of the fuel due to movements of the control bars, as well as to its functionality regarding their geometric localization in the core. Therefore, it intends that the instrumented fuel Flip type, pass from the position C-9 to the C-6. It was selected the turn angle of the fuel of 180 C, for to be the one that presents a smaller influence of the control bars and it allows to register the values of temperature but high. It was as the movements of the control bars they produce local interferences of the neutron flow in the fuels and that in the case of the ring C, these interferences became maximum variations of the fuel temperature of 125 C, for operations to 1 MW in the thermal column. (Author)

  18. Socially selected ornaments and fitness: Signals of fighting ability in paper wasps are positively associated with survival, reproductive success, and rank.

    Science.gov (United States)

    Tibbetts, Elizabeth A; Forrest, Taylor; Vernier, Cassondra; Jinn, Judy; Madagame, Andrew

    2015-11-01

    Many animals have ornaments that mediate choice and competition in social and sexual contexts. Individuals with elaborate sexual ornaments typically have higher fitness than those with less elaborate ornaments, but less is known about whether socially selected ornaments are associated with fitness. Here, we test the relationship between fitness and facial patterns that are a socially selected signal of fighting ability in Polistes dominula wasps. We found wasps that signal higher fighting ability have larger nests, are more likely to survive harsh winters, and obtain higher dominance rank than wasps that signal lower fighting ability. In comparison, body weight was not associated with fitness. Larger wasps were dominant over smaller wasps, but showed no difference in nest size or survival. Overall, the positive relationship between wasp facial patterns and fitness indicates that receivers can obtain diverse information about a signaler's phenotypic quality by paying attention to socially selected ornaments. Therefore, there are surprisingly strong parallels between the information conveyed by socially and sexually selected signals. Similar fitness relationships in social and sexually selected signals may be one reason it can be difficult to distinguish the role of social versus sexual selection in ornament evolution. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  19. Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

    Directory of Open Access Journals (Sweden)

    Pim van Hooft

    Full Text Available Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations, we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has

  20. Constraints on the Richness-Mass Relation and the Optical-SZE Positional Offset Distribution for SZE-Selected Clusters

    CERN Document Server

    Saro, A; Rozo, E; Benson, B A; Mohr, J; Rykoff, E S; Soares-Santos, M; Bleem, L; Dodelson, S; Melchior, P; Sobreira, F; Upadhyay, V; Weller, J; Abbott, T; Abdalla, F B; Allam, S; Armstrong, R; Banerji, M; Bauer, A H; Bayliss, M; Benoit-Lévy, A; Bernstein, G M; Bertin, E; Brodwin, M; Brooks, D; Buckley-Geer, E; Burke, D L; Carlstrom, J E; Capasso, R; Capozzi, D; Carnero Rosell, A; Carrasco Kind, M; Chiu, I; Covarrubias, R; Crawford, T M; Crocce, M; D'Andrea, C B; da Costa, L N; DePoy, D L; Desai, S; de Haan, T; Diehl, H T; Dietrich, J P; Doel, P; Cunha, C E; Eifler, T F; Evrard, A E; Fausti Neto, A; Fernandez, E; Flaugher, B; Fosalba, P; Frieman, J; Gangkofner, C; Gaztanaga, E; Gerdes, D; Gruen, D; Gruendl, R A; Gupta, N; Hennig, C; Holzapfel, W L; Honscheid, K; Jain, B; James, D; Kuehn, K; Kuropatkin, N; Lahav, O; Li, T S; Lin, H; Maia, M A G; March, M; Marshall, J L; Martini, Paul; McDonald, M; Miller, C J; Miquel, R; Nord, B; Ogando, R; Plazas, A A; Reichardt, C L; Romer, A K; Roodman, A; Sako, M; Sanchez, E; Schubnell, M; Sevilla, I; Smith, R C; Stalder, B; Stark, A A; Strazzullo, V; Suchyta, E; Swanson, M E C; Tarle, G; Thaler, J; Thomas, D; Tucker, D; Vikram, V; von der Linden, A; Walker, A R; Wechsler, R H; Wester, W; Zenteno, A; Ziegler, K E

    2015-01-01

    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 (DES) science verification data. We identify 25 clusters between $0.1\\lesssim z\\lesssim 0.8$ 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 $\\lambda$-mass relation with the following function $\\langle\\ln\\lambda|M_{500}\\rangle\\propto B_\\lambda\\ln M_{500}+C_\\lambda\\ln E(z)$ and use SPT-SZ cluster masses and RM richnesses $\\lambda$ to constrain the parameters. We find $B_\\lambda= 1.14^{+0.21}_{-0.18}$ and $C_\\lambda=0.73^{+0.77}_{-0.75}$. The associated scatter in mass at fixed richness is $\\sigma_{\\ln M|\\lambda} = 0.18^{+0.08}_{-0.05}$ at a characteristic richness $\\lambda=70$. We demonstrate that our model provides an adequate description of the ma...

  1. The impact of IFRS 16 on the financial position of selected companies from the WIG30 index

    Directory of Open Access Journals (Sweden)

    Mateusz Krawczak

    2018-05-01

    Full Text Available The main purpose of this article is to analyze the impact of changes in accounting for leases, defined in IFRS 16, on the financial situation of selected Polish entities listed on the Warsaw Stock Exchange. The following qualitative research methods were used to accomplish the goal: analysis of the literature of the subject and analysis of international reporting standards regarding accounting for leases. In the empirical part of the article, a simulation was carried out. It analyzed the impact of capitalization of operating lease on the selected parts of the balance sheet and changes in profitability of four entities listed on the Warsaw Stock Exchange. The results of empirical research indicate an increase in the value of assets and liabili- ties, a decline in the financial results, and an increase in profitability and debt ratios. The largest changes pertained to the equity and asset debt ratio, which confirms that the application of IFRS 16 will show corporate indebtedness, thus increasing investors' knowledge of the actual risk with which the company is burdened. The main value of this article is the originality of the pilot study carried out. To the best of the authors’ knowledge, these are the first practical measurements of the impact of capitalization of operating lease on the changes in profitability and indebtedness of the reporting entities.

  2. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

    Science.gov (United States)

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K.; Mukerji, Mitali

    2016-09-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu’s H  2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges.

  3. Take a look at the bright side: Effects of positive body exposure on selective visual attention in women with high body dissatisfaction.

    Science.gov (United States)

    Glashouwer, Klaske A; Jonker, Nienke C; Thomassen, Karen; de Jong, Peter J

    2016-08-01

    Women with high body dissatisfaction look less at their 'beautiful' body parts than their 'ugly' body parts. This study tested the robustness of this selective viewing pattern and examined the influence of positive body exposure on body-dissatisfied women's attention for 'ugly' and 'beautiful' body parts. In women with high body dissatisfaction (N = 28) and women with low body dissatisfaction (N = 14) eye-tracking was used to assess visual attention towards pictures of their own and other women's bodies. Participants with high body dissatisfaction were randomly assigned to 5 weeks positive body exposure (n = 15) or a no-treatment condition (n = 13). Attention bias was assessed again after 5 weeks. Body-dissatisfied women looked longer at 'ugly' than 'beautiful' body parts of themselves and others, while participants with low body dissatisfaction attended equally long to own/others' 'beautiful' and 'ugly' body parts. Although positive body exposure was very effective in improving participants' body satisfaction, it did not systematically change participants' viewing pattern. The tendency to preferentially allocate attention towards one's 'ugly' body parts seems a robust phenomenon in women with body dissatisfaction. Yet, modifying this selective viewing pattern seems not a prerequisite for successfully improving body satisfaction via positive body exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Stapled Voltage-Gated Calcium Channel (CaV) α-Interaction Domain (AID) Peptides Act As Selective Protein-Protein Interaction Inhibitors of CaV Function.

    Science.gov (United States)

    Findeisen, Felix; Campiglio, Marta; Jo, Hyunil; Abderemane-Ali, Fayal; Rumpf, Christine H; Pope, Lianne; Rossen, Nathan D; Flucher, Bernhard E; DeGrado, William F; Minor, Daniel L

    2017-06-21

    For many voltage-gated ion channels (VGICs), creation of a properly functioning ion channel requires the formation of specific protein-protein interactions between the transmembrane pore-forming subunits and cystoplasmic accessory subunits. Despite the importance of such protein-protein interactions in VGIC function and assembly, their potential as sites for VGIC modulator development has been largely overlooked. Here, we develop meta-xylyl (m-xylyl) stapled peptides that target a prototypic VGIC high affinity protein-protein interaction, the interaction between the voltage-gated calcium channel (Ca V ) pore-forming subunit α-interaction domain (AID) and cytoplasmic β-subunit (Ca V β). We show using circular dichroism spectroscopy, X-ray crystallography, and isothermal titration calorimetry that the m-xylyl staples enhance AID helix formation are structurally compatible with native-like AID:Ca V β interactions and reduce the entropic penalty associated with AID binding to Ca V β. Importantly, electrophysiological studies reveal that stapled AID peptides act as effective inhibitors of the Ca V α 1 :Ca V β interaction that modulate Ca V function in an Ca V β isoform-selective manner. Together, our studies provide a proof-of-concept demonstration of the use of protein-protein interaction inhibitors to control VGIC function and point to strategies for improved AID-based Ca V modulator design.

  5. Factors impacting knowledge and use of long acting and permanent contraceptive methods by postpartum HIV positive and negative women in Cape Town, South Africa: a cross-sectional study.

    Science.gov (United States)

    Credé, Sarah; Hoke, Theresa; Constant, Deborah; Green, Mackenzie S; Moodley, Jennifer; Harries, Jane

    2012-03-16

    The prevention of unintended pregnancies among HIV positive women is a neglected strategy in the fight against HIV/AIDS. Women who want to avoid unintended pregnancies can do this by using a modern contraceptive method. Contraceptive choice, in particular the use of long acting and permanent methods (LAPMs), is poorly understood among HIV-positive women. This study aimed to compare factors that influence women's choice in contraception and women's knowledge and attitudes towards the IUD and female sterilization by HIV-status in a high HIV prevalence setting, Cape Town, South Africa. A quantitative cross-sectional survey was conducted using an interviewer-administered questionnaire amongst 265 HIV positive and 273 HIV-negative postpartum women in Cape Town. Contraceptive use, reproductive history and the future fertility intentions of postpartum women were compared using chi-squared tests, Wilcoxon rank-sum and Fisher's exact tests where appropriate. Women's knowledge and attitudes towards long acting and permanent methods as well as factors that influence women's choice in contraception were examined. The majority of women reported that their most recent pregnancy was unplanned (61.6% HIV positive and 63.2% HIV negative). Current use of contraception was high with no difference by HIV status (89.8% HIV positive and 89% HIV negative). Most women were using short acting methods, primarily the 3-monthly injectable (Depo Provera). Method convenience and health care provider recommendations were found to most commonly influence method choice. A small percentage of women (6.44%) were using long acting and permanent methods, all of whom were using sterilization; however, it was found that poor knowledge regarding LAPMs is likely to be contributing to the poor uptake of these methods. Improving contraceptive counselling to include LAPM and strengthening services for these methods are warranted in this setting for all women regardless of HIV status. These study results

  6. Factors impacting knowledge and use of long acting and permanent contraceptive methods by postpartum HIV positive and negative women in Cape Town, South Africa: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Credé Sarah

    2012-03-01

    Full Text Available Abstract Background The prevention of unintended pregnancies among HIV positive women is a neglected strategy in the fight against HIV/AIDS. Women who want to avoid unintended pregnancies can do this by using a modern contraceptive method. Contraceptive choice, in particular the use of long acting and permanent methods (LAPMs, is poorly understood among HIV-positive women. This study aimed to compare factors that influence women's choice in contraception and women's knowledge and attitudes towards the IUD and female sterilization by HIV-status in a high HIV prevalence setting, Cape Town, South Africa. Methods A quantitative cross-sectional survey was conducted using an interviewer-administered questionnaire amongst 265 HIV positive and 273 HIV-negative postpartum women in Cape Town. Contraceptive use, reproductive history and the future fertility intentions of postpartum women were compared using chi-squared tests, Wilcoxon rank-sum and Fisher's exact tests where appropriate. Women's knowledge and attitudes towards long acting and permanent methods as well as factors that influence women's choice in contraception were examined. Results The majority of women reported that their most recent pregnancy was unplanned (61.6% HIV positive and 63.2% HIV negative. Current use of contraception was high with no difference by HIV status (89.8% HIV positive and 89% HIV negative. Most women were using short acting methods, primarily the 3-monthly injectable (Depo Provera. Method convenience and health care provider recommendations were found to most commonly influence method choice. A small percentage of women (6.44% were using long acting and permanent methods, all of whom were using sterilization; however, it was found that poor knowledge regarding LAPMs is likely to be contributing to the poor uptake of these methods. Conclusions Improving contraceptive counselling to include LAPM and strengthening services for these methods are warranted in this setting

  7. Diethylstilbestrol alters positive and negative selection of T cells in the thymus and modulates T-cell repertoire in the periphery

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Nicole [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Mitzi [Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 (United States); Nagarkatti, Prakash S [Department of Pharmacology and Toxicology, PO Box 980613, Virginia Commonwealth University Medical Center, Richmond, VA 23298-0613 (United States)

    2006-04-15

    Prenatal exposure to diethylstilbestrol (DES) is known to cause altered immune functions and increased susceptibility to autoimmune disease in humans. In the current study, we investigated the effects of DES on T-cell differentiation in the thymus using the HY-TCR transgenic (Tg) mouse model in which the female mice exhibit positive selection of T cells bearing the Tg TCR, while the male mice show negative selection of such T cells. In female HY-TCR-Tg mice, exposure to DES showed more pronounced decrease in thymic cellularity when compared to male mice. Additionally, female mice also showed a significant decrease in the proportion of double-positive (DP) T cells in the thymus and HY-TCR-specific CD8{sup +} T cells in the periphery. Male mice exhibiting negative selection also showed decreased thymic cellularity following DES exposure. Moreover, the male mice showed increased proportion of double-negative (DN) T cells in the thymus and decreased proportion of CD8{sup +} T cells. The density of expression of HY-TCR on CD8{sup +} cells was increased following DES exposure in both females and males. Finally, the proliferative response of thymocytes to mitogens and peripheral lymph node T cells to male H-Y antigen was significantly altered in female and male mice following DES treatment. Taken together, these data suggest that DES alters T-cell differentiation in the thymus by interfering with positive and negative selection processes, which in turn modulates the T-cell repertoire in the periphery.

  8. The location selection act or 'the Emperor's new clothes'; Das Standortauswahlgesetz oder 'Des Kaisers neue Kleider'

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2013-10-15

    As is generally known, the governing parties CDU/CSU and FDP agreed a few weeks ago in the 17{sup th} legislative period of the German Bundestag in a rare show of unanimity, together with the parties SPD and Buendnis 90/Die Gruenen, as well as with the Laender, on a 'law to search and select a location for a permanent disposal site for heat-generating radioactive waste products and to change other laws', in brief a location selection act also called StandAG. The law was received with animated approval from the ranks of the parties - with the exception of the (left-wing) party Die Linke. This praise is a tad bewildering, since the Bundesumweltministerium (Federal Department of the Environment) named solving the task within a single generation as one of the principles for the StandAG, and it was emphasised again and again in the debates about the StandAG that the problem of permanent disposal must not be shifted to the next generation. Conclusion: - The StandAG leads to a postponement of solving the permanent disposal site issue by a least several generations with its predictable, long-winded selection method. - The decision not to explore Gorleben conclusively could lead to the site being permanently ('wasted' or) 'burned'. - The de-central, interim disposal site Gorleben is likewise 'burned' without having a resilient alternative solution for the glass coquilles that must be taken back. - The people's protest is exponentiated by the number of the potential sites for the StandAG. - The costs for the alternative site search will not be shifted to the producers of the waste that are obliged by law to deliver the waste because of the financial provisions of the constitution. - The third party protection dogma has not been broken up, which will at least lead to delays in the procedure and will have effects on other major projects in the long run. (orig.)

  9. Which technology to select for primary focal treatment of prostate cancer?-European Section of Urotechnology (ESUT) position statement.

    Science.gov (United States)

    Ganzer, Roman; Arthanareeswaran, Vinodh Kumar Adithyaa; Ahmed, Hashim U; Cestari, Andrea; Rischmann, Pascal; Salomon, Georg; Teber, Dogu; Liatsikos, Evangelos; Stolzenburg, Jens-Uwe; Barret, Eric

    2018-05-09

    With growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics. Our intention was to review the literature for special aspects of the different technologies that might be of advantage depending on individual patient and tumour characteristics. The current literature on FT was screened for the following factors: morbidity, repeatability, tumour risk category, tumour location, tumour size and prostate volume and anatomical issues. The ESUT expert panel arrived at consensus regarding a position statement on a structured pathway for available FT technologies based on a combination of the literature and expert opinion. Side effects were low across different studies and FT modalities with urinary continence rates of 90-100% and erectile dysfunction between 5 and 52%. Short to medium cancer control based on post-treatment biopsies were variable between ablative modalities. Expert consensus suggested that posterior lesions are better amenable to FT using HIFU. Cryotherapy provides best possible outcomes for anterior tumours. Apical lesions, when treated with FBT, may yield the least urethral morbidity. Further prospective trials are required to assess medium to long term disease control of different ablative modalities for FT. Amongst different available FT modalities our ESUT expert consensus suggests that some may be better for diffe`rent tumour locations. Tumour risk, tumour size, tumour location, and prostate volume are all important factors to consider and might aid in designing future FT trials.

  10. Selective activation around the left occipito-temporal sulcus for words relative to pictures: individual variability or false positives?

    Science.gov (United States)

    Wright, Nicholas D; Mechelli, Andrea; Noppeney, Uta; Veltman, Dick J; Rombouts, Serge A R B; Glensman, Janice; Haynes, John-Dylan; Price, Cathy J

    2008-08-01

    We used high-resolution fMRI to investigate claims that learning to read results in greater left occipito-temporal (OT) activation for written words relative to pictures of objects. In the first experiment, 9/16 subjects performing a one-back task showed activation in > or =1 left OT voxel for words relative to pictures (P or =1 left OT voxel for words relative to pictures. However, at this low statistical threshold false positives need to be excluded. The semantic decision paradigm was therefore repeated, within subject, in two different scanners (1.5 and 3 T). Both scanners consistently localised left OT activation for words relative to fixation and pictures relative to words, but there were no consistent effects for words relative to pictures. Finally, in a third experiment, we minimised the voxel size (1.5 x 1.5 x 1.5 mm(3)) and demonstrated a striking concordance between the voxels activated for words and pictures, irrespective of task (naming vs. one-back) or script (English vs. Hebrew). In summary, although we detected differential activation for words relative to pictures, these effects: (i) do not withstand statistical rigour; (ii) do not replicate within or between subjects; and (iii) are observed in voxels that also respond to pictures of objects. Our findings have implications for the role of left OT activation during reading. More generally, they show that studies using low statistical thresholds in single subject analyses should correct the statistical threshold for the number of comparisons made or replicate effects within subject. (c) 2007 Wiley-Liss, Inc.

  11. Privacy Act

    Science.gov (United States)

    Learn about the Privacy Act of 1974, the Electronic Government Act of 2002, the Federal Information Security Management Act, and other information about the Environmental Protection Agency maintains its records.

  12. Purine salvage in the apicomplexan Sarcocystis neurona, and generation of hypoxanthine-xanthine-guanine phosphoribosyltransferase-deficient clones for positive-negative selection of transgenic parasites.

    Science.gov (United States)

    Dangoudoubiyam, Sriveny; Zhang, Zijing; Howe, Daniel K

    2014-09-01

    Sarcocystis neurona is an apicomplexan parasite that causes severe neurological disease in horses and marine mammals. The Apicomplexa are all obligate intracellular parasites that lack purine biosynthesis pathways and rely on the host cell for their purine requirements. Hypoxanthine-xanthine-guanine phosphoribosyltransferase (HXGPRT) and adenosine kinase (AK) are key enzymes that function in two complementary purine salvage pathways in apicomplexans. Bioinformatic searches of the S. neurona genome revealed genes encoding HXGPRT, AK and all of the major purine salvage enzymes except purine nucleoside phosphorylase. Wild-type S. neurona were able to grow in the presence of mycophenolic acid (MPA) but were inhibited by 6-thioxanthine (6-TX), suggesting that the pathways involving either HXGPRT or AK are functional in this parasite. Prior work with Toxoplasma gondii demonstrated the utility of HXGPRT as a positive-negative selection marker. To enable the use of HXGPRT in S. neurona, the SnHXGPRT gene sequence was determined and a gene-targeting plasmid was transfected into S. neurona. SnHXGPRT-deficient mutants were selected with 6-TX, and single-cell clones were obtained. These Sn∆HXG parasites were susceptible to MPA and could be complemented using the heterologous T. gondii HXGPRT gene. In summary, S. neurona possesses both purine salvage pathways described in apicomplexans, thus allowing the use of HXGPRT as a positive-negative drug selection marker in this parasite.

  13. Hepatic tissue environment in NEMO-deficient mice critically regulates positive selection of donor cells after hepatocyte transplantation.

    Directory of Open Access Journals (Sweden)

    Michaela Kaldenbach

    Full Text Available BACKGROUND: Hepatocyte transplantation (HT is a promising alternative treatment strategy for end-stage liver diseases compared with orthotopic liver transplantation. A limitation for this approach is the low engraftment of donor cells. The deletion of the I-kappa B kinase-regulatory subunit IKKγ/NEMO in hepatocytes prevents nuclear factor (NF-kB activation and triggers spontaneous liver apoptosis, chronic hepatitis and the development of liver fibrosis and hepatocellular carcinoma. We hypothesized that NEMOΔhepa mice may therefore serve as an experimental model to study HT. METHODS: Pre-conditioned NEMOΔhepa mice were transplanted with donor-hepatocytes from wildtype (WT and mice deficient for the pro-apoptotic mediator Caspase-8 (Casp8Δhepa. RESULTS: Transplantation of isolated WT-hepatocytes into pre-conditioned NEMOΔhepa mice resulted in a 6-7 fold increase of donor cells 12 weeks after HT, while WT-recipients showed no liver repopulation. The use of apoptosis-resistant Casp8Δhepa-derived donor cells further enhanced the selection 3-fold after 12-weeks and up to 10-fold increase after 52 weeks compared with WT donors. While analysis of NEMOΔhepa mice revealed strong liver injury, HT-recipient NEMOΔhepa mice showed improved liver morphology and decrease in serum transaminases. Concomitant with these findings, the histological examination elicited an improved liver tissue architecture associated with significantly lower levels of apoptosis, decreased proliferation and a lesser amount of liver fibrogenesis. Altogether, our data clearly support the therapeutic benefit of the HT procedure into NEMOΔhepa mice. CONCLUSION: This study demonstrates the feasibility of the NEMOΔhepa mouse as an in vivo tool to study liver repopulation after HT. The improvement of the characteristic phenotype of chronic liver injury in NEMOΔhepa mice after HT suggests the therapeutic potential of HT in liver diseases with a chronic inflammatory phenotype and

  14. The Atacama Cosmology Telescope: High-Resolution Sunyaev-Zel'dovich Array Observations of ACT SZE-Selected Clusters from the Equatorial Strip

    Science.gov (United States)

    Reese, Erik D.; Mroczkowski, Tony; Menanteau, Felipe; Hilton, Matt; Sievers, Jonathan; Aguirre, Paula; Appel, John William; Baker, Andrew J.; Bond, J. Richard; Das, Sudeep; hide

    2011-01-01

    We present follow-up observations with the Sunyaev-Zel'dovich Array (SZA) of optically-confirmed galaxy clusters found in the equatorial survey region of the Atacama Cosmology Telescope (ACT): ACT-CL J0022-0036, ACT-CL J2051+0057, and ACT-CL J2337+0016. ACT-CL J0022-0036 is a newly-discovered, massive (10(exp 15) Msun), high-redshift (z=0.81) cluster revealed by ACT through the Sunyaev-Zel'dovich effect (SZE). Deep, targeted observations with the SZA allow us to probe a broader range of cluster spatial scales, better disentangle cluster decrements from radio point source emission, and derive more robust integrated SZE flux and mass estimates than we can with ACT data alone. For the two clusters we detect with the SZA we compute integrated SZE signal and derive masses from the SZA data only. ACT-CL J2337+0016, also known as Abell 2631, has archival Chandra data that allow an additional X-ray-based mass estimate. Optical richness is also used to estimate cluster masses and shows good agreement with the SZE and X-ray-based estimates. Based on the point sources detected by the SZA in these three cluster fields and an extrapolation to ACT's frequency, we estimate that point sources could be contaminating the SZE decrement at the less than = 20% level for some fraction of clusters.

  15. The Atacama Cosmology Telescope: High-Resolution Sunyaev-Zeldovich Array Observations of ACT SZE-Selected Clusters from the Equatorial Strip

    Science.gov (United States)

    Reese, Erik; Mroczkowski, Tony; Menateau, Felipe; Hilton, Matt; Sievers, Jonathan; Aguirre, Paula; Appel, John William; Baker, Andrew J.; Bond, J. Richard; Das, Sudeep; hide

    2011-01-01

    We present follow-up observations with the Sunyaev-Zel'dovich Array (SZA) of optically-confirmed galaxy clusters found in the equatorial survey region of the Atacama Cosmology Telescope (ACT): ACT-CL J0022-0036, ACT-CL J2051+0057, and ACT-CL J2337+0016. ACT-CL J0022-0036 is a newly-discovered, massive ( approximately equals 10(exp 15) Solar M), high-redshift (z = 0.81) cluster revealed by ACT through the Sunyaev-Zeldovich effect (SZE). Deep, targeted observations with the SZA allow us to probe a broader range of cluster spatial scales, better disentangle cluster decrements from radio point source emission, and derive more robust integrated SZE flux and mass estimates than we can with ACT data alone. For the two clusters we detect with the SZA we compute integrated SZE signal and derive masses from the SZA data only. ACT-CL J2337+0016, also known as Abell 2631, has archival Chandra data that allow an additional X-ray-based mass estimate. Optical richness is also used to estimate cluster masses and shows good agreement with the SZE and X-ray-based estimates. Based on the point sources detected by the SZA in these three cluster fields and an extrapolation to ACT's frequency, we estimate that point sources could be contaminating the SZE decrement at the approx < 20% level for some fraction of clusters.

  16. THE ATACAMA COSMOLOGY TELESCOPE: HIGH-RESOLUTION SUNYAEV-ZEL'DOVICH ARRAY OBSERVATIONS OF ACT SZE-SELECTED CLUSTERS FROM THE EQUATORIAL STRIP

    Energy Technology Data Exchange (ETDEWEB)

    Reese, Erik D.; Mroczkowski, Tony; Devlin, Mark J.; Dicker, Simon R. [Department of Physics and Astronomy, University of Pennsylvania, 209 South 33rd Street, Philadelphia, PA 19104 (United States); Menanteau, Felipe; Baker, Andrew J. [Department of Physics and Astronomy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8019 (United States); Hilton, Matt [School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, NG7 2RD (United Kingdom); Sievers, Jonathan; Bond, J. Richard; Hajian, Amir [Canadian Institute for Theoretical Astrophysics, University of Toronto, Toronto, ON M5S 3H8 (Canada); Aguirre, Paula; Duenner, Rolando [Departamento de Astronomia y Astrofisica, Facultad de Fisica, Pontificia Universidad Catolica de Chile, Casilla 306, Santiago 22 (Chile); Appel, John William; Das, Sudeep; Essinger-Hileman, Thomas; Hincks, Adam D. [Joseph Henry Laboratories of Physics, Jadwin Hall, Princeton University, Princeton, NJ 08544 (United States); Fowler, Joseph W.; Hill, J. Colin [Department of Astrophysical Sciences, Peyton Hall, Princeton University, Princeton, NJ 08544 (United States); Halpern, Mark; Hasselfield, Matthew [Department of Physics and Astronomy, University of British Columbia, Vancouver, BC V6T 1Z4 (Canada); and others

    2012-05-20

    We present follow-up observations with the Sunyaev-Zel'dovich Array (SZA) of optically confirmed galaxy clusters found in the equatorial survey region of the Atacama Cosmology Telescope (ACT): ACT-CL J0022-0036, ACT-CL J2051+0057, and ACT-CL J2337+0016. ACT-CL J0022-0036 is a newly discovered, massive ({approx_equal} 10{sup 15} M{sub Sun }), high-redshift (z = 0.81) cluster revealed by ACT through the Sunyaev-Zel'dovich effect (SZE). Deep, targeted observations with the SZA allow us to probe a broader range of cluster spatial scales, better disentangle cluster decrements from radio point-source emission, and derive more robust integrated SZE flux and mass estimates than we can with ACT data alone. For the two clusters we detect with the SZA we compute integrated SZE signal and derive masses from the SZA data only. ACT-CL J2337+0016, also known as A2631, has archival Chandra data that allow an additional X-ray-based mass estimate. Optical richness is also used to estimate cluster masses and shows good agreement with the SZE and X-ray-based estimates. Based on the point sources detected by the SZA in these three cluster fields and an extrapolation to ACT's frequency, we estimate that point sources could be contaminating the SZE decrement at the {approx}< 20% level for some fraction of clusters.

  17. Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Haitao, E-mail: xuhaitao@ecust.edu.cn [School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237 (China); Gou, Yongxia; Ye, Jing; Xu, Zhen-liang [School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237 (China); Wang, Zixuan [School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2016-05-15

    Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L){sub 2}(SCN){sub 2}]{sub ∝} (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H{sub 2}O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L){sub 2}(SCN){sub 2}]{sub ∝}. • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.

  18. Selectively catalytic activity of metal–organic frameworks depending on the N-position within the pyridine ring of their building blocks

    International Nuclear Information System (INIS)

    Xu, Haitao; Gou, Yongxia; Ye, Jing; Xu, Zhen-liang; Wang, Zixuan

    2016-01-01

    Iron metal–organic frameworks (MOFs) [Fe(L) 2 (SCN) 2 ] ∝ (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H 2 O solvent system. 1Fe exhibits a two-dimensional extended-grid network, whereas 2Fe exhibits a stair-like double-chain; the N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Furthermore, selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF; micro/nanoparticles of the layered MOF were therefore investigated for new potential applications of micro/nano MOFs. - Graphical abstract: Iron metal–organic frameworks (MOFs) [Fe(L) 2 (SCN) 2 ] ∝ (L1: 4-bpdh=2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene for 1Fe; and L2: 3-bpdh=2,5-bis(3-pyridyl)-3,4-diaza-2,4-hexadiene for 2Fe) were assembled in a MeOH–H 2 O solvent system. The N-position within the pyridine ring of the complexes was observed to regulate the MOF structure as layers or chains. Selectively catalytic activity was observed for the layered MOF but not the chain-structured MOF. - Highlights: • Synthesis and structure of metal–organic framework [Fe(L) 2 (SCN) 2 ] ∝ . • Selectively catalytic activity depending on the N-position within the pyridine ring. • The degradation and conversion of methyl orange.

  19. ZP Domain Proteins in the Abalone Egg Coat Include a Paralog of VERL under Positive Selection That Binds Lysin and 18-kDa Sperm Proteins

    Science.gov (United States)

    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

  20. The Positive Impacts Of American Reinvestment And Recovery Act (ARRA) Funding To The Waste Management Program On Hanford's Plateau Remediation Project

    International Nuclear Information System (INIS)

    Blackford, L.T.

    2010-01-01

    In April 2009, the Department of Energy (DOE) Richland Operations Office (RL) was allocated $1.6 billion (B) in ARRA funding to be applied to cleanup projects at the Hanford Site. DOE-RL selected projects to receive ARRA funding based on 3-criteria: creating/saving jobs, reducing the footprint of the Hanford Site, and reducing life-cycle costs for cleanup. They further selected projects that were currently covered under regulatory documents and existing prime contracts, which allowed work to proceed quickly. CH2M HILL Plateau Remediation Company (CHPRC) is a prime contractor to the DOE focused on the environmental cleanup of the DOE Hanford Site Central Plateau. CHPRC was slated to receive $1.36B in ARRA funding. As of January, 2010, CHPRC has awarded over $200 million (M) in subcontracts (64% to small businesses), created more that 1,100 jobs, and touched more than 2,300 lives - all in support of long-term objectives for remediation of the Central Plateau, on or ahead of schedule. ARRA funding is being used to accelerate and augment cleanup activities already underway under the baseline Plateau Remediation Contract (PRC). This paper details challenges and accomplishments using ARRA funding to meet DOE-RL objectives of creating/saving jobs, expediting cleanup, and reducing lifecycle costs for cleanup during the first months of implementation.

  1. Patterns of Nucleotide Diversity at the Regions Encompassing the Drosophila Insulin-Like Peptide (dilp) Genes: Demography vs. Positive Selection in Drosophila melanogaster

    Science.gov (United States)

    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

  2. Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

    Science.gov (United States)

    Andrews, T Daniel; Gojobori, Takashi

    2004-01-01

    The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

  3. Factors associated with performing tuberculosis screening of HIV-positive patients in Ghana: LASSO-based predictor selection in a large public health data set

    Directory of Open Access Journals (Sweden)

    Susanne Mueller-Using

    2016-07-01

    Full Text Available Abstract Background The purpose of this study is to propose the Least Absolute Shrinkage and Selection Operators procedure (LASSO as an alternative to conventional variable selection models, as it allows for easy interpretation and handles multicollinearities. We developed a model on the basis of LASSO-selected parameters in order to link associated demographical, socio-economical, clinical and immunological factors to performing tuberculosis screening in HIV-positive patients in Ghana. Methods Applying the LASSO method and multivariate logistic regression analysis on a large public health data set, we selected relevant predictors related to tuberculosis screening. Results One Thousand Ninety Five patients infected with HIV were enrolled into this study with 691 (63.2 % of them having tuberculosis screening documented in their patient folders. Predictors found to be significantly associated with performance of tuberculosis screening can be classified into factors related to the clinician’s perception of the clinical state, as well as those related to PLHIV’s awareness. These factors include newly diagnosed HIV infections (n = 354 (32.42 %, aOR 1.84, current CD4+ T cell count (aOR 0.92, non-availability of HIV type (n = 787 (72.07 %, aOR 0.56, chronic cough (n = 32 (2.93 %, aOR 5.07, intake of co-trimoxazole (n = 271 (24.82 %, aOR 2.31, vitamin supplementation (n = 220 (20.15 %, aOR 2.64 as well as the use of mosquito bed nets (n = 613 (56.14 %, aOR 1.53. Conclusions Accelerated TB screening among newly diagnosed HIV-patients indicates that application of the WHO screening form for intensifying tuberculosis case finding among HIV-positive individuals in resource-limited settings is increasingly adopted. However, screening for TB in PLHIV is still impacted by clinician’s perception of patient’s health state and PLHIV’s health awareness. Education of staff, counselling of PLHIV and sufficient financing are

  4. The typical RB76 recombination breakpoint of the invasive recombinant tomato yellow leaf curl virus of Morocco can be generated experimentally but is not positively selected in tomato.

    Science.gov (United States)

    Belabess, Z; Urbino, C; Granier, M; Tahiri, A; Blenzar, A; Peterschmitt, M

    2018-01-02

    TYLCV-IS76 is an unusual recombinant between the highly recombinogenic tomato yellow leaf curl virus (TYLCV) and tomato yellow leaf curl Sardinia virus (TYLCSV), two Mediterranean begomoviruses (Geminiviridae). In contrast with the previously reported TYLCV/TYLCSV recombinants, it has a TYLCSV derived fragment of only 76 nucleotides, and has replaced its parental viruses in natural conditions (Morocco, Souss region). The viral population shift coincided with the deployment of the popular Ty-1 resistant tomato cultivars, and according to experimental studies, has been driven by a strong positive selection in such resistant plants. However, although Ty-1 cultivars were extensively used in Mediterranean countries, TYLCV-IS76 was not reported outside Morocco. This, in combination with its unusual recombination pattern suggests that it was generated through a rare and possibly multistep process. The potential generation of a recombination breakpoint (RB) at locus 76 (RB76) was investigated over time in 10 Ty-1 resistant and 10 nearly isogenic susceptible tomato plants co-inoculated with TYLCV and TYLCSV clones. RB76 could not be detected in the recombinant progeny using the standard PCR/sequencing approach that was previously designed to monitor the emergence of TYLCV-IS76 in Morocco. Using a more sensitive PCR test, RB76 was detected in one resistant and five susceptible plants. The results are consistent with a very low intra-plant frequency of RB76 bearing recombinants throughout the test and support the hypothesis of a rare emergence of TYLCV-IS76. More generally, RBs were more scattered in resistant than in susceptible plants and an unusual RB at position 141 (RB141) was positively selected in the resistant cultivar; interestingly, RB141 bearing recombinants were detected in resistant tomato plants from the field. Scenarios of TYLCV-IS76 pre-emergence are proposed. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Extreme Population Differences in the Human Zinc Transporter ZIP4 (SLC39A4) Are Explained by Positive Selection in Sub-Saharan Africa

    Science.gov (United States)

    Pybus, Marc; Andrews, Glen K.; Lalueza-Fox, Carles; Comas, David; Sekler, Israel; de la Rasilla, Marco; Rosas, Antonio; Stoneking, Mark; Valverde, Miguel A.; Vicente, Rubén; Bosch, Elena

    2014-01-01

    Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val) in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4). By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372), with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg) that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency), was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk. PMID:24586184

  6. Extreme population differences in the human zinc transporter ZIP4 (SLC39A4 are explained by positive selection in Sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Johannes Engelken

    2014-02-01

    Full Text Available Extreme differences in allele frequency between West Africans and Eurasians were observed for a leucine-to-valine substitution (Leu372Val in the human intestinal zinc uptake transporter, ZIP4, yet no further evidence was found for a selective sweep around the ZIP4 gene (SLC39A4. By interrogating allele frequencies in more than 100 diverse human populations and resequencing Neanderthal DNA, we confirmed the ancestral state of this locus and found a strong geographical gradient for the derived allele (Val372, with near fixation in West Africa. In extensive coalescent simulations, we show that the extreme differences in allele frequency, yet absence of a classical sweep signature, can be explained by the effect of a local recombination hotspot, together with directional selection favoring the Val372 allele in Sub-Saharan Africans. The possible functional effect of the Leu372Val substitution, together with two pathological mutations at the same codon (Leu372Pro and Leu372Arg that cause acrodermatitis enteropathica (a disease phenotype characterized by extreme zinc deficiency, was investigated by transient overexpression of human ZIP4 protein in HeLa cells. Both acrodermatitis mutations cause absence of the ZIP4 transporter cell surface expression and nearly absent zinc uptake, while the Val372 variant displayed significantly reduced surface protein expression, reduced basal levels of intracellular zinc, and reduced zinc uptake in comparison with the Leu372 variant. We speculate that reduced zinc uptake by the ZIP4-derived Val372 isoform may act by starving certain pathogens of zinc, and hence may have been advantageous in Sub-Saharan Africa. Moreover, these functional results may indicate differences in zinc homeostasis among modern human populations with possible relevance for disease risk.

  7. Altered Ca2+ kinetics associated with α-actinin-3 deficiency may explain positive selection for ACTN3 null allele in human evolution.

    Directory of Open Access Journals (Sweden)

    Stewart I Head

    Full Text Available Over 1.5 billion people lack the skeletal muscle fast-twitch fibre protein α-actinin-3 due to homozygosity for a common null polymorphism (R577X in the ACTN3 gene. α-Actinin-3 deficiency is detrimental to sprint performance in elite athletes and beneficial to endurance activities. In the human genome, it is very difficult to find single-gene loss-of-function variants that bear signatures of positive selection, yet intriguingly, the ACTN3 null variant has undergone strong positive selection during recent evolution, appearing to provide a survival advantage where food resources are scarce and climate is cold. We have previously demonstrated that α-actinin-3 deficiency in the Actn3 KO mouse results in a shift in fast-twitch fibres towards oxidative metabolism, which would be more "energy efficient" in famine, and beneficial to endurance performance. Prolonged exposure to cold can also induce changes in skeletal muscle similar to those observed with endurance training, and changes in Ca2+ handling by the sarcoplasmic reticulum (SR are a key factor underlying these adaptations. On this basis, we explored the effects of α-actinin-3 deficiency on Ca2+ kinetics in single flexor digitorum brevis muscle fibres from Actn3 KO mice, using the Ca2+-sensitive dye fura-2. Compared to wild-type, fibres of Actn3 KO mice showed: (i an increased rate of decay of the twitch transient; (ii a fourfold increase in the rate of SR Ca2+ leak; (iii a threefold increase in the rate of SR Ca2+ pumping; and (iv enhanced maintenance of tetanic Ca2+ during fatigue. The SR Ca2+ pump, SERCA1, and the Ca2+-binding proteins, calsequestrin and sarcalumenin, showed markedly increased expression in muscles of KO mice. Together, these changes in Ca2+ handling in the absence of α-actinin-3 are consistent with cold acclimatisation and thermogenesis, and offer an additional explanation for the positive selection of the ACTN3 577X null allele in populations living in cold environments

  8. Rejection Positivity Predicts Trial-to-Trial Reaction Times in an Auditory Selective Attention Task: A Computational Analysis of Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Sufen eChen

    2014-08-01

    Full Text Available A series of computer simulations using variants of a formal model of attention (Melara & Algom, 2003 probed the role of rejection positivity (RP, a slow-wave electroencephalographic (EEG component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A model that additionally incorporated momentary fluctuations in EEG as the source of trial-to-trial variation in performance precisely predicted individual RTs within each condition. The results lend support to the linking proposition that RP controls the speed of responding to targets through the inhibitory control of distractors.

  9. Analysis of HLA class II haplotypes in the Cayapa indians of ecuador: A novel DRBI allele reveals evidence for convergent evolution and balancing selection at position 86

    Energy Technology Data Exchange (ETDEWEB)

    Titus-Trachtenberg, E.A.; Erlich, H. (Roche Molecular Systems, Alameda, CA (United States)); Rickards, O.; De Stefano, G.F. (Universita di Roma, Rome (Italy))

    1994-07-01

    PCR amplification, oligonucleotide probe typing, and sequencing were used to analyze the HLA class II loci (DRB1, DQA1, DAB1, and DPB1) of an isolated South Amerindian tribe. Here the authors report HLA class II variation, including the identification of a new DRB1 allele, several novel DR/DQ haplotypes, and an unusual distribution of DPB1 alleles, among the Cayapa Indians (N=100) of Ecuador. A general reduction of HLA class II allelic variation in the Cayapa is consistent with a population bottleneck during the colonization of the Americas. The new Cayapa DRB1 allele, DRB1[sup *]08042, which arose by a G[yields]T point mutation in the parental DRB1[sup *]0802, contains a novel Val codon (GTT) at position 86. The generation of DRB1[sup *]08042 (Val-86) from DRB1[sup *]0802 (Gly-86) in the Cayapa, by a different mechanism than the (GT[yields]TG) change in the creation of DRB1[sub *]08041 (Val-86) from DRB1[sup *]0802 in Africa, implicates selection in the convergent evolution of position 86 DR[beta] variants. The DRB1[sup *]08042 allele has not been found in >1,800 Amerindian haplotypes and thus presumably arose after the Cayapa separated from other South American Amerindians. Selection pressure for increased haplotype diversity can be inferred in the generation and maintenance of three new DRB1[sup *]08042 haplotypes and several novel DR/DQ haplotypes in this population. The DPB1 allelic distribution in the Cayapa is also extraordinary, with two alleles, DPB1[sup *]1401, a very rare allele in North American Amerindian populations, and DPB1[sup *]0402, the most common Amerindian DPB1 allele, constituting 89% of the Cayapa DPB1. These data are consistent with the postulated rapid rate of evolution as noted for the class I HLA-B locus of other South American Indians. 34 refs., 2 figs., 2 tabs.

  10. Kaiser Engineers Hanford internal position paper -- Project W-236A, Multi-function Waste Tank Facility -- Peer reviews of selected activities

    International Nuclear Information System (INIS)

    Stine, M.D.

    1995-01-01

    The purpose of this paper is to develop and document a proposed position on the performance of independent peer reviews on selected design and analysis components of the Title 1 [Preliminary] and Title 2 [Final] design phases of the Multi-Function Waste Tank Facility [MWTF] project. An independent, third-party peer review is defined as a documented critical review of documents, data, designs, design inputs, tests, calculations, or related materials. The peer review should be conducted by persons independent of those who performed the work, but who are technically qualified to perform the original work. The peer review is used to assess the validity of assumptions and functional requirements, to assess the appropriateness and logic of selected methodologies and design inputs, and to verify calculations, analyses and computer software. The peer review can be conducted at the end of the design activity, at specific stages of the design process, or continuously and concurrently with the design activity. This latter method is often referred to as ''Continuous Peer Review.''

  11. ACTS 2014

    DEFF Research Database (Denmark)

    Co-curator of ACTS 2014 together with Rasmus Holmboe, Judith Schwarzbart and Sanne Kofoed. ACTS is the Museum of Contemporary Art’s international bi-annual festival. ACTS was established in 2011 and, while the primary focus is on sound and performance art, it also looks toward socially oriented art....... For the 2014 festival, the museum has entered into a collaboration with the Department for Performance Design at Roskilde University – with continued focus on sound and performance art, and social art in public spaces. With ACTS, art moves out of its usual exhibition space and instead utilizes the city, its...... various possibilities and public spaces as a stage. ACTS takes place in and around the museum and diverse locations in Roskilde city. ACTS is partly curated by the museum staff and partly by guest curators. ACTS 2014 is supported by Nordea-fonden and is a part of the project The Museum goes downtown....

  12. High-throughput and simultaneous analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry in the positive and negative ionization modes.

    Science.gov (United States)

    Ogawa, Tadashi; Hattori, Hideki; Kaneko, Rina; Ito, Kenjiro; Iwai, Masae; Mizutani, Yoko; Arinobu, Tetsuya; Ishii, Akira; Seno, Hiroshi

    2011-06-01

    In this report, a high-throughput and sensitive method for analysis of eight central-acting muscle relaxants in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in the positive and negative ionization modes using tolbutamide as internal standard is presented. After pretreatment of a plasma sample by solid-phase extraction with an Oasis HLB cartridge, muscle relaxants were analyzed by UPLC with Acquity UPLC BEH C(18) column and Acquity TQD tandem quadrupole mass spectrometer equipped with an electrospray ionization interface. The calibration curves for muscle relaxants spiked into human plasma equally showed good linearities in the nanogram per milliliter order range. The detection limits (signal-to-noise ratio = 3) was as low as 0.1-2 ng/mL. The method gave satisfactory recovery rates, accuracy, and precision for quality control samples spiked with muscle relaxants. To further validate the present method, 250 mg of chlorphenesin carbamate was orally administered to a healthy male volunteer, and the concentrations of chlorphenesin carbamate in plasma were measured 0.5, 1, 2, 4, 6, and 8 h after dosing; their concentrations in human plasma were between 0.62 and 2.44 μg/mL. To our knowledge, this is the first report describing simultaneous analysis of over more than two central-acting muscle relaxants by liquid chromatography-tandem mass spectrometry. This has been realized by the capability of our instrument for simultaneous multiple reaction monitoring of the target compounds in both positive and negative ionization modes. Therefore, the present method seems very useful in forensic and clinical toxicology and pharmacokinetic studies.

  13. Dronerarone acts as a selective inhibitor of 3,5,3'-triiodothyronine binding to thyroid hormone receptor-alpha1: in vitro and in vivo evidence

    NARCIS (Netherlands)

    van Beeren, H. C.; Jong, W. M. C.; Kaptein, E.; Visser, T. J.; Bakker, O.; Wiersinga, W. M.

    2003-01-01

    Dronedarone (Dron), without iodine, was developed as an alternative to the iodine-containing antiarrhythmic drug amiodarone (AM). AM acts, via its major metabolite desethylamiodarone, in vitro and in vivo as a thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(1) antagonist. Here we

  14. Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT.

    Science.gov (United States)

    Henriques, Gisela; Hallett, Rachel L; Beshir, Khalid B; Gadalla, Nahla B; Johnson, Rachel E; Burrow, Rebekah; van Schalkwyk, Donelly A; Sawa, Patrick; Omar, Sabah A; Clark, Taane G; Bousema, Teun; Sutherland, Colin J

    2014-12-15

    The efficacy of artemisinin-based combination therapy (ACT) for Plasmodium falciparum malaria may be threatened by parasites with reduced responsiveness to artemisinins. Among 298 ACT-treated children from Mbita, Kenya, submicroscopic persistence of P. falciparum on day 3 posttreatment was associated with subsequent microscopically detected parasitemia at days 28 or 42. DNA sequences of resistance-associated parasite loci pfcrt, pfmdr1, pfubp1, and pfap2mu were determined in the Mbita cohort before treatment, on days 2 and 3 after initiation of treatment, and on the day of treatment failure. Parasites surviving ACT on day 2 or day 3 posttreatment were significantly more likely than the baseline population to carry the wild-type haplotypes of pfcrt (CVMNK at codons 72-76; P < .001) and pfmdr1 (NFD at codons 86, 184, 1246; P < .001). In contrast, variant alleles of the novel candidate resistance genes pfap2mu (S160N/T; P = .006) and pfubp-1 (E1528D; P < .001) were significantly more prevalent posttreatment. No genetic similarities were found to artemisinin-tolerant parasites recently described in Cambodia. Among treated children in western Kenya, certain P. falciparum genotypes defined at pfcrt, pfmdr1, pfap2mu, and pfubp1 more often survive ACT at the submicroscopic level, and contribute to onward transmission and subsequent patent recrudescence. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  15. Selective estrogen receptor modulators and betulinic acid act synergistically to target ERα and SP1 transcription factor dependent Pygopus expression in breast cancer.

    Science.gov (United States)

    Tzenov, Youlian R; Andrews, Phillip; Voisey, Kim; Gai, Luis; Carter, Beverley; Whelan, Kathryn; Popadiuk, Catherine; Kao, Kenneth R

    2016-06-01

    Estrogen and progesterone hormone receptor (ER and PR) expression in invasive breast cancer predicts response to hormone disruptive therapy. Pygopus2 (hPYGO2) encodes a chromatin remodelling protein important for breast cancer growth and cell cycle progression. The aims of this study were to determine the mechanism of expression of hPYGO2 in breast cancer and to examine how this expression is affected therapeutically. hPYGO2 and ER protein expression was examined in a breast tumour microarray by immunohistochemistry. hPYGO2 RNA and protein expression was examined in ER+ and ER- breast cancer cell lines in the presence of selective estrogen hormone receptor modulator drugs and the specificity protein-1 (SP1) inhibitor, betulinic acid (BA). The effects of these drugs on the ability for ER and SP1 to bind the hPYGO2 promoter and affect cell cycle progression were studied using chromatin immunoprecipitation assays. hPYGO2 was expressed in seven of eight lines and in nuclei of 98% of 65 breast tumours, including 3 Ductal carcinoma in situ and 62 invasive specimens representing ER-negative (22%) and ER-positive (78%) cases. Treatment with either 4-Hydroxytamoxifen (OHT) or fulvestrant reduced hPYGO2 mRNA 10-fold and protein 5-10-fold within 4 h. Promoter analysis indicated an ER/SP1 binding site at nt -225 to -531 of hPYGO2. SP1 RNA interference and BA reduced hPYGO2 protein and RNA expression by fivefold in both ER- and ER+ cells. Further attenuation was achieved by combining BA and 4-OHT resulting in eightfold reduction in cell growth. Our findings reveal a mechanistic link between hormone signalling and the growth transcriptional programme. The activation of its expression by ERα and/or SP1 suggests hPYGO2 as a theranostic target for hormone therapy responsive and refractory breast cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Positive mood broadens visual attention to positive stimuli.

    Science.gov (United States)

    Wadlinger, Heather A; Isaacowitz, Derek M

    2006-03-01

    In an attempt to investigate the impact of positive emotions on visual attention within the context of Fredrickson's (1998) broaden-and-build model, eye tracking was used in two studies to measure visual attentional preferences of college students (n=58, n=26) to emotional pictures. Half of each sample experienced induced positive mood immediately before viewing slides of three similarly-valenced images, in varying central-peripheral arrays. Attentional breadth was determined by measuring the percentage viewing time to peripheral images as well as by the number of visual saccades participants made per slide. Consistent with Fredrickson's theory, the first study showed that individuals induced into positive mood fixated more on peripheral stimuli than did control participants; however, this only held true for highly-valenced positive stimuli. Participants under induced positive mood also made more frequent saccades for slides of neutral and positive valence. A second study showed that these effects were not simply due to differences in emotional arousal between stimuli. Selective attentional broadening to positive stimuli may act both to facilitate later building of resources as well as to maintain current positive affective states.

  17. Epstein-Barr virus (EBV) recombinants: use of positive selection markers to rescue mutants in EBV-negative B-lymphoma cells.

    Science.gov (United States)

    Wang, F; Marchini, A; Kieff, E

    1991-04-01

    The objective of these experiments was to develop strategies for creation and identification of recombinant mutant Epstein-Barr viruses (EBV). EBV recombinant molecular genetics has been limited to mutations within a short DNA segment deleted from a nontransforming EBV and an underlying strategy which relies on growth transformation of primary B lymphocytes for identification of recombinants. Thus, mutations outside the deletion or mutations which affect transformation cannot be easily recovered. In these experiments we investigated whether a toxic drug resistance gene, guanine phosphoribosyltransferase or hygromycin phosphotransferase, driven by the simian virus 40 promoter can be recombined into the EBV genome and can function to identify B-lymphoma cells infected with recombinant virus. Two different strategies were used to recombine the drug resistance marker into the EBV genome. Both utilized transfection of partially permissive, EBV-infected B95-8 cells and positive selection for cells which had incorporated a functional drug resistance gene. In the first series of experiments, B95-8 clones were screened for transfected DNA that had recombined into the EBV genome. In the second series of experiments, the transfected drug resistance marker was linked to the plasmid and lytic EBV origins so that it was maintained as an episome and could recombine with the B95-8 EBV genome during virus replication. The recombinant EBV from either experiment could be recovered by infection and toxic drug selection of EBV-negative B-lymphoma cells. The EBV genome in these B-lymphoma cells is frequently an episome. Virus genes associated with latent infection of primary B lymphocytes are expressed. Expression of Epstein-Barr virus nuclear antigen 2 (EBNA-2) and the EBNA-3 genes is variable relative to that of EBNA-1, as is characteristic of some naturally infected Burkitt tumor cells. Moreover, the EBV-infected B-lymphoma cells are often partially permissive for early replicative

  18. Glycogen synthase kinase-3 inhibitors suppress the AR-V7-mediated transcription and selectively inhibit cell growth in AR-V7-positive prostate cancer cells.

    Science.gov (United States)

    Nakata, Daisuke; Koyama, Ryokichi; Nakayama, Kazuhide; Kitazawa, Satoshi; Watanabe, Tatsuya; Hara, Takahito

    2017-06-01

    Recent evidence suggests that androgen receptor (AR) splice variants, including AR-V7, play a pivotal role in resistance to androgen blockade in prostate cancer treatment. The development of new therapeutic agents that can suppress the transcriptional activities of AR splice variants has been anticipated as the next generation treatment of castration-resistant prostate cancer. High-throughput screening of AR-V7 signaling inhibitors was performed using an AR-V7 reporter system. The effects of a glycogen synthase kinase-3 (GSK3) inhibitor, LY-2090314, on endogenous AR-V7 signaling were evaluated in an AR-V7-positive cell line, JDCaP-hr, by quantitative reverse transcription polymerase chain reaction. The relationship between AR-V7 signaling and β-catenin signaling was assessed using RNA interference. The effect of LY-2090314 on cell growth in various prostate cancer cell lines was also evaluated. We identified GSK3 inhibitors as transcriptional suppressors of AR-V7 using a high-throughput screen with an AR-V7 reporter system. LY-2090314 suppressed the reporter activity and endogenous AR-V7 activity in JDCaP-hr cells. Because silencing of β-catenin partly rescued the suppression, it was evident that the suppression was mediated, at least partially, via the activation of β-catenin signaling. AR-V7 signaling and β-catenin signaling reciprocally regulate each other in JDCaP-hr cells, and therefore, GSK3 inhibition can repress AR-V7 transcriptional activity by accumulating intracellular β-catenin. Notably, LY-2090314 selectively inhibited the growth of AR-V7-positive prostate cancer cells in vitro. Our findings demonstrate the potential of GSK3 inhibitors in treating advanced prostate cancer driven by AR splice variants. In vivo evaluation of AR splice variant-positive prostate cancer models will help illustrate the overall significance of GSK3 inhibitors in treating prostate cancer. © 2017 Wiley Periodicals, Inc.

  19. Evolution of type 2 vaccine derived poliovirus lineages. Evidence for codon-specific positive selection at three distinct locations on capsid wall.

    Directory of Open Access Journals (Sweden)

    Tapani Hovi

    Full Text Available Partial sequences of 110 type 2 poliovirus strains isolated from sewage in Slovakia in 2003-2005, and most probably originating from a single dose of oral poliovirus vaccine, were subjected to a detailed genetic analysis. Evolutionary patterns of these vaccine derived poliovirus strains (SVK-aVDPV2 were compared to those of type 1 and type 3 wild poliovirus (WPV lineages considered to have a single seed strain origin, respectively. The 102 unique SVK-aVDPV VP1 sequences were monophyletic differing from that of the most likely parental poliovirus type 2/Sabin (PV2 Sabin by 12.5-15.6%. Judging from this difference and from the rate of accumulation of synonymous transversions during the 22 month observation period, the relevant oral poliovirus vaccine dose had been administered to an unknown recipient more than 12 years earlier. The patterns of nucleotide substitution during the observation period differed from those found in the studied lineages of WPV1 or 3, including a lower transition/transversion (Ts/Tv bias and strikingly lower Ts/Tv rate ratios at the 2(nd codon position for both purines and pyrimidines. A relatively low preference of transitions at the 2(nd codon position was also found in the large set of VP1 sequences of Nigerian circulating (cVDPV2, as well as in the smaller sets from the Hispaniola cVDPV1 and Egypt cVDPV2 outbreaks, and among aVDPV1and aVDPV2 strains recently isolated from sewage in Finland. Codon-wise analysis of synonymous versus non-synonymous substitution rates in the VP1 sequences suggested that in five codons, those coding for amino acids at sites 24, 144, 147, 221 and 222, there may have been positive selection during the observation period. We conclude that pattern of poliovirus VP1 evolution in prolonged infection may differ from that found in WPV epidemics. Further studies on sufficiently large independent datasets are needed to confirm this suggestion and to reveal its potential significance.

  20. Samoocena, a wybrane elementy pozycji społecznej judoków = Self-assessment and selected elements of the social position of judokas

    Directory of Open Access Journals (Sweden)

    Patrycja Janowska

    2016-09-01

    Janowska Patrycja1, Wojdat Marta1, Antkowiak Magdalena1, Stępniak Robert2, Adam Marek3   1Studenckie Koło Naukowe "WyKoNa", Uniwersytet Kazimierza Wielkiego, Bydgoszcz, Polska 2Instytut Kultury Fizycznej, Uniwersytet Kazimierza Wielkiego, Bydgoszcz, Polska 3Zakład Sportów Walki, Akademia Wychowania Fizycznego i Sportu, Gdańsk, Polska   Corresponding author: Stępniak Robert Ph. D Instytut Kultury Fizycznej, Uniwersytet Kazimierza Wielkiego, ul. Sportowa 2, 85-091 Bydgoszcz Polska email:     Słowa kluczowe: samoocena, pozycja społeczna, zawodnicy judo Keywords: self-esteem social position, judo fighters     Samoocena, a wybrane elementy pozycji społecznej judoków Self-assessment and selected elements of the social position of judokas   Streszczenie   Cel: Określenie liczbowe poziomu samooceny populacji judoków, oraz znalezienie ewentualnych związków z czynnikami określającymi pozycje społeczną. Materiał i metody: Przebadano 53 osobowa grupę judoków i byłych -nadal trenujących judoków używając ankiety samooceny Rosenberga SES, w polskiej adaptacji. Wyniki: Podgrupa społeczna judoków wykazuje się wysoką samooceną, wysokim wykształceniem i ponadprzeciętnym wynagrodzeniem za prace zarobkową. Wnioski: Istnieją istotne związki pomiędzy wynikami samooceny SES, a czynnikami określającymi daną osobę w społeczeństwie.         Abstract   Aim: To determine the numerical level of self-esteem of the judokas population and to find possible links with the factors determining the social position. Material and Methods: 53 current and formerly judokas - still trained. Research conducted using the self-assessment surveys Rosenberg SES in Polish adaptation. Results: Subgroup social judokas showed high self-esteem, high education and above-average remuneration paid for the work. Conclusions: There are significant relationships between the results of self-assessment - SES, and the factors defining a person in society.

  1. [Renal denervation for the treatment of resistant hypertension: definition, patient selection and description of the procedure. 2012 Position paper of the Italian Society of Hypertension].

    Science.gov (United States)

    Volpe, Massimo; Agabiti-Rosei, Enrico; Ambrosioni, Ettore; Cottone, Santina; Cuspidi, Cesare; Borghi, Claudio; De Luca, Nicola; Fallo, Francesco; Ferri, Claudio; Mancia, Giuseppe; Morganti, Alberto; Muiesan, Maria Lorenza; Sarzani, Riccardo; Sechi, Leonardo; Tocci, Giuliano; Virdis, Agostino

    2012-12-01

    Hypertension is responsible for a relevant burden of cardiovascular morbidity and mortality worldwide. Although several appropriate and integrated pharmacological strategies are available, blood pressure control still remains largely unsatisfactory. Failure to achieve effective blood pressure control in treated hypertensive patients may have a substantial impact on overall cardiovascular risk, since it significantly increases the risk of both macrovascular and microvascular complications. Hypertension is arbitrarily defined as "resistant" or "refractory" when recommended blood pressure goals (clinic blood pressure hypertension has recently become available. Renal sympathetic denervation is a minimally invasive procedure performed via femoral access that uses radiofrequency catheter ablation to disable renal sympathetic afferent and efferent nerves. It results in isolation of renal parenchymal and juxtaglomerular cells from the abnormal enhancement of renal adrenergic nerve activity. The present position paper of the Italian Society of Hypertension provides a diagnostic and therapeutic approach to the early identification and effective clinical management of patients with resistant hypertension, who may be candidates for renal denervation. These indications may have important implications not only from a clinical viewpoint but also from an economic perspective. The accurate identification of patients with resistant hypertension and the appropriate selection of patients eligible for this procedure may help improve blood pressure control and reduce the risk of cardiovascular and cerebrovascular complications in these patients.

  2. Optimization of Ex Vivo Murine Bone Marrow Derived Immature Dendritic Cells: A Comparative Analysis of Flask Culture Method and Mouse CD11c Positive Selection Kit Method

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    Rahul Ashok Gosavi

    2018-01-01

    Full Text Available 12–14 days of culturing of bone marrow (BM cells containing various growth factors is widely used method for generating dendritic cells (DCs from suspended cell population. Here we compared flask culture method and commercially available CD11c Positive Selection kit method. Immature BMDCs’ purity of adherent as well as suspended cell population was generated in the decreasing concentration of recombinant-murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF in nontreated tissue culture flasks. The expression of CD11c, MHCII, CD40, and CD86 was measured by flow cytometry. We found significant difference (P<0.05 between the two methods in the adherent cells population but no significant difference was observed between the suspended cell populations with respect to CD11c+ count. However, CD11c+ was significantly higher in both adhered and suspended cell population by culture method but kit method gave more CD11c+ from suspended cells population only. On the other hand, using both methods, immature DC expressed moderate level of MHC class II molecules as well as low levels of CD40 and CD86. Our findings suggest that widely used culture method gives the best results in terms of yield, viability, and purity of BMDCs from both adherent and suspended cell population whereas kit method works well for suspended cell population.

  3. Carbon-11 labelling of eticlopride in two different positions - a selective high-affinity ligand for the study of dopamine D-2 receptors using PET

    International Nuclear Information System (INIS)

    Halldin, Christer; Hall, Haakan

    1990-01-01

    A new highly selective high-affinity dopamine D-2 receptor antagonist, eticlopride ((-)-(S)-5-chloro-3-ethyl-N-(1-ethyl-2-pyrrolidinyl)methyl)-6-methoxysalicylamide), was labelled with 11 C in two different positions ([N-ethyl- 11 C]eticlopride (I) and ([methyl- 11 C]eticlopride (II)). Product I was prepared by N-alkylation of the N-desethyl compound with [ 11 C]ethyl iodide. II was prepared by O-alkylation of the diphenolic precursor with [ 11 C]methyl iodide followed by separation of the two methylated products. The radiochemical yields were 15-20% (EOB) with an overall synthesis time of 45-60 min. Both compounds were isolated by semi-preparative HPLC and the radiochemical purity was in both cases > 99%. I was injected i.v. in a Cynomolgus monkey and brain radioactivity was measured by positron emission tomography (PET). The specific activity was 70 Ci/mmol at time of injection. There was a marked accumulation of radioactivity in the basal ganglia, regions known to have a high density of dopamine D-2 receptors. (author)

  4. Positive selection of mutants with cell envelope defects of a Salmonella typhimurium strain hypersensitive to the products of genes hisF and hisH

    International Nuclear Information System (INIS)

    Anton, D.N.

    1979-01-01

    Strain SB564 and its derivative DA78 are hypersensitive to the inhibitory action of the proteins coded for by genes hisF and hisH on cell division. Transduction of hisO1242, a regulatory mutation that elicits a very high level of expression of the histidine operon, into these strains resulted in the production of long filamentous cells carrying large balloons and in growth failure. Forty-one hisO1242 derivatives that escaped inhibition were isolated. These strains showed a large variety of alterations, many of which were related to the cell envelope. The more-frequent alterations included: changes in cell shape, increased sensitivity to one or more of several drugs (deoxycholate, cycloserine, penicillin, novobiocin, acridine orange), increased autolytic activity in alkaline buffer, anomalous fermentation of maltose on eosin--methylene blue plates, and temperature-conditional cell division. The alterations are produced, in some of the strains, by pleiotropic mutations in gene envB. Strains affected in divC, divD, and rodA loci have also been identified. Genetic analaysis has shown that several strains carry more than one envelope mutation. It is assumed that envelope mutations are positively selected because they somehow alleviate the particularly severe inhibition of cell division caused, in strains SB564 and DA78, by the excessive synthesis of hisF and hisH gene products

  5. A Comparison of the 2/3/5 Selective Positive Allosteric Modulators L-838,417 and TPA023 in Preclinical Models of Inflammatory and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Sarah Nickolls

    2011-01-01

    Full Text Available GABAA receptors containing α2/3 subunits are current targets in the battle to develop new pain medications, as they are expressed in the spinal cord where increasing inhibitory drive should result in analgesia. However, this approach is prone to a range of side effects including sedation, cognitive impairment, and abuse as a consequence of the widespread influence of GABA. The ability to make subtype selective low-efficacy benzodiazepine compounds, which potentiate the action of GABA at specific α subunits, has the potential to reduce this side effect profile. In this study, we have investigated the effects of the medium-efficacy positive allosteric modulator (PAM L-838,417 and the low-efficacy PAM TPA023 in a number of preclinical inflammatory and neuropathic pain models. We conclude that either the higher level of efficacy at α2/3 or efficacy at α5 is required for compounds to have a significant analgesic effect in a range of models, and, therefore, although the side-effect profile of compounds can be reduced compared to typical benzodiazepines, it is unlikely that it can be completely eliminated.

  6. Effect of pulse sequence parameter selection on signal strength in positive-contrast MRI markers for MRI-based prostate postimplant assessment

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Tze Yee [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 and The University of Texas at Houston Graduate School of Biomedical Sciences, 6767 Bertner Avenue, Houston, Texas 77030 (United States); Kudchadker, Rajat J., E-mail: rkudchad@mdanderson.org; Wang, Jihong; Ibbott, Geoffrey S. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Stafford, R. Jason [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); MacLellan, Christopher [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 and The University of Texas at Houston Graduate School of Biomedical Sciences, 6767 Bertner Avenue, Houston, Texas 77030 (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States); Frank, Steven J. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030 (United States)

    2016-07-15

    Purpose: For postimplant dosimetric assessment, computed tomography (CT) is commonly used to identify prostate brachytherapy seeds, at the expense of accurate anatomical contouring. Magnetic resonance imaging (MRI) is superior to CT for anatomical delineation, but identification of the negative-contrast seeds is challenging. Positive-contrast MRI markers were proposed to replace spacers to assist seed localization on MRI images. Visualization of these markers under varying scan parameters was investigated. Methods: To simulate a clinical scenario, a prostate phantom was implanted with 66 markers and 86 seeds, and imaged on a 3.0T MRI scanner using a 3D fast radiofrequency-spoiled gradient recalled echo acquisition with various combinations of scan parameters. Scan parameters, including flip angle, number of excitations, bandwidth, field-of-view, slice thickness, and encoding steps were systematically varied to study their effects on signal, noise, scan time, image resolution, and artifacts. Results: The effects of pulse sequence parameter selection on the marker signal strength and image noise were characterized. The authors also examined the tradeoff between signal-to-noise ratio, scan time, and image artifacts, such as the wraparound artifact, susceptibility artifact, chemical shift artifact, and partial volume averaging artifact. Given reasonable scan time and managable artifacts, the authors recommended scan parameter combinations that can provide robust visualization of the MRI markers. Conclusions: The recommended MRI pulse sequence protocol allows for consistent visualization of the markers to assist seed localization, potentially enabling MRI-only prostate postimplant dosimetry.

  7. Curatorial Acts

    NARCIS (Netherlands)

    Bal, M.

    2012-01-01

    In a self-critical inquiry into my own recent work of co-curating and the experience of seeing my video work being curated by others, this article examines acts of framing as performative acts that seek to transform visitors' preconceptions. This affective effect is pursued by means of immersion,

  8. The common good accompaniment on the long road to the site selection. The report of the Commission Disposal of Highly Radioactive Waste and the site selection act; Die gemeinwohlorientierte Begleitung auf dem langen Weg zur Standortauswahl. Zum Bericht der Endlager-Kommission und zur Aenderung des StandAG

    Energy Technology Data Exchange (ETDEWEB)

    Feldmann, Ulrike

    2016-10-15

    Almost in time, on 5 July 2016 the 'Commission Disposal of High Radioactive Waste' presented its report according to the German Site Selection Act (for disposal of radioactive waste). On July 20, 2016, the act for reorganisation of the organisational structure in the field of radioactive waste disposal entered into force. The new law raises a number of institutional, organisational and fundamental questions on the way to a final repository for high-level waste. The path continues to appear rocky and long.

  9. A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans

    Science.gov (United States)

    Acuña-Alonzo, Víctor; Flores-Dorantes, Teresa; Kruit, Janine K.; Villarreal-Molina, Teresa; Arellano-Campos, Olimpia; Hünemeier, Tábita; Moreno-Estrada, Andrés; Ortiz-López, Ma Guadalupe; Villamil-Ramírez, Hugo; León-Mimila, Paola; Villalobos-Comparan, Marisela; Jacobo-Albavera, Leonor; Ramírez-Jiménez, Salvador; Sikora, Martin; Zhang, Lin-Hua; Pape, Terry D.; de Ángeles Granados-Silvestre, Ma; Montufar-Robles, Isela; Tito-Alvarez, Ana M.; Zurita-Salinas, Camilo; Bustos-Arriaga, José; Cedillo-Barrón, Leticia; Gómez-Trejo, Celta; Barquera-Lozano, Rodrigo; Vieira-Filho, Joao P.; Granados, Julio; Romero-Hidalgo, Sandra; Huertas-Vázquez, Adriana; González-Martín, Antonio; Gorostiza, Amaya; Bonatto, Sandro L.; Rodríguez-Cruz, Maricela; Wang, Li; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A.; Lisker, Ruben; Moises, Regina S.; Menjivar, Marta; Salzano, Francisco M.; Knowler, William C.; Bortolini, M. Cátira; Hayden, Michael R.; Baier, Leslie J.; Canizales-Quinteros, Samuel

    2010-01-01

    It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 × 10−11) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations. PMID:20418488

  10. Selective and interactive effects of D2 receptor antagonism and positive allosteric mGluR4 modulation on waiting impulsivity.

    Science.gov (United States)

    Isherwood, Sarah N; Robbins, Trevor W; Nicholson, Janet R; Dalley, Jeffrey W; Pekcec, Anton

    2017-09-01

    Metabotropic glutamate receptor 4 (mGluR4) and dopamine D 2 receptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and D 2 receptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the D 2 receptor antagonist eticlopride, on two distinct forms of impulsivity. Rats were trained on the five-choice serial reaction time task (5-CSRTT) of sustained visual attention and segregated according to low, mid, and high levels of motor impulsivity (LI, MI and HI, respectively), with unscreened rats used as an additional control group. A separate group of rats was trained on a delay discounting task (DDT) to assess choice impulsivity. Systemic administration of Cpd11 dose-dependently increased motor impulsivity and impaired attentional accuracy on the 5-CSRTT in all groups tested. Eticlopride selectively attenuated the increase in impulsivity induced by Cpd11, but not the accompanying attentional impairment, at doses that had no significant effect on behavioural performance when administered alone. Cpd11 also decreased choice impulsivity on the DDT (i.e. increased preference for the large, delayed reward) and decreased locomotor activity. These findings demonstrate that mGluR4s, in conjunction with D 2 receptors, affect motor- and choice-based measures of impulsivity, and therefore may be novel targets to modulate impulsive behaviour associated with a number of neuropsychiatric syndromes. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. ACT Test

    Science.gov (United States)

    ... to clot, the higher the degree of clotting inhibition. During surgery, the ACT is kept above a ... What is ECLS? An Introduction to Extracorporeal Life Support. University of Michigan Health System [On-line information]. ...

  12. Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+) in selected health facilities in Zimbabwe: a qualitative study.

    Science.gov (United States)

    Chadambuka, Addmore; Katirayi, Leila; Muchedzi, Auxilia; Tumbare, Esther; Musarandega, Reuben; Mahomva, Agnes I; Woelk, Godfrey

    2017-07-25

    Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013 World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART) irrespective of clinical stage (Option B+). Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known. A qualitative study was conducted at selected sites in Harare (urban) and Zvimba (rural) to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10. Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART. This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies. Consistent with previous literature, this study demonstrated the

  13. Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+ in selected health facilities in Zimbabwe: a qualitative study

    Directory of Open Access Journals (Sweden)

    Addmore Chadambuka

    2017-07-01

    Full Text Available Abstract Background Zimbabwe’s Ministry of Health and Child Care (MOHCC adopted 2013 World Health Organization (WHO prevention of mother-to-child HIV transmission (PMTCT guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW on lifelong antiretroviral treatment (ART irrespective of clinical stage (Option B+. Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known. Methods A qualitative study was conducted at selected sites in Harare (urban and Zvimba (rural to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs, focus group discussions (FGDs and key informant interviews (KIIs were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10. Results Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART. Conclusions This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies

  14. Nitrogen transporter and assimilation genes exhibit developmental stage-selective expression in maize (Zea mays L.) associated with distinct cis-acting promoter motifs.

    Science.gov (United States)

    Liseron-Monfils, Christophe; Bi, Yong-Mei; Downs, Gregory S; Wu, Wenqing; Signorelli, Tara; Lu, Guangwen; Chen, Xi; Bondo, Eddie; Zhu, Tong; Lukens, Lewis N; Colasanti, Joseph; Rothstein, Steven J; Raizada, Manish N

    2013-10-01

    Nitrogen is considered the most limiting nutrient for maize (Zea mays L.), but there is limited understanding of the regulation of nitrogen-related genes during maize development. An Affymetrix 82K maize array was used to analyze the expression of ≤ 46 unique nitrogen uptake and assimilation probes in 50 maize tissues from seedling emergence to 31 d after pollination. Four nitrogen-related expression clusters were identified in roots and shoots corresponding to, or overlapping, juvenile, adult, and reproductive phases of development. Quantitative real time PCR data was consistent with the existence of these distinct expression clusters. Promoters corresponding to each cluster were screened for over-represented cis-acting elements. The 8-bp distal motif of the Arabidopsis 43-bp nitrogen response element (NRE) was over-represented in nitrogen-related maize gene promoters. This conserved motif, referred to here as NRE43-d8, was previously shown to be critical for nitrate-activated transcription of nitrate reductase (NIA1) and nitrite reductase (NIR1) by the NIN-LIKE PROTEIN 6 (NLP6) in Arabidopsis. Here, NRE43-d8 was over-represented in the promoters of maize nitrate and ammonium transporter genes, specifically those that showed peak expression during early-stage vegetative development. This result predicts an expansion of the NRE-NLP6 regulon and suggests that it may have a developmental component in maize. We also report leaf expression of putative orthologs of nitrite transporters (NiTR1), a transporter not previously reported in maize. We conclude by discussing how each of the four transcriptional modules may be responsible for the different nitrogen uptake and assimilation requirements of leaves and roots at different stages of maize development.

  15. S100A7, a novel Alzheimer's disease biomarker with non-amyloidogenic alpha-secretase activity acts via selective promotion of ADAM-10.

    Directory of Open Access Journals (Sweden)

    Weiping Qin

    Full Text Available Alzheimer's disease (AD is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS proteomic technology, we identified and purified a novel 11.7-kDa metal- binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral-S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of beta-amyloid (Abeta(1-42 and Abeta(1-40 peptides, coincidental with a selective promotion of "non- amyloidogenic" alpha-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of alpha-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote alpha-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker of therapeutic efficacy in the characterization of novel drug agents for

  16. Positive Selection of Deleterious Alleles through Interaction with a Sex-Ratio Suppressor Gene in African Buffalo: A Plausible New Mechanism for a High Frequency Anomaly

    NARCIS (Netherlands)

    Hooft, van W.F.; Greyling, B.J.; Getz, W.M.; Helden, P.D.; Zwaan, B.J.; Bastos, A.D.S.

    2015-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer)

  17. Positive Selection of Deleterious Alleles through Interaction with a Sex-Ratio Suppressor Gene in African Buffalo: A Plausible New Mechanism for a High Frequency Anomaly

    NARCIS (Netherlands)

    Hooft, van W.F.; Greyling, B.J.; Getz, W.M.; Helden, van P.D.; Zwaan, B.J.; Bastos, A.D.S.

    2014-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer)

  18. Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy

    International Nuclear Information System (INIS)

    Truong, Pauline T.; Olivotto, Ivo A.; Kader, Hosam A.; Panades, Miguel; Speers, Caroline H.; Berthelet, Eric

    2005-01-01

    Purpose: To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes. Methods and Materials: The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR ± SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis. Results: The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR ± SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of >20% was identified in women with one to three positive nodes plus at least one of the following factors: age 25% of nodes positive (all p 25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR ± SDR. In the classification model, the first split was according to age ( 25% of nodes positive was associated with a risk of LRR ± SDR of 58.0% compared with 23.8% for those with ≤25% of nodes positive (p = 0.01). Of 698 women >45 years, the presence of >25% of nodes positive also conferred a greater LRR ± SDR risk (26.7%) compared with women with ≤25% of nodes positive (10

  19. Model selection and averaging in the assessment of the drivers of household food waste to reduce the probability of false positives

    Science.gov (United States)

    Aramyan, Lusine; Piras, Simone; Quested, Thomas Edward; Righi, Simone; Setti, Marco; Vittuari, Matteo; Stewart, Gavin Bruce

    2018-01-01

    Food waste from households contributes the greatest proportion to total food waste in developed countries. Therefore, food waste reduction requires an understanding of the socio-economic (contextual and behavioural) factors that lead to its generation within the household. Addressing such a complex subject calls for sound methodological approaches that until now have been conditioned by the large number of factors involved in waste generation, by the lack of a recognised definition, and by limited available data. This work contributes to food waste generation literature by using one of the largest available datasets that includes data on the objective amount of avoidable household food waste, along with information on a series of socio-economic factors. In order to address one aspect of the complexity of the problem, machine learning algorithms (random forests and boruta) for variable selection integrated with linear modelling, model selection and averaging are implemented. Model selection addresses model structural uncertainty, which is not routinely considered in assessments of food waste in literature. The main drivers of food waste in the home selected in the most parsimonious models include household size, the presence of fussy eaters, employment status, home ownership status, and the local authority. Results, regardless of which variable set the models are run on, point toward large households as being a key target element for food waste reduction interventions. PMID:29389949

  20. Model selection and averaging in the assessment of the drivers of household food waste to reduce the probability of false positives.

    Science.gov (United States)

    Grainger, Matthew James; Aramyan, Lusine; Piras, Simone; Quested, Thomas Edward; Righi, Simone; Setti, Marco; Vittuari, Matteo; Stewart, Gavin Bruce

    2018-01-01

    Food waste from households contributes the greatest proportion to total food waste in developed countries. Therefore, food waste reduction requires an understanding of the socio-economic (contextual and behavioural) factors that lead to its generation within the household. Addressing such a complex subject calls for sound methodological approaches that until now have been conditioned by the large number of factors involved in waste generation, by the lack of a recognised definition, and by limited available data. This work contributes to food waste generation literature by using one of the largest available datasets that includes data on the objective amount of avoidable household food waste, along with information on a series of socio-economic factors. In order to address one aspect of the complexity of the problem, machine learning algorithms (random forests and boruta) for variable selection integrated with linear modelling, model selection and averaging are implemented. Model selection addresses model structural uncertainty, which is not routinely considered in assessments of food waste in literature. The main drivers of food waste in the home selected in the most parsimonious models include household size, the presence of fussy eaters, employment status, home ownership status, and the local authority. Results, regardless of which variable set the models are run on, point toward large households as being a key target element for food waste reduction interventions.

  1. Structure-Activity Relationships of New Natural Product-Based Diaryloxazoles with Selective Activity against Androgen Receptor-Positive Breast Cancer Cells.

    Science.gov (United States)

    Robles, Andrew J; McCowen, Shelby; Cai, Shengxin; Glassman, Michaels; Ruiz, Francisco; Cichewicz, Robert H; McHardy, Stanton F; Mooberry, Susan L

    2017-11-22

    Targeted therapies for ER+/PR+ and HER2-amplified breast cancers have improved patient survival, but there are no therapies for triple negative breast cancers (TNBC) that lack expression of estrogen and progesterone receptors (ER/PR), or amplification or overexpression of HER2. Gene expression profiling of TNBC has identified molecular subtypes and representative cell lines. An extract of the Texas native plant Amyris texana was found to have selective activity against MDA-MB-453 cells, a model of the luminal androgen receptor (LAR) subtype of TNBC. Bioassay-guided fractionation identified two oxazole natural products with selective activity against this cell line. Conducted analog synthesis and structure-activity relationship studies provided analogs with more potent and selective activity against two LAR subtype cell line models, culminating in the discovery of compound 30 (CIDD-0067106). Lead compounds discovered have potent and selective antiproliferative activities, and mechanisms of action studies show they inhibit the activity of the mTORC1 pathway.

  2. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    Science.gov (United States)

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-01-01

    We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Effects of "Like Type" Sex Pairings between Applicants-Principals and Type of Focal Position Considered at the Screening Stage of the Selection Process

    Science.gov (United States)

    Young, I. Phillip

    2005-01-01

    This study addresses the screening decisions for a national random sample of high school principals as viewed from the attraction-similarity theory of interpersonal perceptions. Independent variables are the sex of principals, sex of applicants, and the type of focal positions sought by hypothetical job applicants (teacher or counselor). Dependent…

  4. Selective deficits in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania.

    LENUS (Irish Health Repository)

    Kravariti, Eugenia

    2009-05-01

    Neurocognitive dysfunction is likely to represent a trait characteristic of bipolar disorder, but the extent to which it comprises \\'core\\' deficits as opposed to those secondary to longstanding illness or intellectual decline is unclear. We investigated neuropsychological performance in an epidemiologically derived sample of patients with a first affective episode with psychotic symptoms and a positive history of mania, compared to community controls.

  5. Rational Design of a Highly Potent and Selective Peptide Inhibitor of PACE4 by Salt Bridge Interaction with D160 at Position P3.

    Science.gov (United States)

    Dianati, Vahid; Shamloo, Azar; Kwiatkowska, Anna; Desjardins, Roxane; Soldera, Armand; Day, Robert; Dory, Yves L

    2017-08-08

    PACE4, a member of the proprotein convertases (PCs) family of serine proteases, is a validated target for prostate cancer. Our group has developed a potent and selective PACE4 inhibitor: Ac-LLLLRVKR-NH 2 . In seeking for modifications to increase the selectivity of this ligand toward PACE4, we replaced one of its P3 Val methyl groups with a basic group capable of forming a salt bridge with D160 of PACE4. The resulting inhibitor is eight times more potent than the P3 Val parent inhibitor and two times more selective over furin, because the equivalent salt bridge with furin E257 is not optimal. Moreover, the β-branched nature of the new P3 residue favors the extended β-sheet conformation usually associated with substrates of proteases. This work provides new insight for better understanding of β-sheet backbone-backbone interactions between serine proteases and their peptidic ligands. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Genome-wide SNP identification by high-throughput sequencing and selective mapping allows sequence assembly positioning using a framework genetic linkage map

    Directory of Open Access Journals (Sweden)

    Xu Xiangming

    2010-12-01

    Full Text Available Abstract Background Determining the position and order of contigs and scaffolds from a genome assembly within an organism's genome remains a technical challenge in a majority of sequencing projects. In order to exploit contemporary technologies for DNA sequencing, we developed a strategy for whole genome single nucleotide polymorphism sequencing allowing the positioning of sequence contigs onto a linkage map using the bin mapping method. Results The strategy was tested on a draft genome of the fungal pathogen Venturia inaequalis, the causal agent of apple scab, and further validated using sequence contigs derived from the diploid plant genome Fragaria vesca. Using our novel method we were able to anchor 70% and 92% of sequences assemblies for V. inaequalis and F. vesca, respectively, to genetic linkage maps. Conclusions We demonstrated the utility of this approach by accurately determining the bin map positions of the majority of the large sequence contigs from each genome sequence and validated our method by mapping single sequence repeat markers derived from sequence contigs on a full mapping population.

  7. Positive selection of Plasmodium falciparum parasites with multiple var2csa-type PfEMP1 genes during the course of infection in pregnant women

    DEFF Research Database (Denmark)

    Sander, Adam F; Salanti, Ali; Lavstsen, Thomas

    2011-01-01

    multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective...... advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes...

  8. Effect of ionic strength and cationic DNA affinity binders on the DNA sequence selective alkylation of guanine N7-positions by nitrogen mustards

    International Nuclear Information System (INIS)

    Hartley, J.A.; Forrow, S.M.; Souhami, R.L.

    1990-01-01

    Large variations in alkylation intensities exist among guanines in a DNA sequence following treatment with chemotherapeutic alkylating agents such as nitrogen mustards, and the substituent attached to the reactive group can impose a distinct sequence preference for reaction. In order to understand further the structural and electrostatic factors which determine the sequence selectivity of alkylation reactions, the effect of increase ionic strength, the intercalator ethidium bromide, AT-specific minor groove binders distamycin A and netropsin, and the polyamine spermine on guanine N7-alkylation by L-phenylalanine mustard (L-Pam), uracil mustard (UM), and quinacrine mustard (QM) was investigated with a modification of the guanine-specific chemical cleavage technique for DNA sequencing. The result differed with both the nitrogen mustard and the cationic agent used. The effect, which resulted in both enhancement and suppression of alkylation sites, was most striking in the case of netropsin and distamycin A, which differed from each other. DNA footprinting indicated that selective binding to AT sequences in the minor groove of DNA can have long-range effects on the alkylation pattern of DNA in the major groove

  9. Positive end expiratory pressure during one-lung ventilation: Selecting ideal patients and ventilator settings with the aim of improving arterial oxygenation

    Directory of Open Access Journals (Sweden)

    Hoftman Nir

    2011-01-01

    Full Text Available The efficacy of positive end-expiratory pressure (PEEP in treating intraoperative hypoxemia during one-lung ventilation (OLV remains in question given conflicting results of prior studies. This study aims to (1 evaluate the efficacy of PEEP during OLV, (2 assess the utility of preoperative predictors of response to PEEP, and (3 explore optimal intraoperative settings that would maximize the effects of PEEP on oxygenation. Forty-one thoracic surgery patients from a single tertiary care university center were prospectively enrolled in this observational study. After induction of general anesthesia, a double-lumen endotracheal tube was fiberoptically positioned and OLV initiated. Intraoperatively, PEEP = 5 and 10 cmH 2 O were sequentially applied to the ventilated lung during OLV. Arterial oxygenation, cardiovascular performance parameters, and proposed perioperative variables that could predict or enhance response to PEEP were analysed. T-test and c2 tests were utilized for continuous and categorical variables, respectively. Multivariate analyses were carried out using a classification tree model of binary recursive partitioning. PEEP improved arterial oxygenation by ≥20% in 29% of patients (n = 12 and failed to do so in 71% (n = 29; however, no cardiovascular impact was noted. Among the proposed clinical predictors, only intraoperative tidal volume per kilogram differed significantly between responders to PEEP and non-responders (mean 6.6 vs. 5.7 ml/kg, P = 0.013; no preoperative variable predicted response to PEEP. A multivariate analysis did not yield a clinically significant model for predicting PEEP responsiveness. PEEP improved oxygenation in a subset of patients; larger, although still protective tidal volumes favored a positive response to PEEP. No preoperative variables, however, could be identified as reliable predictors for PEEP responders.

  10. Reactivity and selectivity of the electrophile aromatic substitution in the gas phase by positive 80Br and 125I decay ions

    International Nuclear Information System (INIS)

    Knust, E.J.

    1975-02-01

    The nuclear isomeric transition sup(80m)Br(IT) 80 Br or the electron capture decay 125 Xe(EC) 125 I in the presence of high concentrations of a noble gas such as Ar or Xe are suitable for the study of the electrophilic substitution of bromium or iodonium ions in the gas phase. By using this nuclear method, which, unlike physical methods, also allows the determination of the isomer distribution, the electrophilic aromatic bromation and iodation of mono-substituted benzene compounds through unsolvated positive bromine or iodine ions could be investigated for the first time using radio-gas chromatographic techniques. (orig./LH) [de

  11. Formation of double-layered TiO2 structures with selectively-positioned molecular dyes for efficient flexible dye-sensitized solar cells

    International Nuclear Information System (INIS)

    Kim, Eun Yi; Yu, Sora; Moon, Jeong Hoon; Yoo, Seon Mi; Kim, Chulhee; Kim, Hwan Kyu; Lee, Wan In

    2013-01-01

    Graphical abstract: A novel flexible tandem dye-sensitized solar cell, selectively loading different dyes in discrete layers, was successfully formed on a plastic substrate by transferring the high-temperature-processed N719/TiO 2 over an organic dye-adsorbed TiO 2 film by a typical compression process at room temperature. -- Highlights: • A novel flexible dye-sensitized solar cell, selectively loading two different dyes in discrete layers, was successfully formed on a plastic substrate. • η of the flexible tandem cell obtained by transferring the high-temperature-processed TiO 2 layer was enhanced from 2.91% to 6.86%. • Interface control between two TiO 2 layers is crucial for the efficient transport of photo-injected electrons from the top to bottom TiO 2 layer. -- Abstract: To fabricate flexible dye-sensitized solar cells (DSCs) utilizing full solar spectrum, the double-layered TiO 2 films, selectively loading two different dyes in discrete layers, were formed on a plastic substrate by transferring the high-temperature-processed N719/TiO 2 over an organic dye (TA-St-CA)-sensitized TiO 2 film by a typical compression process at room temperature. It was found that interface control between two TiO 2 layers is crucial for the efficient transport of photo-injected electrons from the N719/TiO 2 to the TA-St-CA/TiO 2 layer. Electron impedance spectra (EIS) and transient photoelectron spectroscopic analyses exhibited that introduction of a thin interfacial TiO 2 layer between the two TiO 2 layers remarkably decreased the resistance at the interface, while increasing the electron diffusion constant (D e ) by ∼10 times. As a result, the photovoltaic conversion efficiency (η) of the flexible tandem DSC was 6.64%, whereas that of the flexible cell derived from the single TA-St-CA/TiO 2 layer was only 2.98%. Another organic dye (HC-acid), absorbing a short wavelength region of solar spectrum, was also applied to fabricate flexible tandem DSC. The η of the cell

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

    Science.gov (United States)

    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.

  13. The Effect of Number and Position of P=O/P=S Bridging Units on Cavitand Selectivity toward Methyl Ammonium Salts

    Directory of Open Access Journals (Sweden)

    Daniela Menozzi

    2015-03-01

    Full Text Available The present work reports the synthesis and complexation properties of five mixed bridge P=O/P=S cavitands toward N,N-methyl butyl ammonium chloride (1 as prototype guest. The influence of number and position of P=O and P=S groups on the affinity of phosphonate cavitands toward 1 is assessed via ITC titrations in DCE as solvent. Comparison of the resulting Kass values, the enthalpic and entropic contributions to the overall binding with those of the parent tetraphosphonate Tiiii and tetrathiophosphonate TSiiii cavitands allows one to single out the simultaneous dual H-bond between the cavitand and the salt as the major player in complexation.

  14. The potent antimicrobial properties of cell penetrating peptide-conjugated silver nanoparticles with excellent selectivity for gram-positive bacteria over erythrocytes.

    Science.gov (United States)

    Liu, Lihong; Yang, Jun; Xie, Jianping; Luo, Zhentao; Jiang, Jiang; Yang, Yi Yan; Liu, Shaomin

    2013-05-07

    Silver nanoparticles are of great interest for use as antimicrobial agents. Studies aimed at producing potent nano-silver biocides have focused on manipulation of particle size, shape, composition and surface charge. Here, we report the cell penetrating peptide catalyzed formation of antimicrobial silver nanoparticles in N,N-dimethylformamide. The novel nano-composite demonstrated a distinctly enhanced biocidal effect toward bacteria (gram-positive Bacillus subtilis, gram-negative Escherichia coli) and pathogenic yeast (Candida albicans), as compared to triangular and extremely small silver nanoparticles. In addition, a satisfactory biocompatibility was verified by a haemolysis test. Our results provide a paradigm in developing strategies that can maximize the silver nanoparticle application potentials while minimizing the toxic effects.

  15. Positive Selection of Plasmodium falciparum Parasites With Multiple var2csa-Type PfEMP1 Genes During the Course of Infection in Pregnant Women

    Science.gov (United States)

    Salanti, Ali; Lavstsen, Thomas; Nielsen, Morten A.; Theander, Thor G.; Leke, Rose G. F.; Lo, Yeung Y.; Bobbili, Naveen; Arnot, David E.; Taylor, Diane W.

    2011-01-01

    Placental malaria infections are caused by Plasmodium falciparum–infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses. PMID:21592998

  16. Interest of retro-anal levator plate myorrhaphy in selected cases of descending perineum syndrome with positive anti-sagging test

    Directory of Open Access Journals (Sweden)

    Beco Jacques

    2008-07-01

    Full Text Available Abstract Background Levator plate sagging (LPS, usually called descending perineum syndrome, is one of the main defects encountered in perineology. This defect is classically associated with colo-proctologic functional troubles (dyschesia and anal incontinence but can also induce perineodynia, gynaecological and lower urinary tract symptoms. Methods A retrospective case series of nine female patients (mean age: 44.3 underwent an isolated retro-anal levator plate myorrhaphy (RLPM to treat symptomatic LPS confirmed by rectal examination and/or Perineocaliper®. An anti-sagging test (support of the posterior perineum must significantly improve the symptoms that were resistant to conservative treatment. The effect of the procedure on the symptoms of the 3 axes of the perineum (urological, colo-proctologic and gynecological and on perineodynia was evaluated during a follow up consultation more than 9 months after surgery. The effect of RLPM on the position of the anal margin and on the levator plate angle was studied using rectal examination, Perineocaliper® and retro-anal ultrasound. Results Before surgery, anti-sagging tests were positive for dyschesia, urinary urgency and pain. After a mean follow-up of 16.1 months, RLPM resolved or improved 2/2 cases of stress urinary incontinence, 3/5 of urinary urgency, 3/4 of dysuria, 3/3 of anal incontinence, 7/8 of dyschesia, 3/4 of cystocele, 4/5 of rectocele, 5/8 of dyspareunia and 6/7 of perineodynia. Rectal examination showed a complete suppression of sagging in 4 patients and an improvement in the 5 others. The mean reduction of perineal descent was 1.08 cm (extremes: 0–1.5. Using retro-anal ultrasound of the levator plate, the mean reduction of sagging was 12.67 degrees (extremes: 1 – 21. Conclusion Anti-sagging tests can be used before surgery to simulate the effect of RLPM. This surgical procedure seems to improve stress urinary incontinence, frequency, nocturia, urgency, dysuria, anal

  17. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    Directory of Open Access Journals (Sweden)

    Sabrina Bagaglio

    2016-03-01

    Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

  18. 78 FR 65963 - Antidumping Proceedings: Announcement of Change in Department Practice for Respondent Selection...

    Science.gov (United States)

    2013-11-04

    ... selection practice must comply with the Antidumping Agreement (``ADA'') Article 9.3, under which a company's... revocation under Articles 11.1 and 11.3 of the ADA. Companies not selected as mandatory respondent have no.... The Department's position: Section 777A(c)(2)(A) of the Act provides the Department with authority to...

  19. The positive effect of hot isostatic pressing on improving the anisotropies of bending and impact properties in selective laser melted Ti-6Al-4V alloy

    International Nuclear Information System (INIS)

    Wu, Ming-Wei; Lai, Pang-Hsin

    2016-01-01

    Selective laser melting (SLM) is a versatile additive manufacturing process for fabricating solid or porous metallic materials with complicated three-dimensional shapes. SLM Ti alloys, particularly Ti-6Al-4V, and other alloys have been manufactured and analyzed in numerous studies. However, the high anisotropy of the microstructures and inconsistent mechanical properties of SLM materials have been extensively reported, and these disadvantages could prohibit its widespread use. To clarify how to alleviate the anisotropic behaviors of SLM materials, the main objective of this study was to evaluate the influences of hot isostatic pressing (HIP) on the microstructure, densification, bending strength, impact toughness, and fracture behavior of the as-built Ti-6Al-4V alloy. The results showed that the vertical and horizontal building directions obviously affect the bending and impact properties of as-built alloys. The transverse rupture strength (TRS) and impact energy of the horizontally-built alloy were respectively found to be 48% and 100% higher than those of the vertically-built one. In the vertically-built alloy, disc-shaped building defects, identified by X-ray computed tomography (CT) and microscopy, obviously reduce the effective load-bearing cross-section and deteriorate the bending and impact performances. After HIP at 1000 °C/150 MPa, the α′-martensite structure in the as-built alloy is transformed into an α+β lamellar one, and the disc-shaped building defects are evidently eliminated. As a result, the impact energies of as-built vertical and horizontal specimens are improved by 28 J (560%) and 19 J (190%), respectively, and the TRS of the as-built vertical alloy is raised by 550 MPa (37%). Consequently, the discrepancies in TRS and impact energy between the HIPed vertical and horizontal specimens are merely 3% and 14%, respectively, and the anisotropic behaviors of the SLM Ti-6Al-4V alloy are thus substantially lessened.

  20. The positive effect of hot isostatic pressing on improving the anisotropies of bending and impact properties in selective laser melted Ti-6Al-4V alloy

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Ming-Wei, E-mail: mwwu@ntut.edu.tw; Lai, Pang-Hsin

    2016-03-21

    Selective laser melting (SLM) is a versatile additive manufacturing process for fabricating solid or porous metallic materials with complicated three-dimensional shapes. SLM Ti alloys, particularly Ti-6Al-4V, and other alloys have been manufactured and analyzed in numerous studies. However, the high anisotropy of the microstructures and inconsistent mechanical properties of SLM materials have been extensively reported, and these disadvantages could prohibit its widespread use. To clarify how to alleviate the anisotropic behaviors of SLM materials, the main objective of this study was to evaluate the influences of hot isostatic pressing (HIP) on the microstructure, densification, bending strength, impact toughness, and fracture behavior of the as-built Ti-6Al-4V alloy. The results showed that the vertical and horizontal building directions obviously affect the bending and impact properties of as-built alloys. The transverse rupture strength (TRS) and impact energy of the horizontally-built alloy were respectively found to be 48% and 100% higher than those of the vertically-built one. In the vertically-built alloy, disc-shaped building defects, identified by X-ray computed tomography (CT) and microscopy, obviously reduce the effective load-bearing cross-section and deteriorate the bending and impact performances. After HIP at 1000 °C/150 MPa, the α′-martensite structure in the as-built alloy is transformed into an α+β lamellar one, and the disc-shaped building defects are evidently eliminated. As a result, the impact energies of as-built vertical and horizontal specimens are improved by 28 J (560%) and 19 J (190%), respectively, and the TRS of the as-built vertical alloy is raised by 550 MPa (37%). Consequently, the discrepancies in TRS and impact energy between the HIPed vertical and horizontal specimens are merely 3% and 14%, respectively, and the anisotropic behaviors of the SLM Ti-6Al-4V alloy are thus substantially lessened.

  1. Numerical study on the selective excitation of Helmholtz-Gauss beams in end-pumped solid-state digital lasers with the control of the laser gain transverse position provided by off-axis end pumping

    Science.gov (United States)

    Tsai, Ko-Fan; Chu, Shu-Chun

    2018-03-01

    This study proposes a complete and unified method for selective excitation of any specified nearly nondiffracting Helmholtz-Gauss (HzG) beam in end-pumped solid-state digital lasers. Four types of the HzG beams: cosine-Gauss beams, Bessel-Gauss beams, Mathieu-Gauss beams, and, in particular, parabolic-Gauss beams are successfully demonstrated to be generated with the proposed methods. To the best of the authors’ knowledge, parabolic-Gauss beams have not yet been directly generated from any kind of laser system. The numerical results of this study show that one can successfully achieve any lasing HzG beams directly from the solid-state digital lasers with only added control of the laser gain transverse position provided by off-axis end pumping. This study also presents a practical digital laser set-up for easily manipulating off-axis pumping in order to achieve the control of the laser gain transverse gain position in digital lasers. The reported results in this study provide advancement of digital lasers in dynamically generating nondiffracting beams. The control of the digital laser cavity gain position creates the possibility of achieving real-time selection of more laser modes in digital lasers, and it is worth further investigation in the future.

  2. Teaching Speech Acts

    Directory of Open Access Journals (Sweden)

    Teaching Speech Acts

    2007-01-01

    Full Text Available In this paper I argue that pragmatic ability must become part of what we teach in the classroom if we are to realize the goals of communicative competence for our students. I review the research on pragmatics, especially those articles that point to the effectiveness of teaching pragmatics in an explicit manner, and those that posit methods for teaching. I also note two areas of scholarship that address classroom needs—the use of authentic data and appropriate assessment tools. The essay concludes with a summary of my own experience teaching speech acts in an advanced-level Portuguese class.

  3. Position Information

    Data.gov (United States)

    Social Security Administration — The Position Information Data Asset provides the ability to search for active SSA position descriptions using various search criteria. An individual may search by PD...

  4. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  5. Ubiquitous positioning

    CERN Document Server

    Mannings, Robin

    2008-01-01

    This groundbreaking resource offers a practical, in-depth understanding of Ubiquitous Positioning - positioning systems that identify the location and position of people, vehicles and objects in time and space in the digitized networked economy. The future and growth of ubiquitous positioning will be fueled by the convergence of many other areas of technology, from mobile telematics, Internet technology, and location systems, to sensing systems, geographic information systems, and the semantic web. This first-of-its-kind volume explores ubiquitous positioning from a convergence perspective, of

  6. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...... are the practice maintenance and the practice change position, with different sorts of adapting in between. Media discourse can become a resource for a resistant position against social control or for an appropriating position in favour of space for action. Regardless of the current relation to a particular media......This article analyses the ways in which media discourses become a part of contested consumption activities. We apply a positioning perspective with practice theory to focus on how practitioners relate to media discourse as a symbolic resource in their everyday practices. A typology of performance...

  7. Atomic Energy Commission Act, 2000 (Act 588)

    International Nuclear Information System (INIS)

    2000-01-01

    Act 588 of the Republic of Ghana entitled, Atomic Energy Commission Act, 2000, amends and consolidates the Atomic Energy Commission Act, 204 of 1963 relating to the establishment of the Atomic Energy Commission. Act 588 makes provision for the Ghana Atomic Energy Commission to establish more institutes for the purpose of research in furtherance of its functions and also promote the commercialization of its research and development results. (E.A.A.)

  8. Physicochemical evolution and positive selection of the ...

    Indian Academy of Sciences (India)

    ... adaptation and evolutionary dynamics of gene divergence in matKs. matK sequences were amplified from 27 Taxaceae and 12 Cephalotaxaceae species. matK sequences of 19 Pinaceae species were retrieved from GenBank. The phylogenetic tree was generated using conceptual-translated amino acid sequences.

  9. T cell depleted haploidentical transplantation: positive selection

    Directory of Open Access Journals (Sweden)

    Franco Aversa

    2011-06-01

    Full Text Available Interest in mismatched transplantation arises from the fact that a suitable one-haplotype mismatched donor is immediately available for virtually all patients, particularly for those who urgently need an allogenic transplant. Work on one haplotype-mismatched transplants has been proceeding for over 20 years all over the world and novel transplant techniques have been developed. Some centres have focused on the conditioning regimens and post transplant immune suppression; others have concentrated on manipulating the graft which may be a megadose of extensively T celldepleted or unmanipulated progenitor cells. Excellent engraftment rates are associated with a very low incidence of acute and chronic GVHD and regimen-related mortality even in patients who are over 50 years old. Overall, event-free survival and transplant-related mortality compare favourably with reports on transplants from sources of stem cells other than the matched sibling.

  10. Clinical Positioning Space

    DEFF Research Database (Denmark)

    Williams, Lars Peter Hedegaard; Christensen, Mette Krogh; Rytter, Carsten

    2014-01-01

    In this article, we present a case study of residents’ clinical experiences and communication in outpatient oncology consultations. We apply positioning theory, a dynamic alternative to role theory, to investigate how oncology residents and patients situate themselves as persons with rights...... and duties. Drawing from seven qualitative interviews and six days of observation, we investigate the residents’ social positioning and their conversations with patients or supervisors. Our focus is on how (a) relational shifts in authority depend on each situation and its participants; (b) storylines...... establish acts and positions and narratively frame what participants can expect from a medical consultation viewed as a social episode; and (c) the positioning of rights and duties can lead to misunderstandings and frustrations. We conclude that residents and patients locate themselves in outpatient...

  11. Researcher positioning

    DEFF Research Database (Denmark)

    Mørck, Line Lerche; Khawaja, Iram

    2009-01-01

    abstract  This article focuses on the complex and multi-layered process of researcher positioning, specifically in relation to the politically sensitive study of marginalised and ‘othered' groups such as Muslims living in Denmark. We discuss the impact of different ethnic, religious and racial...... political and personal involvement by the researcher, which challenges traditional perspectives on research and researcher positioning. A key point in this regard is the importance of constant awareness of and reflection on the multiple ways in which one's positioning as a researcher influences the research...

  12. 75 FR 67397 - Sunshine Act Meeting; Notice

    Science.gov (United States)

    2010-11-02

    ... select from among those candidates for further consideration. 3. Consider and act on other business. 4... LEGAL SERVICES CORPORATION Sunshine Act Meeting; Notice Time and Date: The Legal Services Corporation Board of Directors' Search Committee for LSC President (``Search Committee'' or ``Committee...

  13. Radiographic positioning

    International Nuclear Information System (INIS)

    Eisenberg, R.L.; Dennis, C.A.; May, C.

    1989-01-01

    This book concentrates on the routine radiographic examinations commonly performed. It details the wide variety of examinations possible and their place in initial learning and in the radiology department as references for those occasions when an unusual examination is requested. This book provides information ranging from basic terminology to skeletal positioning to special procedures. Positions are discussed and supplemented with a picture of a patient, the resulting radiograph, and a labeled diagram. Immobilization and proper shielding of the patient are also shown

  14. Position encoder

    International Nuclear Information System (INIS)

    Goursky, Vsevolod

    1975-01-01

    A circuitry for deriving the quotient of signal delivered by position-sensitive detectors is described. Digital output is obtained in the form of 10- to 12-bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words

  15. Position encoder

    International Nuclear Information System (INIS)

    Goursky, V.

    1975-05-01

    This paper describes circuitry for deriving the quotient of signals delivered by position-sensitive detectors. Digital output is obtained in the form of 10 to 12 bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less than 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words [fr

  16. Positive selection at codon 38 of the human KCNE1 (= minK gene and sporadic absence of 38Ser-coding mRNAs in Gly38Ser heterozygotes

    Directory of Open Access Journals (Sweden)

    Pfeufer Arne

    2009-08-01

    Full Text Available Abstract Background KCNE1 represents the regulatory beta-subunit of the slowly activating delayed rectifier potassium channel (IKs. Variants of KCNE1 have repeatedly been linked to the long-QT syndrome (LQTS, a disorder which predisposes to deafness, ventricular tachyarrhythmia, syncope, and sudden cardiac death. Results We here analyze the evolution of the common Gly38Ser variant (rs1805127, using genomic DNAs, complementary DNAs, and HEK293-expressed variants of altogether 19 mammalian species. The between species comparison reveals that the human-specific Gly38Ser polymorphism evolved under strong positive Darwinian selection, probably in adaptation to specific challenges in the fine-tuning of IKs channels. The involved amino acid exchanges (Asp > Gly, Gly > Ser are moderately radical and do not induce apparent changes in posttranslational modification. According to population genetic analyses (HapMap phase II a heterozygote advantage accounts for the maintenance of the Gly38Ser polymorphism in humans. On the other hand, the expression of the 38Ser allele seems to be disadvantageous under certain conditions, as suggested by the sporadic deficiency of 38Ser-coding mRNAs in heterozygote Central Europeans and the depletion of homozygotes 38Ser in the Yoruban sample. Conclusion We speculate that individual differences in genomic imprinting or genomic recoding might have contributed to conflicting results of recent association studies between Gly38Ser polymorphism and QT phenotype. The findings thus highlight the relevance of mRNA data in future association studies of genotypes and clinical disorders. To the best of our knowledge, they moreover provide first time evidence for a unique pattern; i.e. coincidence of positive Darwinian selection and polymorphism with a sporadically suppressed expression of one allele.

  17. Specified radioactive waste final disposal act

    International Nuclear Information System (INIS)

    Yasui, Masaya

    2001-01-01

    Radioactive wastes must be finally and safely disposed far from human activities. Disposal act is a long-range task and needs to be understood and accepted by public for site selection. This paper explains basic policy of Japanese Government for final disposal act of specified radioactive wastes, examination for site selection guidelines to promote residential understanding, general concept of multi-barrier system for isolating the specific radioactive wastes, and research and technical development for radioactive waste management. (S. Ohno)

  18. Nuclear Regulatory Authority Act, 2015 (Act 895)

    International Nuclear Information System (INIS)

    2015-04-01

    An Act to establish a Nuclear Regulatory Authority in Ghana. This Act provides for the regulation and management of activities and practices for the peaceful use of nuclear material or energy, and to provide for the protection of persons and the environment against the harmful effects of radiation; and to ensure the effective implementation of the country’s international obligations and for related matters. This Act replaced the Radiation Protection Instrument, of 1993 (LI 1559).

  19. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Science.gov (United States)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  20. Positional games

    CERN Document Server

    Hefetz, Dan; Stojaković, Miloš; Szabó, Tibor

    2014-01-01

    This text serves as a thorough introduction to the rapidly developing field of positional games. This area constitutes an important branch of combinatorics, whose aim it is to systematically develop an extensive mathematical basis for a variety of two-player perfect information games. These range from such popular games as Tic-Tac-Toe and Hex to purely abstract games played on graphs and hypergraphs. The subject of positional games is strongly related to several other branches of combinatorics such as Ramsey theory, extremal graph and set theory, and the probabilistic method. These notes cover a variety of topics in positional games, including both classical results and recent important developments. They are presented in an accessible way and are accompanied by exercises of varying difficulty, helping the reader to better understand the theory. The text will benefit both researchers and graduate students in combinatorics and adjacent fields.

  1. 78 FR 28895 - Sunshine Act Meetings

    Science.gov (United States)

    2013-05-16

    ... Corporate Secretary (Resolution 2013-XXX) 7. Public comment 8. Consider and act on other business 9... discuss a candidate for the position of Vice President of Legal Affairs, General Counsel, and Corporate... General Counsel's Certification that, in his [[Page 28896

  2. Researcher Positioning

    DEFF Research Database (Denmark)

    Khawaja, Iram; Mørck, Line Lerche

    2009-01-01

    involvement by the researcher, which challenges traditional perspectives onresearch and researcher positioning. A key point in this regard is the importance ofconstant awareness of and reflection on the multiple ways in which one's positioningas a researcher influences the research process. Studying the other...

  3. Position detector

    International Nuclear Information System (INIS)

    Hayakawa, Toshifumi.

    1985-01-01

    Purpose: To enable to detect the position of an moving object in a control rod position detector, stably in a digital manner at a high accuracy and free from the undesired effects of circumstantial conditions such as the reactor temperature. Constitution: Coils connected in parallel with each other are disposed along the passage of a moving object and variable resistors and relays are connected in series with each of the coils respectively. Light emitting diodes is connected in series with the contacts of the respective relays. The resistance value of the variable resistors are adjusted depending on the changes in the circumstantial conditions and temperature distribution upon carrying out the positional detection. When the object is inserted into a coils, the relevant relay is deenergized, by which the relay contacts are closed to light up the diode. In the same manner, as the object is successively inserted into the coils, the diodes are lighted-up successively thereby enabling highly accurate and stable positional detection in a digital manner, free from the undesired effects of the circumstantial conditions. (Horiuchi, T.)

  4. Plasma position control device

    International Nuclear Information System (INIS)

    Takase, Haruhiko.

    1987-01-01

    Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

  5. Selective mutism.

    Science.gov (United States)

    Hua, Alexandra; Major, Nili

    2016-02-01

    Selective mutism is a disorder in which an individual fails to speak in certain social situations though speaks normally in other settings. Most commonly, this disorder initially manifests when children fail to speak in school. Selective mutism results in significant social and academic impairment in those affected by it. This review will summarize the current understanding of selective mutism with regard to diagnosis, epidemiology, cause, prognosis, and treatment. Studies over the past 20 years have consistently demonstrated a strong relationship between selective mutism and anxiety, most notably social phobia. These findings have led to the recent reclassification of selective mutism as an anxiety disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition. In addition to anxiety, several other factors have been implicated in the development of selective mutism, including communication delays and immigration/bilingualism, adding to the complexity of the disorder. In the past few years, several randomized studies have supported the efficacy of psychosocial interventions based on a graduated exposure to situations requiring verbal communication. Less data are available regarding the use of pharmacologic treatment, though there are some studies that suggest a potential benefit. Selective mutism is a disorder that typically emerges in early childhood and is currently conceptualized as an anxiety disorder. The development of selective mutism appears to result from the interplay of a variety of genetic, temperamental, environmental, and developmental factors. Although little has been published about selective mutism in the general pediatric literature, pediatric clinicians are in a position to play an important role in the early diagnosis and treatment of this debilitating condition.

  6. Atomic Act amended

    International Nuclear Information System (INIS)

    Drabova, D.

    2002-01-01

    In the paper by the chairwoman of the Czech nuclear regulatory authority, the history of Czech nuclear legislation is outlined, the reasons for the amendment of the Atomic Act (Act No. 18/1997) are explained, and the amendments themselves are highlighted. The Act No. 13/2002 of 18 December 2001 is reproduced from the official Collection of Acts of the Czech Republic in the facsimile form. The following acts were thereby amended: Atomic Act No. 18/1997, Metrology Act No. 505/1990, Public Health Protection Act No. 258/2000, and Act No. 2/1969 on the Establishment of Ministries and Other Governmental Agencies of the Czech Republic. (P.A.)

  7. Maintaining positive

    OpenAIRE

    Gheorghe Gh. IONESCU; Adina Letitia NEGRUSA

    2004-01-01

    Maintaining positive work-force relationships includes in effective labor-management relations and making appropriate responses to current employee issues. Among the major current employee issues are protection from arbitrary dismissal, drug and alcohol abuse, privacy rights and family maters and they impact work. In our paper we discus two problems: first, the meanings of industrial democracy; second, the three principal operational concepts of industrial democracy (1) industrial democracy t...

  8. School Improvement Grants: Selected States Generally Awarded Funds Only to Eligible Schools. American Recovery and Reinvestment Act of 2009. Final Audit Report. ED-OIG/A05L0002

    Science.gov (United States)

    US Department of Education, 2012

    2012-01-01

    This final audit report covers the results of the review of five State educational agencies' monitoring plans and awarding processes for American Recovery and Reinvestment Act of 2009 and regular School Improvement Grants funds that the State educational agencies awarded for fiscal year 2009 (for use during school year 2010-2011). The objectives…

  9. Predictive value and clinical utility of centrally assessed ER, PgR, and Ki-67 to select adjuvant endocrine therapy for premenopausal women with hormone receptor-positive, HER2-negative early breast cancer: TEXT and SOFT trials.

    Science.gov (United States)

    Regan, Meredith M; Pagani, Olivia; Francis, Prudence A; Fleming, Gini F; Walley, Barbara A; Kammler, Roswitha; Dell'Orto, Patrizia; Russo, Leila; Szőke, János; Doimi, Franco; Villani, Laura; Pizzolitto, Stefano; Öhlschlegel, Christian; Sessa, Fausto; Peg Cámara, Vicente; Rodríguez Peralto, José Luis; MacGrogan, Gaëtan; Colleoni, Marco; Goldhirsch, Aron; Price, Karen N; Coates, Alan S; Gelber, Richard D; Viale, Giuseppe

    2015-11-01

    The SOFT and TEXT randomized phase III trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive (HR+) early breast cancer. We investigated the prognostic and predictive value of centrally assessed levels of estrogen receptor (ER), progesterone receptor (PgR), and Ki-67 expression in women with HER2-negative disease. Of 5707 women enrolled, 4115 with HER2-negative (HR+/HER2-) disease had ER, PgR, and Ki-67 centrally assessed by immunohistochemistry. Breast cancer-free interval (BCFI) was defined from randomization to first invasive local, regional, or distant recurrence or contralateral breast cancer. The prognostic and predictive values of ER, PgR and Ki-67 expression levels were assessed using Cox modeling and STEPP methodology. In this HR+/HER2- population, the median ER, PgR, and Ki-67 expressions were 95, 90, and 18 % immunostained cells. As most patients had strongly ER-positive tumors, the predictive value of ER levels could not be investigated. Lower PgR and higher Ki-67 expression were associated with reduced BCFI. There was no consistent evidence of heterogeneity of the relative treatment effects according to PgR or Ki-67 expression levels, though there was a greater 5-year absolute benefit of exemestane + ovarian function suppression (OFS) versus tamoxifen with or without OFS at lower levels of PgR and higher levels of Ki-67. Women with poor prognostic features of low PgR and/or high Ki-67 have greater absolute benefit from exemestane + OFS versus tamoxifen + OFS or tamoxifen alone, but individually PgR and Ki-67 are of limited predictive value for selecting adjuvant endocrine therapy for premenopausal women with HR+/HER2- early breast cancer.

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Therapeutics Lab Developing New Treatments The CF Foundation offers a number of resources for learning about clinical ... her father: Demonstrate and discuss common ACT therapies Offer their tips for fitting ACTs into daily life ...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Treatments and Therapies Airway Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. ... or caregiver. Older kids and adults can choose ACTs that they can do on their own. Share ...

  12. Nuclear Installations Act 1965

    International Nuclear Information System (INIS)

    1965-01-01

    This Act governs all activities related to nuclear installations in the United Kingdom. It provides for the licensing procedure for nuclear installations, the duties of licensees, the competent authorities and carriers of nuclear material in respect of nuclear occurrences, as well as for the system of third party liability and compensation for nuclear damage. The Act repeals the Nuclear Installations (Licensing and Insurance) Act 1959 and the Nuclear Installations (Amendment Act) 1965 except for its Section 17(2). (NEA) [fr

  13. 78 FR 25414 - Privacy Act of 1974, System of Records

    Science.gov (United States)

    2013-05-01

    ... communication cables; facility access authorizations/restrictions; photographs, fingerprints; financial records... Reinvestigating Individuals in Positions of Public Trust; and the Intelligence Reform and Terrorism Prevention Act...

  14. Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy.

    Science.gov (United States)

    Fitz, Nicholas F; Gibbs, Robert B; Johnson, David A

    2008-12-16

    This study tested the hypothesis that septal cholinergic lesions impair acquisition of a delayed matching to position (DMP) T-maze task in male rats by affecting learning strategy. Rats received either the selective cholinergic immunotoxin, 192 IgG-saporin (SAP) or artificial cerebrospinal fluid directly into the medial septum. Two weeks later, animals were trained to acquire the DMP task. SAP-treated rats took significantly longer to acquire the task than corresponding controls. Both SAP-treated and control rats adopted a persistent turn and utilized a response strategy during early periods of training. By the time rats reached criterion the persistent turn was no longer evident, and all rats had shifted to an allocentric strategy, i.e., were relying on extramaze cues to a significant degree. During the acquisition period, SAP-treated rats spent significantly more days showing a persistent turn and using a response strategy than corresponding controls. The added time spent using a response strategy accounted entirely for the added days required to reach criterion among the SAP-treated rats. This suggests that the principal mechanism by which septal cholinergic lesions impair DMP acquisition in male rats is by increasing the predisposition to use a response vs. a place strategy, thereby affecting the ability to switch from one strategy to another.

  15. Acceptance and Commitment Therapy (ACT) as a Career Counselling Strategy

    Science.gov (United States)

    Hoare, P. Nancey; McIlveen, Peter; Hamilton, Nadine

    2012-01-01

    Acceptance and commitment therapy (ACT) has potential to contribute to career counselling. In this paper, the theoretical tenets of ACT and a selection of its counselling techniques are overviewed along with a descriptive case vignette. There is limited empirical research into ACT's application in career counselling. Accordingly, a research agenda…

  16. Jasmonates act positively in adventitious root formation in petunia cuttings

    OpenAIRE

    Lischweski, Sandra; Muchow, Anne; Guthörl, Daniela; Hause, Bettina

    2015-01-01

    Background Petunia is a model to study the process of adventitious root (AR) formation on leafy cuttings. Excision of cuttings leads to a transient increase in jasmonates, which is regarded as an early, transient and critical event for rooting. Here, the role of jasmonates in AR formation on petunia cuttings has been studied by a reverse genetic approach. Results To reduce the endogenous levels of jasmonates, transgenic plants were generated expressing a Petunia hybrida ALLENE OXIDE CYCLASE (...

  17. Enhanced antiadhesive properties of chitosan/hyaluronic acid polyelectrolyte multilayers driven by thermal annealing: Low adherence for mammalian cells and selective decrease in adhesion for Gram-positive bacteria.

    Science.gov (United States)

    Muzzio, Nicolás E; Pasquale, Miguel A; Diamanti, Eleftheria; Gregurec, Danijela; Moro, Marta Martinez; Azzaroni, Omar; Moya, Sergio E

    2017-11-01

    The development of antifouling coatings with restricted cell and bacteria adherence is fundamental for many biomedical applications. A strategy for the fabrication of antifouling coatings based on the layer-by-layer assembly and thermal annealing is presented. Polyelectrolyte multilayers (PEMs) assembled from chitosan and hyaluronic acid were thermally annealed in an oven at 37°C for 72h. The effect of annealing on the PEM properties and topography was studied by atomic force microscopy, ζ-potential, circular dichroism and contact angle measurements. Cell adherence on PEMs before and after annealing was evaluated by measuring the cell spreading area and aspect ratio for the A549 epithelial, BHK kidney fibroblast, C2C12 myoblast and MC-3T3-E1 osteoblast cell lines. Chitosan/hyaluronic acid PEMs show a low cell adherence that decreases with the thermal annealing, as observed from the reduction in the average cell spreading area and more rounded cell morphology. The adhesion of S. aureus (Gram-positive) and E. coli (Gram-negative) bacteria strains was quantified by optical microscopy, counting the number of colony-forming units and measuring the light scattering of bacteria suspension after detachment from the PEM surface. A 20% decrease in bacteria adhesion was selectively observed in the S. aureus strain after annealing. The changes in mammalian cell and bacteria adhesion correlate with the changes in topography of the chitosan/hyaluronic PEMs from a rough fibrillar 3D structure to a smoother and planar surface after thermal annealing. Copyright © 2017. Published by Elsevier B.V.

  18. Positioning and applications

    Directory of Open Access Journals (Sweden)

    Rogowski Jerzy B.

    2015-12-01

    Full Text Available The paper presents national report of Poland for IAG on positioning and applications. The selected research presented was carried out at leading Polish research institutions and concern precise multi-GNSS satellite positioning - relative and absolute - and also GNSS-based ionosphere and troposphere modelling and studies. The research resulted in noticeable advancements in these subjects confirmed by the development of new algorithms and methods. New and improved methods of precise GNSS positioning were developed, and also GNSS metrology was studied. New advanced troposphere models were presented and tested. In particular, these models allowed testing IPW variability on regional and global scales. Also, new regional ionosphere monitoring web-based services were developed and launched.

  19. Bronchodilator treatment of stable COPD: long-acting anticholinergics

    Directory of Open Access Journals (Sweden)

    W. Vincken

    2005-09-01

    Full Text Available Since airflow obstruction in chronic obstructive pulmonary disease (COPD is to some extent reversible, bronchodilators play an important role in the maintenance treatment of COPD the more they reduce hyperinflation and, as a result, improve dyspnoea and exercise capacity. Since parasympathetic activity is the dominant reversible component of airflow obstruction in COPD, inhaled short-acting anticholinergic agents (SAAC, in particular ipratropium, became an efficient and safe first-line treatment, especially when combined with a short-acting beta2-adrenergic receptor agonist. Even better results were obtained when combining the SAAC ipratropium to a long-acting beta2-adrenergic receptor agonist (LABA, once they became available. Recently, tiotropium bromide, the first of a new class of selective and long-acting anticholinergic agents was introduced for once-daily maintenance treatment of COPD patients. Several large long-term randomised clinical trials comparing tiotropium to placebo as well as to the SAAC ipratropium and the LABA salmeterol, have confirmed the long-acting and superior bronchodilator effect of tiotropium without any evidence of drug tolerance developing. These studies also have clearly demonstrated that tiotropium positively affects several other important health outcomes, such as dyspnoea sensation, exercise capacity, utilisation of rescue bronchodilators, health-related quality of life, COPD exacerbations and hospitalisations because of exacerbations. The improvement in these real-life outcomes appears related to the reduction in both static and dynamic hyperinflation. In all these studies, tiotropium was well tolerated and safe; the only relevant side-effect encountered being dry mouth, usually mild and often transitory. Finally, it has been shown that the combination of tiotropium with a LABA affords superior bronchodilatation than both agents alone, indicating that both classes of long-acting bronchodilators should be

  20. Radioactive Substances Act 1960

    International Nuclear Information System (INIS)

    1960-01-01

    This Act regulates the keeping and use of radioactive material and makes provision for the disposal and storage of radioactive waste in the United Kingdom. It provides for a licensing system for such activities and for exemptions therefrom, in particular as concerns the United Kingdom Atomic Energy Authority. The Act repeals Section 4(5) of the Atomic Energy Authority Act, 1954 which made temporary provision for discharge of waste on or from premises occupied by the Authority. (NEA) [fr

  1. Learning dialog act processing

    OpenAIRE

    Wermter, Stefan; Löchel, Matthias

    1996-01-01

    In this paper we describe a new approach for learning dialog act processing. In this approach we integrate a symbolic semantic segmentation parser with a learning dialog act network. In order to support the unforeseeable errors and variations of spoken language we have concentrated on robust data-driven learning. This approach already compares favorably with the statistical average plausibility method, produces a segmentation and dialog act assignment for all utterances in a robust manner,...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory ...

  3. Radiological Protection Act 1970

    International Nuclear Information System (INIS)

    1970-01-01

    This Act provides for the establishment of a Radiological Protection Board to undertake research and advise on protection from radiation hazards. Its functions include provision of advice to Government departments with responsibilities in relation to protection of sectors of the community or the community as a whole against the hazards of ionizing radiation. The Act, which lays down that the Board shall replace certain departments concerned with radiation protection, repeals several Sections of the Radioactive Substances Act 1948 and the Science and Technology Act 1965. (NEA) [fr

  4. 25 CFR 700.33 - Act (The Act).

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Act (The Act). 700.33 Section 700.33 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.33 Act (The Act). (a) The Act. The Act is Pub. L. 93-531, (88 Stat...

  5. Challenges (Obstacles in Reaching Leadership Positions – Experiences of Women Professors at Novi Sad University Serbia

    Directory of Open Access Journals (Sweden)

    Andrić Marijana Mišić

    2017-12-01

    Full Text Available Underrepresentation of women in leadership positions in universities is a phenomenon present in most countries of the world, with some significant differences. In our work we focused on obstacles that women professors in Novi Sad University (Serbia faced in reaching leadership positions. Analysis is based on qualitative research using a semi structured interview, statistical data and selected secondary sources. Obstacles, mentorship and networking have been researched from an idiographic perspective (reflection and the personal experience of the women at Novi Sad University. Results indicate a significant underrepresentation of women in leadership positions at Novi Sad University. Findings point to a general pattern: the more power and authority the leadership position holds, the scarcer the number of women participating in it. According to interviewees’ statements the patriarchal value system makes the leadership positions difficult to attain for women. Interview analysis also suggests additional limiting factors, such as lack of mentorship and inadequate networking, acting as inhibitors in reaching leadership positions.

  6. Fast-acting valve actuator

    Science.gov (United States)

    Cho, Nakwon

    1980-01-01

    A fast-acting valve actuator utilizes a spring driven pneumatically loaded piston to drive a valve gate. Rapid exhaust of pressurized gas from the pneumatically loaded side of the piston facilitates an extremely rapid piston stroke. A flexible selector diaphragm opens and closes an exhaust port in response to pressure differentials created by energizing and de-energizing a solenoid which controls the pneumatic input to the actuator as well as selectively providing a venting action to one side of the selector diaphragm.

  7. Marine Mammal Protection Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Marine Mammal Protection Act (MMPA or Act) prohibits, with certain exceptions, the "take" of marine mammals in U.S. waters and by U.S. citizens on the high seas,...

  8. Collective speech acts

    NARCIS (Netherlands)

    Meijers, A.W.M.; Tsohatzidis, S.L.

    2007-01-01

    From its early development in the 1960s, speech act theory always had an individualistic orientation. It focused exclusively on speech acts performed by individual agents. Paradigmatic examples are ‘I promise that p’, ‘I order that p’, and ‘I declare that p’. There is a single speaker and a single

  9. Americans with Disabilities Act.

    Science.gov (United States)

    Kaesberg, Mary Ann; Murray, Kenneth T.

    1994-01-01

    Presents a 35-item checklist of practical activities for school district compliance with the Americans with Disabilities Act (ADA). The checklist is based on ADA statutes, other civil rights legislation and litigation, as well as pertinent regulations and the legislative history of the act contained in the Congressional Record. (MLF)

  10. Radiation emitting devices act

    International Nuclear Information System (INIS)

    1970-01-01

    This Act, entitled the Radiation Emitting Devices Act, is concerned with the sale and importation of radiation emitting devices. Laws relating to the sale, lease or import, labelling, advertising, packaging, safety standards and inspection of these devices are listed as well as penalties for any person who is convicted of breaking these laws

  11. Nuclear Installations Act 1969

    International Nuclear Information System (INIS)

    1969-01-01

    The purpose of this Act is to amend the Nuclear Installations Act 1965 to bring it into full compliance with the international conventions on nuclear third party liability to which the United Kingdom is a Signatory, namely, the Paris Convention, the Brussels Supplementary Convention and the Vienna Convention. (NEA) [fr

  12. Promiscuity, sexual selection, and genetic diversity: a reply to Spurgin.

    Science.gov (United States)

    Lifjeld, Jan T; Gohli, Jostein; Johnsen, Arild

    2013-10-01

    We recently reported a positive association between female promiscuity and genetic diversity across passerine birds, and launched the hypothesis that female promiscuity acts as a balancing selection, pressure maintaining genetic diversity in populations (Gohli et al.2013). Spurgin (2013) questions both our analyses and interpretations. While we agree that the hypothesis needs more comprehensive empirical testing, we find his specific points of criticism unjustified. In a more general perspective, we call for a more explicit recognition of female mating preferences as mechanisms of selection in population genetics theory. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  13. Homosexual Cohabitees Act, 18 June 1987.

    Science.gov (United States)

    1989-01-01

    The purpose of this Act is to place homosexual cohabitees in the same legal position as heterosexual cohabitees. It provides that if 2 persons are living together in a homosexual relationship, the following legal provisions relating to cohabitation shall apply to them: 1) the Cohabitees (Joint Homes) Act (1987:232), 2) the Inheritance Code, 3) the Real Property Code, 4) Chapter 10, section 9, of the Code of Judicial Procedure, 5) Chapter 4, section 19, 1st paragraph, of the Code of Execution, 6) section 19, 1st paragraph, section 35, subsection 4, and point 2a, 7th paragraph, of the regulations relating to Section 36 of the Municipal Tax Act (1928:370), 7) the Inheritance and Gift Taxes Act (1941:416), 8) Section 6 of the Court Procedures (Miscellaneous Business) Act (1946:807), 9) the Tenant Owner Act (1971:479), 10) section 10 of the Legal Aid Act (1972:429), and 11) the Notice to Unknown Creditors Act (1981:131).

  14. The effect of sexual selection on adaptation and extinction under increasing temperatures.

    Science.gov (United States)

    Parrett, Jonathan M; Knell, Robert J

    2018-04-25

    Strong sexual selection has been reported to both enhance and hinder the adaptive capacity and persistence of populations when exposed to novel environments. Consequently, how sexual selection influences population adaption and persistence under stress remains widely debated. Here, we present two empirical investigations of the fitness consequences of sexual selection on populations of the Indian meal moth, Plodia interpunctella, exposed to stable or gradually increasing temperatures. When faced with increasing temperatures, strong sexual selection was associated with both increased fecundity and offspring survival compared with populations experiencing weak sexual selection, suggesting sexual selection acts to drive adaptive evolution by favouring beneficial alleles. Strong sexual selection did not, however, delay extinction when the temperature became excessively high. By manipulating individuals' mating opportunities during fitness assays, we were able to assess the effect of multiple mating independently from the effect of population-level sexual selection, and found that polyandry has a positive effect on both fecundity and offspring survival under increasing temperatures in those populations evolving with weak sexual selection. Within stable temperatures, there were some benefits from strong sexual selection but these were not consistent across the entire experiment, possibly reflecting changing costs and benefits of sexual selection under stabilizing and directional selection. These results indicate that sexual selection can provide a buffer against climate change and increase adaptation rates within a continuously changing environment. These positive effects of sexual selection may, however, be too small to protect populations and delay extinction when environmental changes are relatively rapid. © 2018 The Author(s).

  15. The Radiation Protection Act

    International Nuclear Information System (INIS)

    Persson, L.

    1989-01-01

    The new Radiation Protection Act (1988:220) entered into force in Sweden on July 1st, 1988. This book presents the Act as well as certain regulations connected to it. As previously, the main responsibility for public radiation protection will rest with one central radiation protection authority. According to the 1988 Act, the general obligations with regard to radiation protection will place a greater responsibility than in the past on persons carrying out activities involving radiation. Under the act, it is possible to adjust the licensing and supervisory procedures to the level of danger of the radiation source and the need for adequate competence, etc. The Act recognises standardised approval procedures combined with technical regulations for areas where the risks are well known. The Act contains several rules providing for more effective supervision. The supervising authority may in particular decide on the necessary regulations and prohibitions for each individual case. The possibilities of using penal provisions have been extended and a rule on the mandatory execution of orders has been introduced. The Ordinance on Radiation Protection (1988:293) designates the National Institute of Radiation Protection (SSI) as the central authority referred to in the Radiation Protection Act. The book also gives a historic review of radiation protection laws in Sweden, lists regulations issued by SSI and presents explanations of radiation effects and international norms in the area. (author)

  16. Canada's Clean Air Act

    International Nuclear Information System (INIS)

    2006-01-01

    This paper provided an outline of Canada's Clean Air Act and examined some of the regulatory changes that will occur as a result of its implementation. The Act is being introduced to strengthen the legislative basis for taking action on reducing air pollution and GHGs, and will allow the government to regulate both indoor and outdoor air pollutants and GHGs. The Act will require the Ministers of the Environment and Health to establish national air quality objectives, as well as to monitor and report on their attainment. The Canadian Environmental Protection Act will be amended to enable the government to regulate the blending of fuels and their components. The Motor Vehicle Fuel Consumption Standards Act will also be amended to enhance the government's authority to regulate vehicle fuel efficiency. The Energy Efficiency Act will also be expanded to allow the government to set energy efficiency standards and labelling requirements for a wider range of consumer and commercial products. The Act will commit to short, medium and long-term industrial air pollution targets. Regulations will be proposed for emissions from industry; on-road and off-road vehicles and engines; and consumer and commercial products. It was concluded that the Government of Canada will continue to consult with provinces, territories, industries and Canadians to set and reach targets for the reduction of both indoor and outdoor air pollutants and GHG emissions. 6 figs

  17. Identification of physicochemical selective pressure on protein encoding nucleotide sequences

    Directory of Open Access Journals (Sweden)

    Sainudiin Raazesh

    2006-03-01

    Full Text Available Abstract Background Statistical methods for identifying positively selected sites in protein coding regions are one of the most commonly used tools in evolutionary bioinformatics. However, they have been limited by not taking the physiochemical properties of amino acids into account. Results We develop a new codon-based likelihood model for detecting site-specific selection pressures acting on specific physicochemical properties. Nonsynonymous substitutions are divided into substitutions that differ with respect to the physicochemical properties of interest, and those that do not. The substitution rates of these two types of changes, relative to the synonymous substitution rate, are then described by two parameters, γ and ω respectively. The new model allows us to perform likelihood ratio tests for positive selection acting on specific physicochemical properties of interest. The new method is first used to analyze simulated data and is shown to have good power and accuracy in detecting physicochemical selective pressure. We then re-analyze data from the class-I alleles of the human Major Histocompatibility Complex (MHC and from the abalone sperm lysine. Conclusion Our new method allows a more flexible framework to identify selection pressure on particular physicochemical properties.

  18. The Energy Act 1983

    International Nuclear Information System (INIS)

    1983-01-01

    Part II of This Act came into force on 1 September 1983 and is concerned with nuclear installations. Its main purpose is to amend the Nuclear Installations Act 1965 to give effect to the provisions of two Protocols amending the Paris Convention on nuclear third party liability and the Brussels Convention Supplementary to the Paris Convention respectively. The principal effect of these modifications is to increase the sums available to meet claims for nuclear damage. The United Kingdom is a Party to both Conventions and the provisions of the 1983 Act will enable it to ratify the Protocols. (NEA) [fr

  19. 75 FR 63703 - Privacy Act of 1974; Privacy Act Regulation

    Science.gov (United States)

    2010-10-18

    ... FEDERAL RESERVE SYSTEM 12 CFR Part 261a [Docket No. R-1313] Privacy Act of 1974; Privacy Act... implementing the Privacy Act of 1974 (Privacy Act). The primary changes concern the waiver of copying fees... records under the Privacy Act; the amendment of special procedures for the release of medical records to...

  20. Abandoned Shipwreck Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data represents the extent of the Abandoned Shipwreck Act (ASA). The ASA allows states to manage a broad range of resources within submerged lands, including...

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy ... the value of tapping into the expertise that only people with CF and their families have. We invite you to share insights to ...

  2. Energy Policy Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Energy Policy Act (EPA) addresses energy production in the United States, including: (1) energy efficiency; (2) renewable energy; (3) oil and gas; (4) coal; (5)...

  3. ACTS – SUCCESS STORY

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. ACTS – SUCCESS STORY. Totally 103 experiments were conducted and the programme succeeded in the areas. Medicine; Education; Defence; Emergency Response; Maritime and Aeronautical Mobile Communications; Science and Astronomy.

  4. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... There are different ways to clear your airways. Most are easy to do. Infants and toddlers will ... best ACT is the one that you are most likely to perform as part of your daily ...

  5. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ... Offer their tips for fitting ACTs into daily life Airway Clearance Techniques | Webcast ... Facebook Twitter ...

  6. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements ...

  7. Clean Water Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — These data represent geographic terms used within the Clean Water Act (CWA). The CWA establishes the basic structure for regulating the addition of pollutants...

  8. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... toddlers will need help from a parent or caregiver. Older kids and adults can choose ACTs that ... into the smaller airways to attack bacteria. Choose What's Best for You Your respiratory therapist or another ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... that help thin and move the mucus, and antibiotics. Bronchodilators should be inhaled before you start ACTs. This medication helps to widen your airways (bronchi) by relaxing the ...

  10. Endangered Species Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The purpose of the Endangered Species Act (ESA) is to protect and recover imperiled species and the ecosystems upon which they depend. The U.S. Fish and Wildlife...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements ... on their own. Share Facebook Twitter Email More options Print Share Facebook Twitter Email Print Permalink All ...

  12. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... 3-D Structure Consortium CFTR Folding Consortium Epithelial Stem Cell Consortium Mucociliary Clearance Consortium SUCCESS WITH THERAPIES RESEARCH ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from ...

  13. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... today. ANNUAL FUND Become a Corporate Supporter Cause Marketing Make a Charitable Gift Our Corporate Supporters Workplace ... Clearance Airway Clearance Techniques (ACTs) There are different ways to clear your airways. Most are easy to ...

  14. Marine Pollution Prevention Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Marine Pollution Prevention Act of 2008 implements the International Convention for the Prevention of Pollution from Ships, including related Protocols (MARPOL)...

  15. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... CF Community in Health Care Reform Milestones in Health Care Reform How Tax Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory ...

  16. Preventive Radiation Protection Act

    International Nuclear Information System (INIS)

    Roewer, H.

    1988-01-01

    The commentary is intended to contribute to protection of the population by a practice-oriented discussion and explanation of questions arising in connection with the Preventive Radiation Protection Act. Leaving aside discussions about abandonment of nuclear power, or criticism from any legal point of view, the commentary adopts the practical approach that accepts, and tries to help implementing, the act as it is. It is a guide for readers who are not experts in the law and gives a line of orientation by means of explanations and sometimes by citations from other acts (in footnotes). The commentary also presents the EURATOM Directive No. 3954/87 dated 22 December 1987, the EC Directive No. 3955/87 dated 22 December 1987, and the EC Directive No. 1983/88 dated 5 July 1988. A tabular survey shows the system of duties and competences defined by the Preventive Radiation Protection Act. (RST) [de

  17. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Contraception and Protection How Does CF Affect the Female Reproductive System? How Does CF Affect the Male ... Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements ...

  18. ACT250 Districts

    Data.gov (United States)

    Vermont Center for Geographic Information — The ACT 250 Districts layer is part of a larger dataset that contains administrative boundaries for Vermont's Agency of Natural Resources. The dataset includes...

  19. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from airway walls. See how different airway clearance techniques work to help you clear the thick, sticky mucus ...

  20. Acts of Research

    DEFF Research Database (Denmark)

    Nelund, Sidsel

    place mostly in seminars and articles, in which knowledge is often discussed as an intrinsic quality of the artwork. Acts of Research, however, is devoted to studying the rise of knowledge production in contemporary art from the perspective of artistic, curatorial and educational research...... described as knowledge producers and exhibitions and art works as instances of knowledge production. Acts of Research: Knowledge Production in Contemporary Arts between Knowledge Economy and Critical Practices analyses this development. The academic discussion of knowledge production in the arts has taken...... with an awareness of larger political, economic, geographical and art-related aspects. The concept of ‘acts of research’ is suggested as a way to understand knowledge production as a creative act in which research carried out in relation to a specific material challenges and resists the protocols of conventional...

  1. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Congressional Cystic Fibrosis Caucus Our Policy Agenda Policy Principles SIGN UP FOR ADVOCACY ACTION ALERTS Community We ... options Print Share Facebook Twitter Email Print Permalink All ACTs involve coughing or huffing . Many of them ...

  2. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... How Does CF Affect the Male Reproductive System? Sex and CF: Some Practical Advice Family Planning and ... need help from a parent or caregiver. Older kids and adults can choose ACTs that they can ...

  3. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... FOR ADVOCACY ACTION ALERTS Community We recognize the value of tapping into the expertise that only people ... ACTs involve coughing or huffing . Many of them use percussion (clapping) or vibration to loosen mucus from ...

  4. National Environmental Policy Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The National Environmental Policy Act (NEPA) was the first major environmental law in the United States and established national environmental policies for the...

  5. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... Reform Could Impact People With CF The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements ... Board of Trustees Our Leadership Careers Reports and Financials Contact Us Governance and Policies What is CF? ...

  6. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... own. Share Facebook Twitter Email More options Print Share Facebook Twitter Email Print Permalink All ACTs involve ... CF Care Team Research About Our Research Developing New Treatments Researcher Resources Assistance Services Find Resources: CF ...

  7. Affordable Care Act (ACA)

    Data.gov (United States)

    Social Security Administration — The Affordable Care Act (ACA) is a federal statute enacted with a goal of increasing the quality and affordability of health insurance. Through a web service, CMS...

  8. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory Comments Congressional Cystic Fibrosis Caucus Our Policy Agenda Policy Principles SIGN UP FOR ADVOCACY ACTION ...

  9. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... people with cystic fibrosis so that they make smart decisions about CF-related research, treatment, and access ... The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory ...

  10. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... What to Consider Regarding a Lung Transplant Medications Antibiotics Bronchodilators CFTR Modulator Therapies Mucus Thinners Nebulizer Care ... that help thin and move the mucus, and antibiotics. Bronchodilators should be inhaled before you start ACTs. ...

  11. Airway Clearance Techniques (ACTs)

    Medline Plus

    Full Text Available ... resources you need to continuously build upon this work. Awards and Grants Career Development Awards Research Awards ... The Preserving Employee Wellness Programs Act Our Advocacy Work Advocacy Achievements Advocacy News Briefings, Testimonies, and Regulatory ...

  12. Exploring primary care activities in ACT teams.

    Science.gov (United States)

    Vanderlip, Erik R; Williams, Nancy A; Fiedorowicz, Jess G; Katon, Wayne

    2014-05-01

    People with serious mental illness often receive inadequate primary and preventive care services. Federal healthcare reform endorses team-based care that provides high quality primary and preventive care to at risk populations. Assertive community treatment (ACT) teams offer a proven, standardized treatment approach effective in improving mental health outcomes for the seriously mentally ill. Much is known about the effectiveness of ACT teams in improving mental health outcomes, but the degree to which medical care needs are addressed is not established. The purpose of this study was to explore the extent to which ACT teams address the physical health of the population they serve. ACT team leaders were invited to complete an anonymous, web-based survey to explore attitudes and activities involving the primary care needs of their clients. Information was collected regarding the use of health screening tools, physical health assessments, provision of medical care and collaboration with primary care systems. Data was analyzed from 127 team leaders across the country, of which 55 completed the entire survey. Nearly every ACT team leader believed ACT teams have a role in identifying and managing the medical co-morbidities of their clientele. ACT teams report participation in many primary care activities. ACT teams are providing a substantial amount of primary and preventive services to their population. The survey suggests standardization of physical health identification, management or referral processes within ACT teams may result in improved quality of medical care. ACT teams are in a unique position to improve physical health care by virtue of having medically trained staff and frequent, close contact with their clients.

  13. The Corporations Act 2001

    OpenAIRE

    Bostock, Tom

    2002-01-01

    The author outlines reforms made in Australia in the area of company law with an analysis of the Corporations Act 2001, which along with the Australian Securities and Investments Commission Act 2001 comprises Corporations legislation in Australia. Article by Tom Bostock (a partner in the law firm Mallesons Stephen Jaques, Melbourne, Australia). Published in Amicus Curiae - Journal of the Institute of Advanced Legal Studies and its Society for Advanced Legal Studies. The Journal is produced by...

  14. Selfing ability and dispersal are positively related, but not affected by range position: a multispecies study on southern African Asteraceae.

    Science.gov (United States)

    de Waal, C; Rodger, J G; Anderson, B; Ellis, A G

    2014-05-01

    Dispersal and breeding system traits are thought to affect colonization success. As species have attained their present distribution ranges through colonization, these traits may vary geographically. Although several theories predict associations between dispersal ability, selfing ability and the relative position of a population within its geographic range, there is little theoretical or empirical consensus on exactly how these three variables are related. We investigated relationships between dispersal ability, selfing ability and range position across 28 populations of 13 annual, wind-dispersed Asteraceae species from the Namaqualand region of South Africa. Controlling for phylogeny, relative dispersal ability--assessed from vertical fall time of fruits--was positively related to an index of autofertility--determined from hand-pollination experiments. These findings support the existence of two discrete syndromes: high selfing ability associated with good dispersal and obligate outcrossing associated with lower dispersal ability. This is consistent with the hypothesis that selection for colonization success drives the evolution of an association between these traits. However, no general effect of range position on dispersal or breeding system traits was evident. This suggests selection on both breeding system and dispersal traits acts consistently across distribution ranges. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  15. Acting green elicits a literal warm glow

    Science.gov (United States)

    Taufik, Danny; Bolderdijk, Jan Willem; Steg, Linda

    2015-01-01

    Environmental policies are often based on the assumption that people only act environmentally friendly if some extrinsic reward is implicated, usually money. We argue that people might also be motivated by intrinsic rewards: doing the right thing (such as acting environmentally friendly) elicits psychological rewards in the form of positive feelings, a phenomenon known as warm glow. Given the fact that people's psychological state may affect their thermal state, we expected that this warm glow could express itself quite literally: people who act environmentally friendly may perceive the temperature to be higher. In two studies, we found that people who learned they acted environmentally friendly perceived a higher temperature than people who learned they acted environmentally unfriendly. The underlying psychological mechanism pertains to the self-concept: learning you acted environmentally friendly signals to yourself that you are a good person. Together, our studies show that acting environmentally friendly can be psychologically rewarding, suggesting that appealing to intrinsic rewards can be an alternative way to encourage pro-environmental actions.

  16. Natural selection and the distribution of identity-by-descent in the human genome

    DEFF Research Database (Denmark)

    Albrechtsen, Anders; Moltke, Ida; Nielsen, Rasmus

    2010-01-01

    There has recently been considerable interest in detecting natural selection in the human genome. Selection will usually tend to increase identity-by-descent (IBD) among individuals in a population, and many methods for detecting recent and ongoing positive selection indirectly take advantage...... of this. In this article we show that excess IBD sharing is a general property of natural selection and we show that this fact makes it possible to detect several types of selection including a type that is otherwise difficult to detect: selection acting on standing genetic variation. Motivated by this......, we use a recently developed method for identifying IBD sharing among individuals from genome-wide data to scan populations from the new HapMap phase 3 project for regions with excess IBD sharing in order to identify regions in the human genome that have been under strong, very recent selection...

  17. EDITORIAL: Nanotechnological selection Nanotechnological selection

    Science.gov (United States)

    Demming, Anna

    2013-01-01

    At the nanoscale measures can move from a mass-scale analogue calibration to counters of discrete units. The shift redefines the possible levels of control that can be achieved in a system if adequate selectivity can be imposed. As an example as ionic substances pass through nanoscale pores, the quantity of ions is low enough that the pore can contain either negative or positive ions. Yet precise control over this selectivity still raises difficulties. In this issue researchers address the challenge of how to regulate the ionic selectivity of negative and positive charges with the use of an external charge. The approach may be useful for controlling the behaviour, properties and chemical composition of liquids and has possible technical applications for nanofluidic field effect transistors [1]. Selectivity is a critical advantage in the administration of drugs. Nanoparticles functionalized with targeting moieties can allow delivery of anti-cancer drugs to tumour cells, whilst avoiding healthy cells and hence reducing some of the debilitating side effects of cancer treatments [2]. Researchers in Belarus and the US developed a new theranostic approach—combining therapy and diagnosis—to support the evident benefits of cellular selectivity that can be achieved when nanoparticles are applied in medicine [3]. Their process uses nanobubbles of photothermal vapour, referred to as plasmonic nanobubbles, generated by plasmonic excitations in gold nanoparticles conjugated to diagnosis-specific antibodies. The intracellular plasmonic nanobubbles are controlled by laser fluence so that the response can be tuned in individual living cells. Lower fluence allows non-invasive high-sensitive imaging for diagnosis and higher fluence can disrupt the cellular membrane for treatments. The selective response of carbon nanotubes to different gases has leant them to be used within various different types of sensors, as summarized in a review by researchers at the University of

  18. 75 FR 8682 - Sunshine Act Meetings

    Science.gov (United States)

    2010-02-25

    ... futures and options in the precious and base metals markets, and to consider Federal position limits in... precious and base metals markets and related hedge exemptions on regulated futures exchanges, derivatives... COMMODITY FUTURES TRADING COMMISSION Sunshine Act Meetings Agency Holding the Meeting: Commodity...

  19. Outer Continental Shelf Lands Act

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data represents geographic terms used within the Outer Continental Shelf Lands Act (OCSLA or Act). The Act defines the United States outer continental shelf...

  20. No 592 - Radiation Act

    International Nuclear Information System (INIS)

    1991-01-01

    This Act will enter into force on 1 January 1992. The scope of the Act is extensive as, in addition to ionizing radiation, it will also apply to activities involving exposure to natural radiation and non-ionizing radiation. Its purpose is to prevent and restrict harmful effects to health resulting from radiation. The basic principles of the Act are that the practice involving radiation should be justified; radiation protection should be optimized; and radiation doses should be as low as reasonably achievable. Licensed organisations using radiation will be responsible for the safety of the activity involving exposure to radiation and for having available the appropriate expertise to this effect. The required so-called safety licence provides the regulatory control to ensure that radiation is used sensibly, that the equipment and shields are technically acceptable and the operating personnel is competent, and that the radioactive waste is dealt with appropriately. The Radiation Act will also apply to nuclear activities within the scope of the 1987 Nuclear Energy Act [fr

  1. Benign positional vertigo

    Science.gov (United States)

    Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional vertigo (BPPV). It is caused by a problem in the inner ear. ...

  2. Acting autonomously versus not acting heteronomously

    NARCIS (Netherlands)

    van Hees, M.V.B.P.M

    This paper presents a formal framework that purports to capture some aspects of Kant's theory of freedom. In particular, we argue that the analysis sheds further light on Kant's distinction between a negative and a positive concept of freedom. The paper shows that the two concepts are not

  3. Acting Autonomously Versus Not Acting Heteronomously

    NARCIS (Netherlands)

    Van Hees, Martin

    This paper presents a formal framework that purports to capture some aspects of Kant's theory of freedom. In particular, we argue that the analysis sheds further light on Kant's distinction between a negative and a positive concept of freedom. The paper shows that the two concepts are not

  4. Detecting selection needs comparative data

    DEFF Research Database (Denmark)

    Nielsen, Rasmus; Hubisz, Melissa J.

    2005-01-01

    Positive selection at the molecular level is usually indicated by an increase in the ratio of non-synonymous to synonymous substitutions (dN/dS) in comparative data. However, Plotkin et al. 1 describe a new method for detecting positive selection based on a single nucleotide sequence. We show here...... that this method is particularly sensitive to assumptions regarding the underlying mutational processes and does not provide a reliable way to identify positive selection....

  5. The Clean Air Act

    International Nuclear Information System (INIS)

    Coburn, L.L.

    1990-01-01

    The Clean Air Act amendments alter the complex laws affecting atmospheric pollution and at the same time have broad implications for energy. Specifically, the Clean Air Act amendments for the first time deal with the environmental problem of acid deposition in a way that minimizes energy and economic impacts. By relying upon a market-based system of emission trading, a least cost solution will be used to reduce sulfur dioxide (SO 2 ) emissions by almost 40 percent. The emission trading system is the centerpiece of the Clean Air Act (CAA) amendments effort to resolve energy and environmental interactions in a manner that will maximize environmental solutions while minimizing energy impacts. This paper will explore how the present CAA amendments deal with the emission trading system and the likely impact of the emission trading system and the CAA amendments upon the electric power industry

  6. ST–ACTS

    DEFF Research Database (Denmark)

    Gidofalvi, Gyozo; Pedersen, Torben Bach

    2006-01-01

    hot issue in the area of spatio–temporal databases [7]. While existing Moving Object Simulators (MOSs) address different physical aspects of mobility, they neglect the important social and geo–demographical aspects of it. This paper presents ST–ACTS, a Spatio–Temporal ACTivity Simulator that, using...... various geo–statistical data sources and intuitive principles, models the so far neglected aspects. ST–ACTS considers that (1) objects (representing mobile users) move from one spatio–temporal location to another with the objective of performing a certain activity at the latter location; (2) not all users...