WorldWideScience

Sample records for multiple interacting loci

  1. Interactions Between SNP Alleles at Multiple Loci and Variation in Skin Pigmentation in 122 Caucasians

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    Sumiko Anno

    2007-01-01

    Full Text Available This study was undertaken to clarify the molecular basis for human skin color variation and the environmental adaptability to ultraviolet irradiation, with the ultimate goal of predicting the impact of changes in future environments on human health risk. One hundred twenty-two Caucasians living in Toledo, Ohio participated. Back and cheek skin were assayed for melanin as a quantitative trait marker. Buccal cell samples were collected and used for DNA extraction. DNA was used for SNP genotyping using the Masscode™ system, which entails two-step PCR amplification and a platform chemistry which allows cleavable mass spectrometry tags. The results show gene-gene interaction between SNP alleles at multiple loci (not necessarily on the same chromosome contributes to inter-individual skin color variation while suggesting a high probability of linkage disequilibrium. Confirmation of these findings requires further study with other ethic groups to analyze the associations between SNP alleles at multiple loci and human skin color variation. Our overarching goal is to use remote sensing data to clarify the interaction between atmospheric environments and SNP allelic frequency and investigate human adaptability to ultraviolet irradiation. Such information should greatly assist in the prediction of the health effects of future environmental changes such as ozone depletion and increased ultraviolet exposure. If such health effects are to some extent predictable, it might be possible to prepare for such changes in advance and thus reduce the extent of their impact.

  2. Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

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    Schnorr, J D; Holdcraft, R; Chevalier, B; Berg, C A

    2001-10-01

    Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

  3. An evolutionary reduction principle for mutation rates at multiple Loci.

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    Altenberg, Lee

    2011-06-01

    A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (Evolutionary Biology, vol. 14, pp. 61-204, 1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models.A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface-a generalization of the hyperplane found by Zhivotovsky et al. (Proc. Natl. Acad. Sci. USA 91, 1079-1083, 1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance.Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.

  4. Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

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    Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

    2015-01-01

    Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation.

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    Andlauer, Till F M; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A; Loleit, Verena; Luessi, Felix; Meuth, Sven G; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-06-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis.

  6. Comparative analysis of methods for detecting interacting loci.

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    Chen, Li; Yu, Guoqiang; Langefeld, Carl D; Miller, David J; Guy, Richard T; Raghuram, Jayaram; Yuan, Xiguo; Herrington, David M; Wang, Yue

    2011-07-05

    Interactions among genetic loci are believed to play an important role in disease risk. While many methods have been proposed for detecting such interactions, their relative performance remains largely unclear, mainly because different data sources, detection performance criteria, and experimental protocols were used in the papers introducing these methods and in subsequent studies. Moreover, there have been very few studies strictly focused on comparison of existing methods. Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted. We report a comparison of eight representative methods, of which seven were specifically designed to detect interactions among single nucleotide polymorphisms (SNPs), with the last a popular main-effect testing method used as a baseline for performance evaluation. The selected methods, multifactor dimensionality reduction (MDR), full interaction model (FIM), information gain (IG), Bayesian epistasis association mapping (BEAM), SNP harvester (SH), maximum entropy conditional probability modeling (MECPM), logistic regression with an interaction term (LRIT), and logistic regression (LR) were compared on a large number of simulated data sets, each, consistent with complex disease models, embedding multiple sets of interacting SNPs, under different interaction models. The assessment criteria included several relevant detection power measures, family-wise type I error rate, and computational complexity. There are several important results from this study. First, while some SNPs in interactions with strong effects are successfully detected, most of the methods miss many interacting SNPs at an acceptable rate of false positives. In this study, the best-performing method was MECPM. Second, the statistical significance assessment criteria, used by some of the methods to control the type I error rate

  7. Comparative analysis of methods for detecting interacting loci

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    Yuan Xiguo

    2011-07-01

    Full Text Available Abstract Background Interactions among genetic loci are believed to play an important role in disease risk. While many methods have been proposed for detecting such interactions, their relative performance remains largely unclear, mainly because different data sources, detection performance criteria, and experimental protocols were used in the papers introducing these methods and in subsequent studies. Moreover, there have been very few studies strictly focused on comparison of existing methods. Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted. Results We report a comparison of eight representative methods, of which seven were specifically designed to detect interactions among single nucleotide polymorphisms (SNPs, with the last a popular main-effect testing method used as a baseline for performance evaluation. The selected methods, multifactor dimensionality reduction (MDR, full interaction model (FIM, information gain (IG, Bayesian epistasis association mapping (BEAM, SNP harvester (SH, maximum entropy conditional probability modeling (MECPM, logistic regression with an interaction term (LRIT, and logistic regression (LR were compared on a large number of simulated data sets, each, consistent with complex disease models, embedding multiple sets of interacting SNPs, under different interaction models. The assessment criteria included several relevant detection power measures, family-wise type I error rate, and computational complexity. There are several important results from this study. First, while some SNPs in interactions with strong effects are successfully detected, most of the methods miss many interacting SNPs at an acceptable rate of false positives. In this study, the best-performing method was MECPM. Second, the statistical significance assessment criteria, used by some of the

  8. Novel multiple sclerosis susceptibility loci implicated in epigenetic regulation

    Science.gov (United States)

    Andlauer, Till F. M.; Buck, Dorothea; Antony, Gisela; Bayas, Antonios; Bechmann, Lukas; Berthele, Achim; Chan, Andrew; Gasperi, Christiane; Gold, Ralf; Graetz, Christiane; Haas, Jürgen; Hecker, Michael; Infante-Duarte, Carmen; Knop, Matthias; Kümpfel, Tania; Limmroth, Volker; Linker, Ralf A.; Loleit, Verena; Luessi, Felix; Meuth, Sven G.; Mühlau, Mark; Nischwitz, Sandra; Paul, Friedemann; Pütz, Michael; Ruck, Tobias; Salmen, Anke; Stangel, Martin; Stellmann, Jan-Patrick; Stürner, Klarissa H.; Tackenberg, Björn; Then Bergh, Florian; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wiendl, Heinz; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Zipp, Frauke; Arloth, Janine; Weber, Peter; Radivojkov-Blagojevic, Milena; Scheinhardt, Markus O.; Dankowski, Theresa; Bettecken, Thomas; Lichtner, Peter; Czamara, Darina; Carrillo-Roa, Tania; Binder, Elisabeth B.; Berger, Klaus; Bertram, Lars; Franke, Andre; Gieger, Christian; Herms, Stefan; Homuth, Georg; Ising, Marcus; Jöckel, Karl-Heinz; Kacprowski, Tim; Kloiber, Stefan; Laudes, Matthias; Lieb, Wolfgang; Lill, Christina M.; Lucae, Susanne; Meitinger, Thomas; Moebus, Susanne; Müller-Nurasyid, Martina; Nöthen, Markus M.; Petersmann, Astrid; Rawal, Rajesh; Schminke, Ulf; Strauch, Konstantin; Völzke, Henry; Waldenberger, Melanie; Wellmann, Jürgen; Porcu, Eleonora; Mulas, Antonella; Pitzalis, Maristella; Sidore, Carlo; Zara, Ilenia; Cucca, Francesco; Zoledziewska, Magdalena; Ziegler, Andreas; Hemmer, Bernhard; Müller-Myhsok, Bertram

    2016-01-01

    We conducted a genome-wide association study (GWAS) on multiple sclerosis (MS) susceptibility in German cohorts with 4888 cases and 10,395 controls. In addition to associations within the major histocompatibility complex (MHC) region, 15 non-MHC loci reached genome-wide significance. Four of these loci are novel MS susceptibility loci. They map to the genes L3MBTL3, MAZ, ERG, and SHMT1. The lead variant at SHMT1 was replicated in an independent Sardinian cohort. Products of the genes L3MBTL3, MAZ, and ERG play important roles in immune cell regulation. SHMT1 encodes a serine hydroxymethyltransferase catalyzing the transfer of a carbon unit to the folate cycle. This reaction is required for regulation of methylation homeostasis, which is important for establishment and maintenance of epigenetic signatures. Our GWAS approach in a defined population with limited genetic substructure detected associations not found in larger, more heterogeneous cohorts, thus providing new clues regarding MS pathogenesis. PMID:27386562

  9. Application of multi-locus analytical methods to identify interacting loci in case-control studies.

    NARCIS (Netherlands)

    Vermeulen, S.; Heijer, M. den; Sham, P.; Knight, J.

    2007-01-01

    To identify interacting loci in genetic epidemiological studies the application of multi-locus methods of analysis is warranted. Several more advanced classification methods have been developed in the past years, including multiple logistic regression, sum statistics, logic regression, and the

  10. New weighting methods for phylogenetic tree reconstruction using multiple loci.

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    Misawa, Kazuharu; Tajima, Fumio

    2012-08-01

    Efficient determination of evolutionary distances is important for the correct reconstruction of phylogenetic trees. The performance of the pooled distance required for reconstructing a phylogenetic tree can be improved by applying large weights to appropriate distances for reconstructing phylogenetic trees and small weights to inappropriate distances. We developed two weighting methods, the modified Tajima-Takezaki method and the modified least-squares method, for reconstructing phylogenetic trees from multiple loci. By computer simulations, we found that both of the new methods were more efficient in reconstructing correct topologies than the no-weight method. Hence, we reconstructed hominoid phylogenetic trees from mitochondrial DNA using our new methods, and found that the levels of bootstrap support were significantly increased by the modified Tajima-Takezaki and by the modified least-squares method.

  11. Genome-wide association study identifies multiple susceptibility loci for multiple myeloma

    DEFF Research Database (Denmark)

    Mitchell, Jonathan S; Li, Ni; Weinhold, Niels

    2016-01-01

    Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a ...

  12. Gene-environment interaction involving recently identified colorectal cancer susceptibility loci

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    Kantor, Elizabeth D.; Hutter, Carolyn M.; Minnier, Jessica; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Campbell, Peter T.; Carlson, Christopher S.; Casey, Graham; Chan, Andrew T.; Chang-Claude, Jenny; Chanock, Stephen J.; Cotterchio, Michelle; Du, Mengmeng; Duggan, David; Fuchs, Charles S.; Giovannucci, Edward L.; Gong, Jian; Harrison, Tabitha A.; Hayes, Richard B.; Henderson, Brian E.; Hoffmeister, Michael; Hopper, John L.; Jenkins, Mark A.; Jiao, Shuo; Kolonel, Laurence N.; Le Marchand, Loic; Lemire, Mathieu; Ma, Jing; Newcomb, Polly A.; Ochs-Balcom, Heather M.; Pflugeisen, Bethann M.; Potter, John D.; Rudolph, Anja; Schoen, Robert E.; Seminara, Daniela; Slattery, Martha L.; Stelling, Deanna L.; Thomas, Fridtjof; Thornquist, Mark; Ulrich, Cornelia M.; Warnick, Greg S.; Zanke, Brent W.; Peters, Ulrike; Hsu, Li; White, Emily

    2014-01-01

    BACKGROUND Genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) that are associated with risk of colorectal cancer (CRC). Prior research has evaluated the presence of gene-environment interaction involving the first 10 identified susceptibility loci, but little work has been conducted on interaction involving SNPs at recently identified susceptibility loci, including: rs10911251, rs6691170, rs6687758, rs11903757, rs10936599, rs647161, rs1321311, rs719725, rs1665650, rs3824999, rs7136702, rs11169552, rs59336, rs3217810, rs4925386, and rs2423279. METHODS Data on 9160 cases and 9280 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and Colon Cancer Family Registry (CCFR) were used to evaluate the presence of interaction involving the above-listed SNPs and sex, body mass index (BMI), alcohol consumption, smoking, aspirin use, post-menopausal hormone (PMH) use, as well as intake of dietary calcium, dietary fiber, dietary folate, red meat, processed meat, fruit, and vegetables. Interaction was evaluated using a fixed-effects meta-analysis of an efficient Empirical Bayes estimator, and permutation was used to account for multiple comparisons. RESULTS None of the permutation-adjusted p-values reached statistical significance. CONCLUSIONS The associations between recently identified genetic susceptibility loci and CRC are not strongly modified by sex, BMI, alcohol, smoking, aspirin, PMH use, and various dietary factors. IMPACT Results suggest no evidence of strong gene-environment interactions involving the recently identified 16 susceptibility loci for CRC taken one at a time. PMID:24994789

  13. Genetic evidence of multiple loci in dystocia - difficult labour

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    Westgren Magnus

    2010-06-01

    Full Text Available Abstract Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT on chromosome 20 and oxytocin-receptor (OXTR on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15 on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts.

  14. Genetic evidence of multiple loci in dystocia - difficult labour

    Science.gov (United States)

    2010-01-01

    Background Dystocia, difficult labour, is a common but also complex problem during childbirth. It can be attributed to either weak contractions of the uterus, a large infant, reduced capacity of the pelvis or combinations of these. Previous studies have indicated that there is a genetic component in the susceptibility of experiencing dystocia. The purpose of this study was to identify susceptibility genes in dystocia. Methods A total of 104 women in 47 families were included where at least two sisters had undergone caesarean section at a gestational length of 286 days or more at their first delivery. Study of medical records and a telephone interview was performed to identify subjects with dystocia. Whole-genome scanning using Affymetrix genotyping-arrays and non-parametric linkage (NPL) analysis was made in 39 women exhibiting the phenotype of dystocia from 19 families. In 68 women re-sequencing was performed of candidate genes showing suggestive linkage: oxytocin (OXT) on chromosome 20 and oxytocin-receptor (OXTR) on chromosome 3. Results We found a trend towards linkage with suggestive NPL-score (3.15) on chromosome 12p12. Suggestive linkage peaks were observed on chromosomes 3, 4, 6, 10, 20. Re-sequencing of OXT and OXTR did not reveal any causal variants. Conclusions Dystocia is likely to have a genetic component with variations in multiple genes affecting the patient outcome. We found 6 loci that could be re-evaluated in larger patient cohorts. PMID:20587075

  15. Multiple loci associated with renal function in African Americans.

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    Daniel Shriner

    Full Text Available The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR. We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.

  16. Laboratory and wild-derived mice with multiple loci for production of xenotropic murine leukemia virus.

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    Kozak, C A; Hartley, J W; Morse, H C

    1984-07-01

    Mendelian segregation analysis was used to define genetic loci for the induction of infectious xenotropic murine leukemia virus in several laboratory and wild-derived mice. MA/My mice contain two loci for xenotropic virus inducibility, one of which, Bxv -1, is the only induction locus carried by five other inbred strains. The second, novel MA/My locus, designated Mxv -1, is unlinked to Bxv -1 and shows a lower efficiency of virus induction. The NZB mouse carries two induction loci; both are distinct from Bxv -1 since neither is linked to the Pep-3 locus on chromosome 1. Finally, one partially inbred strain derived from the wild Japanese mouse, Mus musculus molossinus, carries multiple (at least three) unlinked loci for induction of xenotropic virus. Although it is probable that inbred strains inherited xenotropic virus inducibility from Japanese mice, our data suggest that none of the induction loci carried by this particular M. m. molossinus strain are allelic with Bxv -1.

  17. Multiple loci are associated with white blood cell phenotypes.

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    Michael A Nalls

    2011-06-01

    Full Text Available White blood cell (WBC count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2, including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across

  18. Identification of Multiple Loci Associated with Social Parasitism in Honeybees.

    Science.gov (United States)

    Wallberg, Andreas; Pirk, Christian W; Allsopp, Mike H; Webster, Matthew T

    2016-06-01

    In colonies of the honeybee Apis mellifera, the queen is usually the only reproductive female, which produces new females (queens and workers) by laying fertilized eggs. However, in one subspecies of A. mellifera, known as the Cape bee (A. m. capensis), worker bees reproduce asexually by thelytoky, an abnormal form of meiosis where two daughter nucleii fuse to form single diploid eggs, which develop into females without being fertilized. The Cape bee also exhibits a suite of phenotypes that facilitate social parasitism whereby workers lay such eggs in foreign colonies so their offspring can exploit their resources. The genetic basis of this switch to social parasitism in the Cape bee is unknown. To address this, we compared genome variation in a sample of Cape bees with other African populations. We find genetic divergence between these populations to be very low on average but identify several regions of the genome with extreme differentiation. The regions are strongly enriched for signals of selection in Cape bees, indicating that increased levels of positive selection have produced the unique set of derived phenotypic traits in this subspecies. Genetic variation within these regions allows unambiguous genetic identification of Cape bees and likely underlies the genetic basis of social parasitism. The candidate loci include genes involved in ecdysteroid signaling and juvenile hormone and dopamine biosynthesis, which may regulate worker ovary activation and others whose products localize at the centrosome and are implicated in chromosomal segregation during meiosis. Functional analysis of these loci will yield insights into the processes of reproduction and chemical signaling in both parasitic and non-parasitic populations and advance understanding of the process of normal and atypical meiosis.

  19. Identification of Multiple Loci Associated with Social Parasitism in Honeybees.

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    Andreas Wallberg

    2016-06-01

    Full Text Available In colonies of the honeybee Apis mellifera, the queen is usually the only reproductive female, which produces new females (queens and workers by laying fertilized eggs. However, in one subspecies of A. mellifera, known as the Cape bee (A. m. capensis, worker bees reproduce asexually by thelytoky, an abnormal form of meiosis where two daughter nucleii fuse to form single diploid eggs, which develop into females without being fertilized. The Cape bee also exhibits a suite of phenotypes that facilitate social parasitism whereby workers lay such eggs in foreign colonies so their offspring can exploit their resources. The genetic basis of this switch to social parasitism in the Cape bee is unknown. To address this, we compared genome variation in a sample of Cape bees with other African populations. We find genetic divergence between these populations to be very low on average but identify several regions of the genome with extreme differentiation. The regions are strongly enriched for signals of selection in Cape bees, indicating that increased levels of positive selection have produced the unique set of derived phenotypic traits in this subspecies. Genetic variation within these regions allows unambiguous genetic identification of Cape bees and likely underlies the genetic basis of social parasitism. The candidate loci include genes involved in ecdysteroid signaling and juvenile hormone and dopamine biosynthesis, which may regulate worker ovary activation and others whose products localize at the centrosome and are implicated in chromosomal segregation during meiosis. Functional analysis of these loci will yield insights into the processes of reproduction and chemical signaling in both parasitic and non-parasitic populations and advance understanding of the process of normal and atypical meiosis.

  20. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    NARCIS (Netherlands)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.; Acha, Moshe Ray; Newton-Cheh, Christopher; Pfeufer, Arne; Lyneh, Stacey N.; Olesen, Soren-Peter; Brunak, Soren; Ellinor, Patrick T.; Jukema, J. Wouter; Trompet, Stella; Ford, Ian; Macfarlane, Peter W.; Krijthe, Bouwe P.; Hofman, Albert; Uitterlinden, Andre G.; Stricker, Bruno H.; Nathoe, Hendrik M.; Spiering, Wilko; Daly, Mark J.; Asselbergs, Ikea W.; van der Harst, Pim; Milan, David J.; de Bakker, Paul I. W.; Lage, Kasper; Olsen, Jesper V.

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes

  1. Genome-wide mapping in a house mouse hybrid zone reveals hybrid sterility loci and Dobzhansky-Muller interactions.

    Science.gov (United States)

    Turner, Leslie M; Harr, Bettina

    2014-12-09

    Mapping hybrid defects in contact zones between incipient species can identify genomic regions contributing to reproductive isolation and reveal genetic mechanisms of speciation. The house mouse features a rare combination of sophisticated genetic tools and natural hybrid zones between subspecies. Male hybrids often show reduced fertility, a common reproductive barrier between incipient species. Laboratory crosses have identified sterility loci, but each encompasses hundreds of genes. We map genetic determinants of testis weight and testis gene expression using offspring of mice captured in a hybrid zone between M. musculus musculus and M. m. domesticus. Many generations of admixture enables high-resolution mapping of loci contributing to these sterility-related phenotypes. We identify complex interactions among sterility loci, suggesting multiple, non-independent genetic incompatibilities contribute to barriers to gene flow in the hybrid zone.

  2. Multiple mouse chromosomal loci for dynein-based motility

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, K.T.; Mikami, Atsushi; Paschal, B.M. [Worcester Foundation for Biomedical Research, Shrewsbury, MA (United States)] [and others

    1996-08-15

    Dyneins are multisubunit mechanochemical enzymes capable of interacting with microtubules to generate force. Axonemal dyneins produce the motive force for ciliary and flagellar beating by inducing sliding between adjacent microtubules within the axoneme. Cytoplasmic dyneins translocate membranous organelles and chromosomes toward the minus ends of cytoplasmic microtubules. Dynactin is an accessory complex implicated in tethering cytoplasmic dynein to membranous organelles and mitotic kinetochores. In the studies described here, we have identified a number of new dynein genes and determined their mouse chromosomal locations by interspecific backcross analysis. We have also mapped several dynein and dynactin genes cloned previously. Our studies provide the first comprehensive attempt to map dynein and dynactin genes in mammals and provide a basis for the further analysis of dynein function in development and disease. 65 refs., 6 figs., 1 tab.

  3. Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout.

    Science.gov (United States)

    Rasheed, Humaira; Stamp, Lisa K; Dalbeth, Nicola; Merriman, Tony R

    2017-07-05

    Some gout-associated loci interact with dietary exposures to influence outcome. The aim of this study was to systematically investigate interactions between alcohol exposure and urate-associated loci in gout. A total of 2792 New Zealand European and Polynesian (Māori or Pacific) people with or without gout were genotyped for 29 urate-associated genetic variants and tested for a departure from multiplicative interaction with alcohol exposure in the risk of gout. Publicly available data from 6892 European subjects were used to test for a departure from multiplicative interaction between specific loci and alcohol exposure for the risk of hyperuricemia (HU). Multivariate adjusted logistic and linear regression was done, including an interaction term. Interaction of any alcohol exposure with GCKR (rs780094) and A1CF (rs10821905) influenced the risk of gout in Europeans (interaction term 0.28, P = 1.5 × 10 -4 ; interaction term 0.29, P = 1.4 × 10 -4 , respectively). At A1CF, alcohol exposure suppressed the gout risk conferred by the A-positive genotype. At GCKR, alcohol exposure eliminated the genetic effect on gout. In the Polynesian sample set, there was no experiment-wide evidence for interaction with alcohol in the risk of gout (all P > 8.6 × 10 -4 ). However, at GCKR, there was nominal evidence for an interaction in a direction consistent the European observation (interaction term 0.62, P = 0.05). There was no evidence for an interaction of A1CF or GCKR with alcohol exposure in determining HU. These data support the hypothesis that alcohol influences the risk of gout via glucose and apolipoprotein metabolism. In the absence of alcohol exposure, genetic variants in the GCKR and A1CF genes have a stronger role in gout.

  4. High Resolution of Quantitative Traits Into Multiple Loci via Interval Mapping

    OpenAIRE

    Jansen, Ritsert C.; Stam, Piet

    1994-01-01

    A very general method is described for multiple linear regression of a quantitative phenotype on genotype [putative quantitative trait loci (QTLs) and markers] in segregating generations obtained from line crosses. The method exploits two features, (a) the use of additional parental and F1 data, which fixes the joint QTL effects and the environmental error, and (b) the use of markers as cofactors, which reduces the genetic background noise. As a result, a significant increase of QTL detection...

  5. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    Science.gov (United States)

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

  6. Annotation of loci from genome-wide association studies using tissue-specific quantitative interaction proteomics

    DEFF Research Database (Denmark)

    Lundby, Alicia; Rossin, Elizabeth J.; Steffensen, Annette B.

    2014-01-01

    Genome-wide association studies (GWAS) have identified thousands of loci associated with complex traits, but it is challenging to pinpoint causal genes in these loci and to exploit subtle association signals. We used tissue-specific quantitative interaction proteomics to map a network of five genes...... involved in the Mendelian disorder long QT syndrome (LOTS). We integrated the LOTS network with GWAS loci from the corresponding common complex trait, QT-interval variation, to identify candidate genes that were subsequently confirmed in Xenopus laevis oocytes and zebrafish. We used the LOTS protein...... network to filter weak GWAS signals by identifying single-nucleotide polymorphisms (SNPs) in proximity to genes in the network supported by strong proteomic evidence. Three SNPs passing this filter reached genome-wide significance after replication genotyping. Overall, we present a general strategy...

  7. Dynamic changes in the interchromosomal interaction of early histone gene loci during development of sea urchin.

    Science.gov (United States)

    Matsushita, Masaya; Ochiai, Hiroshi; Suzuki, Ken-Ichi T; Hayashi, Sayaka; Yamamoto, Takashi; Awazu, Akinori; Sakamoto, Naoaki

    2017-12-15

    The nuclear positioning and chromatin dynamics of eukaryotic genes are closely related to the regulation of gene expression, but they have not been well examined during early development, which is accompanied by rapid cell cycle progression and dynamic changes in nuclear organization, such as nuclear size and chromatin constitution. In this study, we focused on the early development of the sea urchin Hemicentrotus pulcherrimus and performed three-dimensional fluorescence in situ hybridization of gene loci encoding early histones (one of the types of histone in sea urchin). There are two non-allelic early histone gene loci per sea urchin genome. We found that during the morula stage, when the early histone gene expression levels are at their maximum, interchromosomal interactions were often formed between the early histone gene loci on separate chromosomes and that the gene loci were directed to locate to more interior positions. Furthermore, these interactions were associated with the active transcription of the early histone genes. Thus, such dynamic interchromosomal interactions may contribute to the efficient synthesis of early histone mRNA during the morula stage of sea urchin development. © 2017. Published by The Company of Biologists Ltd.

  8. Multiple Parton Interactions in ALICE

    CERN Multimedia

    CERN. Geneva

    2013-01-01

    We will present in detail the measurement of the charged particle multiplicity dependence of per-trigger pair yields in azimuthal direction induced by low-energetic di-jets produced in proton-proton collisions. Using two-particle angular correlations with low transverse momentum thresholds, jet properties are measured on a statistical basis down to the lowest possible jet energies. The analysis can give information about the contribution from multiple parton interactions to particle production. Moreover, the results allow to optimize the parametrization of the jet fragmentation in phenomenological mode...

  9. An R package "VariABEL" for genome-wide searching of potentially interacting loci by testing genotypic variance heterogeneity

    Directory of Open Access Journals (Sweden)

    Struchalin Maksim V

    2012-01-01

    Full Text Available Abstract Background Hundreds of new loci have been discovered by genome-wide association studies of human traits. These studies mostly focused on associations between single locus and a trait. Interactions between genes and between genes and environmental factors are of interest as they can improve our understanding of the genetic background underlying complex traits. Genome-wide testing of complex genetic models is a computationally demanding task. Moreover, testing of such models leads to multiple comparison problems that reduce the probability of new findings. Assuming that the genetic model underlying a complex trait can include hundreds of genes and environmental factors, testing of these models in genome-wide association studies represent substantial difficulties. We and Pare with colleagues (2010 developed a method allowing to overcome such difficulties. The method is based on the fact that loci which are involved in interactions can show genotypic variance heterogeneity of a trait. Genome-wide testing of such heterogeneity can be a fast scanning approach which can point to the interacting genetic variants. Results In this work we present a new method, SVLM, allowing for variance heterogeneity analysis of imputed genetic variation. Type I error and power of this test are investigated and contracted with these of the Levene's test. We also present an R package, VariABEL, implementing existing and newly developed tests. Conclusions Variance heterogeneity analysis is a promising method for detection of potentially interacting loci. New method and software package developed in this work will facilitate such analysis in genome-wide context.

  10. Multiple sclerosis and herpesvirus interaction

    Directory of Open Access Journals (Sweden)

    Guilherme Sciascia do Olival

    2013-09-01

    Full Text Available Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system, and its etiology is believed to have both genetic and environmental components. Several viruses have already been implicated as triggers and there are several studies that implicate members of the Herpesviridae family in the pathogenesis of MS. The most important characteristic of these viruses is that they have periods of latency and exacerbations within their biological sanctuary, the central nervous system. The Epstein-Barr, cytomegalovirus, human herpesvirus 6 and human herpesvirus 7 viruses are the members that are most studied as being possible triggers of multiple sclerosis. According to evidence in the literature, the herpesvirus family is strongly involved in the pathogenesis of this disease, but it is unlikely that they are the only component responsible for its development. There are probably multiple triggers and more studies are necessary to investigate and define these interactions.

  11. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

    Science.gov (United States)

    Ried, Janina S.; Jeff M., Janina; Chu, Audrey Y.; Bragg-Gresham, Jennifer L.; van Dongen, Jenny; Huffman, Jennifer E.; Ahluwalia, Tarunveer S.; Cadby, Gemma; Eklund, Niina; Eriksson, Joel; Esko, Tõnu; Feitosa, Mary F.; Goel, Anuj; Gorski, Mathias; Hayward, Caroline; Heard-Costa, Nancy L.; Jackson, Anne U.; Jokinen, Eero; Kanoni, Stavroula; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Luan, Jian'an; Mägi, Reedik; Mahajan, Anubha; Mangino, Massimo; Medina-Gomez, Carolina; Monda, Keri L.; Nolte, Ilja M.; Pérusse, Louis; Prokopenko, Inga; Qi, Lu; Rose, Lynda M.; Salvi, Erika; Smith, Megan T.; Snieder, Harold; Stančáková, Alena; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W.; Wang, Sophie R.; Wild, Sarah H.; Willems, Sara M.; Wong, Andrew; Zhang, Weihua; Albrecht, Eva; Couto Alves, Alexessander; Bakker, Stephan J. L.; Barlassina, Cristina; Bartz, Traci M.; Beilby, John; Bellis, Claire; Bergman, Richard N.; Bergmann, Sven; Blangero, John; Blüher, Matthias; Boerwinkle, Eric; Bonnycastle, Lori L.; Bornstein, Stefan R.; Bruinenberg, Marcel; Campbell, Harry; Chen, Yii-Der Ida; Chiang, Charleston W. K.; Chines, Peter S.; Collins, Francis S; Cucca, Fracensco; Cupples, L Adrienne; D'Avila, Francesca; de Geus, Eco J .C.; Dedoussis, George; Dimitriou, Maria; Döring, Angela; Eriksson, Johan G.; Farmaki, Aliki-Eleni; Farrall, Martin; Ferreira, Teresa; Fischer, Krista; Forouhi, Nita G.; Friedrich, Nele; Gjesing, Anette Prior; Glorioso, Nicola; Graff, Mariaelisa; Grallert, Harald; Grarup, Niels; Gräßler, Jürgen; Grewal, Jagvir; Hamsten, Anders; Harder, Marie Neergaard; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew Tym; Havulinna, Aki S.; Heliövaara, Markku; Hillege, Hans; Hofman, Albert; Holmen, Oddgeir; Homuth, Georg; Hottenga, Jouke-Jan; Hui, Jennie; Husemoen, Lise Lotte; Hysi, Pirro G.; Isaacs, Aaron; Ittermann, Till; Jalilzadeh, Shapour; James, Alan L.; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Marie Justesen, Johanne; Justice, Anne E.; Kähönen, Mika; Karaleftheri, Maria; Tee Khaw, Kay; Keinanen-Kiukaanniemi, Sirkka M.; Kinnunen, Leena; Knekt, Paul B.; Koistinen, Heikki A.; Kolcic, Ivana; Kooner, Ishminder K.; Koskinen, Seppo; Kovacs, Peter; Kyriakou, Theodosios; Laitinen, Tomi; Langenberg, Claudia; Lewin, Alexandra M.; Lichtner, Peter; Lindgren, Cecilia M.; Lindström, Jaana; Linneberg, Allan; Lorbeer, Roberto; Lorentzon, Mattias; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Manunta, Paolo; Leach, Irene Mateo; McArdle, Wendy L.; Mcknight, Barbara; Mohlke, Karen L.; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Montasser, May E.; Morris, Andrew P.; Müller, Gabriele; Musk, Arthur W.; Narisu, Narisu; Ong, Ken K.; Oostra, Ben A.; Osmond, Clive; Palotie, Aarno; Pankow, James S.; Paternoster, Lavinia; Penninx, Brenda W.; Pichler, Irene; Pilia, Maria G.; Polašek, Ozren; Pramstaller, Peter P.; Raitakari, Olli T; Rankinen, Tuomo; Rao, D. C.; Rayner, Nigel W.; Ribel-Madsen, Rasmus; Rice, Treva K.; Richards, Marcus; Ridker, Paul M.; Rivadeneira, Fernando; Ryan, Kathy A.; Sanna, Serena; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Sebert, Sylvain; Southam, Lorraine; Sparsø, Thomas Hempel; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Stolk, Ronald P.; Strauch, Konstantin; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Tönjes, Anke; Tsafantakis, Emmanouil; van der Most, Peter J.; Van Vliet-Ostaptchouk, Jana V.; Vandenput, Liesbeth; Vartiainen, Erkki; Venturini, Cristina; Verweij, Niek; Viikari, Jorma S.; Vitart, Veronique; Vohl, Marie-Claude; Vonk, Judith M.; Waeber, Gérard; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Winkler, Thomas W.; Wright, Alan F.; Yerges-Armstrong, Laura M.; Hua Zhao, Jing; Carola Zillikens, M.; Boomsma, Dorret I.; Bouchard, Claude; Chambers, John C.; Chasman, Daniel I.; Cusi, Daniele; Gansevoort, Ron T.; Gieger, Christian; Hansen, Torben; Hicks, Andrew A.; Hu, Frank; Hveem, Kristian; Jarvelin, Marjo-Riitta; Kajantie, Eero; Kooner, Jaspal S.; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Metspalu, Andres; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Palmer, Lyle J.; Pedersen, Oluf; Perola, Markus; Peters, Annette; Psaty, Bruce M.; Puolijoki, Hannu; Rauramaa, Rainer; Rudan, Igor; Salomaa, Veikko; Schwarz, Peter E. H.; Shudiner, Alan R.; Smit, Jan H.; Sørensen, Thorkild I. A.; Spector, Timothy D.; Stefansson, Kari; Stumvoll, Michael; Tremblay, Angelo; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; Völker, Uwe; Vollenweider, Peter; Wareham, Nicholas J.; Watkins, Hugh; Wilson, James F.; Zeggini, Eleftheria; Abecasis, Goncalo R.; Boehnke, Michael; Borecki, Ingrid B.; Deloukas, Panos; van Duijn, Cornelia M.; Fox, Caroline; Groop, Leif C.; Heid, Iris M.; Hunter, David J.; Kaplan, Robert C.; McCarthy, Mark I.; North, Kari E.; O'Connell, Jeffrey R.; Schlessinger, David; Thorsteinsdottir, Unnur; Strachan, David P.; Frayling, Timothy; Hirschhorn, Joel N.; Müller-Nurasyid, Martina; Loos, Ruth J. F.

    2016-01-01

    Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways. PMID:27876822

  12. Multiple susceptibility loci for radiation-induced mammary tumorigenesis in F2[Dahl S x R]-intercross rats.

    Directory of Open Access Journals (Sweden)

    Victoria L Herrera

    Full Text Available Although two major breast cancer susceptibility genes, BRCA1 and BRCA2, have been identified accounting for 20% of breast cancer genetic risk, identification of other susceptibility genes accounting for 80% risk remains a challenge due to the complex, multi-factorial nature of breast cancer. Complexity derives from multiple genetic determinants, permutations of gene-environment interactions, along with presumptive low-penetrance of breast cancer predisposing genes, and genetic heterogeneity of human populations. As with other complex diseases, dissection of genetic determinants in animal models provides key insight since genetic heterogeneity and environmental factors can be experimentally controlled, thus facilitating the detection of quantitative trait loci (QTL. We therefore, performed the first genome-wide scan for loci contributing to radiation-induced mammary tumorigenesis in female F2-(Dahl S x R-intercross rats. Tumorigenesis was measured as tumor burden index (TBI after induction of rat mammary tumors at forty days of age via ¹²⁷Cs-radiation. We observed a spectrum of tumor latency, size-progression, and pathology from poorly differentiated ductal adenocarcinoma to fibroadenoma, indicating major effects of gene-environment interactions. We identified two mammary tumorigenesis susceptibility quantitative trait loci (Mts-QTLs with significant linkage: Mts-1 on chromosome-9 (LOD-2.98 and Mts-2 on chromosome-1 (LOD-2.61, as well as two Mts-QTLs with suggestive linkage: Mts-3 on chromosome-5 (LOD-1.93 and Mts-4 on chromosome-18 (LOD-1.54. Interestingly, Chr9-Mts-1, Chr5-Mts-3 and Chr18-Mts-4 QTLs are unique to irradiation-induced mammary tumorigenesis, while Chr1-Mts-2 QTL overlaps with a mammary cancer susceptibility QTL (Mcs 3 reported for 7,12-dimethylbenz-[α]antracene (DMBA-induced mammary tumorigenesis in F2[COP x Wistar-Furth]-intercross rats. Altogether, our results suggest at least three distinct susceptibility QTLs for

  13. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene-Environment Interactions

    Science.gov (United States)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra; Dunning, Alison M.; Milne, Roger L.; Bojesen, Stig E.; Swerdlow, Anthony; Andrulis, Irene; Brenner, Hermann; Behrens, Sabine; Orr, Nicholas; Jones, Michael; Ashworth, Alan; Li, Jingmei; Cramp, Helen; Connley, Dan; Czene, Kamila; Darabi, Hatef; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Knight, Julia; Glendon, Gord; Mulligan, Anna M.; Dumont, Martine; Severi, Gianluca; Baglietto, Laura; Olson, Janet; Vachon, Celine; Purrington, Kristen; Moisse, Matthieu; Neven, Patrick; Wildiers, Hans; Spurdle, Amanda; Kosma, Veli-Matti; Kataja, Vesa; Hartikainen, Jaana M.; Hamann, Ute; Ko, Yon-Dschun; Dieffenbach, Aida K.; Arndt, Volker; Stegmaier, Christa; Malats, Núria; Arias Perez, JoséI.; Benítez, Javier; Flyger, Henrik; Nordestgaard, Børge G.; Truong, Théresè; Cordina-Duverger, Emilie; Menegaux, Florence; Silva, Isabel dos Santos; Fletcher, Olivia; Johnson, Nichola; Häberle, Lothar; Beckmann, Matthias W.; Ekici, Arif B.; Braaf, Linde; Atsma, Femke; van den Broek, Alexandra J.; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Cox, Angela; Simard, Jacques; Giles, Graham G.; Lambrechts, Diether; Mannermaa, Arto; Brauch, Hiltrud; Guénel, Pascal; Peto, Julian; Fasching, Peter A.; Hopper, John; Flesch-Janys, Dieter; Couch, Fergus; Chenevix-Trench, Georgia; Pharoah, Paul D. P.; Garcia-Closas, Montserrat; Schmidt, Marjanka K.; Hall, Per; Easton, Douglas F.; Chang-Claude, Jenny

    2014-01-01

    Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10−07), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m2 (OR = 1.26, 95% CI 1.15–1.38) but not in women with a BMI of 30 kg/m2 or higher (OR = 0.89, 95% CI 0.72–1.11, P for interaction = 3.2 × 10−05). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci. PMID:24248812

  14. Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants

    Science.gov (United States)

    Juran, Brian D.; Hirschfield, Gideon M.; Invernizzi, Pietro; Atkinson, Elizabeth J.; Li, Yafang; Xie, Gang; Kosoy, Roman; Ransom, Michael; Sun, Ye; Bianchi, Ilaria; Schlicht, Erik M.; Lleo, Ana; Coltescu, Catalina; Bernuzzi, Francesca; Podda, Mauro; Lammert, Craig; Shigeta, Russell; Chan, Landon L.; Balschun, Tobias; Marconi, Maurizio; Cusi, Daniele; Heathcote, E. Jenny; Mason, Andrew L.; Myers, Robert P.; Milkiewicz, Piotr; Odin, Joseph A.; Luketic, Velimir A.; Bacon, Bruce R.; Bodenheimer, Henry C.; Liakina, Valentina; Vincent, Catherine; Levy, Cynthia; Franke, Andre; Gregersen, Peter K.; Bossa, Fabrizio; Gershwin, M. Eric; deAndrade, Mariza; Amos, Christopher I.; Lazaridis, Konstantinos N.; Seldin, Michael F.; Siminovitch, Katherine A.

    2012-01-01

    To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies. PMID:22936693

  15. Gene interaction at seed-awning loci in the genetic background of wild rice.

    Science.gov (United States)

    Ikemoto, Mai; Otsuka, Mitsuharu; Thanh, Pham Thien; Phan, Phuong Dang Thai; Ishikawa, Ryo; Ishii, Takashige

    2017-09-12

    Seed awning is one of the important traits for successful propagation in wild rice. During the domestication of rice by ancient humans, plants with awnless seeds may have been selected because long awns hindered collection and handling activities. To investigate domestication of awnless rice, QTL analysis for seed awning was first carried out using backcross recombinant inbred lines between Oryza sativa Nipponbare (recurrent parent) and O. rufipogon W630 (donor parent). Two strong QTLs were detected in the same regions as known major seed-awning loci, An-1 and RAE2. Subsequent causal mutation surveying and fine mapping confirmed that O. rufipogon W630 has functional alleles at both loci. The gene effects and interactions at these loci were examined using two backcross populations with reciprocal genetic backgrounds of O. sativa Nipponbare and O. rufipogon W630. As awn length in wild rice varied among seeds even in the same plant, awn length was measured based on spikelet position. In the genetic background of cultivated rice, the wild alleles at An-1 and RAE2 had awning effects, and plants having both wild homozygous alleles produced awns whose length was about 70% of those of the wild parent. On the other hand, in the genetic background of wild rice, the substitution of cultivated alleles at An-1 and RAE2 contributed little to awn length reduction. These results indicate that the domestication process of awnless seeds was complicated because many genes are involved in awn formation in wild rice.

  16. SATB1 tethers multiple gene loci to reprogram expression profiledriving breast cancer metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Han, Hye-Jung; Kohwi, Yoshinori; Kohwi-Shigematsu, Terumi

    2006-07-13

    Global changes in gene expression occur during tumor progression, as indicated by expression profiling of metastatic tumors. How this occurs is poorly understood. SATB1 functions as a genome organizer by folding chromatin via tethering multiple genomic loci and recruiting chromatin remodeling enzymes to regulate chromatin structure and expression of a large number of genes. Here we show that SATB1 is expressed at high levels in aggressive breast cancer cells, and is undetectable in non-malignant breast epithelial cells. Importantly, RNAi-mediated removal of SATB1 from highly-aggressive MDA-MB-231 cells altered the expression levels of over 1200 genes, restored breast-like acinar polarity in three-dimensional cultures, and prevented the metastastic phenotype in vivo. Conversely, overexpression of SATB1 in the less-aggressive breast cancer cell line Hs578T altered the gene expression profile and increased metastasis dramatically in vivo. Thus, SATB1 is a global regulator of gene expression in breast cancer cells, directly regulating crucial metastasis-associated genes, including ERRB2 (HER2/NEU), TGF-{beta}1, matrix metalloproteinase 3, and metastasin. The identification of SATB1 as a protein that re-programs chromatin organization and transcription profiles to promote breast cancer metastasis suggests a new model for metastasis and may provide means of therapeutic intervention.

  17. Genes and quality trait loci (QTLs) associated with firmness in Malus x domestica

    KAUST Repository

    Marondedze, Claudius; Thomas, Ludivine

    2013-01-01

    , crunchiness and crispness. Fruit firmness is affected by the inheritance of alleles at multiple loci and their possible interactions with the environment. Identification of these loci is key for the determination of genetic candidate markers that can

  18. A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

    Science.gov (United States)

    Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

    2016-12-01

    Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Identification of new genetic susceptibility loci for breast cancer through consideration of gene-environment interactions

    DEFF Research Database (Denmark)

    Schoeps, Anja; Rudolph, Anja; Seibold, Petra

    2014-01-01

    recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714......,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three...... in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8...

  20. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

    OpenAIRE

    Berndt, S.I.; Skibola, C.F.; Joseph, V.; Camp, N.J.; Nieters, A.; Wang, Z.; Cozen, W.; Monnereau, A.; Wang, S.S.; Kelly, R.S.; Lan, Q.; Teras, L.R.; Chatterjee, N.; Chung, C.C.; Yeager, M.

    2013-01-01

    Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 × 10...

  1. Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

    KAUST Repository

    James, Tojo

    2018-01-06

    Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS). Since a large proportion of expression quantitative trait loci (eQTLs) are context-specific, we performed RNA-Seq in peripheral blood mononuclear cells (PBMCs) from MS patients (n=145) to identify eQTLs in regions centered on 109 MS risk SNPs and seven associated HLA variants. We identified 77 statistically significant eQTL associations, including pseudogenes and non-coding RNAs. Thirty-eight out of 40 testable eQTL effects were colocalised with the disease association signal. Since many eQTLs are tissue specific, we aimed to detail their significance in different cell types. Approximately 70% of the eQTLs were replicated and characterized in at least one major PBMC derived cell type. Furthermore, 40% of eQTLs were found to be more pronounced in MS patients compared to noninflammatory neurological diseases patients. In addition, we found two SNPs to be significantly associated with the proportions of three different cell types. Mapping to enhancer histone marks and predicted transcription factor binding sites added additional functional evidence for eight eQTL regions. As an example, we found that rs71624119, shared with three other autoimmune diseases and located in a primed enhancer (H3K4me1) with potential binding for STAT transcription factors, significantly associates with ANKRD55 expression. This study provides many novel and validated targets for future functional characterization of MS and other diseases.

  2. Identification of multi-loci hubs from 4C-seq demonstrates the functional importance of simultaneous interactions.

    Science.gov (United States)

    Jiang, Tingting; Raviram, Ramya; Snetkova, Valentina; Rocha, Pedro P; Proudhon, Charlotte; Badri, Sana; Bonneau, Richard; Skok, Jane A; Kluger, Yuval

    2016-10-14

    Use of low resolution single cell DNA FISH and population based high resolution chromosome conformation capture techniques have highlighted the importance of pairwise chromatin interactions in gene regulation. However, it is unlikely that associations involving regulatory elements act in isolation of other interacting partners that also influence their impact. Indeed, the influence of multi-loci interactions remains something of an enigma as beyond low-resolution DNA FISH we do not have the appropriate tools to analyze these. Here we present a method that uses standard 4C-seq data to identify multi-loci interactions from the same cell. We demonstrate the feasibility of our method using 4C-seq data sets that identify known pairwise and novel tri-loci interactions involving the Tcrb and Igk antigen receptor enhancers. We further show that the three Igk enhancers, MiEκ, 3'Eκ and Edκ, interact simultaneously in this super-enhancer cluster, which add to our previous findings showing that loss of one element decreases interactions between all three elements as well as reducing their transcriptional output. These findings underscore the functional importance of simultaneous interactions and provide new insight into the relationship between enhancer elements. Our method opens the door for studying multi-loci interactions and their impact on gene regulation in other biological settings. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Multiplicities in high energy interactions

    International Nuclear Information System (INIS)

    Derrick, M.

    1984-01-01

    Charged particle multiplicities in hadronic collision have been measured for all energies up to √s = 540 GeV in the center of mass. Similar measurements in e + e - annihilation cover the much smaller range - up to √s = 40 GeV. Data are also available from deep inelastic neutrino scattering up to √s approx. 10 GeV. The experiments measure the mean charged multiplicity , the rapidity density at y = O, and the distributions in prong number. The mean number of photons associated with the events can be used to measure the π 0 and eta 0 multiplicities. Some information is also available on the charged pion, kaon, and nucleon fractions as well as the K 0 and Λ 0 rates and for the higher energy data, the identically equal fraction. We review this data and consider the implications of extrapolations to SSC energies. 13 references

  4. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    NARCIS (Netherlands)

    Nakayama, A.; Nakaoka, H.; Yamamoto, K.; Sakiyama, M.; Shaukat, A.; Toyoda, Y.; Okada, Y.; Kamatani, Y.; Nakamura, T.; Takada, T.; Inoue, K.; Yasujima, T.; Yuasa, H.; Shirahama, Y.; Nakashima, H.; Shimizu, S.; Higashino, T.; Kawamura, Y.; Ogata, H.; Kawaguchi, M.; Ohkawa, Y.; Danjoh, I.; Tokumasu, A.; Ooyama, K.; Ito, T.; Kondo, T.; Wakai, K.; Stiburkova, B.; Pavelka, K.; Stamp, L.K.; Dalbeth, N.; Sakurai, Y.; Suzuki, H; Hosoyamada, M.; Fujimori, S.; Yokoo, T.; Hosoya, T.; Inoue, I.; Takahashi, A.; Kubo, M.; Ooyama, H.; Shimizu, T.; Ichida, K.; Shinomiya, N.; Merriman, T.R.; Matsuo, H.; Andres, M; Joosten, L.A.; Janssen, M.C.H.; Jansen, T.L.; Liote, F.; Radstake, T.R.; Riches, P.L.; So, A.; Tauches, A.K.

    2017-01-01

    OBJECTIVE: A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. METHODS: Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were

  5. Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci

    DEFF Research Database (Denmark)

    Boonen, Susanne E; Mackay, Deborah J G; Hahnemann, Johanne M D

    2013-01-01

    Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because...

  6. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

    NARCIS (Netherlands)

    Ried, Janina S; Jeff M, Janina; Bragg-Gresham, Jennifer L; van Dongen, Jenny; Huffman, Jennifer E; Ahluwalia, Tarunveer S; Cadby, Gemma; Eklund, Niina; Eriksson, Joel; Esko, Tõnu; Feitosa, Mary F; Goel, Anuj; Gorski, Mathias; Hayward, Caroline; Heard-Costa, Nancy L; Jackson, Anne U; Jokinen, Eero; Kanoni, Stavroula; Kristiansson, Kati; Kutalik, Zoltán; Lahti, Jari; Luan, Jian'an; Mägi, Reedik; Mahajan, Anubha; Mangino, Massimo; Medina-Gomez, Carolina; Monda, Keri L; Nolte, Ilja M; Pérusse, Louis; Prokopenko, Inga; Qi, Lu; Rose, Lynda M; Salvi, Erika; Smith, Megan T; Snieder, Harold; Stančáková, Alena; Ju Sung, Yun; Tachmazidou, Ioanna; Teumer, Alexander; Thorleifsson, Gudmar; van der Harst, Pim; Walker, Ryan W; Wang, Sophie R; Wild, Sarah H; Willems, Sara M; Wong, Andrew; Zhang, Weihua; Albrecht, Eva; Couto Alves, Alexessander; Bakker, Stephan J L; Barlassina, Cristina; Bartz, Traci M; Beilby, John; Bellis, Claire; Bergman, Richard N; Bergmann, Sven; Blangero, John; Blüher, Matthias; Boerwinkle, Eric; Bonnycastle, Lori L; Bornstein, Stefan R; Bruinenberg, Marcel; Campbell, Harry; Chen, Yii-Der Ida; Chiang, Charleston W K; Chines, Peter S; Collins, Francis S; Cucca, Fracensco; Cupples, L Adrienne; D'Avila, Francesca; de Geus, Eco J C; Dedoussis, George; Dimitriou, Maria; Döring, Angela; Eriksson, Johan G; Farmaki, Aliki-Eleni; Farrall, Martin; Ferreira, Teresa; Fischer, Krista; Forouhi, Nita G; Friedrich, Nele; Gjesing, Anette Prior; Glorioso, Nicola; Graff, Mariaelisa; Grallert, Harald; Grarup, Niels; Gräßler, Jürgen; Grewal, Jagvir; Hamsten, Anders; Harder, Marie Neergaard; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew Tym; Havulinna, Aki S; Heliövaara, Markku; Hillege, Hans; Hofman, Albert; Holmen, Oddgeir; Homuth, Georg; Hottenga, Jouke-Jan; Hui, Jennie; Husemoen, Lise Lotte; Hysi, Pirro G; Isaacs, Aaron; Ittermann, Till; Jalilzadeh, Shapour; James, Alan L; Jørgensen, Torben; Jousilahti, Pekka; Jula, Antti; Marie Justesen, Johanne; Justice, Anne E; Kähönen, Mika; Karaleftheri, Maria; Tee Khaw, Kay; Keinanen-Kiukaanniemi, Sirkka M; Kinnunen, Leena; Knekt, Paul B; Koistinen, Heikki A; Kolcic, Ivana; Kooner, Ishminder K; Koskinen, Seppo; Kovacs, Peter; Kyriakou, Theodosios; Laitinen, Tomi; Langenberg, Claudia; Lewin, Alexandra M; Lichtner, Peter; Lindgren, Cecilia M; Lindström, Jaana; Linneberg, Allan; Lorbeer, Roberto; Lorentzon, Mattias; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Manunta, Paolo; Leach, Irene Mateo; McArdle, Wendy L; Mcknight, Barbara; Mohlke, Karen L; Mihailov, Evelin; Milani, Lili; Mills, Rebecca; Montasser, May E; Morris, Andrew P; Müller, Gabriele; Musk, Arthur W; Narisu, Narisu; Ong, Ken K; Oostra, Ben A; Osmond, Clive; Palotie, Aarno; Pankow, James S; Paternoster, Lavinia; Penninx, Brenda W; Pichler, Irene; Pilia, Maria G; Polašek, Ozren; Pramstaller, Peter P; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rayner, Nigel W; Ribel-Madsen, Rasmus; Rice, Treva K; Richards, Marcus; Ridker, Paul M; Rivadeneira, Fernando; Ryan, Kathy A; Sanna, Serena; Sarzynski, Mark A; Scholtens, Salome; Scott, Robert A; Sebert, Sylvain; Southam, Lorraine; Sparsø, Thomas Hempel; Steinthorsdottir, Valgerdur; Stirrups, Kathleen; Stolk, Ronald P; Strauch, Konstantin; Stringham, Heather M; Swertz, Morris A; Swift, Amy J; Tönjes, Anke; Tsafantakis, Emmanouil; van der Most, Peter J; Van Vliet-Ostaptchouk, Jana V; Vandenput, Liesbeth; Vartiainen, Erkki; Venturini, Cristina; Verweij, Niek; Viikari, Jorma S; Vitart, Veronique; Vohl, Marie-Claude; Vonk, Judith M; Waeber, Gérard; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Winkler, Thomas W; Wright, Alan F; Yerges-Armstrong, Laura M; Hua Zhao, Jing; Carola Zillikens, M; Boomsma, Dorret I; Bouchard, Claude; Chambers, John C; Chasman, Daniel I; Cusi, Daniele; Gansevoort, Ron T; Gieger, Christian; Hansen, Torben; Hicks, Andrew A; Hu, Frank; Hveem, Kristian; Jarvelin, Marjo-Riitta; Kajantie, Eero; Kooner, Jaspal S; Kuh, Diana; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A; Lehtimäki, Terho; Metspalu, Andres; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J; Palmer, Lyle J; Pedersen, Oluf; Perola, Markus; Peters, Annette; Psaty, Bruce M; Puolijoki, Hannu; Rauramaa, Rainer; Rudan, Igor; Salomaa, Veikko; Schwarz, Peter E H; Shudiner, Alan R; Smit, Jan H; Sørensen, Thorkild I A; Spector, Timothy D; Stefansson, Kari; Stumvoll, Michael; Tremblay, Angelo; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; Völker, Uwe; Vollenweider, Peter; Wareham, Nicholas J; Watkins, Hugh; Wilson, James F; Zeggini, Eleftheria; Abecasis, Goncalo R; Boehnke, Michael; Borecki, Ingrid B; Deloukas, Panos; van Duijn, Cornelia M; Fox, Caroline; Groop, Leif C; Heid, Iris M; Hunter, David J; Kaplan, Robert C; McCarthy, Mark I; North, Kari E; O'Connell, Jeffrey R; Schlessinger, David; Thorsteinsdottir, Unnur; Strachan, David P; Frayling, Timothy; Hirschhorn, Joel N; Müller-Nurasyid, Martina; Loos, Ruth J F

    2016-01-01

    Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates

  7. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

    DEFF Research Database (Denmark)

    Ried, Janina S; Jeff M, Janina; Chu, Audrey Y

    2016-01-01

    Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculate...

  8. A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

    NARCIS (Netherlands)

    J.S. Ried (Janina); J. Jeff (Janina); A.Y. Chu (Audrey Y); Bragg-Gresham, J.L. (Jennifer L.); J. van Dongen (Jenny); J.E. Huffman (Jennifer); T.S. Ahluwalia (Tarunveer Singh); G. Cadby (Gemma); N. Eklund (Niina); J. Eriksson (Joel); T. Esko (Tõnu); M.F. Feitosa (Mary Furlan); A. Goel (Anuj); M. Gorski (Mathias); C. Hayward (Caroline); N.L. Heard-Costa (Nancy); A.U. Jackson (Anne); Jokinen, E. (Eero); S. Kanoni (Stavroula); K. Kristiansson (Kati); Z. Kutalik (Zoltán); J. Lahti (Jari); J. Luan (Jian'An); R. Mägi (Reedik); A. Mahajan (Anubha); M. Mangino (Massimo); M.C. Medina-Gomez (Carolina); K.L. Monda (Keri); I.M. Nolte (Ilja); L. Perusse (Louis); I. Prokopenko (Inga); Qi, L. (Lu); L.M. Rose (Lynda); Salvi, E. (Erika); Smith, M.T. (Megan T.); H. Snieder (Harold); Standáková, A. (Alena); Ju Sung, Y. (Yun); I. Tachmazidou (Ioanna); A. Teumer (Alexander); G. Thorleifsson (Gudmar); P. van der Harst (Pim); Walker, R.W. (Ryan W.); S.R. Wang (Sophie); S.H. Wild (Sarah); S.M. Willems (Sara); A. Wong (Andrew); W. Zhang (Weihua); E. Albrecht (Eva); A. Couto-Alves (Alexessander); S.J.L. Bakker (Stephan); Barlassina, C. (Cristina); T.M. Bartz (Traci M.); J.P. Beilby (John); C. Bellis (Claire); Bergman, R.N. (Richard N.); S.M. Bergmann (Sven); J. Blangero (John); M. Blüher (Matthias); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); S.R. Bornstein (Stefan R.); M. Bruinenberg (M.); H. Campbell (Harry); Y.-D.I. Chen (Yii-Der Ida); Chiang, C.W.K. (Charleston W. K.); P.S. Chines (Peter); F.S. Collins (Francis); Cucca, F. (Fracensco); L.A. Cupples (Adrienne); D'avila, F. (Francesca); E.J.C. de Geus (Eco); G.V. Dedoussis (George); M. Dimitriou (Maria); A. Döring (Angela); K. Hagen (Knut); A.-E. Farmaki (Aliki-Eleni); M. Farrall (Martin); T. Ferreira (Teresa); K. Fischer (Krista); N.G. Forouhi (Nita); N. Friedrich (Nele); A.P. Gjesing (Anette); N. Glorioso (Nicola); M.J. Graff (Maud J.L.); H. Grallert (Harald); N. Grarup (Niels); J. Gräßler (Jürgen); J. Grewal (Jagvir); A. Hamsten (Anders); Harder, M.N. (Marie Neergaard); Hartman, C.A. (Catharina A.); Hassinen, M. (Maija); N. Hastie (Nick); A.T. Hattersley (Andrew); A.S. Havulinna (Aki); M. Heliovaara (Markku); H.L. Hillege (Hans); A. Hofman (Albert); O.L. Holmen (Oddgeir); G. Homuth (Georg); J.J. Hottenga (Jouke Jan); J. Hui (Jennie); L.L.N. Husemoen (Lise Lotte); P.G. Hysi (Pirro); A.J. Isaacs (Aaron); T. Ittermann (Till); S. Jalilzadeh (Shapour); A. James (Alan); T. Jorgensen (Torben); P. Jousilahti (Pekka); A. Jula (Antti); Marie Justesen, J. (Johanne); A.E. Justice (Anne); M. Kähönen (Mika); M. Karaleftheri (Maria); Tee Khaw, K. (Kay); S. Keinanen-Kiukaanniemi (Sirkka); L. Kinnunen (Leena); P. Knekt; H. Koistinen (Heikki); I. Kolcic (Ivana); I.K. Kooner (Ishminder K.); S. Koskinen (Seppo); P. Kovacs (Peter); T. Kyriakou (Theodosios); Laitinen, T. (Tomi); C. Langenberg (Claudia); A. Lewin (Alex); P. Lichtner (Peter); C.M. Lindgren (Cecilia); J. Lindström (Jaana); A. Linneberg (Allan); R. Lorbeer (Roberto); M. Lorentzon (Mattias); R.N. Luben (Robert); V. Lyssenko (Valeriya); S. Männistö (Satu); P. Manunta (Paolo); I.M. Leach (Irene Mateo); W.L. McArdle (Wendy); Mcknight, B. (Barbara); K.L. Mohlke (Karen); E. Mihailov (Evelin); L. Milani (Lili); R. Mills (Rebecca); M.E. Montasser (May E.); A.P. Morris (Andrew); G. Müller (Gabriele); Musk, A.W. (Arthur W.); N. Narisu (Narisu); K.K. Ong (Ken K.); B.A. Oostra (Ben); C. Osmond (Clive); A. Palotie (Aarno); J.S. Pankow (James); L. Paternoster (Lavinia); B.W.J.H. Penninx (Brenda); I. Pichler (Irene); M.G. Pilia (Maria Grazia); O. Polasek (Ozren); P.P. Pramstaller (Peter Paul); O.T. Raitakari (Olli T.); T. Rankinen (Tuomo); Rao, D.C.; N.W. Rayner (Nigel William); Ribel-Madsen, R. (Rasmus); Rice, T.K. (Treva K.); Richards, M. (Marcus); P.M. Ridker (Paul); F. Rivadeneira Ramirez (Fernando); Ryan, K.A. (Kathy A.); S. Sanna (Serena); M.A. Sarzynski (Mark A.); S. Scholtens (Salome); R.A. Scott (Robert); S. Sebert (Sylvain); L. Southam (Lorraine); T. Sparsø (Thomas); V. Steinthorsdottir (Valgerdur); K. Stirrups (Kathy); R.P. Stolk (Ronald); K. Strauch (Konstantin); H.M. Stringham (Heather); M. Swertz (Morris); A.J. Swift (Amy); A. Tönjes (Anke); E. Tsafantakis (Emmanouil); P.J. van der Most (Peter); J.V. van Vliet-Ostaptchouk (Jana); L. Vandenput (Liesbeth); Vartiainen, E. (Erkki); C. Venturini (Cristina); N. Verweij (Niek); J. Viikari (Jorma); Vitart, V. (Veronique); M.-C. Vohl (Marie-Claude); J.M. Vonk (Judith); G. Waeber (Gérard); E. Widen (Elisabeth); G.A.H.M. Willemsen (Gonneke); T. Wilsgaard (Tom); T.W. Winkler (Thomas W.); A.F. Wright (Alan); L.M. Yerges-Armstrong (Laura); Zhao, J.H. (Jing Hua); M.C. Zillikens (Carola); D.I. Boomsma (Dorret); C. Bouchard (Claude); J.C. Chambers (John); D.I. Chasman (Daniel); D. Cusi (Daniele); R.T. Gansevoort (Ron); C. Gieger (Christian); T. Hansen (T.); A.A. Hicks (Andrew); Hu, F. (Frank); K. Hveem (Kristian); M.-R. Jarvelin (Marjo-Riitta); E. Kajantie (Eero); J.S. Kooner (Jaspal S.); D. Kuh (Diana); J. Kuusisto (Johanna); M. Laakso (Markku); T.A. Lakka (Timo); T. Lehtimäki (Terho); A. Metspalu (Andres); I. Njølstad (Inger); C. Ohlsson (Claes); A.J. Oldehinkel (Albertine); Palmer, L.J. (Lyle J.); O. Pedersen (Oluf); M. Perola (Markus); A. Peters (Annette); B.M. Psaty (Bruce); Puolijoki, H. (Hannu); R. Rauramaa (Rainer); I. Rudan (Igor); V. Salomaa (Veikko); P.E.H. Schwarz (Peter); Shudiner, A.R. (Alan R.); J.H. Smit (Jan); T.I.A. Sørensen (Thorkild); T.D. Spector (Timothy); J-A. Zwart (John-Anker); M. Stumvoll (Michael); Tremblay, A. (Angelo); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); Uusitupa, M. (Matti); U. Völker (Uwe); P. Vollenweider (Peter); N.J. Wareham (Nick); H. Watkins (Hugh); J.F. Wilson (James); E. Zeggini (Eleftheria); G.R. Abecasis (Gonçalo); M. Boehnke (Michael); I.B. Borecki (Ingrid); P. Deloukas (Panagiotis); C.M. van Duijn (Cornelia); C.S. Fox (Caroline); L. Groop (Leif); I.M. Heid (Iris); Hunter, D.J. (David J.); R.C. Kaplan (Robert); M.I. McCarthy (Mark); K.E. North (Kari); J.R. O´Connell; Schlessinger, D. (David); U. Thorsteinsdottir (Unnur); D.P. Strachan (David); T.M. Frayling (Timothy); J.N. Hirschhorn (Joel); M. Müller-Nurasyid (Martina); R.J.F. Loos (Ruth)

    2016-01-01

    textabstractLarge consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that

  9. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Berndt, Sonja I; Camp, Nicola J; Skibola, Christine F; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S; Smedby, Karin E; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S; Lan, Qing; Teras, Lauren R; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R; Hartge, Patricia; Purdue, Mark P; Birmann, Brenda M; Vajdic, Claire M; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G; Shanafelt, Tait D; Novak, Anne J; Kay, Neil E; Liebow, Mark; Cunningham, Julie M; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A; Diver, W Ryan; Link, Brian K; Weiner, George J; Conde, Lucia; Bracci, Paige M; Riby, Jacques; Arnett, Donna K; Zhi, Degui; Leach, Justin M; Holly, Elizabeth A; Jackson, Rebecca D; Tinker, Lesley F; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G; Achenbach, Sara J; Vachon, Celine M; Goldin, Lynn R; Strom, Sara S; Leis, Jose F; Weinberg, J Brice; Caporaso, Neil E; Norman, Aaron D; De Roos, Anneclaire J; Morton, Lindsay M; Severson, Richard K; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María-Dolores; Vermeulen, Roel C H|info:eu-repo/dai/nl/216532620; Travis, Ruth C; Southey, Melissa C; Milne, Roger L; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R; Villano, Danylo J; Maria, Ann; Spinelli, John J; Gascoyne, Randy D; Connors, Joseph M; Bertrand, Kimberly A; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E; Snowden, John A; Wright, Josh; Fraumeni, Joseph F; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R; Chanock, Stephen J; Rothman, Nathaniel; Slager, Susan L

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and

  10. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    Science.gov (United States)

    Berndt, Sonja I.; Camp, Nicola J.; Skibola, Christine F.; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S.; Smedby, Karin E.; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S.; Lan, Qing; Teras, Lauren R.; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R.; Hartge, Patricia; Purdue, Mark P.; Birmann, Brenda M.; Vajdic, Claire M.; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G.; Shanafelt, Tait D.; Novak, Anne J.; Kay, Neil E.; Liebow, Mark; Cunningham, Julie M.; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T.; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A.; Diver, W Ryan; Link, Brian K.; Weiner, George J.; Conde, Lucia; Bracci, Paige M.; Riby, Jacques; Arnett, Donna K.; Zhi, Degui; Leach, Justin M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Goldin, Lynn R.; Strom, Sara S.; Leis, Jose F.; Weinberg, J. Brice; Caporaso, Neil E.; Norman, Aaron D.; De Roos, Anneclaire J.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María- Dolores; Vermeulen, Roel C. H.; Travis, Ruth C.; Southey, Melissa C.; Milne, Roger L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R.; Villano, Danylo J.; Maria, Ann; Spinelli, John J.; Gascoyne, Randy D.; Connors, Joseph M.; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M.; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E.; Snowden, John A.; Wright, Josh; Fraumeni, Joseph F.; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Slager, Susan L.

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  11. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

    NARCIS (Netherlands)

    Cerhan, James R.; Berndt, Sonja I.; Vijai, Joseph; Ghesquières, Hervé; McKay, James; Wang, Sophia S.; Wang, Zhaoming; Yeager, Meredith; Conde, Lucia; De Bakker, Paul I W; Nieters, Alexandra; Cox, David; Burdett, Laurie; Monnereau, Alain; Flowers, Christopher R.; De Roos, Anneclaire J.; Brooks-Wilson, Angela R.; Lan, Qing; Severi, Gianluca; Melbye, Mads; Gu, Jian; Jackson, Rebecca D.; Kane, Eleanor; Teras, Lauren R.; Purdue, Mark P.; Vajdic, Claire M.; Spinelli, John J.; Giles, Graham G.; Albanes, Demetrius; Kelly, Rachel S.; Zucca, Mariagrazia; Bertrand, Kimberly A.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Hutchinson, Amy; Zhi, Degui; Habermann, Thomas M.; Link, Brian K.; Novak, Anne J.; Dogan, Ahmet; Asmann, Yan W.; Liebow, Mark; Thompson, Carrie A.; Ansell, Stephen M.; Witzig, Thomas E.; Weiner, George J.; Veron, Amelie S.; Zelenika, Diana; Tilly, Hervé; Haioun, Corinne; Molina, Thierry Jo; Hjalgrim, Henrik; Glimelius, Bengt; Adami, Hans Olov; Bracci, Paige M.; Riby, Jacques; Smith, Martyn T.; Holly, Elizabeth A.; Cozen, Wendy; Hartge, Patricia; Morton, Lindsay M.; Severson, Richard K.; Tinker, Lesley F.; North, Kari E.; Becker, Nikolaus; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; Staines, Anthony; Lightfoot, Tracy; Crouch, Simon; Smith, Alex; Roman, Eve; Diver, W. Ryan; Offit, Kenneth; Zelenetz, Andrew; Klein, Robert J.; Villano, Danylo J.; Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Kricker, Anne; Turner, Jenny; Southey, Melissa C.; Clavel, Jacqueline; Virtamo, Jarmo; Weinstein, Stephanie; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Trichopoulos, Dimitrios; Vermeulen, Roel C H; Boeing, Heiner; Tjonneland, Anne; Angelucci, Emanuele; Di Lollo, Simonetta; Rais, Marco; Birmann, Brenda M.; Laden, Francine; Giovannucci, Edward; Kraft, Peter; Huang, Jinyan; Ma, Baoshan; Ye, Yuanqing; Chiu, Brian C H; Sampson, Joshua; Liang, Liming; Park, Ju Hyun; Chung, Charles C.; Weisenburger, Dennis D.; Chatterjee, Nilanjan; Fraumeni, Joseph F.; Slager, Susan L.; Wu, Xifeng; De Sanjose, Silvia; Smedby, Karin E.; Salles, Gilles; Skibola, Christine F.; Rothman, Nathaniel; Chanock, Stephen J.

    2014-01-01

    Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of

  12. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes.

    Science.gov (United States)

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi; Shimizu, Seiko; Higashino, Toshihide; Kawamura, Yusuke; Ogata, Hiraku; Kawaguchi, Makoto; Ohkawa, Yasuyuki; Danjoh, Inaho; Tokumasu, Atsumi; Ooyama, Keiko; Ito, Toshimitsu; Kondo, Takaaki; Wakai, Kenji; Stiburkova, Blanka; Pavelka, Karel; Stamp, Lisa K; Dalbeth, Nicola; Sakurai, Yutaka; Suzuki, Hiroshi; Hosoyamada, Makoto; Fujimori, Shin; Yokoo, Takashi; Hosoya, Tatsuo; Inoue, Ituro; Takahashi, Atsushi; Kubo, Michiaki; Ooyama, Hiroshi; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi; Merriman, Tony R; Matsuo, Hirotaka

    2017-05-01

    A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study. In addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (pgout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (p meta =3.58×10 -8 ). Our findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia. 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/.

  13. iLOCi: a SNP interaction prioritization technique for detecting epistasis in genome-wide association studies

    Directory of Open Access Journals (Sweden)

    Piriyapongsa Jittima

    2012-12-01

    Full Text Available Abstract Background Genome-wide association studies (GWAS do not provide a full account of the heritability of genetic diseases since gene-gene interactions, also known as epistasis are not considered in single locus GWAS. To address this problem, a considerable number of methods have been developed for identifying disease-associated gene-gene interactions. However, these methods typically fail to identify interacting markers explaining more of the disease heritability over single locus GWAS, since many of the interactions significant for disease are obscured by uninformative marker interactions e.g., linkage disequilibrium (LD. Results In this study, we present a novel SNP interaction prioritization algorithm, named iLOCi (Interacting Loci. This algorithm accounts for marker dependencies separately in case and control groups. Disease-associated interactions are then prioritized according to a novel ranking score calculated from the difference in marker dependencies for every possible pair between case and control groups. The analysis of a typical GWAS dataset can be completed in less than a day on a standard workstation with parallel processing capability. The proposed framework was validated using simulated data and applied to real GWAS datasets using the Wellcome Trust Case Control Consortium (WTCCC data. The results from simulated data showed the ability of iLOCi to identify various types of gene-gene interactions, especially for high-order interaction. From the WTCCC data, we found that among the top ranked interacting SNP pairs, several mapped to genes previously known to be associated with disease, and interestingly, other previously unreported genes with biologically related roles. Conclusion iLOCi is a powerful tool for uncovering true disease interacting markers and thus can provide a more complete understanding of the genetic basis underlying complex disease. The program is available for download at http://www4a.biotec.or.th/GI/tools/iloci.

  14. Allelic interaction of F1 pollen sterility loci and abnormal chromosome behaviour caused pollen sterility in intersubspecific autotetraploid rice hybrids.

    Science.gov (United States)

    He, J H; Shahid, M Q; Li, Y J; Guo, H B; Cheng, X A; Liu, X D; Lu, Y G

    2011-08-01

    The intersubspecific hybrids of autotetraploid rice has many features that increase rice yield, but lower seed set is a major hindrance in its utilization. Pollen sterility is one of the most important factors which cause intersubspecific hybrid sterility. The hybrids with greater variation in seed set were used to study how the F(1) pollen sterile loci (S-a, S-b, and S-c) interact with each other and how abnormal chromosome behaviour and allelic interaction of F(1) sterility loci affect pollen fertility and seed set of intersubspecific autotetraploid rice hybrids. The results showed that interaction between pollen sterility loci have significant effects on the pollen fertility of autotetraploid hybrids, and pollen fertility further decreased with an increase in the allelic interaction of F(1) pollen sterility loci. Abnormal ultra-structure and microtubule distribution patterns during pollen mother cell (PMC) meiosis were found in the hybrids with low pollen fertility in interphase and leptotene, suggesting that the effect-time of pollen sterility loci interaction was very early. There were highly significant differences in the number of quadrivalents and bivalents, and in chromosome configuration among all the hybrids, and quadrivalents decreased with an increase in the seed set of autotetraploid hybrids. Many different kinds of chromosomal abnormalities, such as chromosome straggling, chromosome lagging, asynchrony of chromosome disjunction, and tri-fission were found during the various developmental stages of PMC meiosis. All these abnormalities were significantly higher in sterile hybrids than in fertile hybrids, suggesting that pollen sterility gene interactions tend to increase the chromosomal abnormalities which cause the partial abortion of male gametes and leads to the decline in the seed set of the autotetraploid rice hybrids. © 2011 The Author(s).

  15. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    DEFF Research Database (Denmark)

    Nickels, Stefan; Truong, Thérèse; Hein, Rebecca

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cance...

  16. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors

    NARCIS (Netherlands)

    Nickels, S.; Truong, T.; Hein, R.; Stevens, K.; Buck, K.; Behrens, S.; Eilber, U.; Schmidt, M.; Haberle, L.; Vrieling, A.; Gaudet, M.; Figueroa, J.; Schoof, N.; Spurdle, A.B.; Rudolph, A.; Fasching, P.A.; Hopper, J.L.; Makalic, E.; Schmidt, D.F.; Southey, M.C.; Beckmann, M.W.; Ekici, A.B.; Fletcher, O.; Gibson, L.; Idos, S. Silva; Peto, J.; Humphreys, M.K.; Wang, J; Cordina-Duverger, E.; Menegaux, F.; Nordestgaard, B.G.; Bojesen, S.E.; Lanng, C.; Anton-Culver, H.; Ziogas, A.; Bernstein, L.; Clarke, C.A.; Brenner, H.; Muller, H.; Arndt, V.; Stegmaier, C.; Brauch, H.; Bruning, T.; Harth, V.; Genica, N.; Mannermaa, A.; Kataja, V.; Kosma, V.M.; Hartikainen, J.M.; Lambrechts, D.; Smeets, D.; Neven, P.; Paridaens, R.; Flesch-Janys, D.; Obi, N.; Wang-Gohrke, S.; Couch, F.J.; Olson, J.E.; Vachon, C.M.; Giles, G.G.; Severi, G.; Baglietto, L.; Offit, K.; John, E.M.; Miron, A.; Andrulis, I.L.; Knight, J.A.; Glendon, G.; Mulligan, A.M.; Chanock, S.J.; Lissowska, J.; Liu, J.; Cox, A; Cramp, H.; Connley, D.; Balasubramanian, S.; Dunning, A.M.; Shah, M.; Trentham-Dietz, A.; Newcomb, P.; Titus, L.; Egan, K.; Cahoon, E.K.; Rajaraman, P.; Sigurdson, A.J.; Doody, M.M.; Guenel, P.; Pharoah, P.D.; Schmidt, M.K.; Hall, P.; Easton, D.F.; Garcia-Closas, M.; Milne, R.L.; Chang-Claude, J.; et al.,

    2013-01-01

    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer.

  17. GWAS of clinically defined gout and subtypes identifies multiple susceptibility loci that include urate transporter genes

    OpenAIRE

    Nakayama, Akiyoshi; Nakaoka, Hirofumi; Yamamoto, Ken; Sakiyama, Masayuki; Shaukat, Amara; Toyoda, Yu; Okada, Yukinori; Kamatani, Yoichiro; Nakamura, Takahiro; Takada, Tappei; Inoue, Katsuhisa; Yasujima, Tomoya; Yuasa, Hiroaki; Shirahama, Yuko; Nakashima, Hiroshi

    2016-01-01

    Objective A genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific. Methods Putative causal association signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zeala...

  18. H2DB: a heritability database across multiple species by annotating trait-associated genomic loci.

    Science.gov (United States)

    Kaminuma, Eli; Fujisawa, Takatomo; Tanizawa, Yasuhiro; Sakamoto, Naoko; Kurata, Nori; Shimizu, Tokurou; Nakamura, Yasukazu

    2013-01-01

    H2DB (http://tga.nig.ac.jp/h2db/), an annotation database of genetic heritability estimates for humans and other species, has been developed as a knowledge database to connect trait-associated genomic loci. Heritability estimates have been investigated for individual species, particularly in human twin studies and plant/animal breeding studies. However, there appears to be no comprehensive heritability database for both humans and other species. Here, we introduce an annotation database for genetic heritabilities of various species that was annotated by manually curating online public resources in PUBMED abstracts and journal contents. The proposed heritability database contains attribute information for trait descriptions, experimental conditions, trait-associated genomic loci and broad- and narrow-sense heritability specifications. Annotated trait-associated genomic loci, for which most are single-nucleotide polymorphisms derived from genome-wide association studies, may be valuable resources for experimental scientists. In addition, we assigned phenotype ontologies to the annotated traits for the purposes of discussing heritability distributions based on phenotypic classifications.

  19. A Study of Multiplicities in Hadronic Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Estrada Tristan, Nora Patricia; /San Luis Potosi U.

    2006-02-01

    Using data from the SELEX (Fermilab E781) experiment obtained with a minimum-bias trigger, we study multiplicity and angular distributions of secondary particles produced in interactions in the experimental targets. We observe interactions of {Sigma}{sup -}, proton, {pi}{sup -}, and {pi}{sup +}, at beam momenta between 250 GeV/c and 650 GeV/c, in copper, polyethylene, graphite, and beryllium targets. We show that the multiplicity and angular distributions for meson and baryon beams at the same momentum are identical. We also show that the mean multiplicity increases with beam momentum, and presents only small variations with the target material.

  20. Neocentromeres Provide Chromosome Segregation Accuracy and Centromere Clustering to Multiple Loci along a Candida albicans Chromosome.

    Directory of Open Access Journals (Sweden)

    Laura S Burrack

    2016-09-01

    Full Text Available Assembly of kinetochore complexes, involving greater than one hundred proteins, is essential for chromosome segregation and genome stability. Neocentromeres, or new centromeres, occur when kinetochores assemble de novo, at DNA loci not previously associated with kinetochore proteins, and they restore chromosome segregation to chromosomes lacking a functional centromere. Neocentromeres have been observed in a number of diseases and may play an evolutionary role in adaptation or speciation. However, the consequences of neocentromere formation on chromosome missegregation rates, gene expression, and three-dimensional (3D nuclear structure are not well understood. Here, we used Candida albicans, an organism with small, epigenetically-inherited centromeres, as a model system to study the functions of twenty different neocentromere loci along a single chromosome, chromosome 5. Comparison of neocentromere properties relative to native centromere functions revealed that all twenty neocentromeres mediated chromosome segregation, albeit to different degrees. Some neocentromeres also caused reduced levels of transcription from genes found within the neocentromere region. Furthermore, like native centromeres, neocentromeres clustered in 3D with active/functional centromeres, indicating that formation of a new centromere mediates the reorganization of 3D nuclear architecture. This demonstrates that centromere clustering depends on epigenetically defined function and not on the primary DNA sequence, and that neocentromere function is independent of its distance from the native centromere position. Together, the results show that a neocentromere can form at many loci along a chromosome and can support the assembly of a functional kinetochore that exhibits native centromere functions including chromosome segregation accuracy and centromere clustering within the nucleus.

  1. Effects of multiple genetic loci on the pathogenesis from serum urate to gout

    OpenAIRE

    Zheng Dong; Jingru Zhou; Shuai Jiang; Yuan Li; Dongbao Zhao; Chengde Yang; Yanyun Ma; Yi Wang; Hongjun He; Hengdong Ji; Yajun Yang; Xiaofeng Wang; Xia Xu; Yafei Pang; Hejian Zou

    2017-01-01

    Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (P FDR?

  2. Efficient genome-wide association in biobanks using topic modeling identifies multiple novel disease loci.

    Science.gov (United States)

    McCoy, Thomas H; Castro, Victor M; Snapper, Leslie A; Hart, Kamber L; Perlis, Roy H

    2017-08-31

    Biobanks and national registries represent a powerful tool for genomic discovery, but rely on diagnostic codes that may be unreliable and fail to capture the relationship between related diagnoses. We developed an efficient means of conducting genome-wide association studies using combinations of diagnostic codes from electronic health records (EHR) for 10845 participants in a biobanking program at two large academic medical centers. Specifically, we applied latent Dirichilet allocation to fit 50 disease topics based on diagnostic codes, then conducted genome-wide common-variant association for each topic. In sensitivity analysis, these results were contrasted with those obtained from traditional single-diagnosis phenome-wide association analysis, as well as those in which only a subset of diagnostic codes are included per topic. In meta-analysis across three biobank cohorts, we identified 23 disease-associated loci with p<1e-15, including previously associated autoimmune disease loci. In all cases, observed significant associations were of greater magnitude than for single phenome-wide diagnostic codes, and incorporation of less strongly-loading diagnostic codes enhanced association. This strategy provides a more efficient means of phenome-wide association in biobanks with coded clinical data.

  3. Analysis of Multiple Genomic Sequence Alignments: A Web Resource, Online Tools, and Lessons Learned From Analysis of Mammalian SCL Loci

    Science.gov (United States)

    Chapman, Michael A.; Donaldson, Ian J.; Gilbert, James; Grafham, Darren; Rogers, Jane; Green, Anthony R.; Göttgens, Berthold

    2004-01-01

    Comparative analysis of genomic sequences is becoming a standard technique for studying gene regulation. However, only a limited number of tools are currently available for the analysis of multiple genomic sequences. An extensive data set for the testing and training of such tools is provided by the SCL gene locus. Here we have expanded the data set to eight vertebrate species by sequencing the dog SCL locus and by annotating the dog and rat SCL loci. To provide a resource for the bioinformatics community, all SCL sequences and functional annotations, comprising a collation of the extensive experimental evidence pertaining to SCL regulation, have been made available via a Web server. A Web interface to new tools specifically designed for the display and analysis of multiple sequence alignments was also implemented. The unique SCL data set and new sequence comparison tools allowed us to perform a rigorous examination of the true benefits of multiple sequence comparisons. We demonstrate that multiple sequence alignments are, overall, superior to pairwise alignments for identification of mammalian regulatory regions. In the search for individual transcription factor binding sites, multiple alignments markedly increase the signal-to-noise ratio compared to pairwise alignments. PMID:14718377

  4. IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci

    DEFF Research Database (Denmark)

    Sørensen, Per Soelberg

    2010-01-01

    and the same direction of effect observed in the discovery phase. Three loci exceeded genome-wide significance in the joint analysis: RGS1 (P value=3.55 x 10(-9)), IL12A (P=3.08 x 10(-8)) and MPHOSPH9/CDK2AP1 (P=3.96 x 10(-8)). The RGS1 risk allele is shared with celiac disease (CD), and the IL12A risk allele......A recent meta-analysis identified seven single-nucleotide polymorphisms (SNPs) with suggestive evidence of association with multiple sclerosis (MS). We report an analysis of these polymorphisms in a replication study that includes 8,085 cases and 7,777 controls. A meta-analysis across...... the replication collections and a joint analysis with the discovery data set were performed. The possible functional consequences of the validated susceptibility loci were explored using RNA expression data. For all of the tested SNPs, the effect observed in the replication phase involved the same allele...

  5. Modularization and epistatic hierarchy determine homeostatic actions of multiple blood pressure quantitative trait loci.

    Science.gov (United States)

    Chauvet, Cristina; Crespo, Kimberley; Ménard, Annie; Roy, Julie; Deng, Alan Y

    2013-11-15

    Hypertension, the most frequently diagnosed clinical condition world-wide, predisposes individuals to morbidity and mortality, yet its underlying pathological etiologies are poorly understood. So far, a large number of quantitative trait loci (QTLs) have been identified in both humans and animal models, but how they function together in determining overall blood pressure (BP) in physiological settings is unknown. Here, we systematically and comprehensively performed pair-wise comparisons of individual QTLs to create a global picture of their functionality in an inbred rat model. Rather than each of numerous QTLs contributing to infinitesimal BP increments, a modularized pattern arises: two epistatic 'blocks' constitute basic functional 'units' for nearly all QTLs, designated as epistatic module 1 (EM1) and EM2. This modularization dictates the magnitude and scope of BP effects. Any EM1 member can contribute to BP additively to that of EM2, but not to those of the same module. Members of each EM display epistatic hierarchy, which seems to reflect a related functional pathway. Rat homologues of 11 human BP QTLs belong to either EM1 or EM2. Unique insights emerge into the novel genetic mechanism and hierarchy determining BP in the Dahl salt-sensitive SS/Jr (DSS) rat model that implicate a portion of human QTLs. Elucidating the pathways underlying EM1 and EM2 may reveal the genetic regulation of BP.

  6. Effects of multiple genetic loci on the pathogenesis from serum urate to gout.

    Science.gov (United States)

    Dong, Zheng; Zhou, Jingru; Jiang, Shuai; Li, Yuan; Zhao, Dongbao; Yang, Chengde; Ma, Yanyun; Wang, Yi; He, Hongjun; Ji, Hengdong; Yang, Yajun; Wang, Xiaofeng; Xu, Xia; Pang, Yafei; Zou, Hejian; Jin, Li; Wang, Jiucun

    2017-03-02

    Gout is a common arthritis resulting from increased serum urate, and many loci have been identified that are associated with serum urate and gout. However, their influence on the progression from elevated serum urate levels to gout is unclear. This study aims to explore systematically the effects of genetic variants on the pathogenesis in approximately 5,000 Chinese individuals. Six genes (PDZK1, GCKR, TRIM46, HNF4G, SLC17A1, LRRC16A) were determined to be associated with serum urate (P FDR  gene, SLC17A4, contributed to the development of gout from hyperuricemia (OR = 1.56, P FDR  = 3.68E-09; OR = 1.27, P FDR  = 0.013, respectively). Also, HNF4G is a novel gene associated with susceptibility to gout (OR = 1.28, P FDR  = 1.08E-03). In addition, A1CF and TRIM46 were identified as associated with gout in the Chinese population for the first time (P FDR  gout and suggests that urate-associated genes functioning as urate transporters may play a specific role in the pathogenesis of gout. Furthermore, two novel gout-associated genes (HNF4G and SLC17A4) were identified.

  7. Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies

    DEFF Research Database (Denmark)

    George, Michaela F; Briggs, Farren B S; Shao, Xiaorong

    2016-01-01

    associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. CONCLUSIONS......OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded...

  8. Impact of genetic risk loci for multiple sclerosis on expression of proximal genes in patients

    KAUST Repository

    James, Tojo; Lindé n, Magdalena; Morikawa, Hiromasa; Fernandes, Sunjay Jude; Ruhrmann, Sabrina; Huss, Mikael; Brandi, Maya; Piehl, Fredrik; Jagodic, Maja; Tegner, Jesper; Khademi, Mohsen; Olsson, Tomas; Gomez-Cabrero, David; Kockum, Ingrid

    2018-01-01

    Despite advancements in genetic studies, it is difficult to understand and characterize the functional relevance of disease-associated genetic variants, especially in the context of a complex multifactorial disease such as Multiple Sclerosis (MS

  9. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    DEFF Research Database (Denmark)

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P...

  10. Genome-wide meta-analyses identify multiple loci associated with smoking behavior.

    LENUS (Irish Health Repository)

    2010-05-01

    Consistent but indirect evidence has implicated genetic factors in smoking behavior. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], beta = 1.03, standard error (s.e.) = 0.053, P = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], beta = 0.367, s.e. = 0.059, P = 5.7 x 10(-10); and rs1028936[A], beta = 0.446, s.e. = 0.074, P = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], beta = 0.333, s.e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.

  11. Multiple Linkage Disequilibrium Mapping Methods to Validate Additive Quantitative Trait Loci in Korean Native Cattle (Hanwoo

    Directory of Open Access Journals (Sweden)

    Yi Li

    2015-07-01

    Full Text Available The efficiency of genome-wide association analysis (GWAS depends on power of detection for quantitative trait loci (QTL and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM, a combined linkage and linkage disequilibrium analysis (LDLA and a BayesCπ approach. The phenotypes of 486 steers were collected for weaning weight (WWT, yearling weight (YWT, carcass weight (CWT, backfat thickness (BFT, longissimus dorsi muscle area, and marbling score (Marb. Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX] may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions.

  12. Genotyping of Bacillus anthracis strains based on automated capillary 25-loci Multiple Locus Variable-Number Tandem Repeats Analysis

    Directory of Open Access Journals (Sweden)

    Ciervo Alessandra

    2006-04-01

    Full Text Available Abstract Background The genome of Bacillus anthracis, the etiological agent of anthrax, is highly monomorphic which makes differentiation between strains difficult. A Multiple Locus Variable-number tandem repeats (VNTR Analysis (MLVA assay based on 20 markers was previously described. It has considerable discrimination power, reproducibility, and low cost, especially since the markers proposed can be typed by agarose-gel electrophoresis. However in an emergency situation, faster genotyping and access to representative databases is necessary. Results Genotyping of B. anthracis reference strains and isolates from France and Italy was done using a 25 loci MLVA assay combining 21 previously described loci and 4 new ones. DNA was amplified in 4 multiplex PCR reactions and the length of the resulting 25 amplicons was estimated by automated capillary electrophoresis. The results were reproducible and the data were consistent with other gel based methods once differences in mobility patterns were taken into account. Some alleles previously unresolved by agarose gel electrophoresis could be resolved by capillary electrophoresis, thus further increasing the assay resolution. One particular locus, Bams30, is the result of a recombination between a 27 bp tandem repeat and a 9 bp tandem repeat. The analysis of the array illustrates the evolution process of tandem repeats. Conclusion In a crisis situation of suspected bioterrorism, standardization, speed and accuracy, together with the availability of reference typing data are important issues, as illustrated by the 2001 anthrax letters event. In this report we describe an upgrade of the previously published MLVA method for genotyping of B. anthracis and apply the method to the typing of French and Italian B. anthracis strain collections. The increased number of markers studied compared to reports using only 8 loci greatly improves the discrimination power of the technique. An Italian strain belonging to the

  13. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci

    DEFF Research Database (Denmark)

    Stender, Stefan; Kozlitina, Julia; Nordestgaard, Børge G.

    2017-01-01

    sequence variants (encoding PNPLA3 p.I148M, TM6SF2 p.E167K, and GCKR p.P446L) associated with nonalcoholic fatty liver disease (NAFLD). Synergy between adiposity and genotype promoted the full spectrum of NAFLD, from steatosis to hepatic inflammation to cirrhosis. We found no evidence of strong interaction...

  14. Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

    Science.gov (United States)

    Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

    2017-04-01

    Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

  15. Dissecting quantitative trait loci for boron efficiency across multiple environments in Brassica napus.

    Directory of Open Access Journals (Sweden)

    Zunkang Zhao

    Full Text Available High yield is the most important goal in crop breeding, and boron (B is an essential micronutrient for plants. However, B deficiency, leading to yield decreases, is an agricultural problem worldwide. Brassica napus is one of the most sensitive crops to B deficiency, and considerable genotypic variation exists among different cultivars in response to B deficiency. To dissect the genetic basis of tolerance to B deficiency in B. napus, we carried out QTL analysis for seed yield and yield-related traits under low and normal B conditions using the double haploid population (TNDH by two-year and the BQDH population by three-year field trials. In total, 80 putative QTLs and 42 epistatic interactions for seed yield, plant height, branch number, pod number, seed number, seed weight and B efficiency coefficient (BEC were identified under low and normal B conditions, singly explaining 4.15-23.16% and 0.53-14.38% of the phenotypic variation. An additive effect of putative QTLs was a more important controlling factor than the additive-additive effect of epistatic interactions. Four QTL-by-environment interactions and 7 interactions between epistatic interactions and the environment contributed to 1.27-4.95% and 1.17-3.68% of the phenotypic variation, respectively. The chromosome region on A2 of SYLB-A2 for seed yield under low B condition and BEC-A2 for BEC in the two populations was equivalent to the region of a reported major QTL, BE1. The B. napus homologous genes of Bra020592 and Bra020595 mapped to the A2 region and were speculated to be candidate genes for B efficiency. These findings reveal the complex genetic basis of B efficiency in B. napus. They provide a basis for the fine mapping and cloning of the B efficiency genes and for breeding B-efficient cultivars by marker-assisted selection (MAS.

  16. Polyploidy Enhances F1 Pollen Sterility Loci Interactions That Increase Meiosis Abnormalities and Pollen Sterility in Autotetraploid Rice.

    Science.gov (United States)

    Wu, Jinwen; Shahid, Muhammad Qasim; Chen, Lin; Chen, Zhixiong; Wang, Lan; Liu, Xiangdong; Lu, Yonggen

    2015-12-01

    Intersubspecific autotetraploid rice (Oryza sativa ssp. indica × japonica) hybrids have greater biological and yield potentials than diploid rice. However, the low fertility of intersubspecific autotetraploid hybrids, which is largely caused by high pollen abortion rates, limits their commercial utility. To decipher the cytological and molecular mechanisms underlying allelic interactions in autotetraploid rice, we developed an autotetraploid rice hybrid that was heterozygous (S(i)S(j)) at F1 pollen sterility loci (Sa, Sb, and Sc) using near-isogenic lines. Cytological studies showed that the autotetraploid had higher percentages (>30%) of abnormal chromosome behavior and aberrant meiocytes (>50%) during meiosis than did the diploid rice hybrid control. Analysis of gene expression profiles revealed 1,888 genes that were differentially expressed between the autotetraploid and diploid hybrid lines at the meiotic stage, among which 889 and 999 were up- and down-regulated, respectively. Of the 999 down-regulated genes, 940 were associated with the combined effect of polyploidy and pollen sterility loci interactions (IPE). Gene Ontology enrichment analysis identified a prominent functional gene class consisting of seven genes related to photosystem I (Gene Ontology 0009522). Moreover, 55 meiosis-related or meiosis stage-specific genes were associated with IPE in autotetraploid rice, including Os02g0497500, which encodes a DNA repair-recombination protein, and Os02g0490000, which encodes a component of the ubiquitin-proteasome pathway. These results suggest that polyploidy enhances epistatic interactions between alleles of pollen sterility loci, thereby altering the expression profiles of important meiosis-related or meiosis stage-specific genes and resulting in high pollen sterility. © 2015 American Society of Plant Biologists. All Rights Reserved.

  17. Polyploidy Enhances F1 Pollen Sterility Loci Interactions That Increase Meiosis Abnormalities and Pollen Sterility in Autotetraploid Rice1[OPEN

    Science.gov (United States)

    Wu, Jinwen; Chen, Lin; Chen, Zhixiong; Wang, Lan; Lu, Yonggen

    2015-01-01

    Intersubspecific autotetraploid rice (Oryza sativa ssp. indica × japonica) hybrids have greater biological and yield potentials than diploid rice. However, the low fertility of intersubspecific autotetraploid hybrids, which is largely caused by high pollen abortion rates, limits their commercial utility. To decipher the cytological and molecular mechanisms underlying allelic interactions in autotetraploid rice, we developed an autotetraploid rice hybrid that was heterozygous (SiSj) at F1 pollen sterility loci (Sa, Sb, and Sc) using near-isogenic lines. Cytological studies showed that the autotetraploid had higher percentages (>30%) of abnormal chromosome behavior and aberrant meiocytes (>50%) during meiosis than did the diploid rice hybrid control. Analysis of gene expression profiles revealed 1,888 genes that were differentially expressed between the autotetraploid and diploid hybrid lines at the meiotic stage, among which 889 and 999 were up- and down-regulated, respectively. Of the 999 down-regulated genes, 940 were associated with the combined effect of polyploidy and pollen sterility loci interactions (IPE). Gene Ontology enrichment analysis identified a prominent functional gene class consisting of seven genes related to photosystem I (Gene Ontology 0009522). Moreover, 55 meiosis-related or meiosis stage-specific genes were associated with IPE in autotetraploid rice, including Os02g0497500, which encodes a DNA repair-recombination protein, and Os02g0490000, which encodes a component of the ubiquitin-proteasome pathway. These results suggest that polyploidy enhances epistatic interactions between alleles of pollen sterility loci, thereby altering the expression profiles of important meiosis-related or meiosis stage-specific genes and resulting in high pollen sterility. PMID:26511913

  18. Identification of quantitative trait loci influencing wood specific gravity in an outbred pedigree of loblolly pine

    Science.gov (United States)

    A. Groover; M. Devey; T. Fiddler; J. Lee; R. Megraw; T. Mitchel-Olds; B. Sherman; S. Vujcic; C. Williams; D. Neale

    1994-01-01

    We report the identification of quantitative trait loci (QTL) influencing wood specific gravity (WSG) in an outbred pedigree of loblolly pine (Pinus taeda L.) . QTL mapping in an outcrossing species is complicated by the presence of multiple alleles (>2) at QTL and marker loci. Multiple alleles at QTL allow the examination of interaction among...

  19. Stress Effects on Multiple Memory System Interactions

    Science.gov (United States)

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour. PMID:27034845

  20. Multiple parton interactions at the LHC

    CERN Document Server

    Gaunt, Jonathan Richard

    2018-01-01

    Many high-energy collider experiments (including the current Large Hadron Collider at CERN) involve the collision of hadrons. Hadrons are composite particles consisting of partons (quarks and gluons), and this means that in any hadron–hadron collision there will typically be multiple collisions of the constituents — i.e. multiple parton interactions (MPI). Understanding the nature of the MPI is important in terms of searching for new physics in the products of the scatters, and also in its own right to gain a greater understanding of hadron structure. This book aims at providing a pedagogical introduction and a comprehensive review of different research lines linked by an involvement of MPI phenomena. It is written by pioneers as well as young leading scientists, and reviews both experimental findings and theoretical developments, discussing also the remaining open issues.

  1. Stress Effects on Multiple Memory System Interactions

    Directory of Open Access Journals (Sweden)

    Deborah Ness

    2016-01-01

    Full Text Available Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

  2. Stress Effects on Multiple Memory System Interactions.

    Science.gov (United States)

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory systems, we review recent animal and human studies exploring the effects of stress on multiple memory systems. Apart from discussing the interaction between distinct memory systems in stressful situations, we will also outline the fundamental role of the amygdala in mediating such stress effects. Additionally, based on the methods applied in the herein discussed studies, we will discuss how memory translates into behaviour.

  3. Synchronization in networks with multiple interaction layers

    Science.gov (United States)

    del Genio, Charo I.; Gómez-Gardeñes, Jesús; Bonamassa, Ivan; Boccaletti, Stefano

    2016-01-01

    The structure of many real-world systems is best captured by networks consisting of several interaction layers. Understanding how a multilayered structure of connections affects the synchronization properties of dynamical systems evolving on top of it is a highly relevant endeavor in mathematics and physics and has potential applications in several socially relevant topics, such as power grid engineering and neural dynamics. We propose a general framework to assess the stability of the synchronized state in networks with multiple interaction layers, deriving a necessary condition that generalizes the master stability function approach. We validate our method by applying it to a network of Rössler oscillators with a double layer of interactions and show that highly rich phenomenology emerges from this. This includes cases where the stability of synchronization can be induced even if both layers would have individually induced unstable synchrony, an effect genuinely arising from the true multilayer structure of the interactions among the units in the network. PMID:28138540

  4. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

    DEFF Research Database (Denmark)

    Kar, Siddhartha P; Beesley, Jonathan; Amin Al Olama, Ali

    2016-01-01

    UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112...... (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell......-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. SIGNIFICANCE...

  5. Genome-wide Meta-analyses of Breast, Ovarian and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by At Least Two Cancer Types

    Science.gov (United States)

    Kar, Siddhartha P.; Beesley, Jonathan; Al Olama, Ali Amin; Michailidou, Kyriaki; Tyrer, Jonathan; Kote-Jarai, ZSofia; Lawrenson, Kate; Lindstrom, Sara; Ramus, Susan J.; Thompson, Deborah J.; Kibel, Adam S.; Dansonka-Mieszkowska, Agnieszka; Michael, Agnieszka; Dieffenbach, Aida K.; Gentry-Maharaj, Aleksandra; Whittemore, Alice S.; Wolk, Alicja; Monteiro, Alvaro; Peixoto, Ana; Kierzek, Andrzej; Cox, Angela; Rudolph, Anja; Gonzalez-Neira, Anna; Wu, Anna H.; Lindblom, Annika; Swerdlow, Anthony; Ziogas, Argyrios; Ekici, Arif B.; Burwinkel, Barbara; Karlan, Beth Y.; Nordestgaard, Børge G.; Blomqvist, Carl; Phelan, Catherine; McLean, Catriona; Pearce, Celeste Leigh; Vachon, Celine; Cybulski, Cezary; Slavov, Chavdar; Stegmaier, Christa; Maier, Christiane; Ambrosone, Christine B.; Høgdall, Claus K.; Teerlink, Craig C.; Kang, Daehee; Tessier, Daniel C.; Schaid, Daniel J.; Stram, Daniel O.; Cramer, Daniel W.; Neal, David E.; Eccles, Diana; Flesch-Janys, Dieter; Velez Edwards, Digna R.; Wokozorczyk, Dominika; Levine, Douglas A.; Yannoukakos, Drakoulis; Sawyer, Elinor J.; Bandera, Elisa V.; Poole, Elizabeth M.; Goode, Ellen L.; Khusnutdinova, Elza; Høgdall, Estrid; Song, Fengju; Bruinsma, Fiona; Heitz, Florian; Modugno, Francesmary; Hamdy, Freddie C.; Wiklund, Fredrik; Giles, Graham G.; Olsson, Håkan; Wildiers, Hans; Ulmer, Hans-Ulrich; Pandha, Hardev; Risch, Harvey A.; Darabi, Hatef; Salvesen, Helga B.; Nevanlinna, Heli; Gronberg, Henrik; Brenner, Hermann; Brauch, Hiltrud; Anton-Culver, Hoda; Song, Honglin; Lim, Hui-Yi; McNeish, Iain; Campbell, Ian; Vergote, Ignace; Gronwald, Jacek; Lubiński, Jan; Stanford, Janet L.; Benítez, Javier; Doherty, Jennifer A.; Permuth, Jennifer B.; Chang-Claude, Jenny; Donovan, Jenny L.; Dennis, Joe; Schildkraut, Joellen M.; Schleutker, Johanna; Hopper, John L.; Kupryjanczyk, Jolanta; Park, Jong Y.; Figueroa, Jonine; Clements, Judith A.; Knight, Julia A.; Peto, Julian; Cunningham, Julie M.; Pow-Sang, Julio; Batra, Jyotsna; Czene, Kamila; Lu, Karen H.; Herkommer, Kathleen; Khaw, Kay-Tee; Matsuo, Keitaro; Muir, Kenneth; Offitt, Kenneth; Chen, Kexin; Moysich, Kirsten B.; Aittomäki, Kristiina; Odunsi, Kunle; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Fitzgerald, Liesel M.; Cook, Linda S.; Cannon-Albright, Lisa; Hooning, Maartje J.; Pike, Malcolm C.; Bolla, Manjeet K.; Luedeke, Manuel; Teixeira, Manuel R.; Goodman, Marc T.; Schmidt, Marjanka K.; Riggan, Marjorie; Aly, Markus; Rossing, Mary Anne; Beckmann, Matthias W.; Moisse, Matthieu; Sanderson, Maureen; Southey, Melissa C.; Jones, Michael; Lush, Michael; Hildebrandt, Michelle A. T.; Hou, Ming-Feng; Schoemaker, Minouk J.; Garcia-Closas, Montserrat; Bogdanova, Natalia; Rahman, Nazneen; Le, Nhu D.; Orr, Nick; Wentzensen, Nicolas; Pashayan, Nora; Peterlongo, Paolo; Guénel, Pascal; Brennan, Paul; Paulo, Paula; Webb, Penelope M.; Broberg, Per; Fasching, Peter A.; Devilee, Peter; Wang, Qin; Cai, Qiuyin; Li, Qiyuan; Kaneva, Radka; Butzow, Ralf; Kopperud, Reidun Kristin; Schmutzler, Rita K.; Stephenson, Robert A.; MacInnis, Robert J.; Hoover, Robert N.; Winqvist, Robert; Ness, Roberta; Milne, Roger L.; Travis, Ruth C.; Benlloch, Sara; Olson, Sara H.; McDonnell, Shannon K.; Tworoger, Shelley S.; Maia, Sofia; Berndt, Sonja; Lee, Soo Chin; Teo, Soo-Hwang; Thibodeau, Stephen N.; Bojesen, Stig E.; Gapstur, Susan M.; Kjær, Susanne Krüger; Pejovic, Tanja; Tammela, Teuvo L.J.; Dörk, Thilo; Brüning, Thomas; Wahlfors, Tiina; Key, Tim J.; Edwards, Todd L.; Menon, Usha; Hamann, Ute; Mitev, Vanio; Kosma, Veli-Matti; Setiawan, Veronica Wendy; Kristensen, Vessela; Arndt, Volker; Vogel, Walther; Zheng, Wei; Sieh, Weiva; Blot, William J.; Kluzniak, Wojciech; Shu, Xiao-Ou; Gao, Yu-Tang; Schumacher, Fredrick; Freedman, Matthew L.; Berchuck, Andrew; Dunning, Alison M.; Simard, Jacques; Haiman, Christopher A.; Spurdle, Amanda; Sellers, Thomas A.; Hunter, David J.; Henderson, Brian E.; Kraft, Peter; Chanock, Stephen J.; Couch, Fergus J.; Hall, Per; Gayther, Simon A.; Easton, Douglas F.; Chenevix-Trench, Georgia; Eeles, Rosalind; Pharoah, Paul D.P.; Lambrechts, Diether

    2016-01-01

    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P cancer meta-analysis. PMID:27432226

  6. Stripe rust and leaf rust resistance QTL mapping, epistatic interactions, and co-localization with stem rust resistance loci in spring wheat evaluated over three continents.

    Science.gov (United States)

    Singh, A; Knox, R E; DePauw, R M; Singh, A K; Cuthbert, R D; Campbell, H L; Shorter, S; Bhavani, S

    2014-11-01

    In wheat, advantageous gene-rich or pleiotropic regions for stripe, leaf, and stem rust and epistatic interactions between rust resistance loci should be accounted for in plant breeding strategies. Leaf rust (Puccinia triticina Eriks.) and stripe rust (Puccinia striiformis f. tritici Eriks) contribute to major production losses in many regions worldwide. The objectives of this research were to identify and study epistatic interactions of quantitative trait loci (QTL) for stripe and leaf rust resistance in a doubled haploid (DH) population derived from the cross of Canadian wheat cultivars, AC Cadillac and Carberry. The relationship of leaf and stripe rust resistance QTL that co-located with stem rust resistance QTL previously mapped in this population was also investigated. The Carberry/AC Cadillac population was genotyped with DArT(®) and simple sequence repeat markers. The parents and population were phenotyped for stripe rust severity and infection response in field rust nurseries in Kenya (Njoro), Canada (Swift Current), and New Zealand (Lincoln); and for leaf rust severity and infection response in field nurseries in Canada (Swift Current) and New Zealand (Lincoln). AC Cadillac was a source of stripe rust resistance QTL on chromosomes 2A, 2B, 3A, 3B, 5B, and 7B; and Carberry was a source of resistance on chromosomes 2B, 4B, and 7A. AC Cadillac contributed QTL for resistance to leaf rust on chromosome 2A and Carberry contributed QTL on chromosomes 2B and 4B. Stripe rust resistance QTL co-localized with previously reported stem rust resistance QTL on 2B, 3B, and 7B, while leaf rust resistance QTL co-localized with 4B stem rust resistance QTL. Several epistatic interactions were identified both for stripe and leaf rust resistance QTL. We have identified useful combinations of genetic loci with main and epistatic effects. Multiple disease resistance regions identified on chromosomes 2A, 2B, 3B, 4B, 5B, and 7B are prime candidates for further investigation and

  7. Interactions of dietary whole-grain intake with fasting glucose- and insulin-related genetic loci in individuals of European descent: a meta-analysis of 14 cohort studies.

    Science.gov (United States)

    Nettleton, Jennifer A; McKeown, Nicola M; Kanoni, Stavroula; Lemaitre, Rozenn N; Hivert, Marie-France; Ngwa, Julius; van Rooij, Frank J A; Sonestedt, Emily; Wojczynski, Mary K; Ye, Zheng; Tanaka, Tosh; Garcia, Melissa; Anderson, Jennifer S; Follis, Jack L; Djousse, Luc; Mukamal, Kenneth; Papoutsakis, Constantina; Mozaffarian, Dariush; Zillikens, M Carola; Bandinelli, Stefania; Bennett, Amanda J; Borecki, Ingrid B; Feitosa, Mary F; Ferrucci, Luigi; Forouhi, Nita G; Groves, Christopher J; Hallmans, Goran; Harris, Tamara; Hofman, Albert; Houston, Denise K; Hu, Frank B; Johansson, Ingegerd; Kritchevsky, Stephen B; Langenberg, Claudia; Launer, Lenore; Liu, Yongmei; Loos, Ruth J; Nalls, Michael; Orho-Melander, Marju; Renstrom, Frida; Rice, Kenneth; Riserus, Ulf; Rolandsson, Olov; Rotter, Jerome I; Saylor, Georgia; Sijbrands, Eric J G; Sjogren, Per; Smith, Albert; Steingrímsdóttir, Laufey; Uitterlinden, André G; Wareham, Nicholas J; Prokopenko, Inga; Pankow, James S; van Duijn, Cornelia M; Florez, Jose C; Witteman, Jacqueline C M; Dupuis, Josée; Dedoussis, George V; Ordovas, Jose M; Ingelsson, Erik; Cupples, L Adrienne; Siscovick, David S; Franks, Paul W; Meigs, James B

    2010-12-01

    Whole-grain foods are touted for multiple health benefits, including enhancing insulin sensitivity and reducing type 2 diabetes risk. Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) associated with fasting glucose and insulin concentrations in individuals free of diabetes. We tested the hypothesis that whole-grain food intake and genetic variation interact to influence concentrations of fasting glucose and insulin. Via meta-analysis of data from 14 cohorts comprising ∼ 48,000 participants of European descent, we studied interactions of whole-grain intake with loci previously associated in GWAS with fasting glucose (16 loci) and/or insulin (2 loci) concentrations. For tests of interaction, we considered a P value fasting glucose and insulin concentrations independent of demographics, other dietary and lifestyle factors, and BMI (β [95% CI] per 1-serving-greater whole-grain intake: -0.009 mmol/l glucose [-0.013 to -0.005], P fasting insulin (P = 0.006), where greater whole-grain intake was associated with a smaller reduction in fasting insulin concentrations in those with the insulin-raising allele. Our results support the favorable association of whole-grain intake with fasting glucose and insulin and suggest a potential interaction between variation in GCKR and whole-grain intake in influencing fasting insulin concentrations.

  8. Interactions between Glu-1 and Glu-3 loci and associations of selected molecular markers with quality traits in winter wheat (Triticum aestivum L.) DH lines.

    Science.gov (United States)

    Krystkowiak, Karolina; Langner, Monika; Adamski, Tadeusz; Salmanowicz, Bolesław P; Kaczmarek, Zygmunt; Krajewski, Paweł; Surma, Maria

    2017-02-01

    The quality of wheat depends on a large complex of genes and environmental factors. The objective of this study was to identify quantitative trait loci controlling technological quality traits and their stability across environments, and to assess the impact of interaction between alleles at loci Glu-1 and Glu-3 on grain quality. DH lines were evaluated in field experiments over a period of 4 years, and genotyped using simple sequence repeat markers. Lines were analysed for grain yield (GY), thousand grain weight (TGW), protein content (PC), starch content (SC), wet gluten content (WG), Zeleny sedimentation value (ZS), alveograph parameter W (APW), hectolitre weight (HW), and grain hardness (GH). A number of QTLs for these traits were identified in all chromosome groups. The Glu-D1 locus influenced TGW, PC, SC, WG, ZS, APW, GH, while locus Glu-B1 affected only PC, ZS, and WG. Most important marker-trait associations were found on chromosomes 1D and 5D. Significant effects of interaction between Glu-1 and Glu-3 loci on technological properties were recorded, and in all types of this interaction positive effects of Glu-D1 locus on grain quality were observed, whereas effects of Glu-B1 locus depended on alleles at Glu-3 loci. Effects of Glu-A3 and Glu-D3 loci per se were not significant, while their interaction with alleles present at other loci encoding HMW and LMW were important. These results indicate that selection of wheat genotypes with predicted good bread-making properties should be based on the allelic composition both in Glu-1 and Glu-3 loci, and confirm the predominant effect of Glu-D1d allele on technological properties of wheat grains.

  9. Species delimitation in lemurs: multiple genetic loci reveal low levels of species diversity in the genus Cheirogaleus

    Directory of Open Access Journals (Sweden)

    Rasoloarison Rodin M

    2009-02-01

    Full Text Available Abstract Background Species are viewed as the fundamental unit in most subdisciplines of biology. To conservationists this unit represents the currency for global biodiversity assessments. Even though Madagascar belongs to one of the top eight biodiversity hotspots of the world, the taxonomy of its charismatic lemuriform primates is not stable. Within the last 25 years, the number of described lemur species has more than doubled, with many newly described species identified among the nocturnal and small-bodied cheirogaleids. Here, we characterize the diversity of the dwarf lemurs (genus Cheirogaleus and assess the status of the seven described species, based on phylogenetic and population genetic analysis of mtDNA (cytb + cox2 and three nuclear markers (adora3, fiba and vWF. Results This study identified three distinct evolutionary lineages within the genus Cheirogaleus. Population genetic cluster analyses revealed a further layer of population divergence with six distinct genotypic clusters. Conclusion Based on the general metapopulation lineage concept and multiple concordant data sets, we identify three exclusive groups of dwarf lemur populations that correspond to three of the seven named species: C. major, C. medius and C. crossleyi. These three species were found to be genealogically exclusive in both mtDNA and nDNA loci and are morphologically distinguishable. The molecular and morphometric data indicate that C. adipicaudatus and C. ravus are synonymous with C. medius and C. major, respectively. Cheirogaleus sibreei falls into the C. medius mtDNA clade, but in morphological analyses the membership is not clearly resolved. We do not have sufficient data to assess the status of C. minusculus. Although additional patterns of population differentiation are evident, there are no clear subdivisions that would warrant additional specific status. We propose that ecological and more geographic data should be collected to confirm these results.

  10. Coulomb interaction in multiple scattering theory

    International Nuclear Information System (INIS)

    Ray, L.; Hoffmann, G.W.; Thaler, R.M.

    1980-01-01

    The treatment of the Coulomb interaction in the multiple scattering theories of Kerman-McManus-Thaler and Watson is examined in detail. By neglecting virtual Coulomb excitations, the lowest order Coulomb term in the Watson optical potential is shown to be a convolution of the point Coulomb interaction with the distributed nuclear charge, while the equivalent Kerman-McManus-Thaler Coulomb potential is obtained from an averaged, single-particle Coulombic T matrix. The Kerman-McManus-Thaler Coulomb potential is expressed as the Watson Coulomb term plus additional Coulomb-nuclear and Coulomb-Coulomb cross terms, and the omission of the extra terms in usual Kerman-McManus-Thaler applications leads to negative infinite total reaction cross section predictions and incorrect pure Coulomb scattering limits. Approximations are presented which eliminate these anomalies. Using the two-potential formula, the full projectile-nucleus T matrix is separated into two terms, one resulting from the distributed nuclear charge and the other being a Coulomb distorted nuclear T matrix. It is shown that the error resulting from the omission of the Kerman-McManus-Thaler Coulomb terms is effectively removed when the pure Coulomb T matrix in Kerman-McManus-Thaler is replaced by the analogous quantity in the Watson approach. Using the various approximations, theoretical angular distributions are obtained for 800 MeV p+ 208 Pb elastic scattering and compared with experimental data

  11. Relationship of the Interaction Between Two Quantitative Trait Loci with γ-Globin Expression in β-Thalassemia Intermedia Patients.

    Science.gov (United States)

    NickAria, Shiva; Haghpanah, Sezaneh; Ramzi, Mani; Karimi, Mehran

    2018-05-10

    Globin switching is a significant factor on blood hemoglobin (Hb) level but its molecular mechanisms have not yet been identified, however, several quantitative trait loci (QTL) and polymorphisms involved regions on chromosomes 2p, 6q, 8q and X account for variation in the γ-globin expression level. We studied the effect of interaction between a region on intron six of the TOX gene, chromosome 8q (chr8q) and XmnI locus on the γ-globin promoter, chr11p on γ-globin expression in 150 β-thalassemia intermedia (β-TI) patients, evaluated by statistical interaction analysis. Our results showed a significant interaction between one QTL on intron six of the TOX gene (rs9693712) and XmnI locus that effect γ-globin expression. Interchromosomal interaction mediates through transcriptional machanisms to preserve true genome architectural features, chromosomes localization and DNA bending. This interaction can be a part of the unknown molecular mechanism of globin switching and regulation of gene expression.

  12. Investigation of gene-environment interactions between 47 newly identified breast cancer susceptibility loci and environmental risk factors

    DEFF Research Database (Denmark)

    Rudolph, Anja; Milne, Roger L; Truong, Thérèse

    2015-01-01

    and overall BC risk was stronger for women who had had four or more pregnancies (OR = 0.85, p = 2.0 × 10(-4) ), and absent in women who had had just one (OR = 0.96, p = 0.19, pint = 6.1 × 10(-4) ). SNP rs11242675 was inversely associated with overall BC risk in never/former smokers (OR = 0.93, p = 2.8 × 10......(-5) ), but no association was observed in current smokers (OR = 1.07, p = 0.14, pint = 3.4 × 10(-4) ). In conclusion, recently identified BC susceptibility loci are not strongly modified by established risk factors and the observed potential interactions require confirmation in independent studies....

  13. Genes and quality trait loci (QTLs) associated with firmness in Malus ...

    African Journals Online (AJOL)

    ctm

    2013-03-06

    Mar 6, 2013 ... Fruit firmness is affected by the inheritance of alleles at multiple loci and their possible interactions ... influences the sensory perception of fruits by consumers. (Harker et al. ..... direct comparisons between studies are difficult.

  14. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the fi...

  15. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    NARCIS (Netherlands)

    A.D. Børglum; D. Demontis; J. Grove (Jakob); J. Pallesen (J.); M.V. Hollegaard (Mads V); C.B. Pedersen (C.); A. Hedemand (A.); M. Mattheisen (Manuel); A.G. Uitterlinden (André); M. Nyegaard (M.); T.F. Orntoft (Torben); C. Wiuf (Carsten); M. Didriksen (Michael); M. Nordentoft (M.); M.M. Nö then (M.); M. Rietschel (Marcella); R.A. Ophoff (Roel); S. Cichon (Sven); R.H. Yolken (Robert); D.M. Hougaard (David); P.B. Mortensen; O. Mors

    2014-01-01

    textabstractGenetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all

  16. The interaction between smoking and HLA genes in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedström, Anna Karin; Katsoulis, Michail; Hössjer, Ola

    2017-01-01

    Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We us...

  17. Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

    Science.gov (United States)

    Abou-Elnaga, Ahmed F; Torigoe, Daisuke; Fouda, Mohamed M; Darwish, Ragab A; Abou-Ismail, Usama A; Morimatsu, Masami; Agui, Takashi

    2015-05-01

    Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

  18. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

    DEFF Research Database (Denmark)

    Børglum, A D; Demontis, D; Grove, J

    2014-01-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals...... born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases...... was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies....

  19. Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk

    Science.gov (United States)

    Lindström, Sara; Thompson, Deborah J.; Paterson, Andrew D.; Li, Jingmei; Gierach, Gretchen L.; Scott, Christopher; Stone, Jennifer; Douglas, Julie A.; dos-Santos-Silva, Isabel; Fernandez-Navarro, Pablo; Verghase, Jajini; Smith, Paula; Brown, Judith; Luben, Robert; Wareham, Nicholas J.; Loos, Ruth J.F.; Heit, John A.; Pankratz, V. Shane; Norman, Aaron; Goode, Ellen L.; Cunningham, Julie M.; deAndrade, Mariza; Vierkant, Robert A.; Czene, Kamila; Fasching, Peter A.; Baglietto, Laura; Southey, Melissa C.; Giles, Graham G.; Shah, Kaanan P.; Chan, Heang-Ping; Helvie, Mark A.; Beck, Andrew H.; Knoblauch, Nicholas W.; Hazra, Aditi; Hunter, David J.; Kraft, Peter; Pollan, Marina; Figueroa, Jonine D.; Couch, Fergus J.; Hopper, John L.; Hall, Per; Easton, Douglas F.; Boyd, Norman F.; Vachon, Celine M.; Tamimi, Rulla M.

    2015-01-01

    Mammographic density reflects the amount of stromal and epithelial tissues in relation to adipose tissue in the breast and is a strong risk factor for breast cancer. Here we report the results from meta-analysis of genome-wide association studies (GWAS) of three mammographic density phenotypes: dense area, non-dense area and percent density in up to 7,916 women in stage 1 and an additional 10,379 women in stage 2. We identify genome-wide significant (P<5×10−8) loci for dense area (AREG, ESR1, ZNF365, LSP1/TNNT3, IGF1, TMEM184B, SGSM3/MKL1), non-dense area (8p11.23) and percent density (PRDM6, 8p11.23, TMEM184B). Four of these regions are known breast cancer susceptibility loci, and four additional regions were found to be associated with breast cancer (P<0.05) in a large meta-analysis. These results provide further evidence of a shared genetic basis between mammographic density and breast cancer and illustrate the power of studying intermediate quantitative phenotypes to identify putative disease susceptibility loci. PMID:25342443

  20. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility.

    Science.gov (United States)

    Bush, W S; McCauley, J L; DeJager, P L; Dudek, S M; Hafler, D A; Gibson, R A; Matthews, P M; Kappos, L; Naegelin, Y; Polman, C H; Hauser, S L; Oksenberg, J; Haines, J L; Ritchie, M D

    2011-07-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also increases power to detect weak main effects. We conducted a knowledge-driven interaction analysis of a GWAS of 931 multiple sclerosis (MS) trios to discover gene-gene interactions within established biological contexts. We identify heterogeneous signals, including a gene-gene interaction between CHRM3 (muscarinic cholinergic receptor 3) and MYLK (myosin light-chain kinase) (joint P=0.0002), an interaction between two phospholipase C-β isoforms, PLCβ1 and PLCβ4 (joint P=0.0098), and a modest interaction between ACTN1 (actinin alpha 1) and MYH9 (myosin heavy chain 9) (joint P=0.0326), all localized to calcium-signaled cytoskeletal regulation. Furthermore, we discover a main effect (joint P=5.2E-5) previously unidentified by single-locus analysis within another related gene, SCIN (scinderin), a calcium-binding cytoskeleton regulatory protein. This work illustrates that knowledge-driven interaction analysis of GWAS data is a feasible approach to identify new genetic effects. The results of this study are among the first gene-gene interactions and non-immune susceptibility loci for MS. Further, the implicated genes cluster within inter-related biological mechanisms that suggest a neurodegenerative component to MS.

  1. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci.

    Science.gov (United States)

    Børglum, A D; Demontis, D; Grove, J; Pallesen, J; Hollegaard, M V; Pedersen, C B; Hedemand, A; Mattheisen, M; Uitterlinden, A; Nyegaard, M; Ørntoft, T; Wiuf, C; Didriksen, M; Nordentoft, M; Nöthen, M M; Rietschel, M; Ophoff, R A; Cichon, S; Yolken, R H; Hougaard, D M; Mortensen, P B; Mors, O

    2014-03-01

    Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies.

  2. Rapid Generation of Multiple Loci-Engineered Marker-free Poxvirus and Characterization of a Clinical-Grade Oncolytic Vaccinia Virus

    Directory of Open Access Journals (Sweden)

    Zong Sheng Guo

    2017-12-01

    Full Text Available Recombinant poxviruses, utilized as vaccine vectors and oncolytic viruses, often require manipulation at multiple genetic loci in the viral genome. It is essential for viral vectors to possess no adventitious mutations and no (antibiotic selection marker in the final product for human patients in order to comply with the guidance from the regulatory agencies. Rintoul et al. have previously developed a selectable and excisable marker (SEM system for the rapid generation of recombinant vaccinia virus. In the current study, we describe an improved methodology for rapid creation and selection of recombinant poxviruses with multiple genetic manipulations solely based on expression of a fluorescent protein and with no requirement for drug selection that can lead to cellular stress and the risk of adventitious mutations throughout the viral genome. Using this improved procedure combined with the SEM system, we have constructed multiple marker-free oncolytic poxviruses expressing different cytokines and other therapeutic genes. The high fidelity of inserted DNA sequences validates the utility of this improved procedure for generation of therapeutic viruses for human patients. We have created an oncolytic poxvirus expressing human chemokine CCL5, designated as vvDD-A34R-hCCL5, with manipulations at two genetic loci in a single virus. Finally, we have produced and purified this virus in clinical grade for its use in a phase I clinical trial and presented data on initial in vitro characterization of the virus.

  3. Spin-orbit interaction in multiple quantum wells

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Ya-Fei, E-mail: haoyafei@zjnu.cn [Physics Department, Zhejiang Normal University, Zhejiang 321004 (China)

    2015-01-07

    In this paper, we investigate how the structure of multiple quantum wells affects spin-orbit interactions. To increase the interface-related Rashba spin splitting and the strength of the interface-related Rashba spin-orbit interaction, we designed three kinds of multiple quantum wells. We demonstrate that the structure of the multiple quantum wells strongly affected the interface-related Rashba spin-orbit interaction, increasing the interface-related Rashba spin splitting to up to 26% larger in multiple quantum wells than in a stepped quantum well. We also show that the cubic Dresselhaus spin-orbit interaction similarly influenced the spin relaxation time of multiple quantum wells and that of a stepped quantum well. The increase in the interface-related Rashba spin splitting originates from the relationship between interface-related Rashba spin splitting and electron probability density. Our results suggest that multiple quantum wells can be good candidates for spintronic devices.

  4. Spin-orbit interaction in multiple quantum wells

    International Nuclear Information System (INIS)

    Hao, Ya-Fei

    2015-01-01

    In this paper, we investigate how the structure of multiple quantum wells affects spin-orbit interactions. To increase the interface-related Rashba spin splitting and the strength of the interface-related Rashba spin-orbit interaction, we designed three kinds of multiple quantum wells. We demonstrate that the structure of the multiple quantum wells strongly affected the interface-related Rashba spin-orbit interaction, increasing the interface-related Rashba spin splitting to up to 26% larger in multiple quantum wells than in a stepped quantum well. We also show that the cubic Dresselhaus spin-orbit interaction similarly influenced the spin relaxation time of multiple quantum wells and that of a stepped quantum well. The increase in the interface-related Rashba spin splitting originates from the relationship between interface-related Rashba spin splitting and electron probability density. Our results suggest that multiple quantum wells can be good candidates for spintronic devices

  5. Molecular characterization of Verocytotoxigenic Escherichia coli O157:H7 isolates from Argentina by Multiple-Loci VNTR Analysis (MLVA)

    Science.gov (United States)

    Bustamante, Ana V.; Lucchesi, Paula M.A.; Parma, Alberto E.

    2009-01-01

    The aim of this work was to adapt described MLVA protocols to the molecular typing and characterization of VTEC O157:H7 isolates from Argentina. Nine VNTR loci were amplified by PCR showing diversity values from 0.49 to 0.73. Nine MLVA profiles were observed and the cluster analysis indicated both unrelated and closely related VTEC O157:H7 strains. In spite of the limited number of isolates studied, the panel of VNTR used made it possible to perform a first approach of the high genetic diversity of native strains of O157:H7 by MLVA. PMID:24031443

  6. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

    DEFF Research Database (Denmark)

    Amin Al Olama, Ali; Dadaev, Tokhir; Hazelett, Dennis J

    2015-01-01

    associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated...... identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have...

  7. Evolution of multiple additive loci caused divergence between Drosophila yakuba and D. santomea in wing rowing during male courtship.

    Directory of Open Access Journals (Sweden)

    Jessica Cande

    Full Text Available In Drosophila, male flies perform innate, stereotyped courtship behavior. This innate behavior evolves rapidly between fly species, and is likely to have contributed to reproductive isolation and species divergence. We currently understand little about the neurobiological and genetic mechanisms that contributed to the evolution of courtship behavior. Here we describe a novel behavioral difference between the two closely related species D. yakuba and D. santomea: the frequency of wing rowing during courtship. During courtship, D. santomea males repeatedly rotate their wing blades to face forward and then back (rowing, while D. yakuba males rarely row their wings. We found little intraspecific variation in the frequency of wing rowing for both species. We exploited multiplexed shotgun genotyping (MSG to genotype two backcross populations with a single lane of Illumina sequencing. We performed quantitative trait locus (QTL mapping using the ancestry information estimated by MSG and found that the species difference in wing rowing mapped to four or five genetically separable regions. We found no evidence that these loci display epistasis. The identified loci all act in the same direction and can account for most of the species difference.

  8. Stress Effects on Multiple Memory System Interactions

    OpenAIRE

    Ness, Deborah; Calabrese, Pasquale

    2016-01-01

    Extensive behavioural, pharmacological, and neurological research reports stress effects on mammalian memory processes. While stress effects on memory quantity have been known for decades, the influence of stress on multiple memory systems and their distinct contributions to the learning process have only recently been described. In this paper, after summarizing the fundamental biological aspects of stress/emotional arousal and recapitulating functionally and anatomically distinct memory syst...

  9. Evidence of gene-environment interactions between common breast cancer susceptibility loci and established environmental risk factors.

    Directory of Open Access Journals (Sweden)

    Stefan Nickels

    Full Text Available Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6 and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4. Overall, the per-allele odds ratio (95% confidence interval for LSP1-rs3817198 was 1.08 (1.01-1.16 in nulliparous women and ranged from 1.03 (0.96-1.10 in parous women with one birth to 1.26 (1.16-1.37 in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98 in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85 in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5, with a per-allele OR of 1.14 (1.11-1.17 in parous women and 0.98 (0.92-1.05 in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.

  10. [The multiple interactions between infertility and sexuality].

    Science.gov (United States)

    Mimoun, S

    1993-03-01

    After investigating into literature and clinical experience, we shall line out in this study 4 types of interactions between sexuality and infertility: sexual causes to feminine (vaginism, with and without heavy dyspareunia) or masculine (impotency, ante-portas ejaculation, anejaculation, dysejaculation), infertility; influence of tests and of treatments for infertility on sexual life; influence of infertility on sexuality focusing on the various ambiguous feelings (of culpability, inferiority, aggressivity, passivity); and last, the psychological and sexual interactions with medical assisted procreation, reinforcing the sexual separation of man and woman if the body is considered a machine. Psychosomatic guidance of the couple during these steps (with reassurance as the being helped conception) will allow maintaining on removing sexual attraction.

  11. Architecture for Multiple Interacting Robot Intelligences

    Science.gov (United States)

    Peters, Richard Alan, II (Inventor)

    2008-01-01

    An architecture for robot intelligence enables a robot to learn new behaviors and create new behavior sequences autonomously and interact with a dynamically changing environment. Sensory information is mapped onto a Sensory Ego-Sphere (SES) that rapidly identifies important changes in the environment and functions much like short term memory. Behaviors are stored in a database associative memory (DBAM) that creates an active map from the robot's current state to a goal state and functions much like long term memory. A dream state converts recent activities stored in the SES and creates or modifies behaviors in the DBAM.

  12. Genetic susceptibility loci, environmental exposures, and Parkinson's disease: a case-control study of gene-environment interactions.

    Science.gov (United States)

    Chung, Sun Ju; Armasu, Sebastian M; Anderson, Kari J; Biernacka, Joanna M; Lesnick, Timothy G; Rider, David N; Cunningham, Julie M; Ahlskog, J Eric; Frigerio, Roberta; Maraganore, Demetrius M

    2013-06-01

    Prior studies causally linked mutations in SNCA, MAPT, and LRRK2 genes with familial Parkinsonism. Genome-wide association studies have demonstrated association of single nucleotide polymorphisms (SNPs) in those three genes with sporadic Parkinson's disease (PD) susceptibility worldwide. Here we investigated the interactions between SNPs in those three susceptibility genes and environmental exposures (pesticides application, tobacco smoking, coffee drinking, and alcohol drinking) also associated with PD susceptibility. Pairwise interactions between environmental exposures and 18 variants (16 SNPs and two variable number tandem repeats, or "VNTRs") in SNCA, MAPT and LRRK2, were investigated using data from 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Environmental exposures were assessed using a validated telephone interview script. Five pairwise interactions had uncorrected P-values coffee drinking × MAPT H1/H2 haplotype or MAPT rs16940806, and alcohol drinking × MAPT rs2435211. None of these interactions remained significant after Bonferroni correction. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not identify significant interactions after Bonferroni correction. This study documented limited pairwise interactions between established genetic and environmental risk factors for PD; however, the associations were not significant after correction for multiple testing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Multiple cold resistance loci confer the high cold tolerance adaptation of Dongxiang wild rice (Oryza rufipogon) to its high-latitude habitat.

    Science.gov (United States)

    Mao, Donghai; Yu, Li; Chen, Dazhou; Li, Lanying; Zhu, Yuxing; Xiao, Yeqing; Zhang, Dechun; Chen, Caiyan

    2015-07-01

    Dongxiang wild rice is phylogenetically close to temperate japonica and contains multiple cold resistance loci conferring its adaptation to high-latitude habitat. Understanding the nature of adaptation in wild populations will benefit crop breeding in the development of climate-resilient crop varieties. Dongxiang wild rice (DXWR), the northernmost common wild rice known, possesses a high degree of cold tolerance and can survive overwintering in its native habitat. However, to date, it is still unclear how DXWR evolved to cope with low-temperature environment, resulting in limited application of DXWR in rice breeding programs. In this study, we carried out both QTL mapping and phylogenetic analysis to discern the genetic mechanism underlying the strong cold resistance. Through a combination of interval mapping and single locus analysis in two genetic populations, at least 13 QTLs for seedling cold tolerance were identified in DXWR. A phylogenetic study using both genome-wide InDel markers and markers associated with cold tolerance loci reveals that DXWR belongs to the Or-III group, which is most closely related to cold-tolerant Japonica rice rather than to the Indica cultivars that are predominant in the habitat where DXWR grows. Our study paves the way toward an understanding of the nature of adaptation to a northern habitat in O. rufipogon. The QTLs identified in DXWR in this study will be useful for molecular breeding of cold-tolerant rice.

  14. COMT Val(158)Met and 5HTTLPR functional loci interact to predict persistence of anxiety across adolescence: results from the Victorian Adolescent Health Cohort Study.

    Science.gov (United States)

    Olsson, C A; Byrnes, G B; Anney, R J L; Collins, V; Hemphill, S A; Williamson, R; Patton, G C

    2007-10-01

    We investigated whether a composite genetic factor, based on the combined actions of catechol-O-methyltransferase (COMT) (Val(158)Met) and serotonin transporter (5HTTLPR) (Long-Short) functional loci, has a greater capacity to predict persistence of anxiety across adolescence than either locus in isolation. Analyses were performed on DNA collected from 962 young Australians participating in an eight-wave longitudinal study of mental health and well-being (Victorian Adolescent Health Cohort Study). When the effects of each locus were examined separately, small dose-response reductions in the odds of reporting persisting generalized (free-floating) anxiety across adolescence were observed for the COMT Met(158) [odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.76-0.95, P = 0.004] and 5HTTLPR Short alleles (OR = 0.88, CI = 0.79-0.99, P = 0.033). There was no evidence for a dose-response interaction effect between loci. However, there was a double-recessive interaction effect in which the odds of reporting persisting generalized anxiety were more than twofold reduced (OR = 0.45, CI = 0.29-0.70, P anxiety. Exploratory stratified analyses suggested that genetic protection may be more pronounced under conditions of high stress (insecure attachments and sexual abuse), although strata differences did not reach statistical significance. By describing the interaction between genetic loci, it may be possible to describe composite genetic factors that have a more substantial impact on psychosocial development than individual loci alone, and in doing so, enhance understanding of the contribution of constitutional processes in mental health outcomes.

  15. Genome-wide association study of clinically defined gout identifies multiple risk loci and its association with clinical subtypes.

    Science.gov (United States)

    Matsuo, Hirotaka; Yamamoto, Ken; Nakaoka, Hirofumi; Nakayama, Akiyoshi; Sakiyama, Masayuki; Chiba, Toshinori; Takahashi, Atsushi; Nakamura, Takahiro; Nakashima, Hiroshi; Takada, Yuzo; Danjoh, Inaho; Shimizu, Seiko; Abe, Junko; Kawamura, Yusuke; Terashige, Sho; Ogata, Hiraku; Tatsukawa, Seishiro; Yin, Guang; Okada, Rieko; Morita, Emi; Naito, Mariko; Tokumasu, Atsumi; Onoue, Hiroyuki; Iwaya, Keiichi; Ito, Toshimitsu; Takada, Tappei; Inoue, Katsuhisa; Kato, Yukio; Nakamura, Yukio; Sakurai, Yutaka; Suzuki, Hiroshi; Kanai, Yoshikatsu; Hosoya, Tatsuo; Hamajima, Nobuyuki; Inoue, Ituro; Kubo, Michiaki; Ichida, Kimiyoshi; Ooyama, Hiroshi; Shimizu, Toru; Shinomiya, Nariyoshi

    2016-04-01

    Gout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only. A GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls. Five gout susceptibility loci were identified at the genome-wide significance level (pgenes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10(-12); OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10(-23); OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10(-9); OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case-control ORs for two distinct types of gout (r=0.96 [p=4.8×10(-4)] for urate clearance and r=0.96 [p=5.0×10(-4)] for urinary urate excretion). Our findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics. 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. Mapping epistasis and environment × QTX interaction based on four -omics genotypes for the detected QTX loci controlling complex traits in tobacco

    Directory of Open Access Journals (Sweden)

    Liyuan Zhou

    2013-12-01

    Full Text Available Using newly developed methods and software, association mapping was conducted for chromium content and total sugar in tobacco leaf, based on four -omics datasets. Our objective was to collect data on genotype and phenotype for 60 leaf samples at four developmental stages, from three plant architectural positions and for three cultivars that were grown in two locations. Association mapping was conducted to detect genetic variants at quantitative trait SNP (QTS loci, quantitative trait transcript (QTT differences, quantitative trait protein (QTP variability, and quantitative trait metabolite (QTM changes, which can be summarized as QTX locus variation. The total heritabilities of the four -omics loci for both traits tested were 23.60% for epistasis and 15.26% for treatment interaction. Epistasis and environment × treatment interaction had important impacts on complex traits at all -omics levels. For decreasing chromium content and increasing total sugar in tobacco leaf, six methylated loci can be directly used for marker-assisted selection, and expression of ten QTTs, seven QTPs and six QTMs can be modified by selection or cultivation.

  17. Loci Affecting Gamma-Glutamyl Transferase in Adults and Adolescents Show Age X SNP interaction and Cardiometabolic Disease Associations

    NARCIS (Netherlands)

    Middelberg, R.P.S.; Benyamin, B.; de Moor, M.H.M.; Warrington, N.M.; Gordon, S.; Henders, A.K.; Medland, S.E.; Nyholt, DR; de Geus, E.J.C.; Hottenga, J.J.; Willemsen, G.; Beilin, L.J.; Mori, T.A.; Wright, M.J.; Heath, A.C.; Madden, P.A.F.; Boomsma, D.I.; Pennell, C.E.; Montgomery, G.W.; Martin, N.G.; Whitfield, J.B.

    2012-01-01

    Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in

  18. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

    Directory of Open Access Journals (Sweden)

    Dana B Hancock

    Full Text Available Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1, and its ratio to forced vital capacity (FEV(1/FVC. Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA of single nucleotide polymorphism (SNP and SNP-by-smoking (ever-smoking or pack-years associations on FEV(1 and FEV(1/FVC across 19 studies (total N = 50,047. We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = 5.00×10(-11, HLA-DQB1 and HLA-DQA2 (smallest P(JMA = 4.35×10(-9, and KCNJ2 and SOX9 (smallest P(JMA = 1.28×10(-8 were associated with FEV(1/FVC or FEV(1 in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

  19. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    DEFF Research Database (Denmark)

    Kote-Jarai, Zsofia; Saunders, Edward J; Leongamornlert, Daniel A

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that...

  20. Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

    Directory of Open Access Journals (Sweden)

    Nancy L Saccone

    2010-08-01

    Full Text Available Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking, lung cancer, and chronic obstructive pulmonary disease (COPD. We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers, and 2,614 COPD cases and 3,568 COPD-free controls (all smokers. We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35 and <10(-8 respectively. Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6. In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20 and observe a nominally significant association with COPD (p = 0.01; the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765

  1. Evolutionary Dynamics of Tumor-Stroma Interactions in Multiple Myeloma.

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    Full Text Available Cancer cells and stromal cells cooperate by exchanging diffusible factors that sustain tumor growth, a form of frequency-dependent selection that can be studied in the framework of evolutionary game theory. In the case of multiple myeloma, three types of cells (malignant plasma cells, osteoblasts and osteoclasts exchange growth factors with different effects, and tumor-stroma interactions have been analysed using a model of cooperation with pairwise interactions. Here we show that a model in which growth factors have autocrine and paracrine effects on multiple cells, a more realistic assumption for tumor-stroma interactions, leads to different results, with implications for disease progression and treatment. In particular, the model reveals that reducing the number of malignant plasma cells below a critical threshold can lead to their extinction and thus to restore a healthy balance between osteoclast and osteoblast, a result in line with current therapies against multiple myeloma.

  2. Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Ian P M Tomlinson

    2011-06-01

    Full Text Available Genome-wide association studies (GWAS have identified 14 tagging single nucleotide polymorphisms (tagSNPs that are associated with the risk of colorectal cancer (CRC, and several of these tagSNPs are near bone morphogenetic protein (BMP pathway loci. The penalty of multiple testing implicit in GWAS increases the attraction of complementary approaches for disease gene discovery, including candidate gene- or pathway-based analyses. The strongest candidate loci for additional predisposition SNPs are arguably those already known both to have functional relevance and to be involved in disease risk. To investigate this proposition, we searched for novel CRC susceptibility variants close to the BMP pathway genes GREM1 (15q13.3, BMP4 (14q22.2, and BMP2 (20p12.3 using sample sets totalling 24,910 CRC cases and 26,275 controls. We identified new, independent CRC predisposition SNPs close to BMP4 (rs1957636, P = 3.93×10(-10 and BMP2 (rs4813802, P = 4.65×10(-11. Near GREM1, we found using fine-mapping that the previously-identified association between tagSNP rs4779584 and CRC actually resulted from two independent signals represented by rs16969681 (P = 5.33×10(-8 and rs11632715 (P = 2.30×10(-10. As low-penetrance predisposition variants become harder to identify-owing to small effect sizes and/or low risk allele frequencies-approaches based on informed candidate gene selection may become increasingly attractive. Our data emphasise that genetic fine-mapping studies can deconvolute associations that have arisen owing to independent correlation of a tagSNP with more than one functional SNP, thus explaining some of the apparently missing heritability of common diseases.

  3. Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

    Science.gov (United States)

    Kote-Jarai, Zsofia; Saunders, Edward J.; Leongamornlert, Daniel A.; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Jugurnauth-Little, Sarah; Ross-Adams, Helen; Al Olama, Ali Amin; Benlloch, Sara; Halim, Silvia; Russel, Roslin; Dunning, Alison M.; Luccarini, Craig; Dennis, Joe; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Muir, Ken; Giles, Graham G.; Severi, Gianluca; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Le Marchand, Loic; Lindstrom, Sara; Kraft, Peter; Hunter, David J.; Gapstur, Susan; Chanock, Stephen; Berndt, Sonja I.; Albanes, Demetrius; Andriole, Gerald; Schleutker, Johanna; Weischer, Maren; Canzian, Federico; Riboli, Elio; Key, Tim J.; Travis, Ruth C.; Campa, Daniele; Ingles, Sue A.; John, Esther M.; Hayes, Richard B.; Pharoah, Paul; Khaw, Kay-Tee; Stanford, Janet L.; Ostrander, Elaine A.; Signorello, Lisa B.; Thibodeau, Stephen N.; Schaid, Dan; Maier, Christiane; Vogel, Walther; Kibel, Adam S.; Cybulski, Cezary; Lubinski, Jan; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong Y.; Kaneva, Radka; Batra, Jyotsna; Spurdle, Amanda; Clements, Judith A.; Teixeira, Manuel R.; Govindasami, Koveela; Guy, Michelle; Wilkinson, Rosemary A.; Sawyer, Emma J.; Morgan, Angela; Dicks, Ed; Baynes, Caroline; Conroy, Don; Bojesen, Stig E.; Kaaks, Rudolf; Vincent, Daniel; Bacot, François; Tessier, Daniel C.; Easton, Douglas F.; Eeles, Rosalind A.

    2013-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease. PMID:23535824

  4. Evidence for multiple stressor interactions and effects on coral reefs.

    Science.gov (United States)

    Ban, Stephen S; Graham, Nicholas A J; Connolly, Sean R

    2014-03-01

    Concern is growing about the potential effects of interacting multiple stressors, especially as the global climate changes. We provide a comprehensive review of multiple stressor interactions in coral reef ecosystems, which are widely considered to be one of the most sensitive ecosystems to global change. First, we synthesized coral reef studies that examined interactions of two or more stressors, highlighting stressor interactions (where one stressor directly influences another) and potentially synergistic effects on response variables (where two stressors interact to produce an effect that is greater than purely additive). For stressor-stressor interactions, we found 176 studies that examined at least 2 of the 13 stressors of interest. Applying network analysis to analyze relationships between stressors, we found that pathogens were exacerbated by more costressors than any other stressor, with ca. 78% of studies reporting an enhancing effect by another stressor. Sedimentation, storms, and water temperature directly affected the largest number of other stressors. Pathogens, nutrients, and crown-of-thorns starfish were the most-influenced stressors. We found 187 studies that examined the effects of two or more stressors on a third dependent variable. The interaction of irradiance and temperature on corals has been the subject of more research (62 studies, 33% of the total) than any other combination of stressors, with many studies reporting a synergistic effect on coral symbiont photosynthetic performance (n = 19). Second, we performed a quantitative meta-analysis of existing literature on this most-studied interaction (irradiance and temperature). We found that the mean effect size of combined treatments was statistically indistinguishable from a purely additive interaction, although it should be noted that the sample size was relatively small (n = 26). Overall, although in aggregate a large body of literature examines stressor effects on coral reefs and coral

  5. Class II HLA interactions modulate genetic risk for multiple sclerosis

    DEFF Research Database (Denmark)

    Moutsianas, Loukas; Jostins, Luke; Beecham, Ashley H

    2015-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17...

  6. Multiple parton interactions in photoproduction at HERA/H1

    Energy Technology Data Exchange (ETDEWEB)

    Magro, Lluis Marti

    2009-02-15

    Photoproduction data of HERA-I are analysed by requiring dijets with transverse momenta of at least 5 GeV. The two jets define in azimuth a towards region (leading jet), an away region (usually the 2nd jet) and transverse regions between them. The charged particle and jet with low transverse momentum multiplicity, so called minijets, are measured in these regions as a function of the variables x{sup obs}{sub {gamma}} and P{sup Jet{sub 1T}} (leading jet). The measurement is compared to predictions including parton showers and matrix elements at leading order in {alpha}{sub s}. Some predictions include contributions from multiple parton interactions and use different parton evolution equations. It was found that existing MC programs do not fully describe the measurements but the description can be improved by including multiple parton interactions. (orig.)

  7. THE MULTIPLE CHOICE PROBLEM WITH INTERACTIONS BETWEEN CRITERIA

    Directory of Open Access Journals (Sweden)

    Luiz Flavio Autran Monteiro Gomes

    2015-12-01

    Full Text Available ABSTRACT An important problem in Multi-Criteria Decision Analysis arises when one must select at least two alternatives at the same time. This can be denoted as a multiple choice problem. In other words, instead of evaluating each of the alternatives separately, they must be combined into groups of n alternatives, where n = 2. When the multiple choice problem must be solved under multiple criteria, the result is a multi-criteria, multiple choice problem. In this paper, it is shown through examples how this problemcan be tackled on a bipolar scale. The Choquet integral is used in this paper to take care of interactions between criteria. A numerical application example is conducted using data from SEBRAE-RJ, a non-profit private organization that has the mission of promoting competitiveness, sustainable developmentand entrepreneurship in the state of Rio de Janeiro, Brazil. The paper closes with suggestions for future research.

  8. Emergence of Tetracycline Resistance in Helicobacter pylori: Multiple Mutational Changes in 16S Ribosomal DNA and Other Genetic Loci

    Science.gov (United States)

    Dailidiene, Daiva; Bertoli, M. Teresita; Miciuleviciene, Jolanta; Mukhopadhyay, Asish K.; Dailide, Giedrius; Pascasio, Mario Alberto; Kupcinskas, Limas; Berg, Douglas E.

    2002-01-01

    Tetracycline is useful in combination therapies against the gastric pathogen Helicobacter pylori. We found 6 tetracycline-resistant (Tetr) strains among 159 clinical isolates (from El Salvador, Lithuania, and India) and obtained the following four results: (i) 5 of 6 Tetr isolates contained one or two nucleotide substitutions in one part of the primary tetracycline binding site in 16S rRNA (AGA965-967 [Escherichia coli coordinates] changed to gGA, AGc, guA, or gGc [lowercase letters are used to represent the base changes]), whereas the sixth (isolate Ind75) retained AGA965-967; (ii) PCR products containing mutant 16S ribosomal DNA (rDNA) alleles transformed recipient strains to Tetr phenotypes, but transformants containing alleles with single substitutions (gGA and AGc) were less resistant than their Tetr parents; (iii) each of 10 Tetr mutants of reference strain 26695 (in which mutations were induced with metronidazole, a mutagenic anti-H. pylori agent) contained the normal AGA965-967 sequence; and (iv) transformant derivatives of Ind75 and of one of the Tetr 26695 mutants that had acquired mutant rDNA alleles were resistant to tetracycline at levels higher than those to which either parent strain was resistant. Thus, tetracycline resistance in H. pylori results from an accumulation of changes that may affect tetracycline-ribosome affinity and/or other functions (perhaps porins or efflux pumps). We suggest that the rarity of tetracycline resistance among clinical isolates reflects this need for multiple mutations and perhaps also the deleterious effects of such mutations on fitness. Formally equivalent mutations with small but additive effects are postulated to contribute importantly to traits such as host specificity and virulence and to H. pylori's great genetic diversity. PMID:12435699

  9. Mean multiplicity of secondary particles in hadron-nuclear interactions

    International Nuclear Information System (INIS)

    Alaverdyan, G.B.; Pak, A.S.

    1980-01-01

    The mean multiplicity of secondary particles in hA interactions is examined in the framework of the multiplex scattering theory. The dependence of the secondary particle multiplicity coefficient Rsub(6)=anti nsub(hA)/anti nsub(hN) (where anti nsub(hA) and anti nsub(hN) are mean multiplicities of secondary relativistic particles in hA and hN interactions, respectively) on the energy and type of incident particles and atomic number of a target nucleus is analysed. It is shown that predictions of the leading particle cascade model are in satisfactory agreement with the experimental data if the uncertainties of the inelasticity in hN interactions are taken into account. The value Rsub(A) weakly depends both on the incident particle energy and the form of parametrization anti nsub(hN)(E). Allowance of energy losses fluctuation of leading particle results in the Rsub(A) value decrease. From the model of leading particles it does not follow that Rsub(a) strictly depends on the type of incident particles at the fixed value of mean number of collisions. But quantitative values of Rsub(A) for different types of particles and at one value of anti ν, (i.e. at properly chosen value) coincide. The value of Rsub(A) is profoundly dependent on the values of inelasticity factor in hN interactions

  10. Multiplicity distributions in high-energy neutrino interactions

    International Nuclear Information System (INIS)

    Chapman, J.W.; Coffin, C.T.; Diamond, R.N.; French, H.; Louis, W.; Roe, B.P.; Seidl, A.A.; Vander Velde, J.C.; Berge, J.P.; Bogert, D.V.; DiBianca, F.A.; Cundy, D.C.; Dunaitsev, A.; Efremenko, V.; Ermolov, P.; Fowler, W.; Hanft, R.; Harigel, G.; Huson, F.R.; Kolganov, V.; Mukhin, A.; Nezrick, F.A.; Rjabov, Y.; Scott, W.G.; Smart, W.

    1976-01-01

    Results from the Fermilab 15-ft bubble chamber on the charged-particle multiplicity distributions produced in high-energy charged-current neutrino-proton interactions are presented. Comparisons are made to γp, ep, μp, and inclusive pp scattering. The mean hadronic multiplicity appears to depend only on the mass of the excited hadronic state, independent of the mode of excitation. A fit to the neutrino data gives = (1.09+-0.38) +(1.09+-0.03)lnW 2

  11. Interaction dynamics of multiple mobile robots with simple navigation strategies

    Science.gov (United States)

    Wang, P. K. C.

    1989-01-01

    The global dynamic behavior of multiple interacting autonomous mobile robots with simple navigation strategies is studied. Here, the effective spatial domain of each robot is taken to be a closed ball about its mass center. It is assumed that each robot has a specified cone of visibility such that interaction with other robots takes place only when they enter its visibility cone. Based on a particle model for the robots, various simple homing and collision-avoidance navigation strategies are derived. Then, an analysis of the dynamical behavior of the interacting robots in unbounded spatial domains is made. The article concludes with the results of computer simulations studies of two or more interacting robots.

  12. Interactive Visualization of DGA Data Based on Multiple Views

    Science.gov (United States)

    Geng, Yujie; Lin, Ying; Ma, Yan; Guo, Zhihong; Gu, Chao; Wang, Mingtao

    2017-01-01

    The commission and operation of dissolved gas analysis (DGA) online monitoring makes up for the weakness of traditional DGA method. However, volume and high-dimensional DGA data brings a huge challenge for monitoring and analysis. In this paper, we present a novel interactive visualization model of DGA data based on multiple views. This model imitates multi-angle analysis by combining parallel coordinates, scatter plot matrix and data table. By offering brush, collaborative filter and focus + context technology, this model provides a convenient and flexible interactive way to analyze and understand the DGA data.

  13. Pareto-Zipf law in growing systems with multiplicative interactions

    Science.gov (United States)

    Ohtsuki, Toshiya; Tanimoto, Satoshi; Sekiyama, Makoto; Fujihara, Akihiro; Yamamoto, Hiroshi

    2018-06-01

    Numerical simulations of multiplicatively interacting stochastic processes with weighted selections were conducted. A feedback mechanism to control the weight w of selections was proposed. It becomes evident that when w is moderately controlled around 0, such systems spontaneously exhibit the Pareto-Zipf distribution. The simulation results are universal in the sense that microscopic details, such as parameter values and the type of control and weight, are irrelevant. The central ingredient of the Pareto-Zipf law is argued to be the mild control of interactions.

  14. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.

    Directory of Open Access Journals (Sweden)

    Andrea D Coviello

    Full Text Available Sex hormone-binding globulin (SHBG is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106, PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11, GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16, ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09, JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35, SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08, NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12, ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14, TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14, LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07, BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08, and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06. These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08, women p = 0.66, heterogeneity p = 0.003. Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion

  15. Multiple Avirulence Loci and Allele-Specific Effector Recognition Control the Pm3 Race-Specific Resistance of Wheat to Powdery Mildew[OPEN

    Science.gov (United States)

    Roffler, Stefan; Stirnweis, Daniel; Treier, Georges; Herren, Gerhard; Korol, Abraham B.; Wicker, Thomas

    2015-01-01

    In cereals, several mildew resistance genes occur as large allelic series; for example, in wheat (Triticum aestivum and Triticum turgidum), 17 functional Pm3 alleles confer agronomically important race-specific resistance to powdery mildew (Blumeria graminis). The molecular basis of race specificity has been characterized in wheat, but little is known about the corresponding avirulence genes in powdery mildew. Here, we dissected the genetics of avirulence for six Pm3 alleles and found that three major Avr loci affect avirulence, with a common locus_1 involved in all AvrPm3-Pm3 interactions. We cloned the effector gene AvrPm3a2/f2 from locus_2, which is recognized by the Pm3a and Pm3f alleles. Induction of a Pm3 allele-dependent hypersensitive response in transient assays in Nicotiana benthamiana and in wheat demonstrated specificity. Gene expression analysis of Bcg1 (encoded by locus_1) and AvrPm3 a2/f2 revealed significant differences between isolates, indicating that in addition to protein polymorphisms, expression levels play a role in avirulence. We propose a model for race specificity involving three components: an allele-specific avirulence effector, a resistance gene allele, and a pathogen-encoded suppressor of avirulence. Thus, whereas a genetically simple allelic series controls specificity in the plant host, recognition on the pathogen side is more complex, allowing flexible evolutionary responses and adaptation to resistance genes. PMID:26452600

  16. Obesity interacts with infectious mononucleosis in risk of multiple sclerosis.

    Science.gov (United States)

    Hedström, A K; Lima Bomfim, I; Hillert, J; Olsson, T; Alfredsson, L

    2015-03-01

    The possible interaction between adolescent obesity and past infectious mononucleosis (IM) was investigated with regard to multiple sclerosis (MS) risk. This report is based on two population-based case-control studies, one with incident cases (1780 cases, 3885 controls) and one with prevalent cases (4502 cases, 4039 controls). Subjects were categorized based on adolescent body mass index (BMI) and past IM and compared with regard to occurrence of MS by calculating odds ratios with 95% confidence intervals (CIs) employing logistic regression. A potential interaction between adolescent BMI and past IM was evaluated by calculating the attributable proportion due to interaction. Regardless of human leukocyte antigen (HLA) status, a substantial interaction was observed between adolescent obesity and past IM with regard to MS risk. The interaction was most evident when IM after the age of 10 was considered (attributable proportion due to interaction 0.8, 95% CI 0.6-1.0 in the incident study, and attributable proportion due to interaction 0.7, 95% CI 0.5-1.0 in the prevalent study). In the incident study, the odds ratio of MS was 14.7 (95% CI 5.9-36.6) amongst subjects with adolescent obesity and past IM after the age of 10, compared with subjects with none of these exposures. The corresponding odds ratio in the prevalent study was 13.2 (95% CI 5.2-33.6). An obese state both impacts the cellular immune response to infections and induces a state of chronic immune-mediated inflammation which may contribute to explain our finding of an interaction between adolescent BMI and past IM. Measures taken against adolescent obesity may thus be a preventive strategy against MS. © 2014 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

  17. The interaction between multiple bubbles and the free surface

    International Nuclear Information System (INIS)

    Zhang Aman; Yao Xiongliang

    2008-01-01

    The flow is assumed to be potential, and a boundary integral method is used to solve the Laplace equation for the velocity potential to investigate the shape and the position of the bubble. A 3D code to study the bubble dynamics is developed, and the calculation results agree well with the experimental data. Numerical analyses are carried out for the interaction between multiple bubbles near the free surface including in-phase and out-of-phase bubbles. The calculation result shows that the bubble period increases with the decrease of the distance between bubble centres because of the depression effect between multiple bubbles. The depression has no relationship with the free surface and it is more apparent for out-of-phase bubbles. There are great differences in dynamic behaviour between the in-phase bubbles and the out-of-phase bubbles due to the depression effect. Furthermore, the interaction among eight bubbles is simulated with a three-dimensional model, and the evolving process and the relevant physical phenomena are presented. These phenomena can give a reference to the future work on the power of bubbles induced by multiple charges exploding simultaneously or continuously

  18. Parallel Beam-Beam Simulation Incorporating Multiple Bunches and Multiple Interaction Regions

    CERN Document Server

    Jones, F W; Pieloni, T

    2007-01-01

    The simulation code COMBI has been developed to enable the study of coherent beam-beam effects in the full collision scenario of the LHC, with multiple bunches interacting at multiple crossing points over many turns. The program structure and input are conceived in a general way which allows arbitrary numbers and placements of bunches and interaction points (IP's), together with procedural options for head-on and parasitic collisions (in the strong-strong sense), beam transport, statistics gathering, harmonic analysis, and periodic output of simulation data. The scale of this problem, once we go beyond the simplest case of a pair of bunches interacting once per turn, quickly escalates into the parallel computing arena, and herein we will describe the construction of an MPI-based version of COMBI able to utilize arbitrary numbers of processors to support efficient calculation of multi-bunch multi-IP interactions and transport. Implementing the parallel version did not require extensive disruption of the basic ...

  19. Interaction of multiple biomimetic antimicrobial polymers with model bacterial membranes

    Energy Technology Data Exchange (ETDEWEB)

    Baul, Upayan, E-mail: upayanb@imsc.res.in; Vemparala, Satyavani, E-mail: vani@imsc.res.in [The Institute of Mathematical Sciences, C.I.T. Campus, Taramani, Chennai 600113 (India); Kuroda, Kenichi, E-mail: kkuroda@umich.edu [Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109 (United States)

    2014-08-28

    Using atomistic molecular dynamics simulations, interaction of multiple synthetic random copolymers based on methacrylates on prototypical bacterial membranes is investigated. The simulations show that the cationic polymers form a micellar aggregate in water phase and the aggregate, when interacting with the bacterial membrane, induces clustering of oppositely charged anionic lipid molecules to form clusters and enhances ordering of lipid chains. The model bacterial membrane, consequently, develops lateral inhomogeneity in membrane thickness profile compared to polymer-free system. The individual polymers in the aggregate are released into the bacterial membrane in a phased manner and the simulations suggest that the most probable location of the partitioned polymers is near the 1-palmitoyl-2-oleoyl-phosphatidylglycerol (POPG) clusters. The partitioned polymers preferentially adopt facially amphiphilic conformations at lipid-water interface, despite lacking intrinsic secondary structures such as α-helix or β-sheet found in naturally occurring antimicrobial peptides.

  20. Electron-electron interaction in Multiple Quantum Wells

    Science.gov (United States)

    Zybert, M.; Marchewka, M.; Tomaka, G.; Sheregii, E. M.

    2012-07-01

    The complex investigation of the magneto-transport effects in structures containing multiple quantum well (MQWs) based on the GaAs/AlGaAs-heterostructures has been performed. The MQWs investigated have different electron densities in QWs. The parameters of 2DEG in MQWs were determined from the data of the Integer Quantum Hall Effect (IQHE) and Shubnikov-de Haas oscillations (SdH) observed at low temperatures (0.6-4.2 K). The method of calculation of the electron states energies in MQWs has been developed which is based on the splitting of these states due to the exchange interaction (SAS-splitting, see D. Płoch et al., Phys. Rev. B 79 (2009) 195434) including the screening of this interaction. The IQHE and SdH observed in these multilayer structures with the third degree of freedom for electrons are interpreted from this.

  1. Class II HLA interactions modulate genetic risk for multiple sclerosis

    Science.gov (United States)

    Dilthey, Alexander T; Xifara, Dionysia K; Ban, Maria; Shah, Tejas S; Patsopoulos, Nikolaos A; Alfredsson, Lars; Anderson, Carl A; Attfield, Katherine E; Baranzini, Sergio E; Barrett, Jeffrey; Binder, Thomas M C; Booth, David; Buck, Dorothea; Celius, Elisabeth G; Cotsapas, Chris; D’Alfonso, Sandra; Dendrou, Calliope A; Donnelly, Peter; Dubois, Bénédicte; Fontaine, Bertrand; Fugger, Lars; Goris, An; Gourraud, Pierre-Antoine; Graetz, Christiane; Hemmer, Bernhard; Hillert, Jan; Kockum, Ingrid; Leslie, Stephen; Lill, Christina M; Martinelli-Boneschi, Filippo; Oksenberg, Jorge R; Olsson, Tomas; Oturai, Annette; Saarela, Janna; Søndergaard, Helle Bach; Spurkland, Anne; Taylor, Bruce; Winkelmann, Juliane; Zipp, Frauke; Haines, Jonathan L; Pericak-Vance, Margaret A; Spencer, Chris C A; Stewart, Graeme; Hafler, David A; Ivinson, Adrian J; Harbo, Hanne F; Hauser, Stephen L; De Jager, Philip L; Compston, Alastair; McCauley, Jacob L; Sawcer, Stephen; McVean, Gil

    2016-01-01

    Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01–HLA-DRB1*15:01 and HLA-DQB1*03:01–HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles. PMID:26343388

  2. Analysis and application of opinion model with multiple topic interactions.

    Science.gov (United States)

    Xiong, Fei; Liu, Yun; Wang, Liang; Wang, Ximeng

    2017-08-01

    To reveal heterogeneous behaviors of opinion evolution in different scenarios, we propose an opinion model with topic interactions. Individual opinions and topic features are represented by a multidimensional vector. We measure an agent's action towards a specific topic by the product of opinion and topic feature. When pairs of agents interact for a topic, their actions are introduced to opinion updates with bounded confidence. Simulation results show that a transition from a disordered state to a consensus state occurs at a critical point of the tolerance threshold, which depends on the opinion dimension. The critical point increases as the dimension of opinions increases. Multiple topics promote opinion interactions and lead to the formation of macroscopic opinion clusters. In addition, more topics accelerate the evolutionary process and weaken the effect of network topology. We use two sets of large-scale real data to evaluate the model, and the results prove its effectiveness in characterizing a real evolutionary process. Our model achieves high performance in individual action prediction and even outperforms state-of-the-art methods. Meanwhile, our model has much smaller computational complexity. This paper provides a demonstration for possible practical applications of theoretical opinion dynamics.

  3. Higher Magnesium Intake Is Associated with Lower Fasting Glucose and Insulin, with No Evidence of Interaction with Select Genetic Loci, in a Meta-Analysis of 15 CHARGE Consortium Studies1234

    Science.gov (United States)

    Hruby, Adela; Ngwa, Julius S.; Renström, Frida; Wojczynski, Mary K.; Ganna, Andrea; Hallmans, Göran; Houston, Denise K.; Jacques, Paul F.; Kanoni, Stavroula; Lehtimäki, Terho; Lemaitre, Rozenn N.; Manichaikul, Ani; North, Kari E.; Ntalla, Ioanna; Sonestedt, Emily; Tanaka, Toshiko; van Rooij, Frank J. A.; Bandinelli, Stefania; Djoussé, Luc; Grigoriou, Efi; Johansson, Ingegerd; Lohman, Kurt K.; Pankow, James S.; Raitakari, Olli T.; Riserus, Ulf; Yannakoulia, Mary; Zillikens, M. Carola; Hassanali, Neelam; Liu, Yongmei; Mozaffarian, Dariush; Papoutsakis, Constantina; Syvänen, Ann-Christine; Uitterlinden, André G.; Viikari, Jorma; Groves, Christopher J.; Hofman, Albert; Lind, Lars; McCarthy, Mark I.; Mikkilä, Vera; Mukamal, Kenneth; Franco, Oscar H.; Borecki, Ingrid B.; Cupples, L. Adrienne; Dedoussis, George V.; Ferrucci, Luigi; Hu, Frank B.; Ingelsson, Erik; Kähönen, Mika; Kao, W. H. Linda; Kritchevsky, Stephen B.; Orho-Melander, Marju; Prokopenko, Inga; Rotter, Jerome I.; Siscovick, David S.; Witteman, Jacqueline C. M.; Franks, Paul W.; Meigs, James B.; McKeown, Nicola M.; Nettleton, Jennifer A.

    2013-01-01

    Favorable associations between magnesium intake and glycemic traits, such as fasting glucose and insulin, are observed in observational and clinical studies, but whether genetic variation affects these associations is largely unknown. We hypothesized that single nucleotide polymorphisms (SNPs) associated with either glycemic traits or magnesium metabolism affect the association between magnesium intake and fasting glucose and insulin. Fifteen studies from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided data from up to 52,684 participants of European descent without known diabetes. In fixed-effects meta-analyses, we quantified 1) cross-sectional associations of dietary magnesium intake with fasting glucose (mmol/L) and insulin (ln-pmol/L) and 2) interactions between magnesium intake and SNPs related to fasting glucose (16 SNPs), insulin (2 SNPs), or magnesium (8 SNPs) on fasting glucose and insulin. After adjustment for age, sex, energy intake, BMI, and behavioral risk factors, magnesium (per 50-mg/d increment) was inversely associated with fasting glucose [β = −0.009 mmol/L (95% CI: −0.013, −0.005), P magnesium-related SNP or interaction between any SNP and magnesium reached significance after correction for multiple testing. However, rs2274924 in magnesium transporter-encoding TRPM6 showed a nominal association (uncorrected P = 0.03) with glucose, and rs11558471 in SLC30A8 and rs3740393 near CNNM2 showed a nominal interaction (uncorrected, both P = 0.02) with magnesium on glucose. Consistent with other studies, a higher magnesium intake was associated with lower fasting glucose and insulin. Nominal evidence of TRPM6 influence and magnesium interaction with select loci suggests that further investigation is warranted. PMID:23343670

  4. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

    DEFF Research Database (Denmark)

    Sung, Yun J; Winkler, Thomas W; de Las Fuentes, Lisa

    2018-01-01

    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genom...

  5. A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

    NARCIS (Netherlands)

    Sung, Yun J.; Winkler, Thomas W.; de las Fuentes, Lisa; Bentley, Amy R.; Brown, Michael R.; Kraja, Aldi T.; Schwander, Karen; Ntalla, Ioanna; Guo, Xiuqing; Franceschini, Nora; Lu, Yingchang; Cheng, Ching-Yu; Sim, Xueling; Vojinovic, Dina; Marten, Jonathan; Musani, Solomon K.; Li, Changwei; Feitosa, Mary F.; Kilpelainen, Tuomas O.; Richard, Melissa A.; Noordam, Raymond; Aslibekyan, Stella; Aschard, Hugues; Bartz, Traci M.; Dorajoo, Rajkumar; Liu, Yongmei; Manning, Alisa K.; Rankinen, Tuomo; Smith, Albert Vernon; Tajuddin, Salman M.; Tayo, Bamidele O.; Warren, Helen R.; Zhao, Wei; Zhou, Yanhua; Matoba, Nana; Sofer, Tamar; Alver, Maris; Amini, Marzyeh; Boissel, Mathilde; Chai, Jin Fang; Chen, Xu; Divers, Jasmin; Gandin, Ilaria; Gao, Chuan; Giulianini, Franco; Goel, Anuj; Harris, Sarah E.; Hartwig, Fernando Pires; Horimoto, Andrea R. V. R.; Hsu, Fang-Chi; Jackson, Anne U.; Kahonen, Mika; Kasturiratne, Anuradhani; Kuhnel, Brigitte; Leander, Karin; Lee, Wen-Jane; Lin, Keng-Hung; Luan, Jian' an; McKenzie, Colin A.; He Meian,; Nelson, Christopher P.; Rauramaa, Rainer; Schupf, Nicole; Scott, Robert A.; Sheu, Wayne H. H.; Stancakova, Alena; Takeuchi, Fumihiko; van der Most, Peter J.; Varga, Tibor V.; Wang, Heming; Wang, Yajuan; Ware, Erin B.; Weiss, Stefan; Wen, Wanqing; Yanek, Lisa R.; Zhang, Weihua; Zhao, Jing Hua; Afaq, Saima; Alfred, Tamuno; Amin, Najaf; Arking, Dan; Aung, Tin; Barr, R. Graham; Bielak, Lawrence F.; Boerwinkle, Eric; Bottinger, Erwin P.; Braund, Peter S.; Brody, Jennifer A.; Broeckel, Ulrich; Cabrera, Claudia P.; Cade, Brian; Yu Caizheng,; Campbell, Archie; Canouil, Mickael; Chakravarti, Aravinda; Chauhan, Ganesh; Christensen, Kaare; Cocca, Massimiliano; Collins, Francis S.; Connell, John M.; de Mutsert, Renee; de Silva, H. Janaka; Debette, Stephanie; Dorr, Marcus; Duan, Qing; Eaton, Charles B.; Ehret, Georg; Evangelou, Evangelos; Faul, Jessica D.; Fisher, Virginia A.; Forouhi, Nita G.; Franco, Oscar H.; Friedlander, Yechiel; Gao, He; Gigante, Bruna; Graff, Misa; Gu, C. Charles; Gu, Dongfeng; Gupta, Preeti; Hagenaars, Saskia P.; Harris, Tamara B.; He, Jiang; Heikkinen, Sami; Heng, Chew-Kiat; Hirata, Makoto; Hofman, Albert; Howard, Barbara V.; Hunt, Steven; Irvin, Marguerite R.; Jia, Yucheng; Joehanes, Roby; Justice, Anne E.; Katsuya, Tomohiro; Kaufman, Joel; Kerrison, Nicola D.; Khor, Chiea Chuen; Koh, Woon-Puay; Koistinen, Heikki A.; Komulainen, Pirjo; Kooperberg, Charles; Krieger, Jose E.; Kubo, Michiaki; Kuusisto, Johanna; Langefeld, Carl D.; Langenberg, Claudia; Launer, Lenore J.; Lehne, Benjamin; Lewis, Cora E.; Li, Yize; Lim, Sing Hui; Lin, Shiow; Liu, Ching-Ti; Liu, Jianjun; Liu, Jingmin; Liu, Kiang; Liu, Yeheng; Loh, Marie; Lohman, Kurt K.; Long, Jirong; Louie, Tin; Magi, Reedik; Mahajan, Anubha; Meitinger, Thomas; Metspalu, Andres; Milani, Lili; Momozawa, Yukihide; Morris, Andrew P.; Mosley, Thomas H.; Munson, Peter; Murray, Alison D.; Nalls, Mike A.; Nasri, Ubaydah; Norris, Jill M.; North, Kari; Ogunniyi, Adesola; Padmanabhan, Sandosh; Palmas, Walter R.; Palmer, Nicholette D.; Pankow, James S.; Pedersen, Nancy L.; Peters, Annette; Peyser, Patricia A.; Polasek, Ozren; Raitakari, Olli T.; Renstrom, Frida; Rice, Treva K.; Ridker, Paul M.; Robino, Antonietta; Robinson, Jennifer G.; Rose, Lynda M.; Rudan, Igor; Sabanayagam, Charumathi; Salako, Babatunde L.; Sandow, Kevin; Schmidt, Carsten O.; Schreiner, Pamela J.; Scott, William R.; Seshadri, Sudha; Sever, Peter; Sitlani, Colleen M.; Smith, Jennifer A.; Snieder, Harold; Starr, John M.; Strauch, Konstantin; Tang, Hua; Taylor, Kent D.; Teo, Yik Ying; Tham, Yih Chung; Ultterlinden, Andre G.; Waldenberger, Melanie; Wang, Lihua; Wang, Ya X.; Bin Wei, Wen; Williams, Christine; Wilson, Gregory; Wojczynski, Mary K.; Yao, Jie; Yuan, Jian-Min; Zonderman, Alan B.; Becker, Diane M.; Boehnke, Michael; Bowden, Donald W.; Chambers, John C.; Chen, Yii-Der Ida; de Faire, Ulf; Deary, Ian J.; Esko, Tonu; Farrall, Martin; Forrester, Terrence; Franks, Paul W.; Freedman, Barry I.; Froguel, Philippe; Gasparini, Paolo; Gieger, Christian; Horta, Bernardo Lessa; Hung, Yi-Jen; Jonas, Jost B.; Kato, Norihiro; Kooner, Jaspal S.; Laakso, Markku; Lehtimaki, Terho; Liang, Kae-Woei; Magnusson, Patrik K. E.; Newman, Anne B.; Oldehinkel, Albertine J.; Pereira, Alexandre C.; Redline, Susan; Rettig, Rainer; Samani, Nilesh J.; Scott, James; Shu, Xiao-Ou; van der Harst, Pim; Wagenknecht, Lynne E.; Wareham, Nicholas J.; Watkins, Hugh; Weir, David R.; Wickremasinghe, Ananda R.; Wu, Tangchun; Zheng, Wei; Kamatani, Yoichiro; Laurie, Cathy C.; Bouchard, Claude; Cooper, Richard S.; Evans, Michele K.; Gudnason, Vilmundur; Kardia, Sharon L. R.; Kritchevsky, Stephen B.; Levy, Daniel; O'Connell, Jeff R.; Psaty, Bruce M.; van Dam, Rob M.; Sims, Mario; Arnett, Donna K.; Mook-Kanamori, Dennis O.; Kelly, Tanika N.; Fox, Ervin R.; Hayward, Caroline; Fornage, Myriam; Rotimi, Charles N.; Province, Michael A.; van Duijn, Cornelia M.; Tai, E. Shyong; Wong, Tien Yin; Loos, Ruth J. F.; Reiner, Alex P.; Rotter, Jerome I.; Zhu, Xiaofeng; Bierut, Laura J.; Gauderman, W. James; Caulfield, Mark J.; Elliott, Paul; Rice, Kenneth; Munroe, Patricia B.; Morrison, Alanna C.; Cupples, L. Adrienne; Rao, Dabeeru C.; Chasman, Daniel I.; Study, Lifelines Cohort

    2018-01-01

    Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed

  6. Development of a Multiple Loci Variable Number of Tandem Repeats Analysis (MLVA) to Unravel the Intra-Pathovar Structure of Pseudomonas syringae pv. actinidiae Populations Worldwide

    Science.gov (United States)

    Ciarroni, Serena; Gallipoli, Lorenzo; Taratufolo, Maria C.; Butler, Margi I.; Poulter, Russell T. M.; Pourcel, Christine; Vergnaud, Gilles; Balestra, Giorgio M.; Mazzaglia, Angelo

    2015-01-01

    The bacterial canker of kiwifruit by Pseudomonas syringae pv. actinidiae is an emblematic example of a catastrophic disease of fruit crops. In 2008 a new, extremely virulent form of the pathogen emerged and rapidly devastated many Actinidia spp. orchards all over the world. In order to understand differences in populations within this pathovar and to elucidate their diffusion and movements on world scale, it is necessary to be able to quickly and on a routine basis compare new isolates with previous records. In this report a worldwide collection of 142 strains was analyzed by MLVA, chosen as investigative technique for its efficacy, reproducibility, simplicity and low cost. A panel of 13 Variable Number of Tandem Repeats (VNTR) loci was identified and used to describe the pathogen population. The MLVA clustering is highly congruent with the population structure as previously established by other molecular approaches including whole genome sequencing and correlates with geographic origin, time of isolation and virulence. For convenience, we divided the VNTR loci in two panels. Panel 1 assay, using six loci, recognizes 23 different haplotypes, clustered into ten complexes with highest congruence with previous classifications. Panel 2, with seven VNTR loci, provides discriminatory power. Using the total set of 13 VNTR loci, 58 haplotypes can be distinguished. The recent hypervirulent type shows very limited diversity and includes, beside the strains from Europe, New Zealand and Chile, a few strains from Shaanxi, China. A broad genetic variability is observed in China, but different types are also retrievable in Japan and Korea. The low virulent strains cluster together and are very different from the other MLVA genotypes. Data were used to generate a public database in MLVAbank. MLVA represents a very promising first-line assay for large-scale routine genotyping, prior to whole genome sequencing of only the most relevant samples. PMID:26262683

  7. Species-Level Phylogeny and Polyploid Relationships in Hordeum (Poaceae) Inferred by Next-Generation Sequencing and In Silico Cloning of Multiple Nuclear Loci.

    Science.gov (United States)

    Brassac, Jonathan; Blattner, Frank R

    2015-09-01

    Polyploidization is an important speciation mechanism in the barley genus Hordeum. To analyze evolutionary changes after allopolyploidization, knowledge of parental relationships is essential. One chloroplast and 12 nuclear single-copy loci were amplified by polymerase chain reaction (PCR) in all Hordeum plus six out-group species. Amplicons from each of 96 individuals were pooled, sheared, labeled with individual-specific barcodes and sequenced in a single run on a 454 platform. Reference sequences were obtained by cloning and Sanger sequencing of all loci for nine supplementary individuals. The 454 reads were assembled into contigs representing the 13 loci and, for polyploids, also homoeologues. Phylogenetic analyses were conducted for all loci separately and for a concatenated data matrix of all loci. For diploid taxa, a Bayesian concordance analysis and a coalescent-based dated species tree was inferred from all gene trees. Chloroplast matK was used to determine the maternal parent in allopolyploid taxa. The relative performance of different multilocus analyses in the presence of incomplete lineage sorting and hybridization was also assessed. The resulting multilocus phylogeny reveals for the first time species phylogeny and progenitor-derivative relationships of all di- and polyploid Hordeum taxa within a single analysis. Our study proves that it is possible to obtain a multilocus species-level phylogeny for di- and polyploid taxa by combining PCR with next-generation sequencing, without cloning and without creating a heavy load of sequence data. © The Author(s) 2015. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

  8. Quantitative Trait Loci in Inbred Lines

    NARCIS (Netherlands)

    Jansen, R.C.

    2001-01-01

    Quantitative traits result from the influence of multiple genes (quantitative trait loci) and environmental factors. Detecting and mapping the individual genes underlying such 'complex' traits is a difficult task. Fortunately, populations obtained from crosses between inbred lines are relatively

  9. Ranking and characterization of established BMI and lipid associated loci as candidates for gene-environment interactions

    DEFF Research Database (Denmark)

    Shungin, Dmitry; Deng, Wei Q; Varga, Tibor V

    2017-01-01

    Phenotypic variance heterogeneity across genotypes at a single nucleotide polymorphism (SNP) may reflect underlying gene-environment (G×E) or gene-gene interactions. We modeled variance heterogeneity for blood lipids and BMI in up to 44,211 participants and investigated relationships between...... variance effects (Pv), G×E interaction effects (with smoking and physical activity), and marginal genetic effects (Pm). Correlations between Pv and Pm were stronger for SNPs with established marginal effects (Spearman's ρ = 0.401 for triglycerides, and ρ = 0.236 for BMI) compared to all SNPs. When Pv...... and Pm were compared for all pruned SNPs, only BMI was statistically significant (Spearman's ρ = 0.010). Overall, SNPs with established marginal effects were overrepresented in the nominally significant part of the Pv distribution (Pbinomial BMI had...

  10. MSAViewer: interactive JavaScript visualization of multiple sequence alignments.

    Science.gov (United States)

    Yachdav, Guy; Wilzbach, Sebastian; Rauscher, Benedikt; Sheridan, Robert; Sillitoe, Ian; Procter, James; Lewis, Suzanna E; Rost, Burkhard; Goldberg, Tatyana

    2016-11-15

    The MSAViewer is a quick and easy visualization and analysis JavaScript component for Multiple Sequence Alignment data of any size. Core features include interactive navigation through the alignment, application of popular color schemes, sorting, selecting and filtering. The MSAViewer is 'web ready': written entirely in JavaScript, compatible with modern web browsers and does not require any specialized software. The MSAViewer is part of the BioJS collection of components. The MSAViewer is released as open source software under the Boost Software License 1.0. Documentation, source code and the viewer are available at http://msa.biojs.net/Supplementary information: Supplementary data are available at Bioinformatics online. msa@bio.sh. © The Author 2016. Published by Oxford University Press.

  11. Considering Interactions among Multiple Criteria for the Server Selection

    Directory of Open Access Journals (Sweden)

    Vesna Čančer

    2010-06-01

    Full Text Available Decision-making about server selection is one of the multi-criteria decision-making (MCDM processes where interactions among criteria should be considered. The paper introduces and develops some solutions for considering interactions among criteria in the MCDM problems. In the frame procedure for MCDM by using the group of methods, based on assigning weights, special attention is given to the synthesis of the local alternatives’ values into the aggregate values where the mutual preferential independence between two criteria is not assumed. Firstly, we delineate how to complete the additive model into the multiplicative one with synergic and redundancy elements in the case that criteria are structured in one level and in two levels. Furthermore, we adapted the concept of the fuzzy Choquet integral to the multi-attribute value theory. Studying and comparing the results of the example case of the server selection obtained by both aggregation approaches, the paper highlights the advantages of the first one since it does not require from decision makers to determine the weights of all possible combinations of the criteria and it enables the further use of the most preferred MCDM methods.

  12. An Advanced N -body Model for Interacting Multiple Stellar Systems

    Energy Technology Data Exchange (ETDEWEB)

    Brož, Miroslav [Astronomical Institute of the Charles University, Faculty of Mathematics and Physics, V Holešovičkách 2, CZ-18000 Praha 8 (Czech Republic)

    2017-06-01

    We construct an advanced model for interacting multiple stellar systems in which we compute all trajectories with a numerical N -body integrator, namely the Bulirsch–Stoer from the SWIFT package. We can then derive various observables: astrometric positions, radial velocities, minima timings (TTVs), eclipse durations, interferometric visibilities, closure phases, synthetic spectra, spectral energy distribution, and even complete light curves. We use a modified version of the Wilson–Devinney code for the latter, in which the instantaneous true phase and inclination of the eclipsing binary are governed by the N -body integration. If all of these types of observations are at one’s disposal, a joint χ {sup 2} metric and an optimization algorithm (a simplex or simulated annealing) allow one to search for a global minimum and construct very robust models of stellar systems. At the same time, our N -body model is free from artifacts that may arise if mutual gravitational interactions among all components are not self-consistently accounted for. Finally, we present a number of examples showing dynamical effects that can be studied with our code and we discuss how systematic errors may affect the results (and how to prevent this from happening).

  13. Multiple var2csa-type PfEMP1 genes located at different chromosomal loci occur in many Plasmodium falciparum isolates

    DEFF Research Database (Denmark)

    Sander, Adam F; Salanti, Ali; Lavstsen, Thomas

    2009-01-01

    in the VAR2CSA protein, sequence variation in the DBL2X region of var2csa genes in 54 P.falciparum samples was analyzed. Chromosome mapping of var2csa loci was carried out and a quantitative PCR assay was developed to estimate the number of var2csa genes in P.falciparum isolates from the placenta of pregnant....... falciparum isolates. One gene is on chromosome 12 but additional var2csa-type genes are on different chromosomes in different isolates. Multiplicity of var2csa genes appears more common in infected placentae than in samples from non-pregnant donors indicating a possible advantage of this genotype...

  14. Interactions between Meteorus pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus.

    Science.gov (United States)

    Guo, Hui-Fang; Fang, Ji-Chao; Zhong, Wan-Fang; Liu, Bao-Sheng

    2013-01-01

    Baculoviruses may interact with parasitoids in the same host. A previous study has shown that infection of larvae with Spodoptera litura nucleopolyhedrovirus (SpltNPV) was deleterious to the survival and development of Meteorus pulchricornis (Wesmael) (Hymenoptera: Braconidae). In this paper, the interactions between M. pulchricornis and Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) in Spodoptera exigua (Hübner) (Lepidoptera: Noctuidae), a permissive host of the virus and parasitoid, were investigated. The results showed that the effect of M. pulchricornis on SeMNPV and the effect of the virus on the parasitoid both depended on the concentration of the virus and the interval between viral infection and parasitism. Whether S. exigua was treated with the parasitoid and virus simultaneously or 1 day apart, the biological activities of 10(5), 10(6), and 10(7) OBs/mL SeMNPV were all significantly improved by M. pulchricornis. In contrast, the biological activity of 10(3) OBs/mL SeMNPV was significantly decreased when the host was exposed to the virus and parasitoid simultaneously. Regarding the impact of SeMNPV on M. pulchricornis, exposing the host to the parasitoid and SeMNPV with concentrations lower than 10(6) occlusion bodies (OBs)/mL produced no negative effects on the parasitoid. The results also showed that ingestion of SeMNPV by adult stage M. pulchricornis significantly increased the number of parasitoid offspring that successfully emerged from the host. Furthermore, M. pulchricornis was found to transmit SeMNPV among populations of S. exigua. Taken together, these findings indicate that M. pulchricornis integrated with an appropriate concentration of SeMNPV has the potential to improve the efficacy of biological control against S. exigua.

  15. Multiple Wins, Multiple Organizations—How to Manage Institutional Interaction in Financing Forest Landscape Restoration (FLR

    Directory of Open Access Journals (Sweden)

    Astrid Carrapatoso

    2018-03-01

    Full Text Available By restoring forest ecosystems and fostering resilient and sustainable land use practices, Forest Landscape Restoration (FLR contributes to climate change mitigation, adaptation and sustainable development as well as the protection of biological diversity and combating desertification. This integrative approach provides the opportunity for multiple wins, but it necessitates the management of complex institutional interactions arising from the involvement of multiple international organizations. Focusing on the pivotal aspect of financing, this article surveys the landscape of public international institutions supporting FLR and analyzes the effectiveness of existing mechanisms of inter-institutional coordination and harmonization. Methodologically, our research is based on a document analysis, complemented by participant observation of the two Bonn Climate Change Conferences in May and November 2017 as well as the Global Landscapes Forum in December 2017. We find that financial institutions have established fairly effective rules for the management of positive and negative externalities through the introduction of co-benefits and safeguards. The fact that each institution has their own safeguards provisions, however, leads to significant transaction costs for recipient countries. In the discussion, we thus recommend that institutions should refrain from an unnecessary duplication of standards and focus on best practice.

  16. Optimizing Sparse Matrix-Multiple Vectors Multiplication for Nuclear Configuration Interaction Calculations

    Energy Technology Data Exchange (ETDEWEB)

    Aktulga, Hasan Metin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Buluc, Aydin [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Williams, Samuel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Yang, Chao [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-08-14

    Obtaining highly accurate predictions on the properties of light atomic nuclei using the configuration interaction (CI) approach requires computing a few extremal Eigen pairs of the many-body nuclear Hamiltonian matrix. In the Many-body Fermion Dynamics for nuclei (MFDn) code, a block Eigen solver is used for this purpose. Due to the large size of the sparse matrices involved, a significant fraction of the time spent on the Eigen value computations is associated with the multiplication of a sparse matrix (and the transpose of that matrix) with multiple vectors (SpMM and SpMM-T). Existing implementations of SpMM and SpMM-T significantly underperform expectations. Thus, in this paper, we present and analyze optimized implementations of SpMM and SpMM-T. We base our implementation on the compressed sparse blocks (CSB) matrix format and target systems with multi-core architectures. We develop a performance model that allows us to understand and estimate the performance characteristics of our SpMM kernel implementations, and demonstrate the efficiency of our implementation on a series of real-world matrices extracted from MFDn. In particular, we obtain 3-4 speedup on the requisite operations over good implementations based on the commonly used compressed sparse row (CSR) matrix format. The improvements in the SpMM kernel suggest we may attain roughly a 40% speed up in the overall execution time of the block Eigen solver used in MFDn.

  17. Thymocyte migration: an affair of multiple cellular interactions?

    Directory of Open Access Journals (Sweden)

    Savino W.

    2003-01-01

    Full Text Available Cell migration is a crucial event in the general process of thymocyte differentiation. The cellular interactions involved in the control of this migration are beginning to be defined. At least chemokines and extracellular matrix proteins appear to be part of the game. Cells of the thymic microenvironment produce these two groups of molecules, whereas developing thymocytes express the corresponding receptors. Moreover, although chemokines and extracellular matrix can drive thymocyte migration per se, a combined role for these molecules appears to contribute to the resulting migration patterns of thymocytes in their various stages of differentiation. The dynamics of chemokine and extracellular matrix production and degradation is not yet well understood. However, matrix metalloproteinases are likely to play a role in the breakdown of intrathymic extracellular matrix contents. Thus, the physiological migration of thymocytes should be envisioned as a resulting vector of multiple, simultaneous and/or sequential stimuli involving chemokines, adhesive and de-adhesive extracellular matrix proteins, as well as matrix metalloproteinases. Accordingly, it is conceivable that any pathological change in any of these loops may result in the alteration of normal thymocyte migration. This seems to be the case in murine infection by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas' disease. A better knowledge of the physiological mechanisms governing thymocyte migration will provide new clues for designing therapeutic strategies targeting developing T cells.

  18. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Stella Koutros

    Full Text Available Uncovering SNP (single nucleotide polymorphisms-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs and 95% confidence intervals (CIs. Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1 SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15 (P-interaction= 0.003. Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41 (P-interaction= 0.006. In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.

  19. Flame Interactions and Thermoacoustics in Multiple-Nozzle Combustors

    Science.gov (United States)

    Dolan, Brian

    The first major chapter of original research (Chapter 3) examines thermoacoustic oscillations in a low-emission staged multiple-nozzle lean direct injection (MLDI) combustor. This experimental program investigated a relatively practical combustor sector that was designed and built as part of a commercial development program. The research questions are both practical, such as under what conditions the combustor can be safely operated, and fundamental, including what is most significant to driving the combustion oscillations in this system. A comprehensive survey of operating conditions finds that the low-emission (and low-stability) intermediate and outer stages are necessary to drive significant thermoacoustics. Phase-averaged and time-resolved OH* imaging show that dramatic periodic strengthening and weakening of the reaction zone downstream of the low-emission combustion stages. An acoustic modal analysis shows the pressure wave shapes and identifies the dominant thermoacoustic behavior as the first longitudinal mode for this combustor geometry. Finally, a discussion of the likely significant coupling mechanisms is given. Periodic reaction zone behavior in the low-emission fuel stages is the primary contributor to unsteady heat release. Differences between the fuel stages in the air swirler design, the fuel number of the injectors, the lean blowout point, and the nominal operating conditions all likely contribute to the limit cycle behavior of the low-emission stages. Chapter 4 investigates the effects of interaction between two adjacent swirl-stabilized nozzles using experimental and numerical tools. These studies are more fundamental; while the nozzle hardware is the same as the lean direct injection nozzles used in the MLDI combustion concept, the findings are generally applicable to other swirl-stabilized combustion systems as well. Much of the work utilizes a new experiment where the distance between nozzles was varied to change the level of interaction

  20. Investigation of heavy quark and multiple interactions at HERA

    International Nuclear Information System (INIS)

    Magro, L.M.

    2005-09-01

    This thesis is oriented to the study of heavy quark photoproduction and multiple interactions, MI. For this reason we search for D* Mesons, in order to tag the charm quark, and we restrict ourselves in the region: Q 2 2 . For the theoretical calculations we use two Monte Carlo event generators: RAPGAP 3.1 and PYTHIA 6.2. Heavy quark production provides a large hard scale and therefore a small α s , which allows to test the perturbative QCD theory. On the other hand, MI has been proven to be important in hadron-hadron collisions. In this thesis, using MC event generators, we search for possible signals of MI in heavy quark production in electron-proton, ep, collisions. The thesis begins with a Theoretical Overview, with an introduction to ep collisions physics and the heavy quark photoproduction. We also give an introduction to the MI model included in PYTHIA. The next chapter introduces the concept of jet and presents some methods for the Heavy Quark Identification. After these two theoretical chapters there is a study of the direct and photon resolved processes, as well as the parton showering with RAPGAP. Since this thesis is oriented to the study of MI, PYTHIA plays a very important role because it includes a MI model also for ep collisions. Therefore, the fourth chapter is oriented to study the different steps in the event generation in PYTHIA. Chapter 7 is a D* Meson photoproduction study, where we include a comparison between the data, taken from the PhD Thesis of Gero Flucke. Finally, chapter 8 is a search for possible signals on MI. In hadron-hadron collisions it is clear that MI play a role. In ep collisions it is not so clear although MI could play a role in resolved photon events. The aim of this chapter is to find signals where HERA measurements could be sensitive to MI. (orig.)

  1. A molecular phylogenetic study on South Korean Tettigonia species (Orthoptera: Tettigoniidae) using five genetic loci: The possibility of multiple allopatric speciation.

    Science.gov (United States)

    Kim, Tae-Kyu; Han, Taeman; Kim, Tae-Woo; Park, In Gyun; Kim, Seonghyun; Park, Haechul

    2016-03-15

    In Korea, members of the genus Tettigonia have been known as two species, T. ussuriana and T. dolichoptera dolichoptera. However, the taxonomic status of the Jeju Island population of T. ussuriana (JJ-TU) is in question, relative to the mainland population (ML-TU), because of their different body sizes and ratios of wing length. To clarify the relatedness of JJ-TU and ML-TU, we examined the genetic variation and phylogenetic relationships within and between T. ussuriana and related species collected in South Korea, using five genetic loci: three mitochondrial genes (cytochrome c oxidase subunit 1 [CO1], cytochrome c oxidase subunit 2 [CO2], NADH dehydrogenase 1 [ND1]) and two nuclear loci (second internal transcribed spacer [ITS2], and tubulin alpha-1 [TA1]). Unexpectedly, the JJ-TU population is explicitly sister to T. d. dolichoptera, with low genetic distance (0.76-1.22% in CO1), indicating no direct connection with the ML-TU population; this finding suggests a recent divergence involving rapid morphological change without gene flow between JJ-TU and mainland T. d. dolichoptera. The separation of these populations from their common ancestor was caused by geographical isolation during last glacial age. This finding indicates that the JJ-TU population should be elevated to the rank of subspecies, at the very least. Furthermore, the ML-TU population was also revealed to have four genetically divided groups (group A-D) from four localized populations, but no significant morphological differences exist among them. The genetic difference (range 3.19-4.10% in CO1) between group A + B and C + D was especially large, suggesting that cryptic speciation has widely occurred within the mainland areas, caused by allopatric isolations resulting from mountain barriers.

  2. Local tax interaction with multiple tax instruments: evidence from Flemish municipalities

    OpenAIRE

    S. VAN PARYS; B. MERLEVEDE; T. VERBEKE

    2010-01-01

    We investigate the long run result of strategic interaction among local jurisdictions using multiple tax instruments. Most studies about local policy interaction only consider a single policy instrument. With multiple tax instruments, however, tax interaction is more complex. We construct a simple theoretical framework based on a basic spillover model, with two tax rates and immobile resources. We show that the signs of within and cross tax interaction crucially depend on the extent to which ...

  3. Synergistic interactions between Drosophila orthologues of genes spanned by de novo human CNVs support multiple-hit models of autism.

    Science.gov (United States)

    Grice, Stuart J; Liu, Ji-Long; Webber, Caleb

    2015-03-01

    Autism spectrum disorders (ASDs) are highly heritable and characterised by deficits in social interaction and communication, as well as restricted and repetitive behaviours. Although a number of highly penetrant ASD gene variants have been identified, there is growing evidence to support a causal role for combinatorial effects arising from the contributions of multiple loci. By examining synaptic and circadian neurological phenotypes resulting from the dosage variants of unique human:fly orthologues in Drosophila, we observe numerous synergistic interactions between pairs of informatically-identified candidate genes whose orthologues are jointly affected by large de novo copy number variants (CNVs). These CNVs were found in the genomes of individuals with autism, including a patient carrying a 22q11.2 deletion. We first demonstrate that dosage alterations of the unique Drosophila orthologues of candidate genes from de novo CNVs that harbour only a single candidate gene display neurological defects similar to those previously reported in Drosophila models of ASD-associated variants. We then considered pairwise dosage changes within the set of orthologues of candidate genes that were affected by the same single human de novo CNV. For three of four CNVs with complete orthologous relationships, we observed significant synergistic effects following the simultaneous dosage change of gene pairs drawn from a single CNV. The phenotypic variation observed at the Drosophila synapse that results from these interacting genetic variants supports a concordant phenotypic outcome across all interacting gene pairs following the direction of human gene copy number change. We observe both specificity and transitivity between interactors, both within and between CNV candidate gene sets, supporting shared and distinct genetic aetiologies. We then show that different interactions affect divergent synaptic processes, demonstrating distinct molecular aetiologies. Our study illustrates

  4. A crack growth evaluation method for interacting multiple cracks

    International Nuclear Information System (INIS)

    Kamaya, Masayuki

    2003-01-01

    When stress corrosion cracking or corrosion fatigue occurs, multiple cracks are frequently initiated in the same area. According to section XI of the ASME Boiler and Pressure Vessel Code, multiple cracks are considered as a single combined crack in crack growth analysis, if the specified conditions are satisfied. In crack growth processes, however, no prescription for the interference between multiple cracks is given in this code. The JSME Post-Construction Code, issued in May 2000, prescribes the conditions of crack coalescence in the crack growth process. This study aimed to extend this prescription to more general cases. A simulation model was applied, to simulate the crack growth process, taking into account the interference between two cracks. This model made it possible to analyze multiple crack growth behaviors for many cases (e.g. different relative position and length) that could not be studied by experiment only. Based on these analyses, a new crack growth analysis method was suggested for taking into account the interference between multiple cracks. (author)

  5. The empirical content of models with multiple equilibria in economies with social interactions

    OpenAIRE

    Alberto Bisin; Andrea Moro; Giorgio Topa

    2011-01-01

    We study a general class of models with social interactions that might display multiple equilibria. We propose an estimation procedure for these models and evaluate its efficiency and computational feasibility relative to different approaches taken to the curse of dimensionality implied by the multiplicity. Using data on smoking among teenagers, we implement the proposed estimation procedure to understand how group interactions affect health-related choices. We find that interaction effects a...

  6. The Interaction Network Ontology-supported modeling and mining of complex interactions represented with multiple keywords in biomedical literature.

    Science.gov (United States)

    Özgür, Arzucan; Hur, Junguk; He, Yongqun

    2016-01-01

    The Interaction Network Ontology (INO) logically represents biological interactions, pathways, and networks. INO has been demonstrated to be valuable in providing a set of structured ontological terms and associated keywords to support literature mining of gene-gene interactions from biomedical literature. However, previous work using INO focused on single keyword matching, while many interactions are represented with two or more interaction keywords used in combination. This paper reports our extension of INO to include combinatory patterns of two or more literature mining keywords co-existing in one sentence to represent specific INO interaction classes. Such keyword combinations and related INO interaction type information could be automatically obtained via SPARQL queries, formatted in Excel format, and used in an INO-supported SciMiner, an in-house literature mining program. We studied the gene interaction sentences from the commonly used benchmark Learning Logic in Language (LLL) dataset and one internally generated vaccine-related dataset to identify and analyze interaction types containing multiple keywords. Patterns obtained from the dependency parse trees of the sentences were used to identify the interaction keywords that are related to each other and collectively represent an interaction type. The INO ontology currently has 575 terms including 202 terms under the interaction branch. The relations between the INO interaction types and associated keywords are represented using the INO annotation relations: 'has literature mining keywords' and 'has keyword dependency pattern'. The keyword dependency patterns were generated via running the Stanford Parser to obtain dependency relation types. Out of the 107 interactions in the LLL dataset represented with two-keyword interaction types, 86 were identified by using the direct dependency relations. The LLL dataset contained 34 gene regulation interaction types, each of which associated with multiple keywords. A

  7. Demographic histories of adaptively diverged riparian and non-riparian species of Ainsliaea (Asteraceae) inferred from coalescent analyses using multiple nuclear loci.

    Science.gov (United States)

    Mitsui, Yuki; Setoguchi, Hiroaki

    2012-12-28

    Understanding demographic histories, such as divergence time, patterns of gene flow, and population size changes, in ecologically diverging lineages provide implications for the process and maintenance of population differentiation by ecological adaptation. This study addressed the demographic histories in two independently derived lineages of flood-resistant riparian plants and their non-riparian relatives [Ainsliaea linearis (riparian) and A. apiculata (non-riparian); A. oblonga (riparian) and A. macroclinidioides (non-riparian); Asteraceae] using an isolation-with-migration (IM) model based on variation at 10 nuclear DNA loci. The highest posterior probabilities of the divergence time parameters were estimated to be ca. 25,000 years ago for A. linearis and A. apiculata and ca. 9000 years ago for A. oblonga and A. macroclinidioides, although the confidence intervals of the parameters had broad ranges. The likelihood ratio tests detected evidence of historical gene flow between both riparian/non-riparian species pairs. The riparian populations showed lower levels of genetic diversity and a significant reduction in effective population sizes compared to the non-riparian populations and their ancestral populations. This study showed the recent origins of flood-resistant riparian plants, which are remarkable examples of plant ecological adaptation. The recent divergence and genetic signatures of historical gene flow among riparian/non-riparian species implied that they underwent morphological and ecological differentiation within short evolutionary timescales and have maintained their species boundaries in the face of gene flow. Comparative analyses of adaptive divergence in two sets of riparian/non-riparian lineages suggested that strong natural selection by flooding had frequently reduced the genetic diversity and size of riparian populations through genetic drift, possibly leading to fixation of adaptive traits in riparian populations. The two sets of riparian

  8. Variants in TNFAIP3, STAT4 and c12orf30 loci associated with multiple auto-immune diseases are also associated with Juvenile Idiopathic Arthritis

    Science.gov (United States)

    Prahalad, Sampath; Hansen, Sterling; Whiting, April; Guthery, Stephen L.; Clifford, Bronte; McNally, Bernadette; Zeft, Andrew S.; Bohnsack, John F.; Jorde, Lynn B.

    2010-01-01

    Objectives Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA, to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors. Methods Cases were 445 children with JIA, and controls were 643 healthy adults. Eight single nucleotide polymorphisms (SNPs) in 7 loci [TNFAIP3 (rs10499194 and rs6920220), RSBN1 (rs6679677), C12ORF30 (rs17696736), TRAF1 (rs3761847), IL2RA (rs2104286), PTPN2 (rs2542151), and STAT4 (rs7574865)] were genotyped by the TaqMan assay. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Results The strongest associations were observed for TNFAIP3 variants rs10499194 (OR: 0.74 (0.61-0.91); p <0.004), and TNFAIP3 rs6920220 (OR: 1.3 (1.05-1.61); p <0.02). We also observed associations between JIA and STAT4 (OR: 1.24 (1.02-1.51); p <0.03) and C12ORF30 (OR: 1.2 (1.01-1.43); p <0.04) variants. The PTPN2 variant rs2542151 deviated from Hardy-Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1, and RSBN1 were not associated with JIA. After stratification by JIA subtype, TNFAIP3 and C12ORF30 variants were associated with oligoarticular JIA, while the STAT4 variant was associated primarily with polyarticular JIA. Conclusions We have demonstrated associations between JIA and variants in TNFAIP3, STAT4 and C12ORF30 regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors. PMID:19565500

  9. Social Peer Interactions in Persons with Profound Intellectual and Multiple Disabilities: A Literature Review

    Science.gov (United States)

    Nijs, Sara; Maes, Bea

    2014-01-01

    Social interactions may positively influence developmental and quality of life outcomes. Research in persons with profound intellectual and multiple disabilities (PIMD) mostly investigated interactions with caregivers. This literature review focuses on peer interactions of persons with PIMD. A computerized literature search of three databases was…

  10. Potential games and interactive decisions with multiple criteria

    NARCIS (Netherlands)

    Voorneveld, M.

    1999-01-01

    Game theory is a mathematical theory for analyzing strategic interaction between decision makers. This thesis covers two game-theoretic topics. The first part of this thesis deals with potential games: noncooperative games in which the information about the goals of the separate players that is

  11. Framework for Modelling Multiple Input Complex Aggregations for Interactive Installations

    DEFF Research Database (Denmark)

    Padfield, Nicolas; Andreasen, Troels

    2012-01-01

    on fuzzy logic and provides a method for variably balancing interaction and user input with the intention of the artist or director. An experimental design is presented, demonstrating an intuitive interface for parametric modelling of a complex aggregation function. The aggregation function unifies...

  12. Legumes affect alpine tundra community composition via multiple biotic interactions

    NARCIS (Netherlands)

    Soudzilovskaia, N.A.; Aksenova, A.A.; Makarov, M.I.; Onipchenko, V.G.; Logvinenko, O.A.; Braak, ter C.J.F.; Cornelissen, J.H.C.

    2012-01-01

    The soil engineering function of legumes in natural ecosystems is paramount but associated solely with soil nitrogen (N) subsidies, ignoring concomitant biotic interactions such as competitive or inhibitory effects and exchange between mycorrhizas and rhizobia. We aim to (1) disentangle legume

  13. Plant interactions with multiple insect herbivores: from community to genes

    NARCIS (Netherlands)

    Stam, J.M.; Kroes, A.; Li, Y.; Gols, R.; Loon, van J.J.A.; Poelman, E.H.; Dicke, M.

    2014-01-01

    Every plant is a member of a complex insect community that consists of tens to hundreds of species that belong to different trophic levels. The dynamics of this community are critically influenced by the plant, which mediates interactions between community members that can occur on the plant

  14. Additive Main Effects and Multiplicative Interaction Analysis of ...

    African Journals Online (AJOL)

    This work deals with modeling and examining the GxE interaction pattern of the multi-environment trials of 43 genotypes and eight environments from Southern Ethiopia coffee (Coffea Arabica L.) collections using a randomized complete block design (RCBD) with four replications. The work further attempts to predict yield ...

  15. Genius loci / Madis Kõiv

    Index Scriptorium Estoniae

    Kõiv, Madis, 1929-2014

    2005-01-01

    Ettekanne 37. Kreutzwaldi päevadel Tartu Kirjandusmuuseumis 18.-19. dets. 1993, pealkirjaga "Kus on see Valga, kus on see Tartu...: Genius loci B. Kangro ja V. Uibopuu romaanides". Varem ilmunud: Akadeemia, 1994, nr. 4

  16. Multiplicity distribution and multiplicity moment of black and grey particles in high energy nucleus–nucleus interactions

    International Nuclear Information System (INIS)

    Ghosh, Dipak; Deb, Argha; Datta, Utpal; Bhattacharyya, S.

    2011-01-01

    In this paper we have studied the multiplicity distribution of black and grey particles emitted from 16 O–AgBr interactions at 2.1 AGeV and 60 AGeV. We have also calculated the multiplicity moment up to the fifth order for both the interactions and for both kinds of emitted particles. The variation of multiplicity moment with the order number has been investigated. It is seen that in the case of black particles multiplicity moment up to fourth order remains almost constant as energy increases from 2.1 AGeV to 60 AGeV. Fifth order multiplicity moment increases insignificantly with energy. However in the case of grey particles no such constancy of multiplicity moment with energy of the projectile beam is obtained. Later we have extended our study on the basis of Regge–Mueller approach to find the existence of second order correlation during the emission of black as well as the grey particles. The second Mueller moment is found to be positive and it increases as energy increases in the case of black particles. On the contrary in the case of grey particles the second Mueller moment decreases with energy. It can be concluded that as energy increases correlation among the black particles increases. On the other hand with the increase of energy correlation among the grey particles is found to diminish. (author)

  17. Inelastic multiple scattering of interacting bosons in weak random potentials

    International Nuclear Information System (INIS)

    Geiger, Tobias

    2013-01-01

    Within the present thesis we develop a diagrammatic scattering theory for interacting bosons in a three-dimensional, weakly disordered potential. Based on a microscopic N-body scattering theory, we identify the relevant diagrams including elastic and inelastic collision processes that are sufficient to describe quantum transport in the regime of weak disorder. By taking advantage of the statistical properties of the weak disorder potential, we demonstrate how the N-body dynamics can be reduced to a nonlinear integral equation of Boltzmann type for the single-particle diffusive flux. A presently available alternative description - based on the Gross-Pitaevskii equation - only includes elastic collisions. In contrast, we show that far from equilibrium the presence of inelastic collisions - even for weak interaction strength - must be accounted for and can induce the full thermalization of the single-particle current. In addition, we also determine the coherent corrections to the incoherent transport, leading to the effect of coherent backscattering. For the first time, we are able to analyze the influence of inelastic collisions on the coherent backscattering signal, which lead to an enhancement of the backscattered cone in a narrow spectral window, even for increasing non-linearity. With a short recollection of the presently available experimental techniques we furthermore show how an immediate implementation of our suggested setup with confined Bose-Einstein condensates can be accomplished. Thereby, the emergence of collective and/or thermodynamic behavior from fundamental, microscopic constituents can also be assessed experimentally. In a second part of this thesis, we present first results for light scattering off strongly interacting Rydberg atoms trapped in a one-dimensional, chain-like configuration. In order to monitor the time-dependence of this interacting many-body system, we devise a weak measurement scenario for which we derive a master equation for the

  18. Whole-genome comparison of two Campylobacter jejuni isolates of the same sequence type reveals multiple loci of different ancestral lineage.

    Directory of Open Access Journals (Sweden)

    Patrick J Biggs

    Full Text Available Campylobacter jejuni ST-474 is the most important human enteric pathogen in New Zealand, and yet this genotype is rarely found elsewhere in the world. Insight into the evolution of this organism was gained by a whole genome comparison of two ST-474, flaA SVR-14 isolates and other available C. jejuni isolates and genomes. The two isolates were collected from different sources, human (H22082 and retail poultry (P110b, at the same time and from the same geographical location. Solexa sequencing of each isolate resulted in ~1.659 Mb (H22082 and ~1.656 Mb (P110b of assembled sequences within 28 (H22082 and 29 (P110b contigs. We analysed 1502 genes for which we had sequences within both ST-474 isolates and within at least one of 11 C. jejuni reference genomes. Although 94.5% of genes were identical between the two ST-474 isolates, we identified 83 genes that differed by at least one nucleotide, including 55 genes with non-synonymous substitutions. These covered 101 kb and contained 672 point differences. We inferred that 22 (3.3% of these differences were due to mutation and 650 (96.7% were imported via recombination. Our analysis estimated 38 recombinant breakpoints within these 83 genes, which correspond to recombination events affecting at least 19 loci regions and gives a tract length estimate of ~2 kb. This includes a ~12 kb region displaying non-homologous recombination in one of the ST-474 genomes, with the insertion of two genes, including ykgC, a putative oxidoreductase, and a conserved hypothetical protein of unknown function. Furthermore, our analysis indicates that the source of this recombined DNA is more likely to have come from C. jejuni strains that are more closely related to ST-474. This suggests that the rates of recombination and mutation are similar in order of magnitude, but that recombination has been much more important for generating divergence between the two ST-474 isolates.

  19. Exclusive description of multiple production on nuclei in the additive quark model. Multiplicity distributions in interactions with heavy nuclei

    International Nuclear Information System (INIS)

    Levchenko, B.B.; Nikolaev, N.N.

    1985-01-01

    In the framework of the additive quark model of multiple production on nuclei we calculate the multiplicity distributions of secondary particles and the correlations between secondary particles in πA and pA interactions with heavy nuclei. We show that intranuclear cascades are responsible for up to 50% of the nuclear increase of the multiplicity of fast particles. We analyze the sensitivity of the multiplicities and their correlations to the choice of the quark-hadronization function. We show that with good accuracy the yield of relativistic secondary particles from heavy and intermediate nuclei depends only on the number N/sub p/ of protons knocked out of the nucleus, and not on the mass number of the nucleus (N/sub p/ scaling)

  20. Biological interactions and cooperative management of multiple species.

    Science.gov (United States)

    Jiang, Jinwei; Min, Yong; Chang, Jie; Ge, Ying

    2017-01-01

    Coordinated decision making and actions have become the primary solution for the overexploitation of interacting resources within ecosystems. However, the success of coordinated management is highly sensitive to biological, economic, and social conditions. Here, using a game theoretic framework and a 2-species model that considers various biological relationships (competition, predation, and mutualism), we compute cooperative (or joint) and non-cooperative (or separate) management equilibrium outcomes of the model and investigate the effects of the type and strength of the relationships. We find that cooperation does not always show superiority to non-cooperation in all biological interactions: (1) if and only if resources are involved in high-intensity predation relationships, cooperation can achieve a win-win scenario for ecosystem services and resource diversity; (2) for competitive resources, cooperation realizes higher ecosystem services by sacrificing resource diversity; and (3) for mutual resources, cooperation has no obvious advantage for either ecosystem services or resource evenness but can slightly improve resource abundance. Furthermore, by using a fishery model of the North California Current Marine Ecosystem with 63 species and seven fleets, we demonstrate that the theoretical results can be reproduced in real ecosystems. Therefore, effective ecosystem management should consider the interconnection between stakeholders' social relationship and resources' biological relationships.

  1. Multiple Syntrophic Interactions in a Terephthalate-Degrading Methanogenic Consortium

    Energy Technology Data Exchange (ETDEWEB)

    Lykidis, Athanasios; Chen, Chia-Lung; Tringe, Susannah G.; McHardy, Alice C.; Copeland, Alex 5; Kyrpides, Nikos C.; Hugenholtz, Philip; Liu, Wen-Tso

    2010-08-05

    Terephthalate (TA) is one of the top 50 chemicals produced worldwide. Its production results in a TA-containing wastewater that is treated by anaerobic processes through a poorly understood methanogenic syntrophy. Using metagenomics, we characterized the methanogenic consortium tinside a hyper-mesophilic (i.e., between mesophilic and thermophilic), TA-degrading bioreactor. We identified genes belonging to dominant Pelotomaculum species presumably involved in TA degradation through decarboxylation, dearomatization, and modified ?-oxidation to H{sub 2}/CO{sub 2} and acetate. These intermediates are converted to CH{sub 4}/CO{sub 2} by three novel hyper-mesophilic methanogens. Additional secondary syntrophic interactions were predicted in Thermotogae, Syntrophus and candidate phyla OP5 and WWE1 populations. The OP5 encodes genes capable of anaerobic autotrophic butyrate production and Thermotogae, Syntrophus and WWE1 have the genetic potential to oxidize butyrate to COsub 2}/H{sub 2} and acetate. These observations suggest that the TA-degrading consortium consists of additional syntrophic interactions beyond the standard H{sub 2}-producing syntroph ? methanogen partnership that may serve to improve community stability.

  2. Speech comprehension aided by multiple modalities: behavioural and neural interactions

    Science.gov (United States)

    McGettigan, Carolyn; Faulkner, Andrew; Altarelli, Irene; Obleser, Jonas; Baverstock, Harriet; Scott, Sophie K.

    2014-01-01

    Speech comprehension is a complex human skill, the performance of which requires the perceiver to combine information from several sources – e.g. voice, face, gesture, linguistic context – to achieve an intelligible and interpretable percept. We describe a functional imaging investigation of how auditory, visual and linguistic information interact to facilitate comprehension. Our specific aims were to investigate the neural responses to these different information sources, alone and in interaction, and further to use behavioural speech comprehension scores to address sites of intelligibility-related activation in multifactorial speech comprehension. In fMRI, participants passively watched videos of spoken sentences, in which we varied Auditory Clarity (with noise-vocoding), Visual Clarity (with Gaussian blurring) and Linguistic Predictability. Main effects of enhanced signal with increased auditory and visual clarity were observed in overlapping regions of posterior STS. Two-way interactions of the factors (auditory × visual, auditory × predictability) in the neural data were observed outside temporal cortex, where positive signal change in response to clearer facial information and greater semantic predictability was greatest at intermediate levels of auditory clarity. Overall changes in stimulus intelligibility by condition (as determined using an independent behavioural experiment) were reflected in the neural data by increased activation predominantly in bilateral dorsolateral temporal cortex, as well as inferior frontal cortex and left fusiform gyrus. Specific investigation of intelligibility changes at intermediate auditory clarity revealed a set of regions, including posterior STS and fusiform gyrus, showing enhanced responses to both visual and linguistic information. Finally, an individual differences analysis showed that greater comprehension performance in the scanning participants (measured in a post-scan behavioural test) were associated with

  3. IVisTMSA: Interactive Visual Tools for Multiple Sequence Alignments.

    Science.gov (United States)

    Pervez, Muhammad Tariq; Babar, Masroor Ellahi; Nadeem, Asif; Aslam, Naeem; Naveed, Nasir; Ahmad, Sarfraz; Muhammad, Shah; Qadri, Salman; Shahid, Muhammad; Hussain, Tanveer; Javed, Maryam

    2015-01-01

    IVisTMSA is a software package of seven graphical tools for multiple sequence alignments. MSApad is an editing and analysis tool. It can load 409% more data than Jalview, STRAP, CINEMA, and Base-by-Base. MSA comparator allows the user to visualize consistent and inconsistent regions of reference and test alignments of more than 21-MB size in less than 12 seconds. MSA comparator is 5,200% efficient and more than 40% efficient as compared to BALiBASE c program and FastSP, respectively. MSA reconstruction tool provides graphical user interfaces for four popular aligners and allows the user to load several sequence files at a time. FASTA generator converts seven formats of alignments of unlimited size into FASTA format in a few seconds. MSA ID calculator calculates identity matrix of more than 11,000 sequences with a sequence length of 2,696 base pairs in less than 100 seconds. Tree and Distance Matrix calculation tools generate phylogenetic tree and distance matrix, respectively, using neighbor joining% identity and BLOSUM 62 matrix.

  4. Learning Effects of Interactive Whiteboard Pedagogy for Students in Taiwan from the Perspective of Multiple Intelligences

    Science.gov (United States)

    Chen, Hong-Ren; Chiang, Chih-Hao; Lin, Wen-Shan

    2013-01-01

    With the rapid progress in information technology, interactive whiteboards have become IT-integrated in teaching activities. The theory of multiple intelligences argues that every person possesses multiple intelligences, emphasizing learners' cognitive richness and the possible role of these differences in enhanced learning. This study is the…

  5. QTL mapping in multiple populations and development stages reveals dynamic quantitative trait loci for fruit size in cucumbers of different market classes.

    Science.gov (United States)

    Weng, Yiqun; Colle, Marivi; Wang, Yuhui; Yang, Luming; Rubinstein, Mor; Sherman, Amir; Ophir, Ron; Grumet, Rebecca

    2015-09-01

    QTL analysis in multi-development stages with different QTL models identified 12 consensus QTLs underlying fruit elongation and radial growth presenting a dynamic view of genetic control of cucumber fruit development. Fruit size is an important quality trait in cucumber (Cucumis sativus L.) of different market classes. However, the genetic and molecular basis of fruit size variations in cucumber is not well understood. In this study, we conducted QTL mapping of fruit size in cucumber using F2, F2-derived F3 families and recombinant inbred lines (RILs) from a cross between two inbred lines Gy14 (North American picking cucumber) and 9930 (North China fresh market cucumber). Phenotypic data of fruit length and diameter were collected at three development stages (anthesis, immature and mature fruits) in six environments over 4 years. QTL analysis was performed with three QTL models including composite interval mapping (CIM), Bayesian interval mapping (BIM), and multiple QTL mapping (MQM). Twenty-nine consistent and distinct QTLs were detected for nine traits from multiple mapping populations and QTL models. Synthesis of information from available fruit size QTLs allowed establishment of 12 consensus QTLs underlying fruit elongation and radial growth, which presented a dynamic view of genetic control of cucumber fruit development. Results from this study highlighted the benefits of QTL analysis with multiple QTL models and different mapping populations in improving the power of QTL detection. Discussion was presented in the context of domestication and diversifying selection of fruit length and diameter, marker-assisted selection of fruit size, as well as identification of candidate genes for fruit size QTLs in cucumber.

  6. Flexibility and Project Value: Interactions and Multiple Real Options

    Science.gov (United States)

    Čulík, Miroslav

    2010-06-01

    This paper is focused on a project valuation with embedded portfolio of real options including their interactions. Valuation is based on the criterion of Net Present Value on the simulation basis. Portfolio includes selected types of European-type real options: option to expand, contract, abandon and temporarily shut down and restart a project. Due to the fact, that in reality most of the managerial flexibility takes the form of portfolio of real options, selected types of options are valued not only individually, but also in combination. The paper is structured as follows: first, diffusion models for forecasting of output prices and variable costs are derived. Second, project value is estimated on the assumption, that no real options are present. Next, project value is calculated with the presence of selected European-type options; these options and their impact on project value are valued first in isolation and consequently in different combinations. Moreover, intrinsic value evolution of given real options with respect to the time of exercising is analysed. In the end, results are presented graphically; selected statistics and risk measures (Value at Risk, Expected Shortfall) of the NPV's distributions are calculated and commented.

  7. Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population.

    Directory of Open Access Journals (Sweden)

    Nagaraja M Phani

    Full Text Available Several genetic variants for type 2 diabetes (T2D have been identified through genome wide association studies (GWAS from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population.Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR analysis was adopted to determine gene-gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC.We confirm the association of TCF7L2 (rs7903146 and SLC30A8 (rs13266634 with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634, IGF2BP2 (rs4402960, HHEX (rs1111875 and CDKN2A (rs10811661 genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI.These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.

  8. Attentional Processes in Interactions between People with Profound Intellectual and Multiple Disabilities and Direct Support Staff

    Science.gov (United States)

    Ine, Hostyn; Heleen, Neerinckx; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes…

  9. Interaction between Persons with Profound Intellectual and Multiple Disabilities and Their Partners: A Literature Review

    Science.gov (United States)

    Hostyn, Ine; Maes, Bea

    2009-01-01

    Background: High quality interactions are of crucial importance for quality of life of persons with profound intellectual and multiple disabilities (PIMD). This literature review describes and synthesises studies addressing the interaction between persons with PIMD and their partners. Method: A computerised literature search using defined…

  10. Log-Normal Distribution in a Growing System with Weighted and Multiplicatively Interacting Particles

    Science.gov (United States)

    Fujihara, Akihiro; Tanimoto, Satoshi; Yamamoto, Hiroshi; Ohtsuki, Toshiya

    2018-03-01

    A growing system with weighted and multiplicatively interacting particles is investigated. Each particle has a quantity that changes multiplicatively after a binary interaction, with its growth rate controlled by a weight parameter in a homogeneous symmetric kernel. We consider the system using moment inequalities and analytically derive the log-normal-type tail in the probability distribution function of quantities when the parameter is negative, which is different from the result for single-body multiplicative processes. We also find that the system approaches a winner-take-all state when the parameter is positive.

  11. Risk score modeling of multiple gene to gene interactions using aggregated-multifactor dimensionality reduction

    Directory of Open Access Journals (Sweden)

    Dai Hongying

    2013-01-01

    Full Text Available Abstract Background Multifactor Dimensionality Reduction (MDR has been widely applied to detect gene-gene (GxG interactions associated with complex diseases. Existing MDR methods summarize disease risk by a dichotomous predisposing model (high-risk/low-risk from one optimal GxG interaction, which does not take the accumulated effects from multiple GxG interactions into account. Results We propose an Aggregated-Multifactor Dimensionality Reduction (A-MDR method that exhaustively searches for and detects significant GxG interactions to generate an epistasis enriched gene network. An aggregated epistasis enriched risk score, which takes into account multiple GxG interactions simultaneously, replaces the dichotomous predisposing risk variable and provides higher resolution in the quantification of disease susceptibility. We evaluate this new A-MDR approach in a broad range of simulations. Also, we present the results of an application of the A-MDR method to a data set derived from Juvenile Idiopathic Arthritis patients treated with methotrexate (MTX that revealed several GxG interactions in the folate pathway that were associated with treatment response. The epistasis enriched risk score that pooled information from 82 significant GxG interactions distinguished MTX responders from non-responders with 82% accuracy. Conclusions The proposed A-MDR is innovative in the MDR framework to investigate aggregated effects among GxG interactions. New measures (pOR, pRR and pChi are proposed to detect multiple GxG interactions.

  12. Scaling of chaotic multiplicity: A new observation in high-energy interactions

    International Nuclear Information System (INIS)

    Ghosh, D.; Ghosh, P.; Roy, J.

    1990-01-01

    We analyze high-energy-interaction data to study the dependence of chaotic multiplicity on the pseudorapidity window and propose a new scaling function bar Ψ(bar z)=left-angle n 1 right-angle/left-angle n right-angle max where left-angle n 1 right-angle is the chaotic multiplicity and bar z=left-angle n right-angle/left-angle n right-angle max is the reduced multiplicity, following the quantum-optical concept of particle production. It has been observed that the proposed ''chaotic multiplicity scaling'' is obeyed by pp, p bar p, and AA collisions at different available energies

  13. Oscillations in the interactions among multiple solitons in an optical fibre

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Wen-Qiang; Gao, Yi-Tian; Zhao, Chen; Feng, Yu-Jie; Su, Chuan-Qi [Beijing University of Aeronautics and Astronautics (China). Ministry of Education Key Laboratory of Fluid Mechanics; Beijing University of Aeronautics and Astronautics (China). National Laboratory for Computational Fluid Dynamics

    2016-07-01

    In this article, under the investigation on the interactions among multiple solitons for an eighth-order nonlinear Schroedinger equation in an optical fibre, oscillations in the interaction zones are observed theoretically. With different coefficients of the operators in this equation, we find that (1) the oscillations in the solitonic interaction zones have different forms with different spectral parameters of this equation; (2) the oscillations in the interactions among the multiple solitons are affected by the choice of spectral parameters, the dispersive effects and nonlinearity of the eighth-order operator; (3) the second-, fifth-, sixth-, and seventh-order operators restrain oscillations in the solitonic interaction zones and the higher-order operators have stronger attenuated effects than the lower ones, while the third- and fourth-order operators stimulate and extend the scope of oscillations.

  14. Multiplicities of secondary hadrons produced in vp and overlinevp charged current interactions

    Science.gov (United States)

    Grässler, H.; Lanske, D.; Schulte, R.; Jones, G. T.; Middleton, R. P.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Nellen, B.; Grant, A.; Klein, H.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Chima, J. S.; Mobayyen, M. M.; Talebzadeh, M.; Villalobos-Baillie, O.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K. L.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicić, D.; Saitta, B.; Wells, J.; Aachen-Birmingham-Bonn-CERN-Imperial College-München (MPI)-Oxford Collaboration

    1983-08-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in νp and overlinevp interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e +e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and a larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above ˜ 7 GeV and local charge compensation within an event.

  15. Multiplicities of secondary hadrons produced in vp and anti vp charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1983-01-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in vp and anti vp interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e + e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above approx.= 7 GeV and local charge compensation within an event. (orig.)

  16. Acoustically mediated long-range interaction among multiple spherical particles exposed to a plane standing wave

    International Nuclear Information System (INIS)

    Zhang, Shenwei; Qiu, Chunyin; Wang, Mudi; Ke, Manzhu; Liu, Zhengyou

    2016-01-01

    In this work, we study the acoustically mediated interaction forces among multiple well-separated spherical particles trapped in the same node or antinode plane of a standing wave. An analytical expression of the acoustic interaction force is derived, which is accurate even for the particles beyond the Rayleigh limit. Interestingly, the multi-particle system can be decomposed into a series of independent two-particle systems described by pairwise interactions. Each pairwise interaction is a long-range interaction, as characterized by a soft oscillatory attenuation (at the power exponent of n  = −1 or −2). The vector additivity of the acoustic interaction force, which is not well expected considering the nonlinear nature of the acoustic radiation force, is greatly useful for exploring a system consisting of a large number of particles. The capability of self-organizing a big particle cluster can be anticipated through such acoustically controllable long-range interaction. (paper)

  17. Decomposition of the Total Effect in the Presence of Multiple Mediators and Interactions.

    Science.gov (United States)

    Bellavia, Andrea; Valeri, Linda

    2018-06-01

    Mediation analysis allows decomposing a total effect into a direct effect of the exposure on the outcome and an indirect effect operating through a number of possible hypothesized pathways. Recent studies have provided formal definitions of direct and indirect effects when multiple mediators are of interest and have described parametric and semiparametric methods for their estimation. Investigating direct and indirect effects with multiple mediators, however, can be challenging in the presence of multiple exposure-mediator and mediator-mediator interactions. In this paper we derive a decomposition of the total effect that unifies mediation and interaction when multiple mediators are present. We illustrate the properties of the proposed framework in a secondary analysis of a pragmatic trial for the treatment of schizophrenia. The decomposition is employed to investigate the interplay of side effects and psychiatric symptoms in explaining the effect of antipsychotic medication on quality of life in schizophrenia patients. Our result offers a valuable tool to identify the proportions of total effect due to mediation and interaction when more than one mediator is present, providing the finest decomposition of the total effect that unifies multiple mediators and interactions.

  18. Supporting a child with multiple disabilities to participate in social interaction

    DEFF Research Database (Denmark)

    Norén, Niklas; Pilesjö, Maja Sigurd

    2016-01-01

    Asking a question can be a highly challenging task for a person with multiple disabilities, but questions have not received much attention in research on augmentative and alternative communication (AAC). Conversation analysis is employed to examine an instance of multiparty interaction where...... a speech and language therapist supports a child with multiple disabilities to ask a question with a communication board. The question is accomplished through a practice where the action is built as a trajectory of interactional steps. Each step is built using ways of involvement that establish different...

  19. Calculation of contribution of multiple interactions and efficiency of neutron detectors

    International Nuclear Information System (INIS)

    Androsenko, A.A.; Androsenko, P.A.; Kazakov, L.E.; Kononov, V.N.; Poletaev, E.D.

    1986-01-01

    Results of calculation of multiple neutron interactions contribution to efficiency of detectors with 6 Li glass and 10 B plate in the energy range of 0.01-1 MeV are given. The calculation was performed by the Monte-Carlo method using BRAND program complex. It is shown that a correction value for multiple neutron interaction in 6 Li glass of 1 mm thickness constitutes 4.5 % at energy of up to 100 keV and at higher energies has a complex energy dependence reaching 25 % at 440 keV

  20. Effects of multiple modes interaction on the resistive wall mode instability

    International Nuclear Information System (INIS)

    Chen, Longxi; Lei, Wenqing; Ma, Zhiwei; Wu, Bin

    2013-01-01

    The effects of multiple modes interaction on the resistive wall mode (RWM) are studied in a slab geometry with and without plasma flow. The modes interaction can have a large effect on both the linear growth rate and the nonlinear saturation level of the RWM. We found that modes interaction can suppress the linear growth rate for the most unstable mode. The plasma flow can also help to control the growth of the RWM. The RWM can be stabilized completely by a plasma flow when considering the modes interaction. The effect of modes interaction on the RWM is stronger for the mode rational surface in the vacuum than that in the plasma. The modes interaction results in a substantially lowered saturation level for the most unstable RWM. (paper)

  1. Multiple loci affecting photoreactivation in Escherichia coli

    International Nuclear Information System (INIS)

    Sutherland, B.M.; Hausrath, S.G.

    1979-01-01

    Sutherland et al. mapped a phr gene in Escherichia coli at 17 min and found that induction of an E. coli stain lysogenic for a lambda phage carrying this gene increased photoreactivating enzyme levels 2,000-fold. Recently, Smith and Youngs and Sancar and Rupert located a phr gene at 15.9 min. We have therefore investigated the properties of photoreactivating enzyme and cellular photoreactivation in cells containing deletions of the gene at 17 min. Cells with this deletion photoreactivated ultraviolet-induced killing at a rate 20% of normal; they also contained approximately 20% of the normal photoreactivating enzyme level. The residual enzyme in these cells was characterized to determine whether the reduced cellular photoreactivation rate and photoreactivating enzyme levels resulted from reduced numbers of normal enzymes or from an altered enzyme. Photoreactivating enzymes from strains carrying a deletion of the region at 17 min has an apparent K/sub m/ about two- to threefold higher than normal enzyme and showed markedly increased heat lability. The gene at 17 min thus contains information determining the function of the E. coli photoreactivating enzyme rather than the quantity of the enzyme. It is proposed that the gene at 17 min be termed phrA and that located at 15.9 min be termed phrB

  2. XCluSim: a visual analytics tool for interactively comparing multiple clustering results of bioinformatics data

    Science.gov (United States)

    2015-01-01

    Background Though cluster analysis has become a routine analytic task for bioinformatics research, it is still arduous for researchers to assess the quality of a clustering result. To select the best clustering method and its parameters for a dataset, researchers have to run multiple clustering algorithms and compare them. However, such a comparison task with multiple clustering results is cognitively demanding and laborious. Results In this paper, we present XCluSim, a visual analytics tool that enables users to interactively compare multiple clustering results based on the Visual Information Seeking Mantra. We build a taxonomy for categorizing existing techniques of clustering results visualization in terms of the Gestalt principles of grouping. Using the taxonomy, we choose the most appropriate interactive visualizations for presenting individual clustering results from different types of clustering algorithms. The efficacy of XCluSim is shown through case studies with a bioinformatician. Conclusions Compared to other relevant tools, XCluSim enables users to compare multiple clustering results in a more scalable manner. Moreover, XCluSim supports diverse clustering algorithms and dedicated visualizations and interactions for different types of clustering results, allowing more effective exploration of details on demand. Through case studies with a bioinformatics researcher, we received positive feedback on the functionalities of XCluSim, including its ability to help identify stably clustered items across multiple clustering results. PMID:26328893

  3. Dependence of Xmax and multiplicity of electron and muon on different high energy interaction models

    Directory of Open Access Journals (Sweden)

    G Rastegarzadeh

    2010-06-01

    Full Text Available Different high energy interaction models are the applied in CORSIKA code to simulate Extensive Air Showers (EAS generated by Cosmic Rays (CR. In this work the effects of QGSJET01, QGSJETII, DPMJET, SIBYLL models on Xmax and multiplicity of secondary electrons and muons at observation level are studied.

  4. Computational Tools for Probing Interactions in Multiple Linear Regression, Multilevel Modeling, and Latent Curve Analysis

    Science.gov (United States)

    Preacher, Kristopher J.; Curran, Patrick J.; Bauer, Daniel J.

    2006-01-01

    Simple slopes, regions of significance, and confidence bands are commonly used to evaluate interactions in multiple linear regression (MLR) models, and the use of these techniques has recently been extended to multilevel or hierarchical linear modeling (HLM) and latent curve analysis (LCA). However, conducting these tests and plotting the…

  5. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, Richard W. J.; de Rooij, Martin F. M.; Kocemba, Kinga A.; Reijmers, Rogier M.; de Haan-Kramer, Anneke; Overdijk, Marije B.; Aalders, Linda; Rozemuller, Henk; Martens, Anton C. M.; Bergsagel, P. Leif; Kersten, Marie José; Pals, Steven T.; Spaargaren, Marcel

    2011-01-01

    Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow microenvironment plays

  6. N-cadherin-mediated interaction with multiple myeloma cells inhibits osteoblast differentiation

    NARCIS (Netherlands)

    Groen, R.W.J.; de Rooij, M.F.M.; Kocemba, K.A.; Reijmers, R.M.; de Haan-Kramer, A.; Overdijk, M.B.; Aalders, L.; Rozemuller, H.; Martens, A.C.M.; Bergsagel, P.L.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.

    2011-01-01

    Background Multiple myeloma is a hematologic malignancy characterized by a clonal expansion of malignant plasma cells in the bone marrow, which is accompanied by the development of osteolytic lesions and/or diffuse osteopenia. The intricate bi-directional interaction with the bone marrow

  7. Network-based group variable selection for detecting expression quantitative trait loci (eQTL

    Directory of Open Access Journals (Sweden)

    Zhang Xuegong

    2011-06-01

    Full Text Available Abstract Background Analysis of expression quantitative trait loci (eQTL aims to identify the genetic loci associated with the expression level of genes. Penalized regression with a proper penalty is suitable for the high-dimensional biological data. Its performance should be enhanced when we incorporate biological knowledge of gene expression network and linkage disequilibrium (LD structure between loci in high-noise background. Results We propose a network-based group variable selection (NGVS method for QTL detection. Our method simultaneously maps highly correlated expression traits sharing the same biological function to marker sets formed by LD. By grouping markers, complex joint activity of multiple SNPs can be considered and the dimensionality of eQTL problem is reduced dramatically. In order to demonstrate the power and flexibility of our method, we used it to analyze two simulations and a mouse obesity and diabetes dataset. We considered the gene co-expression network, grouped markers into marker sets and treated the additive and dominant effect of each locus as a group: as a consequence, we were able to replicate results previously obtained on the mouse linkage dataset. Furthermore, we observed several possible sex-dependent loci and interactions of multiple SNPs. Conclusions The proposed NGVS method is appropriate for problems with high-dimensional data and high-noise background. On eQTL problem it outperforms the classical Lasso method, which does not consider biological knowledge. Introduction of proper gene expression and loci correlation information makes detecting causal markers more accurate. With reasonable model settings, NGVS can lead to novel biological findings.

  8. Interaction of Multiple Particles with a Solidification Front: From Compacted Particle Layer to Particle Trapping.

    Science.gov (United States)

    Saint-Michel, Brice; Georgelin, Marc; Deville, Sylvain; Pocheau, Alain

    2017-06-13

    The interaction of solidification fronts with objects such as particles, droplets, cells, or bubbles is a phenomenon with many natural and technological occurrences. For an object facing the front, it may yield various fates, from trapping to rejection, with large implications regarding the solidification pattern. However, whereas most situations involve multiple particles interacting with each other and the front, attention has focused almost exclusively on the interaction of a single, isolated object with the front. Here we address experimentally the interaction of multiple particles with a solidification front by performing solidification experiments of a monodisperse particle suspension in a Hele-Shaw cell with precise control of growth conditions and real-time visualization. We evidence the growth of a particle layer ahead of the front at a close-packing volume fraction, and we document its steady-state value at various solidification velocities. We then extend single-particle models to the situation of multiple particles by taking into account the additional force induced on an entering particle by viscous friction in the compacted particle layer. By a force balance model this provides an indirect measure of the repelling mean thermomolecular pressure over a particle entering the front. The presence of multiple particles is found to increase it following a reduction of the thickness of the thin liquid film that separates particles and front. We anticipate the findings reported here to provide a relevant basis to understand many complex solidification situations in geophysics, engineering, biology, or food engineering, where multiple objects interact with the front and control the resulting solidification patterns.

  9. Multiplicity distributions of charged hadrons in vp and charged current interactions

    Science.gov (United States)

    Jones, G. T.; Jones, R. W. L.; Kennedy, B. W.; Morrison, D. R. O.; Mobayyen, M. M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Katz, U. F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H. P.; Myatt, G.; Radojicic, D.; Burke, S.

    1992-03-01

    Using data on vp andbar vp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ˜20000 events with incident v and ˜10000 events with incidentbar v. The invariant mass W of the total hadronic system ranges from 3 GeV to ˜14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for X 2. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling.

  10. A spatial theory for emergent multiple predator-prey interactions in food webs.

    Science.gov (United States)

    Northfield, Tobin D; Barton, Brandon T; Schmitz, Oswald J

    2017-09-01

    Predator-prey interaction is inherently spatial because animals move through landscapes to search for and consume food resources and to avoid being consumed by other species. The spatial nature of species interactions necessitates integrating spatial processes into food web theory and evaluating how predators combine to impact their prey. Here, we present a spatial modeling approach that examines emergent multiple predator effects on prey within landscapes. The modeling is inspired by the habitat domain concept derived from empirical synthesis of spatial movement and interactions studies. Because these principles are motivated by synthesis of short-term experiments, it remains uncertain whether spatial contingency principles hold in dynamical systems. We address this uncertainty by formulating dynamical systems models, guided by core habitat domain principles, to examine long-term multiple predator-prey spatial dynamics. To describe habitat domains, we use classical niche concepts describing resource utilization distributions, and assume species interactions emerge from the degree of overlap between species. The analytical results generally align with those from empirical synthesis and present a theoretical framework capable of demonstrating multiple predator effects that does not depend on the small spatial or temporal scales typical of mesocosm experiments, and help bridge between empirical experiments and long-term dynamics in natural systems.

  11. Charged multiplicity distributions in anti np interactions at 6 GeV/c

    International Nuclear Information System (INIS)

    Batyunya, B.V.; Boguslavskij, I.B.; Gramenitskij, I.M.

    1980-01-01

    Inelastic topological anti np cross sections at 6 GeV/c have been determined based on a study of the charged multiplicity distribution in antideuteron-proton collisions at 12 GeV/c. The data were obtained in an exposure of the ''Ludmila'' JINR 2 m hydrogen bubble chamber at the Serpukhov accelerator. In anti np interactions average charged multiplicity and its ratio to dispersion, /D, were found to be 3.32+-0.13 and 1.86+-0.16, respectively. Comparison with anti pn, anti pp and pp data was made

  12. Proactive control of proactive interference using the method of loci

    OpenAIRE

    Bass, Willa S.; Oswald, Karl M.

    2014-01-01

    Proactive interferencebuilds up with exposure to multiple lists of similar items with a resulting reduction in recall. This study examined the effectiveness of using a proactive strategy of the method of loci to reduce proactive interference in a list recall paradigm of categorically similar words. While all participants reported using some form of strategy to recall list words, this study demonstrated that young adults were able to proactively use the method of loci after 25 min of instructi...

  13. BPS Jumping Loci are Automorphic

    Science.gov (United States)

    Kachru, Shamit; Tripathy, Arnav

    2018-06-01

    We show that BPS jumping loci-loci in the moduli space of string compactifications where the number of BPS states jumps in an upper semi-continuous manner—naturally appear as Fourier coefficients of (vector space-valued) automorphic forms. For the case of T 2 compactification, the jumping loci are governed by a modular form studied by Hirzebruch and Zagier, while the jumping loci in K3 compactification appear in a story developed by Oda and Kudla-Millson in arithmetic geometry. We also comment on some curious related automorphy in the physics of black hole attractors and flux vacua.

  14. Temporal Sequence of Visuo-Auditory Interaction in Multiple Areas of the Guinea Pig Visual Cortex

    Science.gov (United States)

    Nishimura, Masataka; Song, Wen-Jie

    2012-01-01

    Recent studies in humans and monkeys have reported that acoustic stimulation influences visual responses in the primary visual cortex (V1). Such influences can be generated in V1, either by direct auditory projections or by feedback projections from extrastriate cortices. To test these hypotheses, cortical activities were recorded using optical imaging at a high spatiotemporal resolution from multiple areas of the guinea pig visual cortex, to visual and/or acoustic stimulations. Visuo-auditory interactions were evaluated according to differences between responses evoked by combined auditory and visual stimulation, and the sum of responses evoked by separate visual and auditory stimulations. Simultaneous presentation of visual and acoustic stimulations resulted in significant interactions in V1, which occurred earlier than in other visual areas. When acoustic stimulation preceded visual stimulation, significant visuo-auditory interactions were detected only in V1. These results suggest that V1 is a cortical origin of visuo-auditory interaction. PMID:23029483

  15. Comparison of charged particle multiplicity distributions in p tilde p and pp interactions and verification of the dual unitarization scheme

    International Nuclear Information System (INIS)

    Batyunya, B.V.; Boguslavsky, I.V.; Gramenitsky, I.M.

    1979-01-01

    The difference between antiproton annihilation and pp interactions has been discussed. Charged particle multiplicity distributions in anti pp-interactions at 22.4 GeV/c were used to obtain antiproton annihilation characteristics. The comparison of the topological cross section of antipp interactions with those of non-diffractive pp interactions confirms the validity of dual unitarization

  16. Temporal scale dependent interactions between multiple environmental disturbances in microcosm ecosystems.

    Science.gov (United States)

    Garnier, Aurélie; Pennekamp, Frank; Lemoine, Mélissa; Petchey, Owen L

    2017-12-01

    Global environmental change has negative impacts on ecological systems, impacting the stable provision of functions, goods, and services. Whereas effects of individual environmental changes (e.g. temperature change or change in resource availability) are reasonably well understood, we lack information about if and how multiple changes interact. We examined interactions among four types of environmental disturbance (temperature, nutrient ratio, carbon enrichment, and light) in a fully factorial design using a microbial aquatic ecosystem and observed responses of dissolved oxygen saturation at three temporal scales (resistance, resilience, and return time). We tested whether multiple disturbances combine in a dominant, additive, or interactive fashion, and compared the predictability of dissolved oxygen across scales. Carbon enrichment and shading reduced oxygen concentration in the short term (i.e. resistance); although no other effects or interactions were statistically significant, resistance decreased as the number of disturbances increased. In the medium term, only enrichment accelerated recovery, but none of the other effects (including interactions) were significant. In the long term, enrichment and shading lengthened return times, and we found significant two-way synergistic interactions between disturbances. The best performing model (dominant, additive, or interactive) depended on the temporal scale of response. In the short term (i.e. for resistance), the dominance model predicted resistance of dissolved oxygen best, due to a large effect of carbon enrichment, whereas none of the models could predict the medium term (i.e. resilience). The long-term response was best predicted by models including interactions among disturbances. Our results indicate the importance of accounting for the temporal scale of responses when researching the effects of environmental disturbances on ecosystems. © 2017 The Authors. Global Change Biology Published by John Wiley

  17. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

    DEFF Research Database (Denmark)

    Heid, Iris M; Jackson, Anne U; Randall, Joshua C

    2010-01-01

    and CPEB4 (P = 1.9 × 10¿¿ to P = 1.8 × 10¿4°) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10¿³ to P = 1.2 × 10¿¹³). These findings provide evidence for multiple loci that modulate...... body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions....

  18. Interactions between organic anions on multiple transporters in Caco-2 cells

    DEFF Research Database (Denmark)

    Grandvuinet, Anne Sophie; Steffansen, Bente

    2011-01-01

    Caco-2 cell line may be used as an overall model to predict interactions on multiple membrane transporters in the intestine. Taurocholic acid (TCA) and estrone-3-sulfate (E1S) were used as model substrates. Possible inhibitors studied were TCA, E1S, taurolithocholic acid, fluvastatin, and glipizide......-dependent bile acid transporter and the organic solute transporter α/β, and to less extent by the organic anion transporting polypeptide 2B1. However, interactions on efflux transporters were not detected, although they were expected from the literature on the investigated compounds. Biosimulation methods may...

  19. Interaction of multiple plasma plumes in an atmospheric pressure plasma jet array

    International Nuclear Information System (INIS)

    Ghasemi, M; Olszewski, P; Bradley, J W; Walsh, J L

    2013-01-01

    Plasma jet arrays are considered a viable means to enhance the scale of a downstream surface treatment beyond that possible using a single plasma jet. Of paramount importance in many processing applications is the uniformity of the plasma exposure on the substrate, which can be compromised when multiple plasma jets are arranged in close proximity due to their interaction. This contribution explores a dielectric barrier plasma jet array consisting of multiple individually ballasted jets. It is shown that capacitive ballasting is a promising technique to allow simultaneous operation of the plasma plumes without the losses associated with resistive ballasting. The interaction between adjacent plasma plumes and the background gas is investigated with Schlieren imaging; it is shown that the strong repulsive force between each plasma plume causes a divergence in propagation trajectory and a reduction in the laminar flow length with significant ramifications for any downstream surface treatment.

  20. 7th International Workshop on Multiple Partonic Interactions at the LHC

    CERN Document Server

    Treleani, Daniele; Strikman, Mark; van Buuren, Nadia

    2016-01-01

    From the start of the experimental activity of the Large Hadron Collider, Multiple Partonic Interactions (MPI) are experiencing a growing popularity and are widely invoked to account for observations that cannot be explained otherwise. This includes associated hadron production (Underlying Event) in high energy hadronic collisions with jets, the rates for multiple heavy flavor production, the survival probability of large rapidity gaps in hard diffraction, etc. In particular Double Parton Interactions were observed directly and studied by a number of the FNAL and LHC experiments in different reaction channels. At the LHC a new QCD regime has now been reached, where MPIs occur with high rates, in particular in central collisions, where the production of new particles is more likely to take place. Understanding MPIs is therefore crucial, both for their significant contribution to the background of various processes of interest for the search of new physics and because MPIs are an interesting topic of research b...

  1. Multiple genetic interaction experiments provide complementary information useful for gene function prediction.

    Directory of Open Access Journals (Sweden)

    Magali Michaut

    Full Text Available Genetic interactions help map biological processes and their functional relationships. A genetic interaction is defined as a deviation from the expected phenotype when combining multiple genetic mutations. In Saccharomyces cerevisiae, most genetic interactions are measured under a single phenotype - growth rate in standard laboratory conditions. Recently genetic interactions have been collected under different phenotypic readouts and experimental conditions. How different are these networks and what can we learn from their differences? We conducted a systematic analysis of quantitative genetic interaction networks in yeast performed under different experimental conditions. We find that networks obtained using different phenotypic readouts, in different conditions and from different laboratories overlap less than expected and provide significant unique information. To exploit this information, we develop a novel method to combine individual genetic interaction data sets and show that the resulting network improves gene function prediction performance, demonstrating that individual networks provide complementary information. Our results support the notion that using diverse phenotypic readouts and experimental conditions will substantially increase the amount of gene function information produced by genetic interaction screens.

  2. A novel epistatic interaction at two loci causing hybrid male sterility in an inter-subspecific cross of rice (Oryza sativa L.).

    Science.gov (United States)

    Kubo, Takahiko; Yamagata, Yoshiyuki; Eguchi, Maki; Yoshimura, Atsushi

    2008-12-01

    Postzygotic reproductive isolation (RI) often arises in inter-subspecific crosses as well as inter-specific crosses of rice (Oryza sativa L.). To further understand the genetic architecture of the postzygotic RI, we analyzed genes causing hybrid sterility and hybrid breakdown in a rice inter-subspecific cross. Here we report hybrid male sterility caused by epistatic interaction between two novel genes, S24 and S35, which were identified on rice chromosomes 5 and 1, respectively. Genetic analysis using near-isogenic lines (NILs) carrying IR24 (ssp. indica) segments with Asominori (ssp. japonica) genetic background revealed a complicated aspect of the epistasis. Allelic interaction at the S24 locus in the heterozygous plants caused abortion of male gametes carrying the Asominori allele (S24-as) independent of the S35 genotype. On the other hand, male gametes carrying the Asominori allele at the S35 locus (S35-as) showed abortion only when the IR24 allele at the S24 locus (S24-ir) was concurrently introgressed into the S35 heterozygous plants, indicating that the sterility phenotype due to S35 was dependent on the S24 genotype through negative epistasis between S24-ir and S35-as alleles. Due to the interaction between S24 and S35, self-pollination of the double heterozygous plants produced pollen-sterile progeny carrying the S24-ir/S24-ir S35-as/S35-ir genotype in addition to the S24 heterozygous plants. This result suggests that the S35 gene might function as a modifier of S24. This study presents strong evidence for the importance of epistatic interaction as a part of the genetic architecture of hybrid sterility in rice. In addition, it suggests that diverse systems have been developed as postzygotic RI mechanisms within the rice.

  3. Hierarchical folding of multiple sequence alignments for the prediction of structures and RNA-RNA interactions

    DEFF Research Database (Denmark)

    Seemann, Ernst Stefan; Richter, Andreas S.; Gorodkin, Jan

    2010-01-01

    of that used for individual multiple alignments. Results: We derived a rather extensive algorithm. One of the advantages of our approach (in contrast to other RNARNA interaction prediction methods) is the application of covariance detection and prediction of pseudoknots between intra- and inter-molecular base...... pairs. As a proof of concept, we show an example and discuss the strengths and weaknesses of the approach....

  4. Heat Recovery from Multiple-Fracture Enhanced Geothermal Systems: The Effect of Thermoelastic Fracture Interactions

    DEFF Research Database (Denmark)

    Vik, Hedda Slatlem; Salimzadeh, Saeed; Nick, Hamid

    2018-01-01

    This study investigates the effect of thermoelastic interactions between multiple parallel fractures on energy production from a multiple-fracture enhanced geothermal system. A coupled thermo-hydro-mechanical finite element model has been developed that accounts for non-isothermal fluid flow within...... increased to maximise the net energy production from the system. Otherwise, the multiple-fracture system fails to improve the energy recovery from the geothermal reservoir, as initially intended....... aperture in the adjacent fracture, and facilitates the creation of favourable flow pathways between the injection and production wells. These flow paths reduce the energy production from the system. The effects of fracture spacing, reservoir temperature gradient and mechanical properties of the rock matrix...

  5. N-way FRET microscopy of multiple protein-protein interactions in live cells.

    Directory of Open Access Journals (Sweden)

    Adam D Hoppe

    Full Text Available Fluorescence Resonance Energy Transfer (FRET microscopy has emerged as a powerful tool to visualize nanoscale protein-protein interactions while capturing their microscale organization and millisecond dynamics. Recently, FRET microscopy was extended to imaging of multiple donor-acceptor pairs, thereby enabling visualization of multiple biochemical events within a single living cell. These methods require numerous equations that must be defined on a case-by-case basis. Here, we present a universal multispectral microscopy method (N-Way FRET to enable quantitative imaging for any number of interacting and non-interacting FRET pairs. This approach redefines linear unmixing to incorporate the excitation and emission couplings created by FRET, which cannot be accounted for in conventional linear unmixing. Experiments on a three-fluorophore system using blue, yellow and red fluorescent proteins validate the method in living cells. In addition, we propose a simple linear algebra scheme for error propagation from input data to estimate the uncertainty in the computed FRET images. We demonstrate the strength of this approach by monitoring the oligomerization of three FP-tagged HIV Gag proteins whose tight association in the viral capsid is readily observed. Replacement of one FP-Gag molecule with a lipid raft-targeted FP allowed direct observation of Gag oligomerization with no association between FP-Gag and raft-targeted FP. The N-Way FRET method provides a new toolbox for capturing multiple molecular processes with high spatial and temporal resolution in living cells.

  6. Numerical Simulations for Nonlinear Waves Interaction with Multiple Perforated Quasi-Ellipse Caissons

    Directory of Open Access Journals (Sweden)

    Xiaozhong Ren

    2015-01-01

    Full Text Available A three-dimensional numerical flume is developed to study cnoidal wave interaction with multiple arranged perforated quasi-ellipse caissons. The continuity equation and the Navier-Stokes equations are used as the governing equation, and the VOF method is adopted to capture the free surface elevation. The equations are discretized on staggered cells and then solved using a finite difference method. The generation and propagation of cnoidal waves in the numerical flume are tested first. And the ability of the present model to simulate interactions between waves and structures is verified by known experimental results. Then cnoidal waves with varying incident wave height and period are generated and interact with multiple quasi-ellipse caissons with and without perforation. It is found that the perforation plays an effective role in reducing wave runup/rundown and wave forces on the caissons. The wave forces on caissons reduce with the decreasing incident wave period. The influence of the transverse distance of multiple caissons on wave forces is also investigated. A closer transverse distance between caissons can produce larger wave forces. But when relative adjacent distance L/D (L is the transverse distance and D is the width of the quasi-ellipse caisson is larger than 3, the effect of adjacent distance is limited.

  7. Large Display Interaction via Multiple Acceleration Curves and Multifinger Pointer Control

    Directory of Open Access Journals (Sweden)

    Andrey Esakia

    2014-01-01

    Full Text Available Large high-resolution displays combine high pixel density with ample physical dimensions. The combination of these factors creates a multiscale workspace where interactive targeting of on-screen objects requires both high speed for distant targets and high accuracy for small targets. Modern operating systems support implicit dynamic control-display gain adjustment (i.e., a pointer acceleration curve that helps to maintain both speed and accuracy. However, large high-resolution displays require a broader range of control-display gains than a single acceleration curve can usably enable. Some interaction techniques attempt to solve the problem by utilizing multiple explicit modes of interaction, where different modes provide different levels of pointer precision. Here, we investigate the alternative hypothesis of using a single mode of interaction for continuous pointing that enables both (1 standard implicit granularity control via an acceleration curve and (2 explicit switching between multiple acceleration curves in an efficient and dynamic way. We evaluate a sample solution that augments standard touchpad accelerated pointer manipulation with multitouch capability, where the choice of acceleration curve dynamically changes depending on the number of fingers in contact with the touchpad. Specifically, users can dynamically switch among three different acceleration curves by using one, two, or three fingers on the touchpad.

  8. Effects of Pilates exercises on sensory interaction, postural control and fatigue in patients with multiple sclerosis.

    Science.gov (United States)

    Soysal Tomruk, Melda; Uz, Muhammed Zahid; Kara, Bilge; İdiman, Egemen

    2016-05-01

    Decreased postural control, sensory integration deficits and fatigue are important problems that cause functional impairments in patients with multiple sclerosis (pwMS). To examine the effect of modified clinical Pilates exercises on sensory interaction and balance, postural control and fatigue in pwMS. Eleven patients with multiple sclerosis and 12 healthy matched controls were recruited in this study. Limits of stability and postural stability tests were used to evaluate postural control by Biodex Balance System and sensory interaction assessed. Fatigue was assessed by Modified Fatigue Impact Scale. Pilates exercises were applied two times a week for 10 weeks and measurements were repeated to pwMS after exercise training. Postural control and fatigue (except psychosocial parameter) of pwMS were significantly worser than healthy controls (pPilates training (ppilates exercises (p>0.05). Ten-week Pilates training is effective to improve sensory interaction and to decrease fatigue. Pilates exercises can be applied safely in ambulatory pwMS for enhance sensory interaction and balance and combat fatigue. More investigations are needed. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Game Theory of Tumor–Stroma Interactions in Multiple Myeloma: Effect of Nonlinear Benefits

    Directory of Open Access Journals (Sweden)

    Javad Salimi Sartakhti

    2018-05-01

    Full Text Available Cancer cells and stromal cells often exchange growth factors with paracrine effects that promote cell growth: a form of cooperation that can be studied by evolutionary game theory. Previous models have assumed that interactions between cells are pairwise or that the benefit of a growth factor is a linear function of its concentration. Diffusible factors, however, affect multiple cells and generally have nonlinear effects, and these differences are known to have important consequences for evolutionary dynamics. Here, we study tumor–stroma paracrine signaling using a model with multiplayer collective interactions in which growth factors have nonlinear effects. We use multiple myeloma as an example, modelling interactions between malignant plasma cells, osteoblasts, and osteoclasts. Nonlinear benefits can lead to results not observed in linear models, including internal mixed stable equilibria and cyclical dynamics. Models with linear effects, therefore, do not lead to a meaningful characterization of the dynamics of tumor–stroma interactions. To understand the dynamics and the effect of therapies it is necessary to estimate the shape of the benefit functions experimentally and parametrize models based on these functions.

  10. Measurement of Reconstructed Charged Particle Multiplicities of Neutrino Interactions in MicroBooNE

    Energy Technology Data Exchange (ETDEWEB)

    Rafique, Aleena [Kansas State Univ., Manhattan, KS (United States)

    2017-09-25

    Here, we compare the observed charged particle multiplicity distributions in the MicroBooNE liquid argon time projection chamber from neutrino interactions in a restricted final state phase space to predictions of this distribution from several GENIE models. The measurement uses a data sample consisting of neutrino interactions with a final state muon candidate fully contained within the MicroBooNE detector. These data were collected in 2015-2016 with the Fermilab Booster Neutrino Beam (BNB), which has an average neutrino energy of 800 MeV, using an exposure corresponding to 5e19 protons-on-target. The analysis employs fully automatic event selection and charged particle track reconstruction and uses a data-driven technique to determine the contribution to each multiplicity bin from neutrino interactions and cosmic-induced backgrounds. The restricted phase space employed makes the measurement most sensitive to the higher-energy charged particles expected from primary neutrino-argon collisions and less sensitive to lower energy protons expected to be produced in final state interactions of collision products with the target argon nucleus.

  11. Probability distributions in conservative energy exchange models of multiple interacting agents

    International Nuclear Information System (INIS)

    Scafetta, Nicola; West, Bruce J

    2007-01-01

    Herein we study energy exchange models of multiple interacting agents that conserve energy in each interaction. The models differ regarding the rules that regulate the energy exchange and boundary effects. We find a variety of stochastic behaviours that manifest energy equilibrium probability distributions of different types and interaction rules that yield not only the exponential distributions such as the familiar Maxwell-Boltzmann-Gibbs distribution of an elastically colliding ideal particle gas, but also uniform distributions, truncated exponential distributions, Gaussian distributions, Gamma distributions, inverse power law distributions, mixed exponential and inverse power law distributions, and evolving distributions. This wide variety of distributions should be of value in determining the underlying mechanisms generating the statistical properties of complex phenomena including those to be found in complex chemical reactions

  12. Multiple caregivers' touch interactions with young children among the Bofi foragers in Central Africa.

    Science.gov (United States)

    Jung, Min-Jung; Fouts, Hillary N

    2011-02-01

    The current study examined the use of three types of touch (caregiving, active social-affectionate, and passive social-affectionate) by caregivers with young children among the Bofi foragers, a seminomadic group of hunter-gatherers in Central Africa. With the purpose of providing a more holistic view of touch interactions in early childhood, compared to extant Western mother-centric views, this study documents stylistic touch patterns used by multiple caregivers (mother, father, adult relatives, and juvenile relatives) with Bofi forager children. Thirty-five Bofi forager children, between 18 and 59 months of age, and their various caregivers were naturalistically observed over 12 daylight hours using a focal child observational technique. Frequencies of each type of touch and the rank order of types of touch that children received were compared between caregivers and examined by child age and gender. Even though nonmaternal caregivers showed high physical involvement with children, mothers exemplified the highest level of involvement. Overall, passive social-affectionate touch was utilized the most by all types of caregivers. Mothers used more caregiving touch, and fathers and adult relatives had similar frequencies of caregiving touch and active social-affectionate touch. In contrast, juvenile relatives showed more active social-affectionate touch with focal children. This study highlights the importance of examining multiple caregivers and physical interactions when studying early childhood experiences. Furthermore, by focusing on multiple caregivers and multiple types of touch, this study provides a more thorough characterization of the touch experiences of young children than previous studies of touch. Finally, the current study exemplifies the value of considering non-Western populations when investigating touch interactions.

  13. Multiplicities and forward-backward correlations in anti pp interactions at 22.4 GeV/c

    International Nuclear Information System (INIS)

    Boos, E.G.; Samojlov, V.V.; Tashimov, M.A.

    1977-01-01

    Forward-backward multiplicity correlations in anti pp -interactions at 22.4 GeV/c and multiplicities in a simple icle multiplicity distribution is divided into even and odd components, the probability of producting an odd state is found to be higher than that of producing an even state, which may be interpreted to be due to diffraction forward-backward and to everall multiplicities is discussed

  14. Proceedings of the first international workshop on multiple partonic interactions at the LHC. MPI'08

    Energy Technology Data Exchange (ETDEWEB)

    Bartalini, Paolo [National Taiwan Univ., Taipei (China); Fano, Livio [Istituto Nazionale di Fisica Nucleare, Perugia (Italy)

    2009-06-15

    The objective of this first workshop on Multiple Partonic Interactions (MPI) at the LHC, that can be regarded as a continuation and extension of the dedicated meetings held at DESY in the years 2006 and 2007, is to raise the profile of MPI studies, summarizing the legacy from the older phenomenology at hadronic colliders and favouring further specific contacts between the theory and experimental communities. The MPI are experiencing a growing popularity and are currently widely invoked to account for observations that would not be explained otherwise: the activity of the Underlying Event, the cross sections for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of the MPI effects in the Monte Carlo models is quickly proceeding through an increasing level of sophistication and complexity that in perspective achieves deep general implications for the LHC physics. The ultimate ambition of this workshop is to promote the MPI as unification concept between seemingly heterogeneous research lines and to profit of the complete experimental picture in order to constrain their implementation in the models, evaluating the spin offs on the LHC physics program. The workshop is structured in five sections, with the first one dedicated to few selected hot highlights in the High Energy Physics and directly connected to the other ones: Multiple Parton Interactions (in both the soft and the hard regimes), Diffraction, Monte Carlo Generators and Heavy Ions. (orig.)

  15. Proceedings of the first international workshop on multiple partonic interactions at the LHC. MPI'08

    International Nuclear Information System (INIS)

    Bartalini, Paolo; Fano, Livio

    2009-06-01

    The objective of this first workshop on Multiple Partonic Interactions (MPI) at the LHC, that can be regarded as a continuation and extension of the dedicated meetings held at DESY in the years 2006 and 2007, is to raise the profile of MPI studies, summarizing the legacy from the older phenomenology at hadronic colliders and favouring further specific contacts between the theory and experimental communities. The MPI are experiencing a growing popularity and are currently widely invoked to account for observations that would not be explained otherwise: the activity of the Underlying Event, the cross sections for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of the MPI effects in the Monte Carlo models is quickly proceeding through an increasing level of sophistication and complexity that in perspective achieves deep general implications for the LHC physics. The ultimate ambition of this workshop is to promote the MPI as unification concept between seemingly heterogeneous research lines and to profit of the complete experimental picture in order to constrain their implementation in the models, evaluating the spin offs on the LHC physics program. The workshop is structured in five sections, with the first one dedicated to few selected hot highlights in the High Energy Physics and directly connected to the other ones: Multiple Parton Interactions (in both the soft and the hard regimes), Diffraction, Monte Carlo Generators and Heavy Ions. (orig.)

  16. Unravelling Darwin's entangled bank: architecture and robustness of mutualistic networks with multiple interaction types.

    Science.gov (United States)

    Dáttilo, Wesley; Lara-Rodríguez, Nubia; Jordano, Pedro; Guimarães, Paulo R; Thompson, John N; Marquis, Robert J; Medeiros, Lucas P; Ortiz-Pulido, Raul; Marcos-García, Maria A; Rico-Gray, Victor

    2016-11-30

    Trying to unravel Darwin's entangled bank further, we describe the architecture of a network involving multiple forms of mutualism (pollination by animals, seed dispersal by birds and plant protection by ants) and evaluate whether this multi-network shows evidence of a structure that promotes robustness. We found that species differed strongly in their contributions to the organization of the multi-interaction network, and that only a few species contributed to the structuring of these patterns. Moreover, we observed that the multi-interaction networks did not enhance community robustness compared with each of the three independent mutualistic networks when analysed across a range of simulated scenarios of species extinction. By simulating the removal of highly interacting species, we observed that, overall, these species enhance network nestedness and robustness, but decrease modularity. We discuss how the organization of interlinked mutualistic networks may be essential for the maintenance of ecological communities, and therefore the long-term ecological and evolutionary dynamics of interactive, species-rich communities. We suggest that conserving these keystone mutualists and their interactions is crucial to the persistence of species-rich mutualistic assemblages, mainly because they support other species and shape the network organization. © 2016 The Author(s).

  17. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Science.gov (United States)

    Agrawal, Devanshu; Karsai, Istvan

    2016-01-01

    Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  18. Effects of biotic interactions and dispersal on the presence-absence of multiple species

    International Nuclear Information System (INIS)

    Mohd, Mohd Hafiz; Murray, Rua; Plank, Michael J.; Godsoe, William

    2017-01-01

    One of the important issues in ecology is to predict which species will be present (or absent) across a geographical region. Dispersal is thought to have an important influence on the range limits of species, and understanding this problem in a multi-species community with priority effects (i.e. initial abundances determine species presence-absence) is a challenging task because dispersal also interacts with biotic and abiotic factors. Here, we propose a simple multi-species model to investigate the joint effects of biotic interactions and dispersal on species presence-absence. Our results show that dispersal can substantially expand species ranges when biotic and abiotic forces are present; consequently, coexistence of multiple species is possible. The model also exhibits ecologically interesting priority effects, mediated by intense biotic interactions. In the absence of dispersal, competitive exclusion of all but one species occurs. We find that dispersal reduces competitive exclusion effects that occur in no-dispersal case and promotes coexistence of multiple species. These results also show that priority effects are still prevalent in multi-species communities in the presence of dispersal process. We also illustrate the existence of threshold values of competitive strength (i.e. transcritical bifurcations), which results in different species presence-absence in multi-species communities with and without dispersal.

  19. Toward a community ecology of landscapes: predicting multiple predator-prey interactions across geographic space.

    Science.gov (United States)

    Schmitz, Oswald J; Miller, Jennifer R B; Trainor, Anne M; Abrahms, Briana

    2017-09-01

    Community ecology was traditionally an integrative science devoted to studying interactions between species and their abiotic environments in order to predict species' geographic distributions and abundances. Yet for philosophical and methodological reasons, it has become divided into two enterprises: one devoted to local experimentation on species interactions to predict community dynamics; the other devoted to statistical analyses of abiotic and biotic information to describe geographic distribution. Our goal here is to instigate thinking about ways to reconnect the two enterprises and thereby return to a tradition to do integrative science. We focus specifically on the community ecology of predators and prey, which is ripe for integration. This is because there is active, simultaneous interest in experimentally resolving the nature and strength of predator-prey interactions as well as explaining patterns across landscapes and seascapes. We begin by describing a conceptual theory rooted in classical analyses of non-spatial food web modules used to predict species interactions. We show how such modules can be extended to consideration of spatial context using the concept of habitat domain. Habitat domain describes the spatial extent of habitat space that predators and prey use while foraging, which differs from home range, the spatial extent used by an animal to meet all of its daily needs. This conceptual theory can be used to predict how different spatial relations of predators and prey could lead to different emergent multiple predator-prey interactions such as whether predator consumptive or non-consumptive effects should dominate, and whether intraguild predation, predator interference or predator complementarity are expected. We then review the literature on studies of large predator-prey interactions that make conclusions about the nature of multiple predator-prey interactions. This analysis reveals that while many studies provide sufficient information

  20. Possible Synergistic Interactions Among Multiple HPV Genotypes in Women Suffering from Genital Neoplasia

    Science.gov (United States)

    Hajia, Massoud; Sohrabi, Amir

    2018-03-27

    Objective: Persistence of HPV infection is the true cause of cervical disorders. It is reported that competition may exist among HPV genotypes for colonization. This survey was designed to establish the multiple HPV genotype status in our community and the probability of multiple HPV infections involvement. Methods: All multiple HPV infections were selected for investigation in women suffering from genital infections referred to private laboratories in Tehran, Iran. A total of 160 multi HPV positive specimens from cervical scraping were identified by the HPV genotyping methods, "INNO-LiPA and Geno Array". Result: In present study, HPV 6 (LR), 16 (HR), 53 (pHR), 31 (HR) and 11 (LR) were included in 48.8% of detected infections as the most five dominant genotypes. HPV 16 was detected at the highest rate with genotypes 53, 31 and 52, while HPV 53 appeared linked with HPV 16, 51 and 56 in concurrent infections. It appears that HPV 16 and 53 may have significant tendencies to associate with each other rather than with other genotypes. Analysis of the data revealed there may be some synergistic interactions with a few particular genotypes such as "HPV 53". Conclusion: Multiple HPV genotypes appear more likely to be linked with development of cervical abnormalities especially in patients with genital infections. Since, there are various patterns of dominant HPV genotypes in different regions of world, more investigations of this type should be performed for careHPV programs in individual countries. Creative Commons Attribution License

  1. Quantum correlation approach to criticality in the XX spin chain with multiple interaction

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, W.W., E-mail: weien.cheng@gmail.com [Institute of Signal Processing and Transmission, Nanjing University of Posts and Telecommunication, Nanjing 210003 (China); Department of Physics, Hubei Normal University, Huangshi 435002 (China); Key Lab of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education (China); Shan, C.J. [Department of Physics, Hubei Normal University, Huangshi 435002 (China); Sheng, Y.B.; Gong, L.Y.; Zhao, S.M. [Institute of Signal Processing and Transmission, Nanjing University of Posts and Telecommunication, Nanjing 210003 (China); Key Lab of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education (China)

    2012-09-01

    We investigate the quantum critical behavior in the XX spin chain with a XZY-YZX type multiple interaction by means of quantum correlation (Concurrence C, quantum discord D{sub Q} and geometric discord D{sub G}). Around the critical point, the values of these quantum correlations and corresponding derivatives are investigated numerically and analytically. The results show that the non-analyticity property of the concurrence cannot signal well the quantum phase transition, but both the quantum discord and geometric discord can characterize the critical behavior in such model exactly.

  2. Analysis of multiplicities in e+e- interactions using 2-jet rates from different jet algorithms

    International Nuclear Information System (INIS)

    Dahiya, S.; Kaur, M.; Dhamija, S.

    2002-01-01

    The shoulder structure of charged particle multiplicity distribution measured in full phase space in e + e - interactions at various c.m. energies from 91 to 189 GeV has been analysed in terms of weighted superposition of two negative binomial distributions associated with 2-jet and multi-jet production. The 2-jet rates have been obtained from various jet algorithms. This phenomenological parametrization reproduces the shoulder structure behaviour quantitatively and improves the agreement with the experimental distributions than the conventional negative binomial distribution. The analysis at the higher energies where the shoulder structure appears more prominently, is important for the understanding of underlying structure. (author)

  3. Laser-Bioplasma Interaction: The Blood Type Transmutation Induced by Multiple Ultrashort Wavelength Laser Beams

    Science.gov (United States)

    Stefan, V. Alexander

    2015-11-01

    The interaction of ultrashort wavelength multi laser beams with the flowing blood thin films leads to the transmutation of the blood types A, B, and AB into O type. This is a novel mechanism of importance for the transfusion medicine. Laser radiation is in resonance with the eigen-frequency modes of the antigen proteins and forces the proteins to parametrically oscillate until they get kicked out from the surface. The stripping away of antigens is done by the scanning-multiple-lasers of a high repetition rate in the blue-purple frequency domain. The guiding-lasers are in the red-green frequency domain. The laser force, (parametric interaction with the antigen eigen-oscillation), upon the antigen protein molecule must exceed its weight. The scanning laser beam is partially reflected as long as the antigen(s) is not eliminated. The process of the protein detachment can last a few minutes. Supported by Nikola Tesla Labs., Stefan University.

  4. Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival

    DEFF Research Database (Denmark)

    Nielsen, Kaspar René; Rodrigo-Domingo, Maria; Steffensen, Rudi

    2017-01-01

    The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single......3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors......= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential...

  5. A Vietnamese man with selective mutism: the relevance of multiple interacting 'cultures' in clinical psychiatry.

    Science.gov (United States)

    Hollifield, Michael; Geppert, Cynthia; Johnson, Yuam; Fryer, Carol

    2003-09-01

    Multiple cultural variables have effects on the psychobiology and behavioral manifestations of illness, as do patient and physician perceptions of illness. The interaction among these variables is at the heart of clinical psychiatry. This case of a Vietnamese man with selective mutism underscores the relevance of the 'cultures' of medicine, psychiatry, and war and trauma on the manifestations of illness and illness perceptions by patient and physician. The discussion focuses on how these cultures interact and play a crucial role in formulating diagnosis and treatment planning. Suggestions are given for shifts in medical education that will encourage relevant cultural paradigms to make their way into educational and clinical systems, which in turn should improve cultural competence in clinical psychiatry.

  6. Effects of multiple substitution upon the P...N noncovalent interaction

    International Nuclear Information System (INIS)

    Scheiner, Steve

    2011-01-01

    Graphical abstract: The presence of one halogen opposite the N results in strong attraction between P and N. This force is little affected by identity of Y atoms, whether H or halogen. Highlights: → Strong attractive force directly between trivalent P and N atoms. → P...N force is unlike H-bonds or halogen bonds, but stronger than both. → Multiple halogenation beyond a single atom on P slightly weakens the interaction. - Abstract: The attractive noncovalent interaction of a P atom with N is derived primarily from two sources. Charge transfer from the N lone pair into the σ * antibonding orbital of a P-X bond that is turned away from the N atom combines with attractive Coulombic forces. As in the case of H-bonding, which is parallel in some ways to P...N attraction, placement of an electron-withdrawing substituent on the P atom enhances both of these components, and strengthens the overall interaction. However, in stark contrast with H-bonding, halogenation beyond monosubstitution does not lead to any further strengthening of the P...N noncovalent bond. Indeed, di and tri-substitution lead to small reductions in the interaction energy. In all cases, the geometry which contains a P...N bond is more stable than other candidate structures, some of which contain hydrogen or halogen bonds.

  7. Brain Interaction during Cooperation: Evaluating Local Properties of Multiple-Brain Network.

    Science.gov (United States)

    Sciaraffa, Nicolina; Borghini, Gianluca; Aricò, Pietro; Di Flumeri, Gianluca; Colosimo, Alfredo; Bezerianos, Anastasios; Thakor, Nitish V; Babiloni, Fabio

    2017-07-21

    Subjects' interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental effort required by subjects while facing a situation that is getting harder, that is, mental workload, to define an objective measure based on how and if team members are interacting is not so straightforward. In this study, behavioral, subjective and synchronized electroencephalographic data were collected from couples involved in a cooperative task to describe the relationship between task difficulty and team coordination, in the sense of interaction aimed at cooperatively performing the assignment. Multiple-brain connectivity analysis provided information about the whole interacting system. The results showed that averaged local properties of a brain network were affected by task difficulty. In particular, strength changed significantly with task difficulty and clustering coefficients strongly correlated with the workload itself. In particular, a higher workload corresponded to lower clustering values over the central and parietal brain areas. Such results has been interpreted as less efficient organization of the network when the subjects' activities, due to high workload tendencies, were less coordinated.

  8. Assessing interactions among multiple physiological systems during walking outside a laboratory: An Android based gait monitor

    Science.gov (United States)

    Sejdić, E.; Millecamps, A.; Teoli, J.; Rothfuss, M. A.; Franconi, N. G.; Perera, S.; Jones, A. K.; Brach, J. S.; Mickle, M. H.

    2015-01-01

    Gait function is traditionally assessed using well-lit, unobstructed walkways with minimal distractions. In patients with subclinical physiological abnormalities, these conditions may not provide enough stress on their ability to adapt to walking. The introduction of challenging walking conditions in gait can induce responses in physiological systems in addition to the locomotor system. There is a need for a device that is capable of monitoring multiple physiological systems in various walking conditions. To address this need, an Android-based gait-monitoring device was developed that enabled the recording of a patient's physiological systems during walking. The gait-monitoring device was tested during self-regulated overground walking sessions of fifteen healthy subjects that included 6 females and 9 males aged 18 to 35 years. The gait-monitoring device measures the patient's stride interval, acceleration, electrocardiogram, skin conductance and respiratory rate. The data is stored on an Android phone and is analyzed offline through the extraction of features in the time, frequency and time-frequency domains. The analysis of the data depicted multisystem physiological interactions during overground walking in healthy subjects. These interactions included locomotion-electrodermal, locomotion-respiratory and cardiolocomotion couplings. The current results depicting strong interactions between the locomotion system and the other considered systems (i.e., electrodermal, respiratory and cardivascular systems) warrant further investigation into multisystem interactions during walking, particularly in challenging walking conditions with older adults. PMID:26390946

  9. Library Spirit and Genius Loci

    DEFF Research Database (Denmark)

    Dahlkild, Nan

    2009-01-01

    The architecture and design of Nyborg Public Library in the light of the concepts "Library Spirit" and "Genius Loci", related to contemporary social and cultural movements, the development of the early welfare state and the "Scandinavian Style".......The architecture and design of Nyborg Public Library in the light of the concepts "Library Spirit" and "Genius Loci", related to contemporary social and cultural movements, the development of the early welfare state and the "Scandinavian Style"....

  10. Use of multiple correspondence analysis (MCA) to identify interactive meteorological conditions affecting relative throughfall

    Science.gov (United States)

    Van Stan, John T.; Gay, Trent E.; Lewis, Elliott S.

    2016-02-01

    Forest canopies alter rainfall reaching the surface by redistributing it as throughfall. Throughfall supplies water and nutrients to a variety of ecohydrological components (soil microbial communities, stream water discharge/chemistry, and stormflow pathways) and is controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, median wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (⩾73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work relying on more historically common methods (e.g., multiple regression and analytical models). Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy Tillandsia usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

  11. Prediction of protein interaction hot spots using rough set-based multiple criteria linear programming.

    Science.gov (United States)

    Chen, Ruoying; Zhang, Zhiwang; Wu, Di; Zhang, Peng; Zhang, Xinyang; Wang, Yong; Shi, Yong

    2011-01-21

    Protein-protein interactions are fundamentally important in many biological processes and it is in pressing need to understand the principles of protein-protein interactions. Mutagenesis studies have found that only a small fraction of surface residues, known as hot spots, are responsible for the physical binding in protein complexes. However, revealing hot spots by mutagenesis experiments are usually time consuming and expensive. In order to complement the experimental efforts, we propose a new computational approach in this paper to predict hot spots. Our method, Rough Set-based Multiple Criteria Linear Programming (RS-MCLP), integrates rough sets theory and multiple criteria linear programming to choose dominant features and computationally predict hot spots. Our approach is benchmarked by a dataset of 904 alanine-mutated residues and the results show that our RS-MCLP method performs better than other methods, e.g., MCLP, Decision Tree, Bayes Net, and the existing HotSprint database. In addition, we reveal several biological insights based on our analysis. We find that four features (the change of accessible surface area, percentage of the change of accessible surface area, size of a residue, and atomic contacts) are critical in predicting hot spots. Furthermore, we find that three residues (Tyr, Trp, and Phe) are abundant in hot spots through analyzing the distribution of amino acids. Copyright © 2010 Elsevier Ltd. All rights reserved.

  12. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    International Nuclear Information System (INIS)

    Burbery, N.J.; Das, R.; Ferguson, W.G.

    2016-01-01

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  13. Thermo-kinetic mechanisms for grain boundary structure multiplicity, thermal instability and defect interactions

    Energy Technology Data Exchange (ETDEWEB)

    Burbery, N.J. [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Das, R., E-mail: r.das@auckland.ac.nz [Department of Mechanical Engineering, University of Auckland, Auckland 1010 (New Zealand); Ferguson, W.G. [Department of Chemical and Materials Engineering, University of Auckland, Auckland 1010 (New Zealand)

    2016-08-15

    Grain boundaries (GBs) provide a source and/or a sink for crystal defects and store elastic energy due to the non-uniform atomic bonding structure of the GB core. GB structures are thermodynamically driven to transition to the lowest energy configuration possible; however to date there has been little evidence to explain why specific GB structures have a low energy state. Furthermore, there is little quantitative demonstration of the significance of physical and GB structure characteristics on the GB energy, thermal stability, and the effect of temporary local GB structure transformations on defect interactions. This paper evaluates the defect interactions and structure stability of multiple Σ5(310) GB structures in bi-crystals of pure aluminium, and systematically investigates the features at 0 K to characterise multiple metastable structures. Structure stability is evaluated by utilising unstable vacancy defects to initiate GB transformations, and using nudged elastic band simulations to quantify this with the activation energy. The emission of stable vacancy defects from the ‘stable’ and metastable grain boundaries is also evaluated in the same manner. A detailed analysis of dislocation nucleation at the atomistic scale demonstrates that local transformations of GB structure between stable and metastable intermediates can provide a mechanism to accommodate the generation of crystal defects. Kinetic (time-dependent) effects that compete with energetic driving forces for structural transformations of GBs are shown to cause a significant effect on the activation properties that may exceed the influence of GB potential energy. The results demonstrate that GB structural multiplicity can be associated with the generation and absorption of dislocations and vacancies. This paper demonstrates the suitability of atomistic simulations coupled with nudged elastic band simulations to evaluate fundamental thermodynamic properties of pure FCC metals. Overall, this paper

  14. Interaction of amidated single-walled carbon nanotubes with protein by multiple spectroscopic methods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lili [China Pharmaceutical University, Nanjing 210009 (China); The Nursing College of Pingdingshan University, Pingdingshan 467000 (China); Lin, Rui [Yancheng Health Vocational and Technical College, Yancheng 224005 (China); He, Hua, E-mail: dochehua@163.com [China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009 (China); Sun, Meiling, E-mail: sml-nir@sohu.com [China Pharmaceutical University, Nanjing 210009 (China); Jiang, Li; Gao, Mengmeng [China Pharmaceutical University, Nanjing 210009 (China)

    2014-01-15

    The aim of this work was to investigate the detailed interaction between BSA and amidated single walled carbon nanotubes (e-SWNTs) in vitro. Ethylenediamine (EDA) was successfully linked on the surface of single-walled carbon nanotubes (SWNTs) via acylation to improve their dispersion and to introduce active groups. Bovine serum albumin (BSA) was selected as the template protein to inspect the interaction of e-SWNTs with protein. Decreases in fluorescence intensity of BSA induced by e-SWNTs demonstrated the occurrence of interaction between BSA and e-SWNTs. Quenching parameters and different absorption spectra for e-SWNTs–BSA show that the quenching effect of e-SWNTs was static quenching. Hydrophobic force had a leading contribution to the binding roles of BSA on e-SWNTs, which was confirmed by positive enthalpy change and entropy change. The interference of Na{sup +} with the quenching effect of e-SWNTs authenticated that electrostatic force existed in the interactive process simultaneously. The hydrophobicity of amino acid residues markedly increased with the addition of e-SWNTs viewed from UV spectra of BSA. The content of α-helix structure in BSA decreased by 6.8% due to the addition of e-SWNTs, indicating that e-SWNTs have an effect on the secondary conformation of BSA. -- Highlights: • The interaction between e-SWNTs and BSA was investigated by multiple spectroscopic methods. • Quenching mechanism was static quenching. • Changes in structure of BSA were inspected by synchronous fluorescence, UV–vis and CD spectrum.

  15. Designing Kerr interactions using multiple superconducting qubit types in a single circuit

    Science.gov (United States)

    Elliott, Matthew; Joo, Jaewoo; Ginossar, Eran

    2018-02-01

    The engineering of Kerr interactions is of great interest for processing quantum information in multipartite quantum systems and for investigating many-body physics in a complex cavity-qubit network. We study how coupling multiple different types of superconducting qubits to the same cavity modes can be used to modify the self- and cross-Kerr effects acting on the cavities and demonstrate that this type of architecture could be of significant benefit for quantum technologies. Using both analytical perturbation theory results and numerical simulations, we first show that coupling two superconducting qubits with opposite anharmonicities to a single cavity enables the effective self-Kerr interaction to be diminished, while retaining the number splitting effect that enables control and measurement of the cavity field. We demonstrate that this reduction of the self-Kerr effect can maintain the fidelity of coherent states and generalised Schrödinger cat states for much longer than typical coherence times in realistic devices. Next, we find that the cross-Kerr interaction between two cavities can be modified by coupling them both to the same pair of qubit devices. When one of the qubits is tunable in frequency, the strength of entangling interactions between the cavities can be varied on demand, forming the basis for logic operations on the two modes. Finally, we discuss the feasibility of producing an array of cavities and qubits where intermediary and on-site qubits can tune the strength of self- and cross-Kerr interactions across the whole system. This architecture could provide a way to engineer interesting many-body Hamiltonians and be a useful platform for quantum simulation in circuit quantum electrodynamics.

  16. Genes and quality trait loci (QTLs) associated with firmness in Malus x domestica

    KAUST Repository

    Marondedze, Claudius

    2013-03-31

    Fruit firmness, a quality quantitative trait, has long been established as a key textural property and one of the essential parameters for estimating ripening and shelf life of apples. Loss of firmness, also referred to as fruit softening, is undesirable in apples and represents a serious problem for growers in many countries. This results in the reduction of apple shelf life and in turn influences its commercialization. Low firmness impacts negatively on the sensory values of juiciness, crunchiness and crispness. Fruit firmness is affected by the inheritance of alleles at multiple loci and their possible interactions with the environment. Identification of these loci is key for the determination of genetic candidate markers that can be implemented in marker assisted selection and breeding for trees and/or cultivars that can yield firmer fruits with economic value. In turn, this technique can help reduce the time needed to evaluate plants and new cultivars could become available faster. This review provides an overview of quantitative trait loci (QTL), including additional putative QTLs that we have identified, and genes associated with firmness and their importance to biotechnology, the breeding industry and eventually the consumers.

  17. A silicon multiplicity detector system for an experiment on the interaction of antiprotons with nuclei at BNL

    International Nuclear Information System (INIS)

    Ahmad, S.; Bonner, B.E.; Buchanan, J.A.; Clement, J.M.; Empl, A.; Mutchler, G.S.; Toshkov, S.; Chan, C.S.; Kramer, M.A.; Lindenbaum, S.J.; Hallman, T.J.; Madansky, L.; Peaslee, D.C.

    1991-01-01

    A Large Angle Multiplicity Detector (LAMD) system has been developed and used at the BNL experiment E854: Antiproton Nucleus Interactions. This system performed well with an energetic antiproton beam. Charged particle multiplicity distributions from pbar annihilations were measured. We discuss the design and performance of the LAMD system in this paper. 6 refs., 10 figs

  18. A low-complexity interacting multiple model filter for maneuvering target tracking

    KAUST Repository

    Khalid, Syed Safwan

    2017-01-22

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  19. Embracing interactions in ocean acidification research: confronting multiple stressor scenarios and context dependence.

    Science.gov (United States)

    Kroeker, Kristy J; Kordas, Rebecca L; Harley, Christopher D G

    2017-03-01

    Changes in the Earth's environment are now sufficiently complex that our ability to forecast the emergent ecological consequences of ocean acidification (OA) is limited. Such projections are challenging because the effects of OA may be enhanced, reduced or even reversed by other environmental stressors or interactions among species. Despite an increasing emphasis on multifactor and multispecies studies in global change biology, our ability to forecast outcomes at higher levels of organization remains low. Much of our failure lies in a poor mechanistic understanding of nonlinear responses, a lack of specificity regarding the levels of organization at which interactions can arise, and an incomplete appreciation for linkages across these levels. To move forward, we need to fully embrace interactions. Mechanistic studies on physiological processes and individual performance in response to OA must be complemented by work on population and community dynamics. We must also increase our understanding of how linkages and feedback among multiple environmental stressors and levels of organization can generate nonlinear responses to OA. This will not be a simple undertaking, but advances are of the utmost importance as we attempt to mitigate the effects of ongoing global change. © 2017 The Authors.

  20. A low-complexity interacting multiple model filter for maneuvering target tracking

    KAUST Repository

    Khalid, Syed Safwan; Abrar, Shafayat

    2017-01-01

    In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

  1. Confidence intervals for distinguishing ordinal and disordinal interactions in multiple regression.

    Science.gov (United States)

    Lee, Sunbok; Lei, Man-Kit; Brody, Gene H

    2015-06-01

    Distinguishing between ordinal and disordinal interaction in multiple regression is useful in testing many interesting theoretical hypotheses. Because the distinction is made based on the location of a crossover point of 2 simple regression lines, confidence intervals of the crossover point can be used to distinguish ordinal and disordinal interactions. This study examined 2 factors that need to be considered in constructing confidence intervals of the crossover point: (a) the assumption about the sampling distribution of the crossover point, and (b) the possibility of abnormally wide confidence intervals for the crossover point. A Monte Carlo simulation study was conducted to compare 6 different methods for constructing confidence intervals of the crossover point in terms of the coverage rate, the proportion of true values that fall to the left or right of the confidence intervals, and the average width of the confidence intervals. The methods include the reparameterization, delta, Fieller, basic bootstrap, percentile bootstrap, and bias-corrected accelerated bootstrap methods. The results of our Monte Carlo simulation study suggest that statistical inference using confidence intervals to distinguish ordinal and disordinal interaction requires sample sizes more than 500 to be able to provide sufficiently narrow confidence intervals to identify the location of the crossover point. (c) 2015 APA, all rights reserved).

  2. Emotional pictures and sounds: A review of multimodal interactions of emotion cues in multiple domains

    Directory of Open Access Journals (Sweden)

    Antje B M Gerdes

    2014-12-01

    Full Text Available In everyday life, multiple sensory channels jointly trigger emotional experiences and one channel may alter processing in another channel. For example, seeing an emotional facial expression and hearing the voice’s emotional tone will jointly create the emotional experience. This example, where auditory and visual input is related to social communication, has gained considerable attention by researchers. However, interactions of visual and auditory emotional information are not limited to social communication but can extend to much broader contexts including human, animal, and environmental cues. In this article, we review current research on audiovisual emotion processing beyond face-voice stimuli to develop a broader perspective on multimodal interactions in emotion processing. We argue that current concepts of multimodality should be extended in considering an ecologically valid variety of stimuli in audiovisual emotion processing. Therefore, we provide an overview of studies in which emotional sounds and interactions with complex pictures of scenes were investigated. In addition to behavioral studies, we focus on neuroimaging, electro- and peripher-physiological findings. Furthermore, we integrate these findings and identify similarities or differences. We conclude with suggestions for future research.

  3. Multiplicity fluctuations of identified hadrons in p+p interactions at SPS energies

    CERN Document Server

    Maćkowiak-Pawłowska, Maja

    2014-01-01

    Study of energy and system size fluctuations of identified hadrons is one of the key goals of NA61/SHINE at the CERN SPS. Results may allow to discover the critical point (CP) of strongly interacting matter as well as to uncover properties of the onset of deconfinement (OD). But fluctuations exhibit numerous other sources starting from most basic ones like volume effects and conservation laws. NA49 seems to observe fluctuations related to CP in collisions of medium size nuclei at top SPS energy. However, this result will remain inconclusive until systematic data on energy and system size dependence will be available. Moreover, fluctuations in p+p as well as in Pb+Pb interactions should be better understood. In this contribution results on multiplicity fluctuations of identified hadrons in p+p interactions at the CERN SPS energies will be presented. The NA61 data will be compared with the corresponding results from central Pb+Pb collisions of NA49 in the common acceptance region of both experiments. Moreover, ...

  4. Attentional processes in interactions between people with profound intellectual and multiple disabilities and direct support staff.

    Science.gov (United States)

    Hostyn, Ine; Ine, Hostyn; Neerinckx, Heleen; Heleen, Neerinckx; Maes, Bea; Bea, Maes

    2011-01-01

    Few studies have examined joint attention in interactions with persons with profound intellectual and multiple disabilities (PIMD), despite its important role in high-quality interaction. The purpose of this study is to describe the attention-directing behaviours of persons with PIMD and their direct support staff and the attention episodes resulting from their interactions, and to understand how these variables relate to each other. Video observations of 17 staff-client dyads were coded using partial interval recording. The results showed considerable variation across individuals and dyads. In general, persons with PIMD directed the attention of staff members infrequently. The staff members frequently directed their clients' attention towards a topic of interest but did not often use the tactile modality. Within the staff-client dyad, there was not much joint attention; however, shared attention episodes occurred frequently. Shared attention and joint attention are strongly correlated. A negative correlation was found between clients not using attention-directing behaviours and staff members using tactile methods to direct the attention, and joint attention episodes. This study presents both directions for future research and practical implications. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Multiplicative interaction of functional inflammasome genetic variants in determining the risk of gout.

    Science.gov (United States)

    McKinney, Cushla; Stamp, Lisa K; Dalbeth, Nicola; Topless, Ruth K; Day, Richard O; Kannangara, Diluk Rw; Williams, Kenneth M; Janssen, Matthijs; Jansen, Timothy L; Joosten, Leo A; Radstake, Timothy R; Riches, Philip L; Tausche, Anne-Kathrin; Lioté, Frederic; So, Alexander; Merriman, Tony R

    2015-10-13

    The acute gout flare results from a localised self-limiting innate immune response to monosodium urate (MSU) crystals deposited in joints in hyperuricaemic individuals. Activation of the caspase recruitment domain-containing protein 8 (CARD8) NOD-like receptor pyrin-containing 3 (NLRP3) inflammasome by MSU crystals and production of mature interleukin-1β (IL-1β) is central to acute gouty arthritis. However very little is known about genetic control of the innate immune response involved in acute gouty arthritis. Therefore our aim was to test functional single nucleotide polymorphism (SNP) variants in the toll-like receptor (TLR)-inflammasome-IL-1β axis for association with gout. 1,494 gout cases of European and 863 gout cases of New Zealand (NZ) Polynesian (Māori and Pacific Island) ancestry were included. Gout was diagnosed by the 1977 ARA gout classification criteria. There were 1,030 Polynesian controls and 10,942 European controls including from the publicly-available Atherosclerosis Risk in Communities (ARIC) and Framingham Heart (FHS) studies. The ten SNPs were either genotyped by Sequenom MassArray or by Affymetrix SNP array or imputed in the ARIC and FHS datasets. Allelic association was done by logistic regression adjusting by age and sex with European and Polynesian data combined by meta-analysis. Sample sets were pooled for multiplicative interaction analysis, which was also adjusted by sample set. Eleven SNPs were tested in the TLR2, CD14, IL1B, CARD8, NLRP3, MYD88, P2RX7, DAPK1 and TNXIP genes. Nominally significant (P gout were detected at CARD8 rs2043211 (OR = 1.12, P = 0.007), IL1B rs1143623 (OR = 1.10, P = 0.020) and CD14 rs2569190 (OR = 1.08; P = 0.036). There was significant multiplicative interaction between CARD8 and IL1B (P = 0.005), with the IL1B risk genotype amplifying the risk effect of CARD8. There is evidence for association of gout with functional variants in CARD8, IL1B and CD14. The gout-associated allele of IL1B increases

  6. Infectious Bursal Disease Virus-Host Interactions: Multifunctional Viral Proteins that Perform Multiple and Differing Jobs

    Directory of Open Access Journals (Sweden)

    Yao Qin

    2017-01-01

    Full Text Available Infectious bursal disease (IBD is an acute, highly contagious and immunosuppressive poultry disease caused by IBD virus (IBDV. The consequent immunosuppression increases susceptibility to other infectious diseases and the risk of subsequent vaccination failure as well. Since the genome of IBDV is relatively small, it has a limited number of proteins inhibiting the cellular antiviral responses and acting as destroyers to the host defense system. Thus, these virulence factors must be multifunctional in order to complete the viral replication cycle in a host cell. Insights into the roles of these viral proteins along with their multiple cellular targets in different pathways will give rise to a rational design for safer and effective vaccines. Here we summarize the recent findings that focus on the virus–cell interactions during IBDV infection at the protein level.

  7. Multi-sensor fusion with interacting multiple model filter for improved aircraft position accuracy.

    Science.gov (United States)

    Cho, Taehwan; Lee, Changho; Choi, Sangbang

    2013-03-27

    The International Civil Aviation Organization (ICAO) has decided to adopt Communications, Navigation, and Surveillance/Air Traffic Management (CNS/ATM) as the 21st century standard for navigation. Accordingly, ICAO members have provided an impetus to develop related technology and build sufficient infrastructure. For aviation surveillance with CNS/ATM, Ground-Based Augmentation System (GBAS), Automatic Dependent Surveillance-Broadcast (ADS-B), multilateration (MLAT) and wide-area multilateration (WAM) systems are being established. These sensors can track aircraft positions more accurately than existing radar and can compensate for the blind spots in aircraft surveillance. In this paper, we applied a novel sensor fusion method with Interacting Multiple Model (IMM) filter to GBAS, ADS-B, MLAT, and WAM data in order to improve the reliability of the aircraft position. Results of performance analysis show that the position accuracy is improved by the proposed sensor fusion method with the IMM filter.

  8. Multiple hard interactions in $\\gamma\\gamma$ and $\\gamma$p physics at LEP and HERA

    CERN Document Server

    Butterworth, J.M.; Seymour, M.H.; Storrow, J.K.; Walker, R.

    1995-01-01

    At e^+e^- and ep colliders, the large fluxes of almost on-shell photons accompanying the lepton beams lead to the photoproduction of jets. As the centre-of-mass energy is increased, regions of smaller x in the parton densities are explored and these are regions of high parton density. As a result, the probability for more than one hard partonic scattering occurring in a single \\gamma \\gamma or \\gamma p collision can become significant. This effect has been simulated using an eikonal prescription combined with the HERWIG Monte Carlo program. The possible effects of multiple hard interactions on event shapes and jet cross sections have been studied in this framework at a range of energies relevant to HERA and LEPII. The results indicate that the effects could be significant.

  9. The interaction between 4-aminoantipyrine and bovine serum albumin: Multiple spectroscopic and molecular docking investigations

    International Nuclear Information System (INIS)

    Teng Yue; Liu Rutao; Li Chao; Xia Qing; Zhang Pengjun

    2011-01-01

    4-Aminoantipyrine (AAP) is widely used in the pharmaceutical industry, in biochemical experiments and in environmental monitoring. AAP as an aromatic pollutant in the environment poses a great threat to human health. To evaluate the toxicity of AAP at the protein level, the effects of AAP on bovine serum albumin (BSA) were investigated by multiple spectroscopic techniques and molecular modeling. After the inner filter effect was eliminated, the experimental results showed that AAP effectively quenched the intrinsic fluorescence of BSA via static quenching. The number of binding sites, the binding constant, the thermodynamic parameters and binding subdomain were measured, and indicated that AAP could spontaneously bind with BSA on subdomain IIIA through electrostatic forces. Molecular docking results revealed that AAP interacted with the Glu 488 and Glu 502 residues of BSA. Furthermore, the conformation of BSA was demonstrably changed in the presence of AAP. The skeletal structure of BSA loosened, exposing internal hydrophobic aromatic ring amino acids and peptide strands to the solution.

  10. Giant graviton interactions and M2-branes ending on multiple M5-branes

    Science.gov (United States)

    Hirano, Shinji; Sato, Yuki

    2018-05-01

    We study splitting and joining interactions of giant gravitons with angular momenta N 1/2 ≪ J ≪ N in the type IIB string theory on AdS 5 × S 5 by describing them as instantons in the tiny graviton matrix model introduced by Sheikh-Jabbari. At large J the instanton equation can be mapped to the four-dimensional Laplace equation and the Coulomb potential for m point charges in an n-sheeted Riemann space corresponds to the m-to- n interaction process of giant gravitons. These instantons provide the holographic dual of correlators of all semi-heavy operators and the instanton amplitudes exactly agree with the pp-wave limit of Schur polynomial correlators in N = 4 SYM computed by Corley, Jevicki and Ramgoolam. By making a slight change of variables the same instanton equation is mathematically transformed into the Basu-Harvey equation which describes the system of M2-branes ending on M5-branes. As it turns out, the solutions to the sourceless Laplace equation on an n-sheeted Riemann space correspond to n M5-branes connected by M2-branes and we find general solutions representing M2-branes ending on multiple M5-branes. Among other solutions, the n = 3 case describes an M2-branes junction ending on three M5-branes. The effective theory on the moduli space of our solutions might shed light on the low energy effective theory of multiple M5-branes.

  11. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

    Science.gov (United States)

    Wang, Zhaoming; Zhu, Bin; Zhang, Mingfeng; Parikh, Hemang; Jia, Jinping; Chung, Charles C.; Sampson, Joshua N.; Hoskins, Jason W.; Hutchinson, Amy; Burdette, Laurie; Ibrahim, Abdisamad; Hautman, Christopher; Raj, Preethi S.; Abnet, Christian C.; Adjei, Andrew A.; Ahlbom, Anders; Albanes, Demetrius; Allen, Naomi E.; Ambrosone, Christine B.; Aldrich, Melinda; Amiano, Pilar; Amos, Christopher; Andersson, Ulrika; Andriole, Gerald; Andrulis, Irene L.; Arici, Cecilia; Arslan, Alan A.; Austin, Melissa A.; Baris, Dalsu; Barkauskas, Donald A.; Bassig, Bryan A.; Beane Freeman, Laura E.; Berg, Christine D.; Berndt, Sonja I.; Bertazzi, Pier Alberto; Biritwum, Richard B.; Black, Amanda; Blot, William; Boeing, Heiner; Boffetta, Paolo; Bolton, Kelly; Boutron-Ruault, Marie-Christine; Bracci, Paige M.; Brennan, Paul; Brinton, Louise A.; Brotzman, Michelle; Bueno-de-Mesquita, H. Bas; Buring, Julie E.; Butler, Mary Ann; Cai, Qiuyin; Cancel-Tassin, Geraldine; Canzian, Federico; Cao, Guangwen; Caporaso, Neil E.; Carrato, Alfredo; Carreon, Tania; Carta, Angela; Chang, Gee-Chen; Chang, I-Shou; Chang-Claude, Jenny; Che, Xu; Chen, Chien-Jen; Chen, Chih-Yi; Chen, Chung-Hsing; Chen, Constance; Chen, Kuan-Yu; Chen, Yuh-Min; Chokkalingam, Anand P.; Chu, Lisa W.; Clavel-Chapelon, Francoise; Colditz, Graham A.; Colt, Joanne S.; Conti, David; Cook, Michael B.; Cortessis, Victoria K.; Crawford, E. David; Cussenot, Olivier; Davis, Faith G.; De Vivo, Immaculata; Deng, Xiang; Ding, Ti; Dinney, Colin P.; Di Stefano, Anna Luisa; Diver, W. Ryan; Duell, Eric J.; Elena, Joanne W.; Fan, Jin-Hu; Feigelson, Heather Spencer; Feychting, Maria; Figueroa, Jonine D.; Flanagan, Adrienne M.; Fraumeni, Joseph F.; Freedman, Neal D.; Fridley, Brooke L.; Fuchs, Charles S.; Gago-Dominguez, Manuela; Gallinger, Steven; Gao, Yu-Tang; Gapstur, Susan M.; Garcia-Closas, Montserrat; Garcia-Closas, Reina; Gastier-Foster, Julie M.; Gaziano, J. Michael; Gerhard, Daniela S.; Giffen, Carol A.; Giles, Graham G.; Gillanders, Elizabeth M.; Giovannucci, Edward L.; Goggins, Michael; Gokgoz, Nalan; Goldstein, Alisa M.; Gonzalez, Carlos; Gorlick, Richard; Greene, Mark H.; Gross, Myron; Grossman, H. Barton; Grubb, Robert; Gu, Jian; Guan, Peng; Haiman, Christopher A.; Hallmans, Goran; Hankinson, Susan E.; Harris, Curtis C.; Hartge, Patricia; Hattinger, Claudia; Hayes, Richard B.; He, Qincheng; Helman, Lee; Henderson, Brian E.; Henriksson, Roger; Hoffman-Bolton, Judith; Hohensee, Chancellor; Holly, Elizabeth A.; Hong, Yun-Chul; Hoover, Robert N.; Hosgood, H. Dean; Hsiao, Chin-Fu; Hsing, Ann W.; Hsiung, Chao Agnes; Hu, Nan; Hu, Wei; Hu, Zhibin; Huang, Ming-Shyan; Hunter, David J.; Inskip, Peter D.; Ito, Hidemi; Jacobs, Eric J.; Jacobs, Kevin B.; Jenab, Mazda; Ji, Bu-Tian; Johansen, Christoffer; Johansson, Mattias; Johnson, Alison; Kaaks, Rudolf; Kamat, Ashish M.; Kamineni, Aruna; Karagas, Margaret; Khanna, Chand; Khaw, Kay-Tee; Kim, Christopher; Kim, In-Sam; Kim, Jin Hee; Kim, Yeul Hong; Kim, Young-Chul; Kim, Young Tae; Kang, Chang Hyun; Jung, Yoo Jin; Kitahara, Cari M.; Klein, Alison P.; Klein, Robert; Kogevinas, Manolis; Koh, Woon-Puay; Kohno, Takashi; Kolonel, Laurence N.; Kooperberg, Charles; Kratz, Christian P.; Krogh, Vittorio; Kunitoh, Hideo; Kurtz, Robert C.; Kurucu, Nilgun; Lan, Qing; Lathrop, Mark; Lau, Ching C.; Lecanda, Fernando; Lee, Kyoung-Mu; Lee, Maxwell P.; Le Marchand, Loic; Lerner, Seth P.; Li, Donghui; Liao, Linda M.; Lim, Wei-Yen; Lin, Dongxin; Lin, Jie; Lindstrom, Sara; Linet, Martha S.; Lissowska, Jolanta; Liu, Jianjun; Ljungberg, Börje; Lloreta, Josep; Lu, Daru; Ma, Jing; Malats, Nuria; Mannisto, Satu; Marina, Neyssa; Mastrangelo, Giuseppe; Matsuo, Keitaro; McGlynn, Katherine A.; McKean-Cowdin, Roberta; McNeill, Lorna H.; McWilliams, Robert R.; Melin, Beatrice S.; Meltzer, Paul S.; Mensah, James E.; Miao, Xiaoping; Michaud, Dominique S.; Mondul, Alison M.; Moore, Lee E.; Muir, Kenneth; Niwa, Shelley; Olson, Sara H.; Orr, Nick; Panico, Salvatore; Park, Jae Yong; Patel, Alpa V.; Patino-Garcia, Ana; Pavanello, Sofia; Peeters, Petra H. M.; Peplonska, Beata; Peters, Ulrike; Petersen, Gloria M.; Picci, Piero; Pike, Malcolm C.; Porru, Stefano; Prescott, Jennifer; Pu, Xia; Purdue, Mark P.; Qiao, You-Lin; Rajaraman, Preetha; Riboli, Elio; Risch, Harvey A.; Rodabough, Rebecca J.; Rothman, Nathaniel; Ruder, Avima M.; Ryu, Jeong-Seon; Sanson, Marc; Schned, Alan; Schumacher, Fredrick R.; Schwartz, Ann G.; Schwartz, Kendra L.; Schwenn, Molly; Scotlandi, Katia; Seow, Adeline; Serra, Consol; Serra, Massimo; Sesso, Howard D.; Severi, Gianluca; Shen, Hongbing; Shen, Min; Shete, Sanjay; Shiraishi, Kouya; Shu, Xiao-Ou; Siddiq, Afshan; Sierrasesumaga, Luis; Sierri, Sabina; Loon Sihoe, Alan Dart; Silverman, Debra T.; Simon, Matthias; Southey, Melissa C.; Spector, Logan; Spitz, Margaret; Stampfer, Meir; Stattin, Par; Stern, Mariana C.; Stevens, Victoria L.; Stolzenberg-Solomon, Rachael Z.; Stram, Daniel O.; Strom, Sara S.; Su, Wu-Chou; Sund, Malin; Sung, Sook Whan; Swerdlow, Anthony; Tan, Wen; Tanaka, Hideo; Tang, Wei; Tang, Ze-Zhang; Tardon, Adonina; Tay, Evelyn; Taylor, Philip R.; Tettey, Yao; Thomas, David M.; Tirabosco, Roberto; Tjonneland, Anne; Tobias, Geoffrey S.; Toro, Jorge R.; Travis, Ruth C.; Trichopoulos, Dimitrios; Troisi, Rebecca; Truelove, Ann; Tsai, Ying-Huang; Tucker, Margaret A.; Tumino, Rosario; Van Den Berg, David; Van Den Eeden, Stephen K.; Vermeulen, Roel; Vineis, Paolo; Visvanathan, Kala; Vogel, Ulla; Wang, Chaoyu; Wang, Chengfeng; Wang, Junwen; Wang, Sophia S.; Weiderpass, Elisabete; Weinstein, Stephanie J.; Wentzensen, Nicolas; Wheeler, William; White, Emily; Wiencke, John K.; Wolk, Alicja; Wolpin, Brian M.; Wong, Maria Pik; Wrensch, Margaret; Wu, Chen; Wu, Tangchun; Wu, Xifeng; Wu, Yi-Long; Wunder, Jay S.; Xiang, Yong-Bing; Xu, Jun; Yang, Hannah P.; Yang, Pan-Chyr; Yatabe, Yasushi; Ye, Yuanqing; Yeboah, Edward D.; Yin, Zhihua; Ying, Chen; Yu, Chong-Jen; Yu, Kai; Yuan, Jian-Min; Zanetti, Krista A.; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Zhou, Baosen; Mirabello, Lisa; Savage, Sharon A.; Kraft, Peter; Chanock, Stephen J.; Yeager, Meredith; Landi, Maria Terese; Shi, Jianxin; Chatterjee, Nilanjan; Amundadottir, Laufey T.

    2014-01-01

    Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10−39; Region 3: rs2853677, P = 3.30 × 10−36 and PConditional = 2.36 × 10−8; Region 4: rs2736098, P = 3.87 × 10−12 and PConditional = 5.19 × 10−6, Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10−6; and Region 6: rs10069690, P = 7.49 × 10−15 and PConditional = 5.35 × 10−7) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10−18 and PConditional = 7.06 × 10−16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. PMID:25027329

  12. The function of communities in protein interaction networks at multiple scales

    Directory of Open Access Journals (Sweden)

    Jones Nick S

    2010-07-01

    Full Text Available Abstract Background If biology is modular then clusters, or communities, of proteins derived using only protein interaction network structure should define protein modules with similar biological roles. We investigate the link between biological modules and network communities in yeast and its relationship to the scale at which we probe the network. Results Our results demonstrate that the functional homogeneity of communities depends on the scale selected, and that almost all proteins lie in a functionally homogeneous community at some scale. We judge functional homogeneity using a novel test and three independent characterizations of protein function, and find a high degree of overlap between these measures. We show that a high mean clustering coefficient of a community can be used to identify those that are functionally homogeneous. By tracing the community membership of a protein through multiple scales we demonstrate how our approach could be useful to biologists focusing on a particular protein. Conclusions We show that there is no one scale of interest in the community structure of the yeast protein interaction network, but we can identify the range of resolution parameters that yield the most functionally coherent communities, and predict which communities are most likely to be functionally homogeneous.

  13. Interaction effects among multiple job demands: an examination of healthcare workers across different contexts.

    Science.gov (United States)

    Jimmieson, Nerina L; Tucker, Michelle K; Walsh, Alexandra J

    2017-05-01

    Simultaneous exposure to time, cognitive, and emotional demands is a feature of the work environment for healthcare workers, yet effects of these common stressors in combination are not well established. Survey data were collected from 125 hospital employees (Sample 1, Study 1), 93 ambulance service employees (Sample 2, Study 1), and 380 aged care/disability workers (Study 2). Hierarchical multiple regressions were conducted. In Sample 1, high cognitive demand exacerbated high emotional demand on psychological strain and job burnout, whereas the negative effect of high emotional demand was not present at low cognitive demand. In Sample 2, a similar pattern between emotional demand and time demand on stress-remedial intentions was observed. In Study 2, emotional demand × time demand and time demand × cognitive demand interactions again revealed that high levels of two demands were stress-exacerbating and low levels of one demand neutralized the other. A three-way interaction on job satisfaction showed the negative impact of emotional demand was exacerbated when both time and cognitive demands were high, creating a "triple disadvantage" of job demands. The results demonstrate that reducing some job demands helps attenuate the stressful effects of other job demands on different employee outcomes.

  14. Using Nucleon Multiplicities to Analyze Anti-Neutrino Interactions with Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Elkins, Miranda J. [Univ. of Minnesota, Duluth, MN (United States)

    2017-05-01

    The most commonly used, simple interaction models have not accurately described the nuclear effects on either neutrino-nucleus or anti-neutrino-nucleus interactions. Comparison of data collected by the MINERvA experiment and these models shows a discrepancy in the reconstructed hadronic energy distribution at momentum transfers below 0.8 GeV. Two nuclear model effects that were previously not modeled are possible culprits of this discrepancy. The first is known as random-phase-approximation and the second is the addition of a meson exchange current process, also known as two-particle two-hole due to its result in two particles leaving the nucleus with two holes left in their place. For the first time a neutron counting software algorithm has been created and used to compare the multiplicity and spatial distributions of neutrons between the simulation and data. There is localized sensitivity to the RPA and 2p2h effects and both help the simulation better describe the data. Ad ditional systematic or model effects are present which cause the simulation to overproduce neutrons, and potential causes are discussed.

  15. Urban land use decouples plant-herbivore-parasitoid interactions at multiple spatial scales.

    Directory of Open Access Journals (Sweden)

    Amanda E Nelson

    Full Text Available Intense urban and agricultural development alters habitats, increases fragmentation, and may decouple trophic interactions if plants or animals cannot disperse to needed resources. Specialist insects represent a substantial proportion of global biodiversity and their fidelity to discrete microhabitats provides a powerful framework for investigating organismal responses to human land use. We sampled site occupancy and densities for two plant-herbivore-parasitoid systems from 250 sites across a 360 km2 urban/agricultural landscape to ask whether and how human development decouples interactions between trophic levels. We compared patterns of site occupancy, host plant density, herbivory and parasitism rates of insects at two trophic levels with respect to landcover at multiple spatial scales. Geospatial analyses were used to identify landcover characters predictive of insect distributions. We found that herbivorous insect densities were decoupled from host tree densities in urban landcover types at several spatial scales. This effect was amplified for the third trophic level in one of the two insect systems: despite being abundant regionally, a parasitoid species was absent from all urban/suburban landcover even where its herbivore host was common. Our results indicate that human land use patterns limit distributions of specialist insects. Dispersal constraints associated with urban built development are specifically implicated as a limiting factor.

  16. Global map of physical interactions among differentially expressed genes in multiple sclerosis relapses and remissions.

    Science.gov (United States)

    Tuller, Tamir; Atar, Shimshi; Ruppin, Eytan; Gurevich, Michael; Achiron, Anat

    2011-09-15

    Multiple sclerosis (MS) is a central nervous system autoimmune inflammatory T-cell-mediated disease with a relapsing-remitting course in the majority of patients. In this study, we performed a high-resolution systems biology analysis of gene expression and physical interactions in MS relapse and remission. To this end, we integrated 164 large-scale measurements of gene expression in peripheral blood mononuclear cells of MS patients in relapse or remission and healthy subjects, with large-scale information about the physical interactions between these genes obtained from public databases. These data were analyzed with a variety of computational methods. We find that there is a clear and significant global network-level signal that is related to the changes in gene expression of MS patients in comparison to healthy subjects. However, despite the clear differences in the clinical symptoms of MS patients in relapse versus remission, the network level signal is weaker when comparing patients in these two stages of the disease. This result suggests that most of the genes have relatively similar expression levels in the two stages of the disease. In accordance with previous studies, we found that the pathways related to regulation of cell death, chemotaxis and inflammatory response are differentially expressed in the disease in comparison to healthy subjects, while pathways related to cell adhesion, cell migration and cell-cell signaling are activated in relapse in comparison to remission. However, the current study includes a detailed report of the exact set of genes involved in these pathways and the interactions between them. For example, we found that the genes TP53 and IL1 are 'network-hub' that interacts with many of the differentially expressed genes in MS patients versus healthy subjects, and the epidermal growth factor receptor is a 'network-hub' in the case of MS patients with relapse versus remission. The statistical approaches employed in this study enabled us

  17. Context, emotion, and the strategic pursuit of goals: Interactions among multiple brain systems controlling motivated behaviour

    Directory of Open Access Journals (Sweden)

    Aaron J Gruber

    2012-08-01

    Full Text Available Motivated behaviour exhibits properties that change with experience and partially dissociate among a number of brain structures. Here, we review evidence from rodent experiments demonstrating that multiple brain systems acquire information in parallel and either cooperate or compete for behavioural control. We propose a conceptual model of systems interaction wherein a ventral emotional memory network involving ventral striatum, amygdala, ventral hippocampus, and ventromedial prefrontal cortex triages behavioural responding to stimuli according to their associated affective outcomes. This system engages autonomic and postural responding (avoiding, ignoring, approaching in accordance with associated stimulus valence (negative, neutral, positive, but does not engage particular operant responses. Rather, this emotional system suppresses or invigorates actions that are selected through competition between goal-directed control involving dorsomedial striatum and habitual control involving dorsolateral striatum. The hippocampus provides contextual specificity to the emotional system, and provides an information rich input to the goal-directed system for navigation and discriminations involving ambiguous contexts, complex sensory configurations, or temporal ordering. The rapid acquisition and high capacity for episodic associations in the emotional system may unburden the more complex goal-directed system and reduce interference in the habit system from processing contingencies of neutral stimuli. Interactions among these systems likely involve inhibitory mechanisms and neuromodulation in the basal ganglia to form a dominant response strategy. Innate traits, training methods, and task demands contribute to the nature of these interactions, which can include incidental learning in non-dominant systems. Addition of these features to reinforcement learning models of decision making may better align theoretical predictions with behavioural and neural

  18. A field comparison of multiple techniques to quantify groundwater - surface-water interactions

    Science.gov (United States)

    González-Pinzón, Ricardo; Ward, Adam S; Hatch, Christine E; Wlostowski, Adam N; Singha, Kamini; Gooseff, Michael N.; Haggerty, Roy; Harvey, Judson; Cirpka, Olaf A; Brock, James T

    2015-01-01

    Groundwater–surface-water (GW-SW) interactions in streams are difficult to quantify because of heterogeneity in hydraulic and reactive processes across a range of spatial and temporal scales. The challenge of quantifying these interactions has led to the development of several techniques, from centimeter-scale probes to whole-system tracers, including chemical, thermal, and electrical methods. We co-applied conservative and smart reactive solute-tracer tests, measurement of hydraulic heads, distributed temperature sensing, vertical profiles of solute tracer and temperature in the stream bed, and electrical resistivity imaging in a 450-m reach of a 3rd-order stream. GW-SW interactions were not spatially expansive, but were high in flux through a shallow hyporheic zone surrounding the reach. NaCl and resazurin tracers suggested different surface–subsurface exchange patterns in the upper ⅔ and lower ⅓ of the reach. Subsurface sampling of tracers and vertical thermal profiles quantified relatively high fluxes through a 10- to 20-cm deep hyporheic zone with chemical reactivity of the resazurin tracer indicated at 3-, 6-, and 9-cm sampling depths. Monitoring of hydraulic gradients along transects with MINIPOINT streambed samplers starting ∼40 m from the stream indicated that groundwater discharge prevented development of a larger hyporheic zone, which progressively decreased from the stream thalweg toward the banks. Distributed temperature sensing did not detect extensive inflow of ground water to the stream, and electrical resistivity imaging showed limited large-scale hyporheic exchange. We recommend choosing technique(s) based on: 1) clear definition of the questions to be addressed (physical, biological, or chemical processes), 2) explicit identification of the spatial and temporal scales to be covered and those required to provide an appropriate context for interpretation, and 3) maximizing generation of mechanistic understanding and reducing costs of

  19. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Korkaric, Muris [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland); Behra, Renata; Fischer, Beat B. [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); Junghans, Marion [Swiss Center for Applied Ecotoxicology Eawag-EPFL, 8600, Duebendorf (Switzerland); Eggen, Rik I.L., E-mail: rik.eggen@eawag.ch [Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, 8600, Duebendorf (Switzerland); ETH Zürich, Institute of Biogeochemistry and Pollutant Dynamics, 8092 Zürich (Switzerland)

    2015-05-15

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  20. Multiple stressor effects in Chlamydomonas reinhardtii – Toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants

    International Nuclear Information System (INIS)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B.; Junghans, Marion; Eggen, Rik I.L.

    2015-01-01

    Highlights: • Systematic study of multiple stressor effects of UVR and chemicals in C. reinhardtii. • UVR and chemicals did not act independently on algal photosynthesis and reproduction. • Multiple stressor effects of UVR and chemicals depended on chemical MOA. • Synergistic effect interactions not limited to oxidative stress inducing chemicals. • Multiple MOAs of UVR may limit applicability of current prediction models. - Abstract: The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are

  1. SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

    Science.gov (United States)

    Watanabe, Hideo; Ma, Qiuping; Peng, Shouyong; Adelmant, Guillaume; Swain, Danielle; Song, Wenyu; Fox, Cameron; Francis, Joshua M; Pedamallu, Chandra Sekhar; DeLuca, David S; Brooks, Angela N; Wang, Su; Que, Jianwen; Rustgi, Anil K; Wong, Kwok-kin; Ligon, Keith L; Liu, X Shirley; Marto, Jarrod A; Meyerson, Matthew; Bass, Adam J

    2014-04-01

    The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.

  2. Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking.

    Science.gov (United States)

    Liu, Hua; Wu, Wen

    2017-06-13

    For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF).

  3. Interacting Multiple Model (IMM Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking

    Directory of Open Access Journals (Sweden)

    Hua Liu

    2017-06-01

    Full Text Available For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF. The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF, the interacting multiple model cubature Kalman filter (IMMCKF and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF.

  4. Multiplicities of secondary hadrons produced in #betta#p and anti #betta#p charged current interactions

    International Nuclear Information System (INIS)

    Graessler, H.; Lanske, D.; Schulte, R.; Chima, J.S.; Mobayyen, M.M.; Talebzadeh, M.; Villalobos-Baillie, O.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

    1983-02-01

    In an experiment with the hydrogen bubble chamber BEBC at CERN multiplicities of hadrons produced in #betta#p and anti #betta# interactions have been investigated. Results are presented on the multiplicities of charged hadrons and neutral pions, forward and backward multiplicities of charged hadrons and correlations between forward and backward multiplicities. Comparisons are made with hadronic reactions and e + e - annihilation. In the framework of the quark-parton model the data imply similar charged multiplicities for the fragments of a u- and a d-quark, and larger multiplicities for the fragments of a uu- than for a ud-diquark. The correlation data suggest independent fragmentation of the quark and diquark for hadronic masses above approx.=7 GeV and local charge compensation within an event. (orig.)

  5. Proactive control of proactive interference using the method of loci.

    Science.gov (United States)

    Bass, Willa S; Oswald, Karl M

    2014-01-01

    Proactive interferencebuilds up with exposure to multiple lists of similar items with a resulting reduction in recall. This study examined the effectiveness of using a proactive strategy of the method of loci to reduce proactive interference in a list recall paradigm of categorically similar words. While all participants reported using some form of strategy to recall list words, this study demonstrated that young adults were able to proactively use the method of loci after 25 min of instruction to reduce proactive interference as compared with other personal spontaneous strategies. The implications of this study are that top-down proactive strategies such as the method of loci can significantly reduce proactive interference, and that the use of image and sequence or location are especially useful in this regard.

  6. Multiple interacting factors influence adherence, and outcomes associated with surgical safety checklists: a qualitative study.

    Directory of Open Access Journals (Sweden)

    Anna R Gagliardi

    Full Text Available The surgical safety checklist (SSC is meant to enhance patient safety but studies of its impact conflict. This study explored factors that influenced SSC adherence to suggest how its impact could be optimized.Participants were recruited purposively by profession, region, hospital type and time using the SSC. They were asked to describe how the SSC was adopted, associated challenges, perceived impact, and suggestions for improving its use. Grounded theory and thematic analysis were used to collect and analyse data. Findings were interpreted using an implementation fidelity conceptual framework.Fifty-one participants were interviewed (29 nurses, 13 surgeons, 9 anaesthetists; 18 small, 14 large and 19 teaching hospitals; 8 regions; 31 had used the SC for ≤12 months, 20 for 13+ months. The SSC was inconsistently reviewed, and often inaccurately documented as complete. Adherence was influenced by multiple issues. Extensive modification to accommodate existing practice patterns eliminated essential interaction at key time points to discuss patient management. Staff were often absent or not paying attention. They did not feel it was relevant to their work given limited evidence of its effectiveness, and because they were not engaged in its implementation. Organizations provided little support for implementation, training, monitoring and feedback, which are needed to overcome these, and other individual and team factors that challenged SSC adherence. Responses were similar across participants with different characteristics.Multiple processes and factors influenced SSC adherence. This may explain why, in studies evaluating SSC impact, outcomes were variable. Recommendations included continuing education, time for pilot-testing, and engaging all staff in SSC review. Others may use the implementation fidelity framework to plan SSC implementation or evaluate SSC adherence. Further research is needed to establish which SSC components can be modified

  7. LES of n-Dodecane Spray Combustion Using a Multiple Representative Interactive Flamelets Model

    Directory of Open Access Journals (Sweden)

    Davidovic Marco

    2017-09-01

    Full Text Available A single-hole n-dodecane spray flame is studied in a Large-Eddy Simulation (LES framework under Diesel-relevant conditions using a Multiple Representative Interactive Flamelets (MRIF combustion model. Diesel spray combustion is strongly affected by the mixture formation process, which is dominated by several physical processes such as the flow within the injector, break-up of the liquid fuel jet, evaporation and turbulent mixing with the surrounding gas. While the effects of nozzle-internal flow and primary breakup are captured within tuned model parameters in traditional Lagrangian spray models, an alternative approach is applied in this study, where the initial droplet conditions and primary fuel jet breakup are modeled based on results from highly resolved multiphase simulations with resolved interface. A highly reduced chemical mechanism consisting of 57 species and 217 reactions has been developed for n-dodecane achiving a good computational performance at solving the chemical reactions. The MRIF model, which has demonstrated its capability of capturing combustion and pollutant formation under typical Diesel conditions in Reynolds-Averaged Navier-Stokes (RANS simulations is extended for the application in LES. In the standard RIF combustion model, representative chemistry conditioned on mixture fraction is solved interactively with the flow. Subfilter-scale mixing is modeled by the scalar dissipation rate. While the standard RIF model only includes temporal changes of the scalar dissipation rate, the spatial distribution can be accounted for by extending the model to multiple flamelets, which also enables the possibility of capturing different fuel residence times. Overall, the model shows good agreement with experimental data regarding both, low and high temperature combustion characteristics. It is shown that the ignition process and pollutant formation are affected by turbulent mixing. First, a cool flame is initiated at approximately

  8. Neutrino interactions with e+μ- and multiple K0's

    International Nuclear Information System (INIS)

    Stevenson, M.L.

    1976-07-01

    A scan for directly produced positrons in 5,000 neutrino interactions in the neon (21 percent) hydrogen filled bubble chamber at Fermilab has yielded 15 events, 9 of which have μ - 's identified in the external muon identifier. On correcting for detection efficiency one obtains sigma(e + μ - )/sigma(μ - ) approximately 1 x 10 -2 for E/sub e + / > .8 GeV and E/sub ν/ > 5 GeV. The kaon multiplicity is unexpectedly high. Eleven of the events have one or more Vees and three have two or more. Among the 11 events are two clear Λ's and two ambiguous K 0 /Λ. There are four events with identifiable charged kaons. A 16th e + event (9) is a definite ν/sub e/. From this information one concludes that the kaon multiplicity is 2 +- .6 K 0 's and 2 +- 1 K +- 's per interaction. From the observation - />/ + /> = 6.6, one concludes that the e + 's are probably not uniquely from heavy lepton decay. From a variety of analyses involving the e + and/or K 0 's one learns that the mass of the hadron (C) that produces the e + 's is greater than 1.6 GeV. By determining the fraction of normal charged current (CC) events that have K 0 /sub s/ → π + π - one is able to compare this fraction with the fraction of CC events that have e + μ - (K 0 /sub s/ → π + π - ) to establish a conservative lower limit to the semileptonic branching ratio, C → (e + and μ + ) ν/C → all > 0.33 (1 +- .42), provided that the same number of K 0 /sub s/ exists in thenonleptonic decays as in the semileptonic ones, and that the phase space for μ + and e + are nearly equal. There is no compelling evidence for an energy threshold and there is a hint of some neutral current events among the e + events

  9. On the thermoluminescent interactive multiple-trap system (IMTS) model: is it a simple model?

    International Nuclear Information System (INIS)

    Gil T, M. I.; Perez C, L.; Cruz Z, E.; Furetta, C.; Roman L, J.

    2016-10-01

    In the thermally stimulated luminescence phenomenon, named thermoluminescence (Tl), the electrons and holes generated by the radiation-matter interaction can be trapped by the metastable levels in the band gap of the solid. Following, the electron can be thermally releases into the conduction band and a radiatively recombination with hole close to the recombination center occurred and the glow curve is emitted. However, the complex mechanism of trapping and thermally releases occurred in the band gap of solid. Some models, such as; first, second and general-order kinetics, have been well established to explain the behaviour of the glow curves and their defects recombination mechanism. In this work, expressions for and Interactive Multiple-Trap System model (IMTS) was obtained assuming: a set of discrete electron traps (active traps At), another set of thermally disconnected trap (TDT) and a recombination center (Rc) too. A numerical analysis based on the Levenberg-Marquardt method in conjunction with an implicit Rosenbrock method was taken into account to simulate the glow curve. The numerical method was tested through synthetic Tl glow curves for a wide range of trap parameters. The activation energy and kinetics order were determined using values from the General Order Kinetics (GOK) model as entry data to IMTS model. This model was tested using the experimental glow curves obtained from Ce or Eu-doped MgF 2 (LiF) polycrystals samples. Results shown that the IMTS model can predict more accurately the behavior of the Tl glow curves that those obtained by the GOK modified by Rasheedy and by the Mixed Order Kinetics model. (Author)

  10. On the thermoluminescent interactive multiple-trap system (IMTS) model: is it a simple model?

    Energy Technology Data Exchange (ETDEWEB)

    Gil T, M. I.; Perez C, L. [UNAM, Facultad de Quimica, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico); Cruz Z, E.; Furetta, C.; Roman L, J., E-mail: ecruz@nucleares.unam.mx [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Ciudad de Mexico (Mexico)

    2016-10-15

    In the thermally stimulated luminescence phenomenon, named thermoluminescence (Tl), the electrons and holes generated by the radiation-matter interaction can be trapped by the metastable levels in the band gap of the solid. Following, the electron can be thermally releases into the conduction band and a radiatively recombination with hole close to the recombination center occurred and the glow curve is emitted. However, the complex mechanism of trapping and thermally releases occurred in the band gap of solid. Some models, such as; first, second and general-order kinetics, have been well established to explain the behaviour of the glow curves and their defects recombination mechanism. In this work, expressions for and Interactive Multiple-Trap System model (IMTS) was obtained assuming: a set of discrete electron traps (active traps At), another set of thermally disconnected trap (TDT) and a recombination center (Rc) too. A numerical analysis based on the Levenberg-Marquardt method in conjunction with an implicit Rosenbrock method was taken into account to simulate the glow curve. The numerical method was tested through synthetic Tl glow curves for a wide range of trap parameters. The activation energy and kinetics order were determined using values from the General Order Kinetics (GOK) model as entry data to IMTS model. This model was tested using the experimental glow curves obtained from Ce or Eu-doped MgF{sub 2}(LiF) polycrystals samples. Results shown that the IMTS model can predict more accurately the behavior of the Tl glow curves that those obtained by the GOK modified by Rasheedy and by the Mixed Order Kinetics model. (Author)

  11. A Fast Multiple-Kernel Method With Applications to Detect Gene-Environment Interaction.

    Science.gov (United States)

    Marceau, Rachel; Lu, Wenbin; Holloway, Shannon; Sale, Michèle M; Worrall, Bradford B; Williams, Stephen R; Hsu, Fang-Chi; Tzeng, Jung-Ying

    2015-09-01

    Kernel machine (KM) models are a powerful tool for exploring associations between sets of genetic variants and complex traits. Although most KM methods use a single kernel function to assess the marginal effect of a variable set, KM analyses involving multiple kernels have become increasingly popular. Multikernel analysis allows researchers to study more complex problems, such as assessing gene-gene or gene-environment interactions, incorporating variance-component based methods for population substructure into rare-variant association testing, and assessing the conditional effects of a variable set adjusting for other variable sets. The KM framework is robust, powerful, and provides efficient dimension reduction for multifactor analyses, but requires the estimation of high dimensional nuisance parameters. Traditional estimation techniques, including regularization and the "expectation-maximization (EM)" algorithm, have a large computational cost and are not scalable to large sample sizes needed for rare variant analysis. Therefore, under the context of gene-environment interaction, we propose a computationally efficient and statistically rigorous "fastKM" algorithm for multikernel analysis that is based on a low-rank approximation to the nuisance effect kernel matrices. Our algorithm is applicable to various trait types (e.g., continuous, binary, and survival traits) and can be implemented using any existing single-kernel analysis software. Through extensive simulation studies, we show that our algorithm has similar performance to an EM-based KM approach for quantitative traits while running much faster. We also apply our method to the Vitamin Intervention for Stroke Prevention (VISP) clinical trial, examining gene-by-vitamin effects on recurrent stroke risk and gene-by-age effects on change in homocysteine level. © 2015 WILEY PERIODICALS, INC.

  12. Study of charged hadron multiplicities in charged-current neutrino-lead interactions in the OPERA detector

    Energy Technology Data Exchange (ETDEWEB)

    Agafonova, N.; Malgin, A.; Matveev, V.; Ryazhskaya, O.; Shakirianova, I. [INR - Institute for Nuclear Research, Russian Academy of Sciences, Moscow (Russian Federation); Aleksandrov, A.; Buontempo, S.; Consiglio, L.; Tioukov, V.; Voevodina, E. [INFN Sezione di Napoli, Naples (Italy); Anokhina, A.; Dzhatdoev, T.; Podgrudkov, D.; Roganova, T. [Lomonosov Moscow State University, SINP MSU - Skobeltsyn Institute of Nuclear Physics, Moscow (Russian Federation); Aoki, S.; Hara, T.; Mizutani, F.; Ozaki, K.; Shibayama, E.; Takahashi, S. [Kobe University, Kobe (Japan); Ariga, A.; Ereditato, A.; Kreslo, I.; Vuilleumier, J.L. [University of Bern, Laboratory for High Energy Physics (LHEP), Albert Einstein Center for Fundamental Physics, Bern (Switzerland); Ariga, T. [University of Bern, Laboratory for High Energy Physics (LHEP), Albert Einstein Center for Fundamental Physics, Bern (Switzerland); Kyushu University, Faculty of Arts and Science, Fukuoka (Japan); Bertolin, A.; Dusini, S.; Kose, U.; Longhin, A.; Pupilli, F.; Stanco, L. [INFN Sezione di Padova, Padua (Italy); Bodnarchuk, I.; Chukanov, A.; Dmitrievski, S.; Gornushkin, Y.; Sotnikov, A.; Vasina, S. [JINR - Joint Institute for Nuclear Research, Dubna (Russian Federation); Bozza, C.; Grella, G.; Stellacci, S.M. [Dipartimento di Fisica, Universita di Salerno (Italy); ' ' Gruppo Collegato' ' INFN, Fisciano, Salerno (Italy); Brugnera, R.; Garfagnini, A.; Laudisio, F.; Medinaceli, E.; Roda, M.; Sirignano, C. [INFN Sezione di Padova, Padua (Italy); Dipartimento di Fisica e Astronomia, Universita di Padova, Padua (Italy); Buonaura, A.; De Lellis, G.; Di Crescenzo, A.; Galati, G.; Hosseini, B.; Lauria, A.; Montesi, M.C.; Strolin, P. [INFN Sezione di Napoli, Naples (Italy); Dipartimento di Fisica, Universita Federico II di Napoli, Naples (Italy); Chernyavskiy, M.; Gorbunov, S.; Okateva, N.; Shchedrina, T.; Starkov, N. [LPI - Lebedev Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); D' Ambrosio, N.; Di Marco, N.; Schembri, A. [INFN-Laboratori Nazionali del Gran Sasso, Assergi, L' Aquila (Italy); De Serio, M.; Muciaccia, M.T.; Paparella, L.; Pastore, A.; Simone, S. [Dipartimento di Fisica, Universita di Bari, Bari (Italy); INFN Sezione di Bari, Bari (Italy); Amo Sanchez, P. del; Duchesneau, D.; Pessard, H. [LAPP, Universite Savoie Mont Blanc, CNRS/IN2P3, Annecy-le-Vieux (France); Di Ferdinando, D.; Mandrioli, G.; Patrizii, L.; Sirri, G.; Tenti, M. [INFN Sezione di Bologna, Bologna (Italy); Dracos, M.; Jollet, C.; Meregaglia, A. [IPHC, Universite de Strasbourg, CNRS/IN2P3, Strasbourg (France); Ebert, J.; Hagner, C.; Hollnagel, A.; Wonsak, B. [Hamburg University, Hamburg (Germany); Fini, R.A. [INFN Sezione di Bari, Bari (Italy); Fornari, F.; Mauri, N.; Pasqualini, L.; Pozzato, M. [INFN Sezione di Bologna, Bologna (Italy); Dipartimento di Fisica e Astronomia, Universita di Bologna, Bologna (Italy); Fukuda, T.; Hayakawa, T.; Ishiguro, K.; Kitagawa, N.; Komatsu, M.; Miyanishi, M.; Morishima, K.; Naganawa, N.; Naka, T.; Nakamura, M.; Nakano, T.; Niwa, K.; Rokujo, H.; Sato, O.; Shiraishi, T. [Nagoya University, Nagoya (Japan); Gentile, V. [Gran Sasso Science Institute, L' Aquila (Italy); Goldberg, J. [Technion, Department of Physics, Haifa (Israel); Guler, A.M.; Kamiscioglu, M. [METU - Middle East Technical University, Ankara (Turkey); Gustavino, C.; Loverre, P.; Monacelli, P.; Rosa, G. [INFN Sezione di Roma, Rome (Italy); Jakovcic, K.; Ljubicic, A.; Malenica, M. [Rudjer Boskovic Institute, Zagreb (Croatia); Kamiscioglu, C. [METU - Middle East Technical University, Ankara (Turkey); Ankara University, Ankara (Turkey); Kim, S.H.; Park, B.D.; Yoon, C.S. [Gyeongsang National University, Jinju (Korea, Republic of); Klicek, B.; Stipcevic, M. [Center of Excellence for Advanced Materials and Sensing Devices, Ruder Boskovic Institute, Zagreb (Croatia); Kodama, K. [Aichi University of Education, Kariya, Aichi (Japan); Matsuo, T.; Ogawa, S.; Shibuya, H. [Toho University, Funabashi (Japan); Mikado, S. [Nihon University, Narashino, Chiba (Japan); Paoloni, A.; Spinetti, M.; Votano, L. [INFN - Laboratori Nazionali di Frascati, Rome (Italy); Polukhina, N. [LPI - Lebedev Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); Moscow Engineering Physical Institute Moscow, Moscow (Russian Federation); Terranova, F. [Dipartimento di Fisica, Universita di Milano-Bicocca, Milan (Italy); Vilain, P.; Wilquet, G. [IIHE, Universite Libre de Bruxelles, Brussels (Belgium)

    2018-01-15

    The OPERA experiment was designed to search for ν{sub μ} → ν{sub τ} oscillations in appearance mode through the direct observation of tau neutrinos in the CNGS neutrino beam. In this paper, we report a study of the multiplicity of charged particles produced in charged-current neutrino interactions in lead. We present charged hadron average multiplicities, their dispersion and investigate the KNO scaling in different kinematical regions. The results are presented in detail in the form of tables that can be used in the validation of Monte Carlo generators of neutrino-lead interactions. (orig.)

  13. Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

    International Nuclear Information System (INIS)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M.; Ali, Y.; Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O.; Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L.; Anticic, T.; Kadija, K.; Susa, T.; Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M.; Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V.; Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D.; Blondel, A.; Bravar, A.; Debieux, S.; Haesler, A.; Korzenev, A.; Ravonel, M.; Bluemer, J.; Dembinski, H.; Engel, R.; Herve, A.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D.; Bogomilov, M.; Kolev, D.; Tsenov, R.; Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Sadovsky, A.; Cirkovic, M.; Manic, D.; Puzovic, J.; Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D.; Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H.; Dumarchez, J.; Robert, A.; Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A.; Fodor, Z.; Garibov, A.; Gazdzicki, M.; Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A.; Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M.; Kowalik, K.; Rondio, E.; Stepaniak, J.; Laszlo, A.; Marton, K.; Vesztergombi, G.; Lewicki, M.; Naskret, M.; Turko, L.; Marcinek, A.; Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A.; Pavin, M.; Popov, B.A.; Rauch, W.; Roehrich, D.; Rustamov, A.; Zambelli, L.

    2016-01-01

    Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80, and 158 GeV/c beam momentum. Results for the scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations Δ[P_T,N], Σ[P_T,N] and Φ_p__T are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models Epos and Urqmd do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions of the Wounded Nucleon Model. Within the statistical framework the enhanced multiplicity fluctuations in inelastic p+p interactions can be interpreted as due to event-by-event fluctuations of the fireball energy and/or volume. (orig.)

  14. Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

    Energy Technology Data Exchange (ETDEWEB)

    Aduszkiewicz, A.; Dominik, W.; Kuich, M.; Matulewicz, T.; Posiadala, M. [University of Warsaw, Faculty of Physics, Warsaw (Poland); Ali, Y.; Brzychczyk, J.; Larsen, D.; Planeta, R.; Richter-Was, E.; Staszel, P.; Wyszynski, O. [Jagiellonian University, Cracow (Poland); Andronov, E.; Feofilov, G.A.; Igolkin, S.; Kondratiev, V.P.; Seryakov, A.; Vechernin, V.V.; Vinogradov, L. [St. Petersburg State University, St. Petersburg (Russian Federation); Anticic, T.; Kadija, K.; Susa, T. [Ruder Boskovic Institute, Zagreb (Croatia); Antoniou, N.; Christakoglou, P.; Davis, N.; Diakonos, F.; Kapoyannis, A.; Panagiotou, A.D.; Vassiliou, M. [University of Athens, Athens (Greece); Baatar, B.; Bunyatov, S.A.; Kolesnikov, V.I.; Krasnoperov, A.; Lyubushkin, V.V.; Malakhov, A.I.; Matveev, V.; Melkumov, G.L.; Tereshchenko, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Bay, F.; Di Luise, S.; Rubbia, A.; Sgalaberna, D. [ETH Zuerich, Zurich (Switzerland); Blondel, A.; Bravar, A.; Debieux, S.; Haesler, A.; Korzenev, A.; Ravonel, M. [University of Geneva, Geneva (Switzerland); Bluemer, J.; Dembinski, H.; Engel, R.; Herve, A.; Mathes, H.J.; Roth, M.; Szuba, M.; Ulrich, R.; Unger, M.; Veberic, D. [Karlsruhe Institute of Technology, Karlsruhe (Germany); Bogomilov, M.; Kolev, D.; Tsenov, R. [University of Sofia, Faculty of Physics, Sofia (Bulgaria); Busygina, O.; Golubeva, M.; Guber, F.; Ivashkin, A.; Kurepin, A.; Morozov, S.; Petukhov, O.; Sadovsky, A. [Institute for Nuclear Research, Moscow (Russian Federation); Cirkovic, M.; Manic, D.; Puzovic, J. [University of Belgrade, Belgrade (Serbia); Czopowicz, T.; Dynowski, K.; Grebieszkow, K.; Mackowiak-Pawlowska, M.; Maksiak, B.; Sarnecki, R.; Slodkowski, M.; Tefelska, A.; Tefelski, D. [Warsaw University of Technology, Warsaw (Poland); Deveaux, M.; Koziel, M.; Renfordt, R.; Stroebele, H. [University of Frankfurt, Frankfurt (Germany); Dumarchez, J.; Robert, A. [University of Paris VI and VII, LPNHE, Paris (France); Ereditato, A.; Hierholzer, M.; Nirkko, M.; Pistillo, C.; Redij, A. [University of Bern, Bern (Switzerland); Fodor, Z. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); University of Wroclaw, Wroclaw (Poland); Garibov, A. [National Nuclear Research Center, Baku (Azerbaijan); Gazdzicki, M. [University of Frankfurt, Frankfurt (Germany); Jan Kochanowski University in Kielce, Kielce (Poland); Grzeszczuk, A.; Kaptur, E.; Kisiel, J.; Kowalski, S.; Pulawski, S.; Schmidt, K.; Wilczek, A. [University of Silesia, Katowice (Poland); Hasegawa, T.; Kobayashi, T.; Nakadaira, T.; Nishikawa, K.; Sakashita, K.; Sekiguchi, T.; Shibata, M.; Tada, M. [Institute for Particle and Nuclear Studies, KEK, Tsukuba (Japan); Kowalik, K.; Rondio, E.; Stepaniak, J. [National Center for Nuclear Research, Warsaw (Poland); Laszlo, A.; Marton, K.; Vesztergombi, G. [Wigner Research Centre for Physics of the Hungarian Academy of Sciences, Budapest (Hungary); Lewicki, M.; Naskret, M.; Turko, L. [University of Wroclaw, Wroclaw (Poland); Marcinek, A. [Jagiellonian University, Cracow (Poland); University of Wroclaw, Wroclaw (Poland); Mrowczynski, S.; Rybczynski, M.; Seyboth, P.; Stefanek, G.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A. [Jan Kochanowski University in Kielce, Kielce (Poland); Pavin, M. [Ruder Boskovic Institute, Zagreb (Croatia); University of Paris VI and VII, LPNHE, Paris (France); Popov, B.A. [University of Paris VI and VII, LPNHE, Paris (France); Joint Institute for Nuclear Research, Dubna (RU); Rauch, W. [Fachhochschule Frankfurt, Frankfurt (DE); Roehrich, D. [University of Bergen, Bergen (NO); Rustamov, A. [National Nuclear Research Center, Baku (AZ); University of Frankfurt, Frankfurt (DE); Zambelli, L. [University of Paris VI and VII, LPNHE, Paris (FR); Institute for Particle and Nuclear Studies, KEK, Tsukuba (JP)

    2016-11-15

    Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80, and 158 GeV/c beam momentum. Results for the scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations Δ[P{sub T},N], Σ[P{sub T},N] and Φ{sub p{sub T}} are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models Epos and Urqmd do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions of the Wounded Nucleon Model. Within the statistical framework the enhanced multiplicity fluctuations in inelastic p+p interactions can be interpreted as due to event-by-event fluctuations of the fireball energy and/or volume. (orig.)

  15. Multiple parton interactions in deep inelastic ep-scattering at HERA

    Energy Technology Data Exchange (ETDEWEB)

    Osman, Sakar

    2008-12-15

    The production of jets with low transverse momenta (mini-jets) in deep inelastic electron-proton scattering is studied. The analyses uses data taken with the H1 detector at HERA during the years 1999 to 2000. The events are required to contain either at least one leading jet of P{sub T}>5 GeV (the inclusive 1-jet sample) or at least two hard jets where one of them has to be at an angle larger than 140 degrees with respect to the leading jet (inclusive 2-jet sample). Mini-jet multiplicities and their average transverse momenta are presented as a function of Q{sup 2}, in two regions of psuedo-rapidity and for two bins in the hadronic mass, W for the inclusive 1-jet sample. For the inclusive 2-jet sample the results are shown for direct and resolved photon interactions in two bins of W. The results are compared to various QCD based models. A new method for calibrating jet energy measurements up to 10 GeV has been developed and its performance has been studied. (orig.)

  16. A new adaptive control scheme based on the interacting multiple model (IMM) estimation

    International Nuclear Information System (INIS)

    Afshari, Hamed H.; Al-Ani, Dhafar; Habibi, Saeid

    2016-01-01

    In this paper, an Interacting multiple model (IMM) adaptive estimation approach is incorporated to design an optimal adaptive control law for stabilizing an Unmanned vehicle. Due to variations of the forward velocity of the Unmanned vehicle, its aerodynamic derivatives are constantly changing. In order to stabilize the unmanned vehicle and achieve the control objectives for in-flight conditions, one seeks for an adaptive control strategy that can adjust itself to varying flight conditions. In this context, a bank of linear models is used to describe the vehicle dynamics in different operating modes. Each operating mode represents a particular dynamic with a different forward velocity. These models are then used within an IMM filter containing a bank of Kalman filters (KF) in a parallel operating mechanism. To regulate and stabilize the vehicle, a Linear quadratic regulator (LQR) law is designed and implemented for each mode. The IMM structure determines the particular mode based on the stored models and in-flight input-output measurements. The LQR controller also provides a set of controllers; each corresponds to a particular flight mode and minimizes the tracking error. Finally, the ultimate control law is obtained as a weighted summation of all individual controllers whereas weights are obtained using mode probabilities of each operating mode.

  17. Beating Heart Motion Accurate Prediction Method Based on Interactive Multiple Model: An Information Fusion Approach

    Science.gov (United States)

    Xie, Weihong; Yu, Yang

    2017-01-01

    Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG) in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM) estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively “switch” from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly. PMID:29124062

  18. Beating Heart Motion Accurate Prediction Method Based on Interactive Multiple Model: An Information Fusion Approach

    Directory of Open Access Journals (Sweden)

    Fan Liang

    2017-01-01

    Full Text Available Robot-assisted motion compensated beating heart surgery has the advantage over the conventional Coronary Artery Bypass Graft (CABG in terms of reduced trauma to the surrounding structures that leads to shortened recovery time. The severe nonlinear and diverse nature of irregular heart rhythm causes enormous difficulty for the robot to realize the clinic requirements, especially under arrhythmias. In this paper, we propose a fusion prediction framework based on Interactive Multiple Model (IMM estimator, allowing each model to cover a distinguishing feature of the heart motion in underlying dynamics. We find that, at normal state, the nonlinearity of the heart motion with slow time-variant changing dominates the beating process. When an arrhythmia occurs, the irregularity mode, the fast uncertainties with random patterns become the leading factor of the heart motion. We deal with prediction problem in the case of arrhythmias by estimating the state with two behavior modes which can adaptively “switch” from one to the other. Also, we employed the signal quality index to adaptively determine the switch transition probability in the framework of IMM. We conduct comparative experiments to evaluate the proposed approach with four distinguished datasets. The test results indicate that the new proposed approach reduces prediction errors significantly.

  19. Multiple parton interactions in deep inelastic ep-scattering at HERA

    International Nuclear Information System (INIS)

    Osman, Sakar

    2008-12-01

    The production of jets with low transverse momenta (mini-jets) in deep inelastic electron-proton scattering is studied. The analyses uses data taken with the H1 detector at HERA during the years 1999 to 2000. The events are required to contain either at least one leading jet of P T >5 GeV (the inclusive 1-jet sample) or at least two hard jets where one of them has to be at an angle larger than 140 degrees with respect to the leading jet (inclusive 2-jet sample). Mini-jet multiplicities and their average transverse momenta are presented as a function of Q 2 , in two regions of psuedo-rapidity and for two bins in the hadronic mass, W for the inclusive 1-jet sample. For the inclusive 2-jet sample the results are shown for direct and resolved photon interactions in two bins of W. The results are compared to various QCD based models. A new method for calibrating jet energy measurements up to 10 GeV has been developed and its performance has been studied. (orig.)

  20. The Interactive Effect of Multiple Stressors on Crustacean Zooplankton Communities in Montane Lakes

    Science.gov (United States)

    Brittain, Jeffrey T.; Strecker, Angela L.

    2018-02-01

    Nonnative fish introductions have altered thousands of naturally fishless montane lakes, resulting in cascading food web repercussions. Nitrogen deposition has been recognized as an anthropogenic contributor to acidification and eutrophication of freshwater ecosystems, which may affect the abundance and composition of planktonic communities. This study identified responses of zooplankton communities from two lakes (fish present versus absent) in Mount Rainier National Park to manipulations simulating an episodic disturbance of acidification and eutrophication via nitrogen addition in mesocosms. Zooplankton communities from lakes with different food web structure (i.e., fish present or absent) responded differently to the singular effects of acid and nitrogen addition. For instance, zooplankton biomass decreased in the acid treatment of the fishless lake experiment, but increased in response to acid in the fish-present experiment. In contrast, the combination of acid and nitrogen often resulted in weak responses for both lake types, resulting in nonadditive effects, i.e., the net effect of the stressors was in the opposite direction than predicted, which is known as a reversal or "ecological surprise." This experiment demonstrates the difficulty in predicting the interactive effects of multiple stressors on aquatic communities, which may pose significant challenges for habitat restoration through fish removal.

  1. On Thermally Interacting Multiple Boreholes with Variable Heating Strength: Comparison between Analytical and Numerical Approaches

    Directory of Open Access Journals (Sweden)

    Marc A. Rosen

    2012-08-01

    Full Text Available The temperature response in the soil surrounding multiple boreholes is evaluated analytically and numerically. The assumption of constant heat flux along the borehole wall is examined by coupling the problem to the heat transfer problem inside the borehole and presenting a model with variable heat flux along the borehole length. In the analytical approach, a line source of heat with a finite length is used to model the conduction of heat in the soil surrounding the boreholes. In the numerical method, a finite volume method in a three dimensional meshed domain is used. In order to determine the heat flux boundary condition, the analytical quasi-three-dimensional solution to the heat transfer problem of the U-tube configuration inside the borehole is used. This solution takes into account the variation in heating strength along the borehole length due to the temperature variation of the fluid running in the U-tube. Thus, critical depths at which thermal interaction occurs can be determined. Finally, in order to examine the validity of the numerical method, a comparison is made with the results of line source method.

  2. Method and Apparatus for Virtual Interactive Medical Imaging by Multiple Remotely-Located Users

    Science.gov (United States)

    Ross, Muriel D. (Inventor); Twombly, Ian Alexander (Inventor); Senger, Steven O. (Inventor)

    2003-01-01

    A virtual interactive imaging system allows the displaying of high-resolution, three-dimensional images of medical data to a user and allows the user to manipulate the images, including rotation of images in any of various axes. The system includes a mesh component that generates a mesh to represent a surface of an anatomical object, based on a set of data of the object, such as from a CT or MRI scan or the like. The mesh is generated so as to avoid tears, or holes, in the mesh, providing very high-quality representations of topographical features of the object, particularly at high- resolution. The system further includes a virtual surgical cutting tool that enables the user to simulate the removal of a piece or layer of a displayed object, such as a piece of skin or bone, view the interior of the object, manipulate the removed piece, and reattach the removed piece if desired. The system further includes a virtual collaborative clinic component, which allows the users of multiple, remotely-located computer systems to collaboratively and simultaneously view and manipulate the high-resolution, three-dimensional images of the object in real-time.

  3. Multiple tuned mass damper based vibration mitigation of offshore wind turbine considering soil-structure interaction

    Science.gov (United States)

    Hussan, Mosaruf; Sharmin, Faria; Kim, Dookie

    2017-08-01

    The dynamics of jacket supported offshore wind turbine (OWT) in earthquake environment is one of the progressing focuses in the renewable energy field. Soil-structure interaction (SSI) is a fundamental principle to analyze stability and safety of the structure. This study focuses on the performance of the multiple tuned mass damper (MTMD) in minimizing the dynamic responses of the structures objected to seismic loads combined with static wind and wave loads. Response surface methodology (RSM) has been applied to design the MTMD parameters. The analyses have been performed under two different boundary conditions: fixed base (without SSI) and flexible base (with SSI). Two vibration modes of the structure have been suppressed by multi-mode vibration control principle in both cases. The effectiveness of the MTMD in reducing the dynamic response of the structure is presented. The dynamic SSI plays an important role in the seismic behavior of the jacket supported OWT, especially resting on the soft soil deposit. Finally, it shows that excluding the SSI effect could be the reason of overestimating the MTMD performance.

  4. Multiple stressor effects in Chlamydomonas reinhardtii--toward understanding mechanisms of interaction between effects of ultraviolet radiation and chemical pollutants.

    Science.gov (United States)

    Korkaric, Muris; Behra, Renata; Fischer, Beat B; Junghans, Marion; Eggen, Rik I L

    2015-05-01

    The effects of chemical pollutants and environmental stressors, such as ultraviolet radiation (UVR), can interact when organisms are simultaneously exposed, resulting in higher (synergistic) or lower (antagonistic) multiple stressor effects than expected based on the effects of single stressors. Current understanding of interactive effects is limited due to a lack of mechanism-based multiple stressor studies. It has been hypothesized that effect interactions may generally occur if chemical and non-chemical stressors cause similar physiological effects in the organism. To test this hypothesis, we exposed the model green alga Chlamydomonas reinhardtii to combinations of UVR and single chemicals displaying modes of action (MOA) similar or dissimilar to the impact of UVR on photosynthesis. Stressor interactions were analyzed based on the independent action model. Effect interactions were found to depend on the MOA of the chemicals, and also on their concentrations, the exposure time and the measured endpoint. Indeed, only chemicals assumed to cause effects on photosynthesis similar to UVR showed interactions with UVR on photosynthetic yield: synergistic in case of Cd(II) and paraquat and antagonistic in case of diuron. No interaction on photosynthesis was observed for S-metolachlor, which acts dissimilarly to UVR. However, combined effects of S-metolachlor and UVR on algal reproduction were synergistic, highlighting the importance of considering additional MOA of UVR. Possible mechanisms of stressor effect interactions are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Quantitative trait loci and metabolic pathways

    Science.gov (United States)

    McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

    1998-01-01

    The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

  6. Relevance of the hadronic interaction model in the interpretation of multiple muon data as detected with the MACRO experiment

    CERN Document Server

    Ambrosio, M; Aramo, C; Auriemma, G; Baldini, A; Barbarino, G C; Barish, B C; Battistoni, G; Bellotti, R; Bemporad, C; Bernardini, P; Bilokon, H; Bisi, V; Bloise, C; Bower, C; Bussino, S; Cafagna, F; Calicchio, M; Campana, D; Carboni, M; Castellano, M G; Cecchini, S; Cei, F; Chiarella, V; Coutu, S; De Benedictis, L; De Cataldo, G; Dekhissi, H; De Marzo, C; De Mitri, I; De Vincenzi, M; Di Credico, A; Erriquez, O; Favuzzi, C; Forti, C; Fusco, P; Giacomelli, G; Giannini, G; Giglietto, N; Grassi, M; Gray, L; Grillo, A; Guarino, F; Guarnaccia, P; Gustavino, C; Habig, A; Hanson, K; Hawthorne, A; Heinz, R; Iarocci, Enzo; Katsavounidis, E; Kearns, E T; Kyriazopoulou, S; Lamanna, E; Lane, C; Levin, D S; Lipari, P; Longley, N P; Longo, M J; Maaroufi, F; Mancarella, G; Mandrioli, G; Manzoor, S; Margiotta-Neri, A; Marini, A; Martello, D; Marzari-Chiesa, A; Mazziotta, M N; Mazzotta, C; Michael, D G; Mikheyev, S P; Miller, L; Monacelli, P; Montaruli, T; Monteno, M; Mufson, S L; Musser, J; Nicolò, D; Nolty, R; Okada, C; Orth, C; Osteria, G; Palamara, O; Patera, V; Patrizii, L; Pazzi, R; Peck, C W; Petrera, S; Pistilli, P; Popa, V; Rainó, A; Rastelli, A; Reynoldson, J; Ronga, F; Rubizzo, U; Sanzgiri, A; Satriano, C; Satta, L; Scapparone, E; Scholberg, K; Sciubba, A; Serra-Lugaresi, P; Severi, M; Sioli, M; Sitta, M; Spinelli, P; Spinetti, M; Spurio, M; Steinberg, R; Stone, J L; Sulak, Lawrence R; Surdo, A; Tarle, G; Togo, V; Walter, C W; Webb, R

    1999-01-01

    With the aim of discussing the effect of the possible sources of systematic uncertainties in simulation models, the analysis of multiple muon events from the MACRO experiment at Gran Sasso is reviewed. In particular, the predictions $9 from different currently available hadronic interaction models are compared. (9 refs).

  7. Relevance of the hadronic interaction model in the interpretation of multiple muon data as detected with the MACRO experiment

    International Nuclear Information System (INIS)

    Ambrosio, M.; Antolini, R.; Aramo, C.; Auriemma, G.; Baldini, A.; Barbarino, G. C.; Barish, B. C.; Battistoni, G.; Bellotti, R.; Bemporad, C.; Bernardini, P.; Bilokon, H.; Bisi, V.; Bloise, C.; Bower, C.; Bussino, S.; Cafagna, F.; Calicchio, M.; Campana, D.; Carboni, M.; Castellano, M.; Cecchini, S.; Cei, F.; Chiarella, V.; Coutu, S.; De Benedictis, L.; De Cataldo, G.; Dekhissi, H.; De Marzo, C.; De Mitri, I.; De Vincenzi, M.; Di Credico, A.; Erriquez, O.; Favuzzi, C.; Forti, C.; Fusco, P.; Giacomelli, G.; Giannini, G.; Giglietto, N.; Grassi, M.; Gray, L.; Grillo, A.; Guarino, F.; Guarnaccia, P.; Gustavino, C.; Habig, A.; Hanson, K.; Hawthorne, A.; Heinz, R.; Iarocci, E.; Katsavounidis, E.; Kearns, E.; Kyriazopoulou, S.; Lamanna, E.; Lane, C.; Levin, D. S.; Lipari, P.; Longley, N. P.; Longo, M. J.; Maaroufi, F.; Mancarella, G.; Mandrioli, G.; Manzoor, S.; Neri, A. Margiotta; Marini, A.; Martello, D.; Marzari-Chiesa, A.; Mazziotta, M. N.; Mazzotta, C.; Michael, D. G.; Mikheyev, S.; Miller, L.; Monacelli, P.; Montaruli, T.; Monteno, M.; Mufson, S.; Musser, J.; Nicolo, D.; Nolty, R.; Okada, C.; Orth, C.; Osteria, G.; Palamara, O.; Patera, V.; Patrizii, L.; Pazzi, R.; Peck, C. W.; Petrera, S.; Pistilli, P.; Popa, V.; Raino, A.; Rastelli, A.; Reynoldson, J.; Ronga, F.; Rubizzo, U.; Sanzgiri, A.; Satriano, C.; Satta, L.; Scapparone, E.; Scholberg, K.; Sciubba, A.; Serra-Lugaresi, P.; Severi, M.; Sioli, M.; Sitta, M.; Spinelli, P.; Spinetti, M.; Spurio, M.; Steinberg, R.; Stone, J. L.; Sulak, L. R.; Surdo, A.; Tarle, G.; Togo, V.; Walter, C. W.; Webb, R.

    1999-01-01

    With the aim of discussing the effect of the possible sources of systematic uncertainties in simulation models, the analysis of multiple muon events from the MACRO experiment at Gran Sasso is reviewed. In particular, the predictions from different currently available hadronic interaction models are compared

  8. Effects of a Voice Output Communication Aid on Interactions between Support Personnel and an Individual with Multiple Disabilities.

    Science.gov (United States)

    Schepis, Maureen M.; Reid, Dennis H.

    1995-01-01

    A young adult with multiple disabilities (profound mental retardation, spastic quadriplegia, and visual impairment) was provided with a voice output communication aid (VOCA) which allowed communication through synthesized speech. Both educational and residential staff members interacted with the individual more frequently when she had access to…

  9. Multiple Homicide as a Function of Prisonization and Concurrent Instrumental Violence: Testing an Interactive Model--A Research Note

    Science.gov (United States)

    DeLisi, Matt; Walters, Glenn D.

    2011-01-01

    Prisonization (as measured by number of prior incarcerations) and concurrent instrumental offending (as measured by contemporaneous kidnapping, rape, robbery, and burglary offenses) were found to interact in 160 multiple-homicide offenders and 494 single-homicide offenders. Controlling for age, gender, race, criminal history, prior incarcerations,…

  10. Multiplicity distributions of charged hadrons produced in (anti)neutrino-deuterium charged- and neutral-current interactions

    International Nuclear Information System (INIS)

    Jongejans, B.; Tenner, A.G.; Apeldoorn, G.W. van

    1989-01-01

    Results are presented on the multiplicity distributions of charged hadrons produced in νn, νp, antiνn and antiνp charged-current interactions for the hadronic energy range 2GeV ≤ W ≤ 14GeV (corresponding approximately to the neutrino energy range 5GeV ≤ E ≤ 150GeV). The experimental distributions are analysed in terms of binomial distributions. With increasing hadronic energy it is found a smooth transition from an ordinary binomial via Poissonian to the negative binomial function. KNO scaling holds approximately for the multiplicity distribution for the whole phase space. Data on the multiplicity distributions for neutral-current interactions are also presented

  11. Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis.

    Science.gov (United States)

    Disanto, Giulio; Hall, Carolina; Lucas, Robyn; Ponsonby, Anne-Louise; Berlanga-Taylor, Antonio J; Giovannoni, Gavin; Ramagopalan, Sreeram V

    2013-09-01

    Gene-environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92-10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79-2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59-2.59; excess risk due to interaction=3.30, 95%CI=0.47-6.12; attributable proportion due to interaction=45%, 95% CI=22-68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene-environment interactions on both a multiplicative and additive scale.

  12. Seed harvesting by a generalist consumer is context-dependent: Interactive effects across multiple spatial scales

    Science.gov (United States)

    Ostoja, Steven M.; Schupp, Eugene W.; Klinger, Rob

    2013-01-01

    Granivore foraging decisions affect consumer success and determine the quantity and spatial pattern of seed survival. These decisions are influenced by environmental variation at spatial scales ranging from landscapes to local foraging patches. In a field experiment, the effects of seed patch variation across three spatial scales on seed removal by western harvester ants Pogonomyrmex occidentalis were evaluated. At the largest scale we assessed harvesting in different plant communities, at the intermediate scale we assessed harvesting at different distances from ant mounds, and at the smallest scale we assessed the effects of interactions among seed species in local seed neighborhoods on seed harvesting (i.e. resource–consumer interface). Selected seed species were presented alone (monospecific treatment) and in mixture with Bromus tectorum (cheatgrass; mixture treatment) at four distances from P. occidentalis mounds in adjacent intact sagebrush and non-native cheatgrass-dominated communities in the Great Basin, Utah, USA. Seed species differed in harvest, with B. tectorum being least preferred. Large and intermediate scale variation influenced harvest. More seeds were harvested in sagebrush than in cheatgrass-dominated communities (largest scale), and the quantity of seed harvested varied with distance from mounds (intermediate-scale), although the form of the distance effect differed between plant communities. At the smallest scale, seed neighborhood affected harvest, but the patterns differed among seed species considered. Ants harvested fewer seeds from mixed-seed neighborhoods than from monospecific neighborhoods, suggesting context dependence and potential associational resistance. Further, the effects of plant community and distance from mound on seed harvest in mixtures differed from their effects in monospecific treatments. Beyond the local seed neighborhood, selection of seed resources is better understood by simultaneously evaluating removal at

  13. Eye and hand motor interactions with the Symbol Digit Modalities Test in early multiple sclerosis.

    Science.gov (United States)

    Nygaard, Gro O; de Rodez Benavent, Sigrid A; Harbo, Hanne F; Laeng, Bruno; Sowa, Piotr; Damangir, Soheil; Bernhard Nilsen, Kristian; Etholm, Lars; Tønnesen, Siren; Kerty, Emilia; Drolsum, Liv; Inge Landrø, Nils; Celius, Elisabeth G

    2015-11-01

    Eye and hand motor dysfunction may be present early in the disease course of relapsing-remitting multiple sclerosis (RRMS), and can affect the results on visual and written cognitive tests. We aimed to test for differences in saccadic initiation time (SI time) between RRMS patients and healthy controls, and whether SI time and hand motor speed interacted with the written version of the Symbol Digit Modalities Test (wSDMT). Patients with RRMS (N = 44, age 35.1 ± 7.3 years), time since diagnosis < 3 years and matched controls (N = 41, age 33.2 ± 6.8 years) were examined with ophthalmological, neurological and neuropsychological tests, as well as structural MRI (white matter lesion load (WMLL) and brainstem lesions), visual evoked potentials (VEP) and eye-tracker examinations of saccades. SI time was longer in RRMS than controls (p < 0.05). SI time was not related to the Paced Auditory Serial Addition Test (PASAT), WMLL or to the presence of brainstem lesions. 9 hole peg test (9HP) correlated significantly with WMLL (r = 0.58, p < 0.01). Both SI time and 9HP correlated negatively with the results of wSDMT (r = -0.32, p < 0.05, r = -0.47, p < 0.01), but none correlated with the results of PASAT. RRMS patients have an increased SI time compared to controls. Cognitive tests results, exemplified by the wSDMT, may be confounded by eye and hand motor function. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Wave interactions with multiple semi-immersed Jarlan-type perforated breakwaters

    Science.gov (United States)

    Elbisy, Moussa S.

    2017-06-01

    This study examines wave interactions with multiple semi-immersed Jarlan-type perforated breakwaters. A numerical model based on linear wave theory and an eigenfunction expansion method has been developed to study the hydrodynamic characteristics of breakwaters. The numerical results show a good agreement with previous analytical results and experimental data for limiting cases of double partially immersed impermeable walls and double and triple Jarlan-type breakwaters. The wave transmission coefficient C T; reflection coefficient C R, and energy dissipation coefficient C E coefficients and the horizontal wave force exerted on the front and rear walls are examined. The results show that C R reaches the maximum value when B/L = 0.46 n while it is smallest when B/L=0.46 n+0.24 ( n=0, 1, 2,...). An economical triple semi-immersed Jarlan-type perforated breakwater can be designed with B/L = 0.25 and C R and C T ranging from 0.25 to 0.32 by choosing a relative draft d/h of 0.35 and a permeability parameter of the perforated front walls being 0.5 for an incident wave number kh nearly equal to 2.0. The triple semi-immersed Jarlan-type perforated breakwaters with significantly reduced C R, will enhance the structure's wave absorption ability, and lead to smaller wave forces compared with the double one. The proposed model may be used to predict the response of a structure in the preliminary design stage for practical engineering.

  15. Integrating Multiple Geophysical Methods to Quantify Alpine Groundwater- Surface Water Interactions: Cordillera Blanca, Peru

    Science.gov (United States)

    Glas, R. L.; Lautz, L.; McKenzie, J. M.; Baker, E. A.; Somers, L. D.; Aubry-Wake, C.; Wigmore, O.; Mark, B. G.; Moucha, R.

    2016-12-01

    Groundwater- surface water interactions in alpine catchments are often poorly understood as groundwater and hydrologic data are difficult to acquire in these remote areas. The Cordillera Blanca of Peru is a region where dry-season water supply is increasingly stressed due to the accelerated melting of glaciers throughout the range, affecting millions of people country-wide. The alpine valleys of the Cordillera Blanca have shown potential for significant groundwater storage and discharge to valley streams, which could buffer the dry-season variability of streamflow throughout the watershed as glaciers continue to recede. Known as pampas, the clay-rich, low-relief valley bottoms are interfingered with talus deposits, providing a likely pathway for groundwater recharged at the valley edges to be stored and slowly released to the stream throughout the year by springs. Multiple geophysical methods were used to determine areas of groundwater recharge and discharge as well as aquifer geometry of the pampa system. Seismic refraction tomography, vertical electrical sounding (VES), electrical resistivity tomography (ERT), and horizontal-to-vertical spectral ratio (HVSR) seismic methods were used to determine the physical properties of the unconsolidated valley sediments, the depth to saturation, and the depth to bedrock for a representative section of the Quilcayhuanca Valley in the Cordillera Blanca. Depth to saturation and lithological boundaries were constrained by comparing geophysical results to continuous records of water levels and sediment core logs from a network of seven piezometers installed to depths of up to 6 m. Preliminary results show an average depth to bedrock for the study area of 25 m, which varies spatially along with water table depths across the valley. The conceptual model of groundwater flow and storage derived from these geophysical data will be used to inform future groundwater flow models of the area, allowing for the prediction of groundwater

  16. Radar tracking with an interacting multiple model and probabilistic data association filter for civil aviation applications.

    Science.gov (United States)

    Jan, Shau-Shiun; Kao, Yu-Chun

    2013-05-17

    The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC) system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM) system that is enabled by global positioning system (GPS) technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF), is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF), is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.

  17. Radar Tracking with an Interacting Multiple Model and Probabilistic Data Association Filter for Civil Aviation Applications

    Directory of Open Access Journals (Sweden)

    Shau-Shiun Jan

    2013-05-01

    Full Text Available The current trend of the civil aviation technology is to modernize the legacy air traffic control (ATC system that is mainly supported by many ground based navigation aids to be the new air traffic management (ATM system that is enabled by global positioning system (GPS technology. Due to the low receiving power of GPS signal, it is a major concern to aviation authorities that the operation of the ATM system might experience service interruption when the GPS signal is jammed by either intentional or unintentional radio-frequency interference. To maintain the normal operation of the ATM system during the period of GPS outage, the use of the current radar system is proposed in this paper. However, the tracking performance of the current radar system could not meet the required performance of the ATM system, and an enhanced tracking algorithm, the interacting multiple model and probabilistic data association filter (IMMPDAF, is therefore developed to support the navigation and surveillance services of the ATM system. The conventional radar tracking algorithm, the nearest neighbor Kalman filter (NNKF, is used as the baseline to evaluate the proposed radar tracking algorithm, and the real flight data is used to validate the IMMPDAF algorithm. As shown in the results, the proposed IMMPDAF algorithm could enhance the tracking performance of the current aviation radar system and meets the required performance of the new ATM system. Thus, the current radar system with the IMMPDAF algorithm could be used as an alternative system to continue aviation navigation and surveillance services of the ATM system during GPS outage periods.

  18. The influence of the interactions between anthropogenic activities and multiple ecological factors on land surface temperatures of urban forests

    Science.gov (United States)

    Ren, Y.

    2017-12-01

    Context Land surface temperatures (LSTs) spatio-temporal distribution pattern of urban forests are influenced by many ecological factors; the identification of interaction between these factors can improve simulations and predictions of spatial patterns of urban cold islands. This quantitative research requires an integrated method that combines multiple sources data with spatial statistical analysis. Objectives The purpose of this study was to clarify urban forest LST influence interaction between anthropogenic activities and multiple ecological factors using cluster analysis of hot and cold spots and Geogdetector model. We introduced the hypothesis that anthropogenic activity interacts with certain ecological factors, and their combination influences urban forests LST. We also assumed that spatio-temporal distributions of urban forest LST should be similar to those of ecological factors and can be represented quantitatively. Methods We used Jinjiang as a representative city in China as a case study. Population density was employed to represent anthropogenic activity. We built up a multi-source data (forest inventory, digital elevation models (DEM), population, and remote sensing imagery) on a unified urban scale to support urban forest LST influence interaction research. Through a combination of spatial statistical analysis results, multi-source spatial data, and Geogdetector model, the interaction mechanisms of urban forest LST were revealed. Results Although different ecological factors have different influences on forest LST, in two periods with different hot spots and cold spots, the patch area and dominant tree species were the main factors contributing to LST clustering in urban forests. The interaction between anthropogenic activity and multiple ecological factors increased LST in urban forest stands, linearly and nonlinearly. Strong interactions between elevation and dominant species were generally observed and were prevalent in either hot or cold spots

  19. Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis.

    Science.gov (United States)

    Curcic, Marijana; Buha, Aleksandra; Stankovic, Sanja; Milovanovic, Vesna; Bulat, Zorica; Đukić-Ćosić, Danijela; Antonijević, Evica; Vučinić, Slavica; Matović, Vesna; Antonijevic, Biljana

    2017-02-01

    The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200-240g for 28days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE-209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight antagonism

  20. Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats—Multiple factorial regression analysis

    International Nuclear Information System (INIS)

    Curcic, Marijana; Buha, Aleksandra; Stankovic, Sanja; Milovanovic, Vesna; Bulat, Zorica; Đukić-Ćosić, Danijela; Antonijević, Evica; Vučinić, Slavica; Matović, Vesna; Antonijevic, Biljana

    2017-01-01

    The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200–240 g for 28 days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15 mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000 mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE-209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight

  1. Interactive processes link the multiple symptoms of fatigue in sport competition.

    Science.gov (United States)

    Knicker, Axel J; Renshaw, Ian; Oldham, Anthony R H; Cairns, Simeon P

    2011-04-01

    kinematic components. Longer sport events involve pacing strategies, central and peripheral fatigue contributions and elevated RPE. During match play, the work rate can decline late in a match (or tournament) and/or transiently after intense exercise bursts. Repeated sprint ability, agility and leg strength become slightly impaired. Technique outcomes, such as velocity and accuracy for throwing, passing, hitting and kicking, can deteriorate. Physical and subjective changes are both less severe in real rather than simulated sport activities. Little objective evidence exists to support exercise-induced mental lapses during sport. A model depicting mind-body interactions during sport competition shows that the RPE centre-motor cortex-working muscle sequence drives overall performance levels and, hence, fatigue symptoms. The sporting outputs from this sequence can be modulated by interactions with muscle afferent and circulatory feedback, psychological and decision-making inputs. Importantly, compensatory processes exist at many levels to protect against performance decrements. Small changes of putative fatigue factors can also be protective. We show that individual fatigue factors including diminished carbohydrate availability, elevated serotonin, hypoxia, acidosis, hyperkalaemia, hyperthermia, dehydration and reactive oxygen species, each contribute to several fatigue symptoms. Thus, multiple symptoms of fatigue can occur simultaneously and the underlying mechanisms overlap and interact. Based on this understanding, we reinforce the proposal that fatigue is best described globally as an exercise-induced decline of performance as this is inclusive of all viewpoints. © 2011 Adis Data Information BV. All rights reserved.

  2. Biotic interactions modify multiple-stressor effects on juvenile brown trout in an experimental stream food web.

    Science.gov (United States)

    Bruder, Andreas; Salis, Romana K; Jones, Peter E; Matthaei, Christoph D

    2017-09-01

    Agricultural land use results in multiple stressors affecting stream ecosystems. Flow reduction due to water abstraction, elevated levels of nutrients and chemical contaminants are common agricultural stressors worldwide. Concurrently, stream ecosystems are also increasingly affected by climate change. Interactions among multiple co-occurring stressors result in biological responses that cannot be predicted from single-stressor effects (i.e. synergisms and antagonisms). At the ecosystem level, multiple-stressor effects can be further modified by biotic interactions (e.g. trophic interactions). We conducted a field experiment using 128 flow-through stream mesocosms to examine the individual and combined effects of water abstraction, nutrient enrichment and elevated levels of the nitrification inhibitor dicyandiamide (DCD) on survival, condition and gut content of juvenile brown trout and on benthic abundance of their invertebrate prey. Flow velocity reduction decreased fish survival (-12% compared to controls) and condition (-8% compared to initial condition), whereas effects of nutrient and DCD additions and interactions among these stressors were not significant. Negative effects of flow velocity reduction on fish survival and condition were consistent with effects on fish gut content (-25% compared to controls) and abundance of dominant invertebrate prey (-30% compared to controls), suggesting a negative metabolic balance driving fish mortality and condition decline, which was confirmed by structural equation modelling. Fish mortality under reduced flow velocity increased as maximal daily water temperatures approached the upper limit of their tolerance range, reflecting synergistic interactions between these stressors. Our study highlights the importance of indirect stressor effects such as those transferred through trophic interactions, which need to be considered when assessing and managing fish populations and stream food webs in multiple-stressor situations

  3. Multiplicity distributions of charged hadrons in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; Morrison, D.R.O.; Mobayyen, M.M.; Wainstein, S.; Borner, H.P.; Myatt, G.; Radojicic, D.; Burke, S.; Aderholz, M.; Hantke, D.; Katz, U.F.; Kern, J.; Schmitz, N.; Wittek, W.

    1991-10-01

    Using data on νp and anti νp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ∝ 20 000 events with incident ν and ∝ 10 000 events with incident anti ν. The invariant mass W of the total hadronic system ranges from 3 GeV to ∝ 14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for χ 2 /NDF. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling. (orig.)

  4. Multiplicity distributions of charged hadrons in νp and anti νp charged current interactions

    International Nuclear Information System (INIS)

    Jones, G.T.; Jones, R.W.L.; Kennedy, B.W.; Morrison, D.R.O.; Mobayyen, M.M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Katz, U.F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H.P.; Myatt, G.; Radojicic, D.; Burke, S.

    1992-01-01

    Using data on νp and anti νp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ∝20 000 events with incident ν and ∝10 000 events with incident anti ν. The invariant mass W of the total hadronic system ranges from 3 GeV to ∝14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for χ 2 /NDF. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling. (orig.)

  5. Education and health and well-being: direct and indirect effects with multiple mediators and interactions with multiple imputed data in Stata.

    Science.gov (United States)

    Sheikh, Mashhood Ahmed; Abelsen, Birgit; Olsen, Jan Abel

    2017-11-01

    Previous methods for assessing mediation assume no multiplicative interactions. The inverse odds weighting (IOW) approach has been presented as a method that can be used even when interactions exist. The substantive aim of this study was to assess the indirect effect of education on health and well-being via four indicators of adult socioeconomic status (SES): income, management position, occupational hierarchy position and subjective social status. 8516 men and women from the Tromsø Study (Norway) were followed for 17 years. Education was measured at age 25-74 years, while SES and health and well-being were measured at age 42-91 years. Natural direct and indirect effects (NIE) were estimated using weighted Poisson regression models with IOW. Stata code is provided that makes it easy to assess mediation in any multiple imputed dataset with multiple mediators and interactions. Low education was associated with lower SES. Consequently, low SES was associated with being unhealthy and having a low level of well-being. The effect (NIE) of education on health and well-being is mediated by income, management position, occupational hierarchy position and subjective social status. This study contributes to the literature on mediation analysis, as well as the literature on the importance of education for health-related quality of life and subjective well-being. The influence of education on health and well-being had different pathways in this Norwegian sample. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. Multiple-beam laser–plasma interactions in inertial confinement fusion

    Energy Technology Data Exchange (ETDEWEB)

    Myatt, J. F., E-mail: jmya@lle.rochester.edu; Zhang, J.; Maximov, A. V. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623-1299 (United States); Department of Mechanical Engineering, University of Rochester, Rochester, New York 14627 (United States); Short, R. W.; Seka, W.; Edgell, D. H.; Michel, D. T.; Igumenshchev, I. V. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623-1299 (United States); Froula, D. H. [Laboratory for Laser Energetics, University of Rochester, 250 East River Road, Rochester, New York 14623-1299 (United States); Department of Physics and Astronomy, University of Rochester, Rochester, New York 14627-0171 (United States); Hinkel, D. E.; Michel, P.; Moody, J. D. [Lawrence Livermore National Laboratory, P.O. Box 808, Livermore, California 94551-0808 (United States)

    2014-05-15

    The experimental evidence for multiple-beam laser-plasma instabilities of relevance to laser driven inertial confinement fusion at the ignition scale is reviewed, in both the indirect and direct-drive approaches. The instabilities described are cross-beam energy transfer (in both indirectly driven targets on the NIF and in direct-drive targets), multiple-beam stimulated Raman scattering (for indirect-drive), and multiple-beam two-plasmon decay instability (in direct drive). Advances in theoretical understanding and in the numerical modeling of these multiple beam instabilities are presented.

  7. An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome

    NARCIS (Netherlands)

    Fox, J.E.; Bridgham, J.T.; Bovee, T.F.H.; Thornton, J.W.

    2007-01-01

    To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a

  8. Attending to Multiple Visual Streams: Interactions between Location-Based and Category-Based Attentional Selection

    Science.gov (United States)

    Fagioli, Sabrina; Macaluso, Emiliano

    2009-01-01

    Behavioral studies indicate that subjects are able to divide attention between multiple streams of information at different locations. However, it is still unclear to what extent the observed costs reflect processes specifically associated with spatial attention, versus more general interference due the concurrent monitoring of multiple streams of…

  9. Multiplicity and transverse momentum fluctuations in inelastic proton-proton interactions at the CERN Super Proton Synchrotron

    CERN Document Server

    Aduszkiewicz, A.; Andronov, E.; Antićić, T.; Antoniou, N.; Baatar, B.; Bay, F.; Blondel, A.; Blümer, J.; Bogomilov, M.; Bravar, A.; Brzychczyk, J.; Bunyatov, S.A.; Busygina, O.; Christakoglou, P.; Cirković, M.; Czopowicz, T.; Davis, N.; Debieux, S.; Dembinski, H.; Deveaux, M.; Diakonos, F.; Di Luise, S.; Dominik, W.; Dumarchez, J.; Dynowski, K.; Engel, R.; Ereditato, A.; Feofilov, G.A.; Fodor, Z.; Garibov, A.; Gaździcki, M.; Golubeva, M.; Grebieszkow, K.; Grzeszczuk, A.; Guber, F.; Haesler, A.; Hasegawa, T.; Herve, A.; Hierholzer, M.; Igolkin, S.; Ivashkin, A.; Kadija, K.; Kapoyannis, A.; Kaptur, E.; Kisiel, J.; Kobayashi, T.; Kolesnikov, V.I.; Kolev, D.; Kondratiev, V.P.; Korzenev, A.; Kowalik, K.; Kowalski, S.; Koziel, M.; Krasnoperov, A.; Kuich, M.; Kurepin, A.; Larsen, D.; László, A.; Lewicki, M.; Lyubushkin, V.V.; Maćkowiak-Pawłowska, M.; Maksiak, B.; Malakhov, A.I.; Manić, D.; Marcinek, A.; Marton, K.; Mathes, H.J.; Matulewicz, T.; Matveev, V.; Melkumov, G.L.; Morozov, S.; Mrówczyński, S.; Nakadaira, T.; Naskręt, M.; Nirkko, M.; Nishikawa, K.; Panagiotou, A.D.; Pavin, M.; Petukhov, O.; Pistillo, C.; Płaneta, R.; Popov, B.A.; Posiadała, M.; Puławski, S.; Puzović, J.; Rauch, W.; Ravonel, M.; Redij, A.; Renfordt, R.; Richter-Was, E.; Robert, A.; Röhrich, D.; Rondio, E.; Roth, M.; Rubbia, A.; Rustamov, A.; Rybczynski, M.; Sadovsky, A.; Sakashita, K.; Sarnecki, R.; Schmidt, K.; Sekiguchi, T.; Seryakov, A.; Seyboth, P.; Sgalaberna, D.; Shibata, M.; Słodkowski, M.; Staszel, P.; Stefanek, G.; Stepaniak, J.; Ströbele, H.; Šuša, T.; Szuba, M.; Tada, M.; Tefelska, A.; Tefelski, D.; Tereshchenko, V.; Tsenov, R.; Turko, L.; Ulrich, R.; Unger, M.; Vassiliou, M.; Veberič, D.; Vechernin, V.V.; Vesztergombi, G.; Vinogradov, L.; Wilczek, A.; Wlodarczyk, Z.; Wojtaszek-Szwarc, A.; Wyszyński, O.; Zambelli, L.

    2016-11-21

    Measurements of multiplicity and transverse momentum fluctuations of charged particles were performed in inelastic p+p interactions at 20, 31, 40, 80 and 158 GeV/c beam momentum. Results for the scaled variance of the multiplicity distribution and for three strongly intensive measures of multiplicity and transverse momentum fluctuations \\$\\Delta[P_{T},N]\\$, \\$\\Sigma[P_{T},N]\\$ and \\$\\Phi_{p_T}\\$ are presented. For the first time the results on fluctuations are fully corrected for experimental biases. The results on multiplicity and transverse momentum fluctuations significantly deviate from expectations for the independent particle production. They also depend on charges of selected hadrons. The string-resonance Monte Carlo models EPOS and UrQMD do not describe the data. The scaled variance of multiplicity fluctuations is significantly higher in inelastic p+p interactions than in central Pb+Pb collisions measured by NA49 at the same energy per nucleon. This is in qualitative disagreement with the predictions ...

  10. Computational Study of Shock/Plume Interactions Between Multiple Jets in Supersonic Crossflow

    Science.gov (United States)

    Tylczak, Erik B.

    The interaction of multiple jets in supersonic crossflow is simulated using hybrid Reynolds- Averaged Navier Stokes and Large Eddy Simulation turbulence models. The blockage of a jet generates a curved bow shock, and in multi-jet flows, each shock impinges on the other fuel plumes. The curved nature of each shock generates vorticity directly, and the impingement of each shock on the vortical structures within the adjacent fuel plumes strengthens vortical structures already present. These stirring motions are the major driver of fuel-air mixing, and so mixing enhancement is predicted to occur in multi-port configurations. The primary geometry considered is that of the combustion duct at the Calspan- University of Buffalo Research Center 48" Large Energy National Shock (LENS) tunnel. This geometry was developed to be representative of the geometry and flow physics of the Flight 2 test vehicle of the Hypersonic International Flight Research Experimenta- tion Program (HiFIRE-2). This geometry takes the form of a symmetric pair of external compression ramps that feed an isolator of approximately 4" x 1" cross-section. Nine interdigitated flush-wall injectors, four on one wall and five on the other, inject hydrogen at an angle of 30 degrees to the freestream. Two freestream flow conditions are consid- ered: approximately Mach 7.2 at a static temperature of 214K and a density of 0.039 kg/m3 for the five-injector case, and approximately Mach 8.9 at a static temperature of 167K and density of 0.014 kg/m 3 for the nine-injector case. Validation computations are performed on a single-port experiment with an imposed shock wave. Unsteady calculations are performed on five-port and nine-port configura- tions, and the five-port configuration is compared to calculations performed with only a single active port on the same geometry. Analysis of statistical data demonstrates enhanced mixing in the multi-port configurations in regions where shock impingement occurs.

  11. Numerical Investigation of Multiple-, Interacting-Scale Variable-Density Ground Water Flow Systems

    Science.gov (United States)

    Cosler, D.; Ibaraki, M.

    2004-12-01

    The goal of our study is to elucidate the nonlinear processes that are important for multiple-, interacting-scale flow and solute transport in subsurface environments. In particular, we are focusing on the influence of small-scale instability development on variable-density ground water flow behavior in large-scale systems. Convective mixing caused by these instabilities may mix the fluids to a greater extent than would be the case with classical, Fickian dispersion. Most current numerical schemes for interpreting field-scale variable-density flow systems do not explicitly account for the complexities caused by small-scale instabilities and treat such processes as "lumped" Fickian dispersive mixing. Such approaches may greatly underestimate the mixing behavior and misrepresent the overall large-scale flow field dynamics. The specific objectives of our study are: (i) to develop an adaptive (spatial and temporal scales) three-dimensional numerical model that is fully capable of simulating field-scale variable-density flow systems with fine resolution (~1 cm); and (ii) to evaluate the importance of scale-dependent process interactions by performing a series of simulations on different problem scales ranging from laboratory experiments to field settings, including an aquifer storage and freshwater recovery (ASR) system similar to those planned for the Florida Everglades and in-situ contaminant remediation systems. We are examining (1) methods to create instabilities in field-scale systems, (2) porous media heterogeneity effects, and (3) the relation between heterogeneity characteristics (e.g., permeability variance and correlation length scales) and the mixing scales that develop for varying degrees of unstable stratification. Applications of our work include the design of new water supply and conservation measures (e.g., ASR systems), assessment of saltwater intrusion problems in coastal aquifers, and the design of in-situ remediation systems for aquifer restoration

  12. Evaluation of white spot syndrome virus variable DNA loci as molecular markers of virus spread at intermediate spatiotemporal scales

    NARCIS (Netherlands)

    Bui Thi Minh Dieu,; Marks, H.; Zwart, M.P.; Vlak, J.M.

    2010-01-01

    Variable genomic loci have been employed in a number of molecular epidemiology studies of white spot syndrome virus (WSSV), but it is unknown which loci are suitable molecular markers for determining WSSV spread on different spatiotemporal scales. Although previous work suggests that multiple

  13. Effects of multiple enzyme–substrate interactions in basic units of cellular signal processing

    International Nuclear Information System (INIS)

    Seaton, D D; Krishnan, J

    2012-01-01

    Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme–substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme–substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein–protein interactions are important in determining the signalling properties of enzymatic signalling pathways. (paper)

  14. The validity of the negative binomial multiplicity distribution in the case of the relativistic nucleus-nucleus interaction

    International Nuclear Information System (INIS)

    Ghosh, D.; Mukhopadhyay, A.; Ghosh, A.; Roy, J.

    1989-01-01

    This letter presents new data on the multiplicity distribution of charged secondaries in 24 Mg interactions with AgBr at 4.5 GeV/c per nucleon. The validity of the negative binomial distribution (NBD) is studied. It is observed that the data can be well parametrized in terms of the NBD law for the whole phase space and also for different pseudo-rapidity bins. A comparison of different parameters with those in the case of h-h interactions reveals some interesting results, the implications of which are discussed. (orig.)

  15. Multiple Parton Interactions in p$bar{p}$ Collisions in D0 Experiment at the Tevatron Collider

    Energy Technology Data Exchange (ETDEWEB)

    Golovanov, Georgy [Joint Inst. for Nuclear Research (JINR), Dubna (Russia)

    2016-01-01

    The thesis is devoted to the study of processes with multiple parton interactions (MPI) in a ppbar collision collected by D0 detector at the Fermilab Tevatron collider at sqrt(s) = 1.96 TeV. The study includes measurements of MPI event fraction and effective cross section, a process-independent parameter related to the effective interaction region inside the nucleon. The measurements are done using events with a photon and three hadronic jets in the final state. The measured effective cross section is used to estimate background from MPI for WH production at the Tevatron energy

  16. Multiple mobility edges in a 1D Aubry chain with Hubbard interaction in presence of electric field: Controlled electron transport

    Science.gov (United States)

    Saha, Srilekha; Maiti, Santanu K.; Karmakar, S. N.

    2016-09-01

    Electronic behavior of a 1D Aubry chain with Hubbard interaction is critically analyzed in presence of electric field. Multiple energy bands are generated as a result of Hubbard correlation and Aubry potential, and, within these bands localized states are developed under the application of electric field. Within a tight-binding framework we compute electronic transmission probability and average density of states using Green's function approach where the interaction parameter is treated under Hartree-Fock mean field scheme. From our analysis we find that selective transmission can be obtained by tuning injecting electron energy, and thus, the present model can be utilized as a controlled switching device.

  17. arXiv Proceedings of the Sixth International Workshop on Multiple Partonic Interactions at the Large Hadron Collider

    CERN Document Server

    Astalos, R.; Bartalini, P.; Belyaev, I.; Bierlich, Ch.; Blok, B.; Buckley, A.; Ceccopieri, F.A.; Cherednikov, I.; Christiansen, J.R.; Ciangottini, D.; Deak, M.; Ducloue, B.; Field, R.; Gaunt, J.R.; Golec-Biernat, K.; Goerlich, L.; Grebenyuk, A.; Gueta, O.; Gunnellini, P.; Helenius, I.; Jung, H.; Kar, D.; Kepka, O.; Klusek-Gawenda, M.; Knutsson, A.; Kotko, P.; Krasny, M.W.; Kutak, K.; Lewandowska, E.; Lykasov, G.; Maciula, R.; Moraes, A.M.; Martin, T.; Mitsuka, G.; Motyka, L.; Myska, M.; Otwinowski, J.; Pierog, T.; Pleskot, V.; Rinaldi, M.; Schafer, W.; Siodmok, A.; Sjostrand, T.; Snigirev, A.; Stasto, A.; Staszewski, R.; Stebel, T.; Strikman, M.; Szczurek, A.; Treleani, D.; Trzebinski, M.; van Haevermaet, H.; van Hameren, A.; van Mechelen, P.; Waalewijn, W.; Wang, W.Y.; MPI@LHC 2014

    2014-01-01

    Multiple Partonic Interactions are often crucial for interpreting results obtained at the Large Hadron Collider (LHC). The quest for a sound understanding of the dynamics behind MPI - particularly at this time when the LHC is due to start its "Run II" operations - has focused the aim of this workshop. MPI@LHC2014 concentrated mainly on the phenomenology of LHC measurements whilst keeping in perspective those results obtained at previous hadron colliders. The workshop has also debated some of the state-of-the-art theoretical considerations and the modeling of MPI in Monte Carlo event generators. The topics debated in the workshop included: Phenomenology of MPI processes and multiparton distributions; Considerations for the description of MPI in Quantum Chromodynamics (QCD); Measuring multiple partonic interactions; Experimental results on inelastic hadronic collisions: underlying event, minimum bias, forward energy flow; Monte Carlo generator development and tuning; Connections with low-x phenomena, diffractio...

  18. An Interactive Platform to Visualize Data-Driven Clinical Pathways for the Management of Multiple Chronic Conditions.

    Science.gov (United States)

    Zhang, Yiye; Padman, Rema

    2017-01-01

    Patients with multiple chronic conditions (MCC) pose an increasingly complex health management challenge worldwide, particularly due to the significant gap in our understanding of how to provide coordinated care. Drawing on our prior research on learning data-driven clinical pathways from actual practice data, this paper describes a prototype, interactive platform for visualizing the pathways of MCC to support shared decision making. Created using Python web framework, JavaScript library and our clinical pathway learning algorithm, the visualization platform allows clinicians and patients to learn the dominant patterns of co-progression of multiple clinical events from their own data, and interactively explore and interpret the pathways. We demonstrate functionalities of the platform using a cluster of 36 patients, identified from a dataset of 1,084 patients, who are diagnosed with at least chronic kidney disease, hypertension, and diabetes. Future evaluation studies will explore the use of this platform to better understand and manage MCC.

  19. Salinity tolerance loci revealed in rice using high-throughput non-invasive phenotyping

    KAUST Repository

    Al-Tamimi, Nadia Ali; Brien, Chris; Oakey, Helena; Berger, Bettina; Saade, Stephanie; Ho, Yung Shwen; Schmö ckel, Sandra M.; Tester, Mark A.; Negrã o, Só nia

    2016-01-01

    High-throughput phenotyping produces multiple measurements over time, which require new methods of analyses that are flexible in their quantification of plant growth and transpiration, yet are computationally economic. Here we develop such analyses and apply this to a rice population genotyped with a 700k SNP high-density array. Two rice diversity panels, indica and aus, containing a total of 553 genotypes, are phenotyped in waterlogged conditions. Using cubic smoothing splines to estimate plant growth and transpiration, we identify four time intervals that characterize the early responses of rice to salinity. Relative growth rate, transpiration rate and transpiration use efficiency (TUE) are analysed using a new association model that takes into account the interaction between treatment (control and salt) and genetic marker. This model allows the identification of previously undetected loci affecting TUE on chromosome 11, providing insights into the early responses of rice to salinity, in particular into the effects of salinity on plant growth and transpiration.

  20. Salinity tolerance loci revealed in rice using high-throughput non-invasive phenotyping

    KAUST Repository

    Al-Tamimi, Nadia Ali

    2016-11-17

    High-throughput phenotyping produces multiple measurements over time, which require new methods of analyses that are flexible in their quantification of plant growth and transpiration, yet are computationally economic. Here we develop such analyses and apply this to a rice population genotyped with a 700k SNP high-density array. Two rice diversity panels, indica and aus, containing a total of 553 genotypes, are phenotyped in waterlogged conditions. Using cubic smoothing splines to estimate plant growth and transpiration, we identify four time intervals that characterize the early responses of rice to salinity. Relative growth rate, transpiration rate and transpiration use efficiency (TUE) are analysed using a new association model that takes into account the interaction between treatment (control and salt) and genetic marker. This model allows the identification of previously undetected loci affecting TUE on chromosome 11, providing insights into the early responses of rice to salinity, in particular into the effects of salinity on plant growth and transpiration.

  1. Dominant Epistasis Between Two Quantitative Trait Loci Governing Sporulation Efficiency in Yeast Saccharomyces cerevisiae

    Science.gov (United States)

    Bergman, Juraj; Mitrikeski, Petar T.

    2015-01-01

    Summary Sporulation efficiency in the yeast Saccharomyces cerevisiae is a well-established model for studying quantitative traits. A variety of genes and nucleotides causing different sporulation efficiencies in laboratory, as well as in wild strains, has already been extensively characterised (mainly by reciprocal hemizygosity analysis and nucleotide exchange methods). We applied a different strategy in order to analyze the variation in sporulation efficiency of laboratory yeast strains. Coupling classical quantitative genetic analysis with simulations of phenotypic distributions (a method we call phenotype modelling) enabled us to obtain a detailed picture of the quantitative trait loci (QTLs) relationships underlying the phenotypic variation of this trait. Using this approach, we were able to uncover a dominant epistatic inheritance of loci governing the phenotype. Moreover, a molecular analysis of known causative quantitative trait genes and nucleotides allowed for the detection of novel alleles, potentially responsible for the observed phenotypic variation. Based on the molecular data, we hypothesise that the observed dominant epistatic relationship could be caused by the interaction of multiple quantitative trait nucleotides distributed across a 60--kb QTL region located on chromosome XIV and the RME1 locus on chromosome VII. Furthermore, we propose a model of molecular pathways which possibly underlie the phenotypic variation of this trait. PMID:27904371

  2. Observed Sensitivity during Family Interactions and Cumulative Risk: A Study of Multiple Dyads per Family

    Science.gov (United States)

    Browne, Dillon T.; Leckie, George; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M.

    2016-01-01

    The present study sought to investigate the family, individual, and dyad-specific contributions to observed cognitive sensitivity during family interactions. Moreover, the influence of cumulative risk on sensitivity at the aforementioned levels of the family was examined. Mothers and 2 children per family were observed interacting in a round robin…

  3. A knowledge-driven interaction analysis reveals potential neurodegenerative mechanism of multiple sclerosis susceptibility

    NARCIS (Netherlands)

    Bush, W.S.; McCauley, J.L.; DeJager, P.L.; Dudek, S.M.; Hafler, D.A.; Gibson, R.A.; Matthews, P.M.; Kappos, L.; Naegelin, Y.; Polman, C.H.; Hauser, S.L.; Oksenberg, J.; Haines, J.L.; Ritchie, M.D.

    2011-01-01

    Gene-gene interactions are proposed as an important component of the genetic architecture of complex diseases, and are just beginning to be evaluated in the context of genome-wide association studies (GWAS). In addition to detecting epistasis, a benefit to interaction analysis is that it also

  4. Multiple forms of stakeholder interaction in environmental management: business arguments regarding differences in stakeholder relationships

    OpenAIRE

    Onkila, Tiina

    2011-01-01

    This study describes and interprets differences in stakeholder interaction as rhetorically constructed in environmental reports and in interviews with environmental managers. It also interprets the role of the natural environment among stakeholders, and discusses how that role is justified or not justified. The study focuses in a business perspective on stakeholder interaction in environmental management. Characteristically, stakeholder studies of environmental management have concentrated on...

  5. Genetic Risk by Experience Interaction for Childhood Internalizing Problems: Converging Evidence across Multiple Methods

    Science.gov (United States)

    Vendlinski, Matthew K.; Lemery-Chalfant, Kathryn; Essex, Marilyn J.; Goldsmith, H. Hill

    2011-01-01

    Background: Identifying how genetic risk interacts with experience to predict psychopathology is an important step toward understanding the etiology of mental health problems. Few studies have examined genetic risk by experience interaction (GxE) in the development of childhood psychopathology. Methods: We used both co-twin and parent mental…

  6. On the multiplicity of secondary particles in the interactions of hadrons with nuclei

    International Nuclear Information System (INIS)

    Babecki, J.

    1976-01-01

    An analysis of the interactions of hadrons at different primary energies (from a few GeV to some thousands of GeV) with nuclei of various mass numbers A was made. Experimental data were compared with the prediction sof a simple model of non-interacting fireballs. (author)

  7. Impedance-Based Harmonic Instability Assessment in Multiple Electric Trains and Traction Network Interaction System

    DEFF Research Database (Denmark)

    Tao, Haidong; Hu, Haitao; Wang, Xiongfei

    2018-01-01

    This paper presents an impedance-based method to systematically investigate the interaction between multi-train and traction networks, focusing on evaluating the harmonic instability problems. Firstly, the interaction mechanism of multi-train and the traction network is represented as a feedback ...

  8. Evaluation of multiple intelligences in children aged 7 to 11 years through the implementation of an interactive software

    OpenAIRE

    Rebolledo Rodríguez, Rigel A.; Samaniego González, Euclides

    2017-01-01

    This document describes the evaluation project of multiple intelligences in children aged 7 to 11 years through the implementation of an interactive software, developed on Android for tablets, allowing parents, teachers, tutors, psy-chologists or other responsible adult, identifying the different types of intelligences that have children in order to know each other and develop their skills and their future potential. Similarly, research was developed to evaluate the effective-ness of the t...

  9. Energy, target, projectile and multiplicity dependences of intermittency behaviour in high energy O(Si,S) induced interactions

    International Nuclear Information System (INIS)

    Adamovich, M.I.; Alexandrov, Y.A.; Chernyavski, M.M.; Gerassimov, S.G.; Kharlamov, S.P.; Larionova, V.G.; Maslennikova, N.V.; Orlova, G.I.; Peresadko, N.G.; Salmanova, N.A.; Tretyakova, M.I.; Ameeva, Z.U.; Andreeva, N.P.; Anzon, Z.V.; Bubnov, V.I.; Chasnikov, I.Y.; Eligbaeva, G.Z.; Eremenko, G.Z.; Gaitinov, A.S.; Kalyachkina, G.S.; Kanygina, E.K.; Skakhova, C.I.; Bhalla, K.B.; Kumar, V.; Lal, P.; Lokanathan, S.; Mookerjee, S.; Raniwala, R.; Raniwala, S.; Burnett, T.H.; Grote, J.; Koss, T.; Lord, J.; Skelding, D.; Strausz, S.C.; Wilkes, R.J.; Cai, X.; Huang, H.; Liu, L.S.; Qian, W.Y.; Wang, H.Q.; Zhou, D.C.; Zhou, J.C.; Chernova, L.P.; Gadzhieva, S.I.; Gulamov, K.G.; Kadyrov, F.G.; Lukicheva, N.S.; Navotny, V.S.; Svechnikova, L.N.; Friedlander, E.M.; Heckman, H.H.; Lindstrom, P.J.; Garpman, S.; Jakobsson, B.; Otterlund, I.; Persson, S.; Soederstroem, K.; Stenlund, E.; Judek, B.; Nasyrov, S.H.; Petrov, N.V.; Xu, G.F.; Zheng, P.Y.

    1991-01-01

    Fluctuations of charged particles in high energy oxygen, silicon and sulphur induced interactions are investigated with the method of scaled factorial moments. It is found that for decreasing bin size down to δη∝0.1 the EMU01 data exhibits intermittent behaviour. The intermittency indexes are found to decrease with increasing incident energy and multiplicity and to increase with increasing target mass. It seems also to increase as the projectile mass increases. (orig.)

  10. On the dependance of the ''normalized multiplicity'' of particles produced in proton-nucleus interactions on the primary energy

    International Nuclear Information System (INIS)

    Babecki, J.

    1975-01-01

    The mean ''normalized multiplicities'' of particles produced in p-nucleus interactions: with the leading particles (R 1 ) and without them (R 2 ) were calculated from the emulsion data. The independence of R 2 of the primary energy E 0 were stated in very wide interval of E 0 from 6.2 to thousands of GeV. R 2 is approximately equal to the mean number of collisions of the primary particle in the nucleus. (author)

  11. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    DEFF Research Database (Denmark)

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A

    2016-01-01

    . Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching PFTO....... Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown...

  12. Relevancies of multiple-interaction events and signal-to-noise ratio for Anger-logic based PET detector designs

    Science.gov (United States)

    Peng, Hao

    2015-10-01

    A fundamental challenge for PET block detector designs is to deploy finer crystal elements while limiting the number of readout channels. The standard Anger-logic scheme including light sharing (an 8 by 8 crystal array coupled to a 2×2 photodetector array with an optical diffuser, multiplexing ratio: 16:1) has been widely used to address such a challenge. Our work proposes a generalized model to study the impacts of two critical parameters on spatial resolution performance of a PET block detector: multiple interaction events and signal-to-noise ratio (SNR). The study consists of the following three parts: (1) studying light output profile and multiple interactions of 511 keV photons within crystal arrays of different crystal widths (from 4 mm down to 1 mm, constant height: 20 mm); (2) applying the Anger-logic positioning algorithm to investigate positioning/decoding uncertainties (i.e., "block effect") in terms of peak-to-valley ratio (PVR), with light sharing, multiple interactions and photodetector SNR taken into account; and (3) studying the dependency of spatial resolution on SNR in the context of modulation transfer function (MTF). The proposed model can be used to guide the development and evaluation of a standard Anger-logic based PET block detector including: (1) selecting/optimizing the configuration of crystal elements for a given photodetector SNR; and (2) predicting to what extent additional electronic multiplexing may be implemented to further reduce the number of readout channels.

  13. M-GCAT: interactively and efficiently constructing large-scale multiple genome comparison frameworks in closely related species

    Directory of Open Access Journals (Sweden)

    Messeguer Xavier

    2006-10-01

    Full Text Available Abstract Background Due to recent advances in whole genome shotgun sequencing and assembly technologies, the financial cost of decoding an organism's DNA has been drastically reduced, resulting in a recent explosion of genomic sequencing projects. This increase in related genomic data will allow for in depth studies of evolution in closely related species through multiple whole genome comparisons. Results To facilitate such comparisons, we present an interactive multiple genome comparison and alignment tool, M-GCAT, that can efficiently construct multiple genome comparison frameworks in closely related species. M-GCAT is able to compare and identify highly conserved regions in up to 20 closely related bacterial species in minutes on a standard computer, and as many as 90 (containing 75 cloned genomes from a set of 15 published enterobacterial genomes in an hour. M-GCAT also incorporates a novel comparative genomics data visualization interface allowing the user to globally and locally examine and inspect the conserved regions and gene annotations. Conclusion M-GCAT is an interactive comparative genomics tool well suited for quickly generating multiple genome comparisons frameworks and alignments among closely related species. M-GCAT is freely available for download for academic and non-commercial use at: http://alggen.lsi.upc.es/recerca/align/mgcat/intro-mgcat.html.

  14. I just ran a thousand analyses: benefits of multiple testing in understanding equivocal evidence on gene-environment interactions.

    Directory of Open Access Journals (Sweden)

    Vera E Heininga

    Full Text Available In psychiatric genetics research, the volume of ambivalent findings on gene-environment interactions (G x E is growing at an accelerating pace. In response to the surging suspicions of systematic distortion, we challenge the notion of chance capitalization as a possible contributor. Beyond qualifying multiple testing as a mere methodological issue that, if uncorrected, leads to chance capitalization, we advance towards illustrating the potential benefits of multiple tests in understanding equivocal evidence in genetics literature.We focused on the interaction between the serotonin-transporter-linked promotor region (5-HTTLPR and childhood adversities with regard to depression. After testing 2160 interactions with all relevant measures available within the Dutch population study of adolescents TRAILS, we calculated percentages of significant (p < .05 effects for several subsets of regressions. Using chance capitalization (i.e. overall significance rate of 5% alpha and randomly distributed findings as a competing hypothesis, we expected more significant effects in the subsets of regressions involving: 1 interview-based instead of questionnaire-based measures; 2 abuse instead of milder childhood adversities; and 3 early instead of later adversities. Furthermore, we expected equal significance percentages across 4 male and female subsamples, and 5 various genotypic models of 5-HTTLPR.We found differences in the percentages of significant interactions among the subsets of analyses, including those regarding sex-specific subsamples and genetic modeling, but often in unexpected directions. Overall, the percentage of significant interactions was 7.9% which is only slightly above the 5% that might be expected based on chance.Taken together, multiple testing provides a novel approach to better understand equivocal evidence on G x E, showing that methodological differences across studies are a likely reason for heterogeneity in findings - but chance

  15. Interaction cross sections and pions minus multiplicities on nucleus-nucleus collisions at 4.2 GeV/c per nucleon

    International Nuclear Information System (INIS)

    Angelov, N.; Ahababyan, N.; Anoshin, A.I.

    1979-01-01

    Data are presented on inelastic cross sections and multiplicities of pions minus produced on collisions of protons, deuterons, helium-4 and carbon-12 nuclei at 4.2 GeV/c per nucleon in the propane bubble chamber witn tantalum and carbon plates. Average multiplicities and dispersions of multiplicity distributions are compared with those in nucleon-nucleon interactions. Deviation of C-Ta interaction data from universal dependence of dispersion on multiplicity is observed. Pion multiplicities are found proportional to the number of nucleons from incident nucleus which interacted in the target. The results are not in contradiction with the assumption that nucleons from the incident nucleus interact independently in the target. For C-Ta interactions the average radius of the pion emission volume has been determined by the interference method to be r=(3.3+-0.6) fm

  16. Seismic Analysis of Intake Towers Considering Multiple-Support Excitation and Soil-Structure Interaction Effects

    National Research Council Canada - National Science Library

    Vidot, Aidcer

    2004-01-01

    .... The other effect examined is the soil-structure interaction. First, a direct approach based on a finite element model of the tower, bridge, and dam with the earthquake motion applied at the bedrock is used...

  17. Charged-particle multiplicities in pp interactions measured with the ATLAS detector at the LHC

    CERN Document Server

    Aad, G.; Abdallah, J.; Abdelalim, A.A.; Abdesselam, A.; Abdinov, O.; Abi, B.; Abolins, M.; Abramowicz, H.; Abreu, H.; Acerbi, E.; Acharya, B.S.; Ackers, M.; Adams, D.L.; Addy, T.N.; Adelman, J.; Aderholz, M.; Adomeit, S.; Adragna, P.; Adye, T.; Aefsky, S.; Aguilar-Saavedra, J.A.; Aharrouche, M.; Ahlen, S.P.; Ahles, F.; Ahmad, A.; Ahsan, M.; Aielli, G.; Akdogan, T.; Akesson, T.P.A.; Akimoto, G.; Akimov, A.V.; Alam, M.S.; Alam, M.A.; Albrand, S.; Aleksa, M.; Aleksandrov, I.N.; Aleppo, M.; Alessandria, F.; Alexa, C.; Alexander, G.; Alexandre, G.; Alexopoulos, T.; Alhroob, M.; Aliev, M.; Alimonti, G.; Alison, J.; Aliyev, M.; Allport, P.P.; Allwood-Spiers, S.E.; Almond, J.; Aloisio, A.; Alon, R.; Alonso, A.; Alonso, J.; Alviggi, M.G.; Amako, K.; Amaral, P.; Amelung, C.; Ammosov, V.V.; Amorim, A.; Amoros, G.; Amram, N.; Anastopoulos, C.; Andeen, T.; Anders, C.F.; Anderson, K.J.; Andreazza, A.; Andrei, V.; Andrieux, M-L.; Anduaga, X.S.; Angerami, A.; Anghinolfi, F.; Anjos, N.; Annovi, A.; Antonaki, A.; Antonelli, M.; Antonelli, S.; Antos, J.; Anulli, F.; Aoun, S.; Aperio Bella, L.; Apolle, R.; Arabidze, G.; Aracena, I.; Arai, Y.; Arce, A.T.H.; Archambault, J.P.; Arfaoui, S.; Arguin, J-F.; Arik, E.; Arik, M.; Armbruster, A.J.; Arms, K.E.; Armstrong, S.R.; Arnaez, O.; Arnault, C.; Artamonov, A.; Artoni, G.; Arutinov, D.; Asai, S.; Silva, J.; Asfandiyarov, R.; Ask, S.; Asman, B.; Asquith, L.; Assamagan, K.; Astbury, A.; Astvatsatourov, A.; Atoian, G.; Aubert, B.; Auerbach, B.; Auge, E.; Augsten, K.; Aurousseau, M.; Austin, N.; Avramidou, R.; Axen, D.; Ay, C.; Azuelos, G.; Azuma, Y.; Baak, M.A.; Baccaglioni, G.; Bacci, C.; Bach, A.M.; Bachacou, H.; Bachas, K.; Bachy, G.; Backes, M.; Badescu, E.; Bagnaia, P.; Bahinipati, S.; Bai, Y.; Bailey, D.C.; Bain, T.; Baines, J.T.; Baker, O.K.; Baker, S.; Baltasar Dos Santos Pedrosa, F.; Banas, E.; Banerjee, P.; Banerjee, Sw.; Banfi, D.; Bangert, A.; Bansal, V.; Bansil, H.S.; Barak, L.; Baranov, S.P.; Barashkou, A.; Barbaro Galtieri, A.; Barber, T.; Barberio, E.L.; Barberis, D.; Barbero, M.; Bardin, D.Y.; Barillari, T.; Barisonzi, M.; Barklow, T.; Barlow, N.; Barnett, B.M.; Barnett, R.M.; Baroncelli, A.; Barr, A.J.; Barreiro, F.; Barreiro Guimaraes da Costa, J.; Barrillon, P.; Bartoldus, R.; Barton, A.E.; Bartsch, D.; Bates, R.L.; Batkova, L.; Batley, J.R.; Battaglia, A.; Battistin, M.; Battistoni, G.; Bauer, F.; Bawa, H.S.; Beare, B.; Beau, T.; Beauchemin, P.H.; Beccherle, R.; Bechtle, P.; Beck, H.P.; Beckingham, M.; Becks, K.H.; Beddall, A.J.; Beddall, A.; Bednyakov, V.A.; Bee, C.; Begel, M.; Behar Harpaz, S.; Behera, P.K.; Beimforde, M.; Belanger-Champagne, C.; Bell, P.J.; Bell, W.H.; Bella, G.; Bellagamba, L.; Bellina, F.; Bellomo, G.; Bellomo, M.; Belloni, A.; Belotskiy, K.; Beltramello, O.; Ben Ami, S.; Benary, O.; Benchekroun, D.; Benchouk, C.; Bendel, M.; Benedict, B.H.; Benekos, N.; Benhammou, Y.; Benjamin, D.P.; Benoit, M.; Bensinger, J.R.; Benslama, K.; Bentvelsen, S.; Berge, D.; Bergeaas Kuutmann, E.; Berger, N.; Berghaus, F.; Berglund, E.; Beringer, J.; Bernardet, K.; Bernat, P.; Bernhard, R.; Bernius, C.; Berry, T.; Bertin, A.; Bertinelli, F.; Bertolucci, F.; Besana, M.I.; Besson, N.; Bethke, S.; Bhimji, W.; Bianchi, R.M.; Bianco, M.; Biebel, O.; Biesiada, J.; Biglietti, M.; Bilokon, H.; Bindi, M.; Bingul, A.; Bini, C.; Biscarat, C.; Bitenc, U.; Black, K.M.; Blair, R.E.; Blanchard, J.B.; Blanchot, G.; Blocker, C.; Blocki, J.; Blondel, A.; Blum, W.; Blumenschein, U.; Bobbink, G.J.; Bobrovnikov, V.B.; Bocci, A.; Bock, R.; Boddy, C.R.; Boehler, M.; Boek, J.; Boelaert, N.; Boser, S.; Bogaerts, J.A.; Bogdanchikov, A.; Bogouch, A.; Bohm, C.; Boisvert, V.; Bold, T.; Boldea, V.; Boonekamp, M.; Boorman, G.; Booth, C.N.; Booth, P.; Booth, J.R.A.; Bordoni, S.; Borer, C.; Borisov, A.; Borissov, G.; Borjanovic, I.; Borroni, S.; Bos, K.; Boscherini, D.; Bosman, M.; Boterenbrood, H.; Botterill, D.; Bouchami, J.; Boudreau, J.; Bouhova-Thacker, E.V.; Boulahouache, C.; Bourdarios, C.; Bousson, N.; Boveia, A.; Boyd, J.; Boyko, I.R.; Bozhko, N.I.; Bozovic-Jelisavcic, I.; Bracinik, J.; Braem, A.; Brambilla, E.; Branchini, P.; Brandenburg, G.W.; Brandt, A.; Brandt, G.; Brandt, O.; Bratzler, U.; Brau, B.; Brau, J.E.; Braun, H.M.; Brelier, B.; Bremer, J.; Brenner, R.; Bressler, S.; Breton, D.; Brett, N.D.; Bright-Thomas, P.G.; Britton, D.; Brochu, F.M.; Brock, I.; Brock, R.; Brodbeck, T.J.; Brodet, E.; Broggi, F.; Bromberg, C.; Brooijmans, G.; Brooks, W.K.; Brown, G.; Brubaker, E.; Bruckman de Renstrom, P.A.; Bruncko, D.; Bruneliere, R.; Brunet, S.; Bruni, A.; Bruni, G.; Bruschi, M.; Buanes, T.; Bucci, F.; Buchanan, J.; Buchanan, N.J.; Buchholz, P.; Buckingham, R.M.; Buckley, A.G.; Buda, S.I.; Budagov, I.A.; Budick, B.; Buscher, V.; Bugge, L.; Buira-Clark, D.; Buis, E.J.; Bulekov, O.; Bunse, M.; Buran, T.; Burckhart, H.; Burdin, S.; Burgess, T.; Burke, S.; Busato, E.; Bussey, P.; Buszello, C.P.; Butin, F.; Butler, B.; Butler, J.M.; Buttar, C.M.; Butterworth, J.M.; Buttinger, W.; Byatt, T.; Cabrera Urban, S.; Caccia, M.; Caforio, D.; Cakir, O.; Calafiura, P.; Calderini, G.; Calfayan, P.; Calkins, R.; Caloba, L.P.; Caloi, R.; Calvet, D.; Calvet, S.; Camard, A.; Camarri, P.; Cambiaghi, M.; Cameron, D.; Cammin, J.; Campana, S.; Campanelli, M.; Canale, V.; Canelli, F.; Canepa, A.; Cantero, J.; Capasso, L.; Capeans Garrido, M.D.M.; Caprini, I.; Caprini, M.; Capriotti, D.; Capua, M.; Caputo, R.; Caramarcu, C.; Cardarelli, R.; Carli, T.; Carlino, G.; Carminati, L.; Caron, B.; Caron, S.; Carpentieri, C.; Carrillo Montoya, G.D.; Carron Montero, S.; Carter, A.A.; Carter, J.R.; Carvalho, J.; Casadei, D.; Casado, M.P.; Cascella, M.; Caso, C.; Castaneda Hernandez, A.M.; Castaneda-Miranda, E.; Castillo Gimenez, V.; Castro, N.F.; Cataldi, G.; Cataneo, F.; Catinaccio, A.; Catmore, J.R.; Cattai, A.; Cattani, G.; Caughron, S.; Cavallari, A.; Cavalleri, P.; Cavalli, D.; Cavalli-Sforza, M.; Cavasinni, V.; Cazzato, A.; Ceradini, F.; Cerna, C.; Cerqueira, A.S.; Cerri, A.; Cerrito, L.; Cerutti, F.; Cetin, S.A.; Cevenini, F.; Chafaq, A.; Chakraborty, D.; Chan, K.; Chapleau, B.; Chapman, J.D.; Chapman, J.W.; Chareyre, E.; Charlton, D.G.; Chavda, V.; Cheatham, S.; Chekanov, S.; Chekulaev, S.V.; Chelkov, G.A.; Chen, H.; Chen, L.; Chen, S.; Chen, T.; Chen, X.; Cheng, S.; Cheplakov, A.; Chepurnov, V.F.; Cherkaoui El Moursli, R.; Chernyatin, V.; Cheu, E.; Cheung, S.L.; Chevalier, L.; Chevallier, F.; Chiefari, G.; Chikovani, L.; Childers, J.T.; Chilingarov, A.; Chiodini, G.; Chizhov, M.V.; Choudalakis, G.; Chouridou, S.; Christidi, I.A.; Christov, A.; Chromek-Burckhart, D.; Chu, M.L.; Chudoba, J.; Ciapetti, G.; Ciftci, A.K.; Ciftci, R.; Cinca, D.; Cindro, V.; Ciobotaru, M.D.; Ciocca, C.; Ciocio, A.; Cirilli, M.; Ciubancan, M.; Clark, A.; Clark, P.J.; Cleland, W.; Clemens, J.C.; Clement, B.; Clement, C.; Clifft, R.W.; Coadou, Y.; Cobal, M.; Coccaro, A.; Cochran, J.; Coe, P.; Cogan, J.G.; Coggeshall, J.; Cogneras, E.; Cojocaru, C.D.; Colas, J.; Colijn, A.P.; Collard, C.; Collins, N.J.; Collins-Tooth, C.; Collot, J.; Colon, G.; Coluccia, R.; Comune, G.; Conde Muino, P.; Coniavitis, E.; Conidi, M.C.; Consonni, M.; Constantinescu, S.; Conta, C.; Conventi, F.; Cook, J.; Cooke, M.; Cooper, B.D.; Cooper-Sarkar, A.M.; Cooper-Smith, N.J.; Copic, K.; Cornelissen, T.; Corradi, M.; Correard, S.; Corriveau, F.; Cortes-Gonzalez, A.; Cortiana, G.; Costa, G.; Costa, M.J.; Costanzo, D.; Costin, T.; Cote, D.; Coura Torres, R.; Courneyea, L.; Cowan, G.; Cowden, C.; Cox, B.E.; Cranmer, K.; Cristinziani, M.; Crosetti, G.; Crupi, R.; Crepe-Renaudin, S.; Cuenca Almenar, C.; Cuhadar Donszelmann, T.; Cuneo, S.; Curatolo, M.; Curtis, C.J.; Cwetanski, P.; Czirr, H.; Czyczula, Z.; D'Auria, S.; D'Onofrio, M.; D'Orazio, A.; Da Rocha Gesualdi Mello, A.; Da Silva, P.V.M.; Da Via, C.; Dabrowski, W.; Dahlhoff, A.; Dai, T.; Dallapiccola, C.; Dallison, S.J.; Dam, M.; Dameri, M.; Damiani, D.S.; Danielsson, H.O.; Dankers, R.; Dannheim, D.; Dao, V.; Darbo, G.; Darlea, G.L.; Daum, C.; Dauvergne, J.P.; Davey, W.; Davidek, T.; Davidson, N.; Davidson, R.; Davies, M.; Davison, A.R.; Dawe, E.; Dawson, I.; Dawson, J.W.; Daya, R.K.; De, K.; de Asmundis, R.; De Castro, S.; De Cecco, S.; de Graat, J.; De Groot, N.; de Jong, P.; De La Cruz-Burelo, E.; De La Taille, C.; De Lotto, B.; De Mora, L.; De Nooij, L.; De Oliveira Branco, M.; De Pedis, D.; de Saintignon, P.; De Salvo, A.; De Sanctis, U.; De Santo, A.; De Vivie De Regie, J.B.; Dean, S.; Dedes, G.; Dedovich, D.V.; Degenhardt, J.; Dehchar, M.; Deile, M.; Del Papa, C.; Del Peso, J.; Del Prete, T.; Dell'Acqua, A.; Dell'Asta, L.; Della Pietra, M.; della Volpe, D.; Delmastro, M.; Delpierre, P.; Delruelle, N.; Delsart, P.A.; Deluca, C.; Demers, S.; Demichev, M.; Demirkoz, B.; Deng, J.; Denisov, S.P.; Dennis, C.; Derendarz, D.; Derkaoui, J.E.; Derue, F.; Dervan, P.; Desch, K.; Devetak, E.; Deviveiros, P.O.; Dewhurst, A.; DeWilde, B.; Dhaliwal, S.; Dhullipudi, R.; Di Ciaccio, A.; Di Ciaccio, L.; Di Girolamo, A.; Di Girolamo, B.; Di Luise, S.; Di Mattia, A.; Di Nardo, R.; Di Simone, A.; Di Sipio, R.; Diaz, M.A.; Diblen, F.; Diehl, E.B.; Dietl, H.; Dietrich, J.; Dietzsch, T.A.; Diglio, S.; Dindar Yagci, K.; Dingfelder, J.; Dionisi, C.; Dita, P.; Dita, S.; Dittus, F.; Djama, F.; Djilkibaev, R.; Djobava, T.; do Vale, M.A.B.; Do Valle Wemans, A.; Doan, T.K.O.; Dobbs, M.; Dobinson, R.; Dobos, D.; Dobson, E.; Dobson, M.; Dodd, J.; Dogan, O.B.; Doglioni, C.; Doherty, T.; Doi, Y.; Dolejsi, J.; Dolenc, I.; Dolezal, Z.; Dolgoshein, B.A.; Dohmae, T.; Donadelli, M.; Donega, M.; Donini, J.; Dopke, J.; Doria, A.; Dos Anjos, A.; Dosil, M.; Dotti, A.; Dova, M.T.; Dowell, J.D.; Doxiadis, A.D.; Doyle, A.T.; Drasal, Z.; Drees, J.; Dressnandt, N.; Drevermann, H.; Driouichi, C.; Dris, M.; Drohan, J.G.; Dubbert, J.; Dubbs, T.; Dube, S.; Duchovni, E.; Duckeck, G.; Dudarev, A.; Dudziak, F.; Duhrssen, M.; Duerdoth, I.P.; Duflot, L.; Dufour, M-A.; Dunford, M.; Duran Yildiz, H.; Duxfield, R.; Dwuznik, M.; Dydak, F.; Dzahini, D.; Duren, M.; Ebke, J.; Eckert, S.; Eckweiler, S.; Edmonds, K.; Edwards, C.A.; Efthymiopoulos, I.; Ehrenfeld, W.; Ehrich, T.; Eifert, T.; Eigen, G.; Einsweiler, K.; Eisenhandler, E.; Ekelof, T.; El Kacimi, M.; Ellert, M.; Elles, S.; Ellinghaus, F.; Ellis, K.; Ellis, N.; Elmsheuser, J.; Elsing, M.; Ely, R.; Emeliyanov, D.; Engelmann, R.; Engl, A.; Epp, B.; Eppig, A.; Erdmann, J.; Ereditato, A.; Eriksson, D.; Ernst, J.; Ernst, M.; Ernwein, J.; Errede, D.; Errede, S.; Ertel, E.; Escalier, M.; Escobar, C.; Espinal Curull, X.; Esposito, B.; Etienne, F.; Etienvre, A.I.; Etzion, E.; Evangelakou, D.; Evans, H.; Fabbri, L.; Fabre, C.; Facius, K.; Fakhrutdinov, R.M.; Falciano, S.; Falou, A.C.; Fang, Y.; Fanti, M.; Farbin, A.; Farilla, A.; Farley, J.; Farooque, T.; Farrington, S.M.; Farthouat, P.; Fasching, D.; Fassnacht, P.; Fassouliotis, D.; Fatholahzadeh, B.; Favareto, A.; Fayard, L.; Fazio, S.; Febbraro, R.; Federic, P.; Fedin, O.L.; Fedorko, I.; Fedorko, W.; Fehling-Kaschek, M.; Feligioni, L.; Fellmann, D.; Felzmann, C.U.; Feng, C.; Feng, E.J.; Fenyuk, A.B.; Ferencei, J.; 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Seiden, A.; Seifert, F.; Seixas, J.M.; Sekhniaidze, G.; Seliverstov, D.M.; Sellden, B.; Sellers, G.; Seman, M.; Semprini-Cesari, N.; Serfon, C.; Serin, L.; Seuster, R.; Severini, H.; Sevior, M.E.; Sfyrla, A.; Shabalina, E.; Shamim, M.; Shan, L.Y.; Shank, J.T.; Shao, Q.T.; Shapiro, M.; Shatalov, P.B.; Shaver, L.; Shaw, C.; Shaw, K.; Sherman, D.; Sherwood, P.; Shibata, A.; Shimizu, S.; Shimojima, M.; Shin, T.; Shmeleva, A.; Shochet, M.J.; Short, D.; Shupe, M.A.; Sicho, P.; Sidoti, A.; Siebel, A.; Siegert, F.; Siegrist, J.; Sijacki, Dj.; Silbert, O.; Silver, Y.; Silverstein, D.; Silverstein, S.B.; Simak, V.; Simic, Lj.; Simion, S.; Simmons, B.; Simonyan, M.; Sinervo, P.; Sinev, N.B.; Sipica, V.; Siragusa, G.; Sisakyan, A.N.; Sivoklokov, S.Yu.; Sjolin, J.; Sjursen, T.B.; Skinnari, L.A.; Skovpen, K.; Skubic, P.; Skvorodnev, N.; Slater, M.; Slavicek, T.; Sliwa, K.; Sloan, T.J.; Sloper, J.; Smakhtin, V.; Smirnov, S.Yu.; Smirnova, L.N.; Smirnova, O.; Smith, B.C.; Smith, D.; Smith, K.M.; Smizanska, M.; 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Wotschack, J.; Woudstra, M.J.; Wraight, K.; Wright, C.; Wrona, B.; Wu, S.L.; Wu, X.; Wu, Y.; Wulf, E.; Wunstorf, R.; Wynne, B.M.; Xaplanteris, L.; Xella, S.; Xie, S.; Xie, Y.; Xu, C.; Xu, D.; Xu, G.; Yabsley, B.; Yamada, M.; Yamamoto, A.; Yamamoto, K.; Yamamoto, S.; Yamamura, T.; Yamaoka, J.; Yamazaki, T.; Yamazaki, Y.; Yan, Z.; Yang, H.; Yang, U.K.; Yang, Y.; Yang, Y.; Yang, Z.; Yanush, S.; Yao, W-M.; Yao, Y.; Yasu, Y.; Ye, J.; Ye, S.; Yilmaz, M.; Yoosoofmiya, R.; Yorita, K.; Yoshida, R.; Young, C.; Youssef, S.; Yu, D.; Yu, J.; Yu, J.; Yuan, L.; Yurkewicz, A.; Zaets, V.G.; Zaidan, R.; Zaitsev, A.M.; Zajacova, Z.; Zalite, Yo.K.; Zanello, L.; Zarzhitsky, P.; Zaytsev, A.; Zdrazil, M.; Zeitnitz, C.; Zeller, M.; Zema, P.F.; Zemla, A.; Zendler, C.; Zenin, A.V.; Zenin, O.; Zenis, T.; Zenonos, Z.; Zenz, S.; Zerwas, D.; Zevi della Porta, G.; Zhan, Z.; Zhang, D.; Zhang, H.; Zhang, J.; Zhang, X.; Zhang, Z.; Zhao, L.; Zhao, T.; Zhao, Z.; Zhemchugov, A.; Zheng, S.; Zhong, J.; Zhou, B.; Zhou, N.; Zhou, Y.; Zhu, C.G.; Zhu, H.; Zhu, Y.; Zhuang, X.; Zhuravlov, V.; Zieminska, D.; Zilka, B.; Zimmermann, R.; Zimmermann, S.; Zimmermann, S.; Ziolkowski, M.; Zitoun, R.; Zivkovic, L.; Zmouchko, V.V.; Zobernig, G.; Zoccoli, A.; Zolnierowski, Y.; Zsenei, A.; zur Nedden, M.; Zutshi, V.; Zwalinski, L.

    2011-01-01

    Measurements are presented from proton-proton collisions at centre-of-mass energies of sqrt(s) = 0.9, 2.36 and 7 TeV recorded with the ATLAS detector at the LHC. Events were collected using a single-arm minimum-bias trigger. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the relationship between the mean transverse momentum and charged-particle multiplicity are measured. Measurements in different regions of phase-space are shown, providing diffraction-reduced measurements as well as more inclusive ones. The observed distributions are corrected to well-defined phase-space regions, using model-independent corrections. The results are compared to each other and to various Monte Carlo models, including a new AMBT1 PYTHIA 6 tune. In all the kinematic regions considered, the particle multiplicities are higher than predicted by the Monte Carlo models. The central charged-particle multiplicity per event and unit of pseudorapidity, for tracks with pT >100 MeV, is...

  18. Eoet-Wash constraints on multiple Yukawa interactions and on a coupling to ''isospin''

    International Nuclear Information System (INIS)

    Stubbs, C.W.

    1989-01-01

    The final results of our lead-source runs are presented. Our data rule out at 2σ the possibility of accounting for all the composition-dependent results in terms of a coupling to ''isospin.'' By exploiting the fact that our hillside layout is fairly complex, we have also set limits on multiple-Yukawa scenarios. 15 refs., 3 figs

  19. Effects of multiple interacting disturbances and salvage logging on forest carbon stocks

    Science.gov (United States)

    John B. Bradford; Shawn Fraver; Amy M. Milo; Anthony W. D' Amato; Brian J. Palik

    2012-01-01

    Climate change is anticipated to increase the frequency of disturbances, potentially impacting carbon stocks in terrestrial ecosystems. However, little is known about the implications of either multiple disturbances or post-disturbance forest management activities on ecosystem carbon stocks. This study quantified how forest carbon stocks responded to stand-replacing...

  20. A multiple identity approach to gender : Identification with women, identification with feminists, and their interaction

    NARCIS (Netherlands)

    van Breen, Jolien A.; Spears, Russell; Kuppens, Toon; de Lemus, Soledad

    2017-01-01

    Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that

  1. Probing for the Multiplicative Term in Modern Expectancy-Value Theory: A Latent Interaction Modeling Study

    Science.gov (United States)

    Trautwein, Ulrich; Marsh, Herbert W.; Nagengast, Benjamin; Ludtke, Oliver; Nagy, Gabriel; Jonkmann, Kathrin

    2012-01-01

    In modern expectancy-value theory (EVT) in educational psychology, expectancy and value beliefs additively predict performance, persistence, and task choice. In contrast to earlier formulations of EVT, the multiplicative term Expectancy x Value in regression-type models typically plays no major role in educational psychology. The present study…

  2. Possible signature of multiple parton interactions in collider four-jet events

    International Nuclear Information System (INIS)

    Ametller, L.; Paver, N.; Treleani, D.

    1985-07-01

    We discuss the role of multiple parton scattering in the production of four-jet events of the Ssub(pp-bar)S Collider. Taking into account the experimental conditions, we find that such a mechanism can contribute to the psub(out) distribution appreciably enough to be differentiated from the leading perturbative QCD. (author)

  3. STARVATION RESISTANCE IN DROSOPHILA-MELANOGASTER IN RELATION TO THE POLYMORPHISMS AT THE ADH AND ALPHA-GPDH LOCI

    NARCIS (Netherlands)

    OUDMAN, L; VANDELDEN, W; KAMPING, A; BIJLSMA, R

    In view of the world-wide latitudinal cline of the Adh and alpha Gpdh allozyme frequencies of Drosophila melanogaster and the interactions between these loci, experiments were performed to study the phenotypic effects of these loci. Starvation resistance, oxygen consumption, body weight, protein

  4. Coincidence in map positions between pathogen-induced defense-responsive genes and quantitative resistance loci in rice

    Institute of Scientific and Technical Information of China (English)

    熊敏; 王石平; 张启发

    2002-01-01

    Quantitative disease resistance conferred by quantitative trait loci (QTLs) is presumably of wider spectrum and durable. Forty-four cDNA clones, representing 44 defense-responsive genes, were fine mapped to 56 loci distributed on 9 of the 12 rice chromosomes. The locations of 32 loci detected by 27 cDNA clones were associated with previously identified resistance QTLs for different rice diseases, including blast, bacterial blight, sheath blight and yellow mottle virus. The loci detected by the same multiple-copy cDNA clones were frequently located on similar locations of different chromosomes. Some of the multiple loci detected by the same clones were all associated with resistance QTLs. These results suggest that some of the genes may be important components in regulation of defense responses against pathogen invasion and they may be the candidates for studying the mechanism of quantitative disease resistance in rice.

  5. Probing the stereoselective interaction of ofloxacin enantiomers with corresponding monoclonal antibodies by multiple spectrometry

    Science.gov (United States)

    Mu, Hongtao; Xu, Zhenlin; Liu, Yingju; Sun, Yuanming; Wang, Baoling; Sun, Xiulan; Wang, Zhanhui; Eremin, Sergei; Zherdev, Anatoly V.; Dzantiev, Boris B.; Lei, Hongtao

    2018-04-01

    Although stereoselective antibody has immense potential in chiral compounds detection and separation, the interaction traits between stereoselective antibody and the corresponding antigenic enantiomers are not yet fully exploited. In this study, the stereospecific interactions between ofloxacin isomers and corresponding monoclonal antibodies (McAb-WR1 and McAb-MS1) were investigated using time-resolved fluorescence, steady-state fluorescence, and circular dichroism (CD) spectroscopic methods. The chiral recognition discrepancies of antibodies with ofloxacin isomers were reflected through binding constant, number of binding sites, driving forces and conformational changes. The major interacting forces of McAb-WR1 and McAb-MS1 chiral interaction systems were hydrophobic force and van der Waals forces joined up with hydrogen bonds, respectively. Synchronous fluorescence spectra and CD spectra results showed that the disturbing of tyrosine and tryptophan micro-environments were so slightly that no obvious secondary structure changes were found during the chiral hapten binding. Clarification of stereospecific interaction of antibody will facilitate the application of immunoassay to analyze chiral contaminants in food and other areas.

  6. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  7. Comparative Interactions of Dihydroquinazolin Derivatives with Human Serum Albumin Observed via Multiple Spectroscopy

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2017-02-01

    Full Text Available The interactions of dihydroquinazolines with human serum albumin (HSA were studied in pH 7.4 aqueous solution via fluorescence, circular dichroism (CD and Fourier transform infrared (FTIR spectroscopic techniques. In this work, 6-chloro-1-(3,3-dimethyl-butanoyl-2(unsubstitutedphenyl-2,3-dihydroquinazolin-4(1H-one (PDQL derivatives were designed and synthesized to study the impact of five similar substituents (methyl, methoxy, cyano, trifluoromethyl and isopropyl on the interactions between PDQL and HSA using a comparative methodology. The results revealed that PDQL quenched the intrinsic fluorescence of HSA through a static quenching process. Displacement experiments with site-specific markers revealed that PDQL binds to HSA at site II (subdomain IIIA and that there may be only one binding site for PDQL on HSA. The thermodynamic parameters indicated that hydrophobic interactions mainly drove the interactions between PDQL and HSA. The substitution using five similar groups in the benzene ring could increase the interactions between PDQL and HSA to some extent through the van der Waals force or hydrogen bond effects in the proper temperature range. Isopropyl substitution could particularly enhance the binding affinity, as observed via comparative studies

  8. A Multiple Identity Approach to Gender: Identification with Women, Identification with Feminists, and Their Interaction

    Science.gov (United States)

    van Breen, Jolien A.; Spears, Russell; Kuppens, Toon; de Lemus, Soledad

    2017-01-01

    Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that identification with women reflects attitudes toward the content society gives to group membership: what does it mean to be a woman in terms of group characteristics, interests and values? Identification with feminists, on the other hand, is a politicized identity dimension reflecting attitudes toward the social position of the group: what does it mean to be a woman in terms of disadvantage, inequality, and relative status? We examine the utility of this multiple identity approach in four studies. Study 1 showed that identification with women reflects attitudes toward group characteristics, such as femininity and self-stereotyping, while identification with feminists reflects attitudes toward the group's social position, such as perceived sexism. The two dimensions are shown to be largely independent, and as such provide support for the multiple identity approach. In Studies 2–4, we examine the utility of this multiple identity approach in predicting qualitative differences in gender attitudes. Results show that specific combinations of identification with women and feminists predicted attitudes toward collective action and gender stereotypes. Higher identification with feminists led to endorsement of radical collective action (Study 2) and critical attitudes toward gender stereotypes (Studies 3–4), especially at lower levels of identification with women. The different combinations of high vs. low identification with women and feminists can be thought of as reflecting four theoretical identity “types.” A woman can be (1) strongly identified with neither women nor feminists (“low identifier”), (2) strongly identified with women but less so with feminists (

  9. A Multiple Identity Approach to Gender: Identification with Women, Identification with Feminists, and Their Interaction

    Directory of Open Access Journals (Sweden)

    Jolien A. van Breen

    2017-06-01

    Full Text Available Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that identification with women reflects attitudes toward the content society gives to group membership: what does it mean to be a woman in terms of group characteristics, interests and values? Identification with feminists, on the other hand, is a politicized identity dimension reflecting attitudes toward the social position of the group: what does it mean to be a woman in terms of disadvantage, inequality, and relative status? We examine the utility of this multiple identity approach in four studies. Study 1 showed that identification with women reflects attitudes toward group characteristics, such as femininity and self-stereotyping, while identification with feminists reflects attitudes toward the group's social position, such as perceived sexism. The two dimensions are shown to be largely independent, and as such provide support for the multiple identity approach. In Studies 2–4, we examine the utility of this multiple identity approach in predicting qualitative differences in gender attitudes. Results show that specific combinations of identification with women and feminists predicted attitudes toward collective action and gender stereotypes. Higher identification with feminists led to endorsement of radical collective action (Study 2 and critical attitudes toward gender stereotypes (Studies 3–4, especially at lower levels of identification with women. The different combinations of high vs. low identification with women and feminists can be thought of as reflecting four theoretical identity “types.” A woman can be (1 strongly identified with neither women nor feminists (“low identifier”, (2 strongly identified with women but less so with feminists (

  10. A Multiple Identity Approach to Gender: Identification with Women, Identification with Feminists, and Their Interaction.

    Science.gov (United States)

    van Breen, Jolien A; Spears, Russell; Kuppens, Toon; de Lemus, Soledad

    2017-01-01

    Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that identification with women reflects attitudes toward the content society gives to group membership: what does it mean to be a woman in terms of group characteristics, interests and values? Identification with feminists, on the other hand, is a politicized identity dimension reflecting attitudes toward the social position of the group: what does it mean to be a woman in terms of disadvantage, inequality, and relative status? We examine the utility of this multiple identity approach in four studies. Study 1 showed that identification with women reflects attitudes toward group characteristics, such as femininity and self-stereotyping, while identification with feminists reflects attitudes toward the group's social position, such as perceived sexism. The two dimensions are shown to be largely independent, and as such provide support for the multiple identity approach. In Studies 2-4, we examine the utility of this multiple identity approach in predicting qualitative differences in gender attitudes. Results show that specific combinations of identification with women and feminists predicted attitudes toward collective action and gender stereotypes. Higher identification with feminists led to endorsement of radical collective action (Study 2) and critical attitudes toward gender stereotypes (Studies 3-4), especially at lower levels of identification with women. The different combinations of high vs. low identification with women and feminists can be thought of as reflecting four theoretical identity "types." A woman can be (1) strongly identified with neither women nor feminists ("low identifier"), (2) strongly identified with women but less so with feminists ("traditional identifier"), (3

  11. Proceedings of the first international workshop on multiple partonic interactions at the LHC. MPI'08

    Energy Technology Data Exchange (ETDEWEB)

    Bartalini, Paolo [National Taiwan Univ., Taipei (China); Fano, Livio (eds.) [Istituto Nazionale di Fisica Nucleare, Perugia (Italy)

    2009-06-15

    The objective of this first workshop on Multiple Partonic Interactions (MPI) at the LHC, that can be regarded as a continuation and extension of the dedicated meetings held at DESY in the years 2006 and 2007, is to raise the profile of MPI studies, summarizing the legacy from the older phenomenology at hadronic colliders and favouring further specific contacts between the theory and experimental communities. The MPI are experiencing a growing popularity and are currently widely invoked to account for observations that would not be explained otherwise: the activity of the Underlying Event, the cross sections for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of the MPI effects in the Monte Carlo models is quickly proceeding through an increasing level of sophistication and complexity that in perspective achieves deep general implications for the LHC physics. The ultimate ambition of this workshop is to promote the MPI as unification concept between seemingly heterogeneous research lines and to profit of the complete experimental picture in order to constrain their implementation in the models, evaluating the spin offs on the LHC physics program. The workshop is structured in five sections, with the first one dedicated to few selected hot highlights in the High Energy Physics and directly connected to the other ones: Multiple Parton Interactions (in both the soft and the hard regimes), Diffraction, Monte Carlo Generators and Heavy Ions. (orig.)

  12. Right-wing authoritarianism and stereotype-driven expectations interact in shaping intergroup trust in one-shot vs multiple-round social interactions.

    Science.gov (United States)

    Ponsi, Giorgia; Panasiti, Maria Serena; Aglioti, Salvatore Maria; Liuzza, Marco Tullio

    2017-01-01

    Trust towards unrelated individuals is often conditioned by information about previous social interactions that can be derived from either personal or vicarious experience (e.g., reputation). Intergroup stereotypes can be operationalized as expectations about other groups' traits/attitudes/behaviors that heavily influence our behavioral predictions when interacting with them. In this study we investigated the role of perceived social dimensions of the Stereotype Content Model (SCM)-Warmth (W) and Competence (C)-in affecting trusting behavior towards different European national group members during the Trust Game. Given the well-known role of ideological attitudes in regulating stereotypes, we also measured individual differences in right-wing authoritarianism (RWA). In Experiment 1, we designed an online survey to study one-shot intergroup trust decisions by employing putative members of the European Union states which were also rated along SCM dimensions. We found that low-RWA participants' trusting behavior was driven by perceived warmth (i.e., the dimension signaling the benevolence of social intentions) when interacting with low-C groups. In Experiment 2, we investigated the dynamics of trust in a multiple-round version of the European Trust Game. We found that in low-RWA participants trusting behavior decreased over time when interacting with high-W groups (i.e., expected to reciprocate trust), but did not change when interacting with low-W groups (i.e., expected not to reciprocate trust). Moreover, we found that high-RWA participants' trusting behavior decreased when facing low-W groups but not high-W ones. This suggests that low-RWA individuals employ reputational priors but are also permeable to external evidence when learning about others' trustworthiness. In contrast, high-RWA individuals kept relying on stereotypes despite contextual information. These results confirm the pivotal role played by reputational priors triggered by perceived warmth in shaping

  13. Right-wing authoritarianism and stereotype-driven expectations interact in shaping intergroup trust in one-shot vs multiple-round social interactions.

    Directory of Open Access Journals (Sweden)

    Giorgia Ponsi

    Full Text Available Trust towards unrelated individuals is often conditioned by information about previous social interactions that can be derived from either personal or vicarious experience (e.g., reputation. Intergroup stereotypes can be operationalized as expectations about other groups' traits/attitudes/behaviors that heavily influence our behavioral predictions when interacting with them. In this study we investigated the role of perceived social dimensions of the Stereotype Content Model (SCM-Warmth (W and Competence (C-in affecting trusting behavior towards different European national group members during the Trust Game. Given the well-known role of ideological attitudes in regulating stereotypes, we also measured individual differences in right-wing authoritarianism (RWA. In Experiment 1, we designed an online survey to study one-shot intergroup trust decisions by employing putative members of the European Union states which were also rated along SCM dimensions. We found that low-RWA participants' trusting behavior was driven by perceived warmth (i.e., the dimension signaling the benevolence of social intentions when interacting with low-C groups. In Experiment 2, we investigated the dynamics of trust in a multiple-round version of the European Trust Game. We found that in low-RWA participants trusting behavior decreased over time when interacting with high-W groups (i.e., expected to reciprocate trust, but did not change when interacting with low-W groups (i.e., expected not to reciprocate trust. Moreover, we found that high-RWA participants' trusting behavior decreased when facing low-W groups but not high-W ones. This suggests that low-RWA individuals employ reputational priors but are also permeable to external evidence when learning about others' trustworthiness. In contrast, high-RWA individuals kept relying on stereotypes despite contextual information. These results confirm the pivotal role played by reputational priors triggered by perceived

  14. A Multiple Identity Approach to Gender: Identification with Women, Identification with Feminists, and Their Interaction

    OpenAIRE

    van Breen, Jolien A.; Spears, Russell; Kuppens, Toon; de Lemus, Soledad

    2017-01-01

    Across four studies, we examine multiple identities in the context of gender and propose that women's attitudes toward gender group membership are governed by two largely orthogonal dimensions of gender identity: identification with women and identification with feminists. We argue that identification with women reflects attitudes toward the content society gives to group membership: what does it mean to be a woman in terms of group characteristics, interests and values? Identification with f...

  15. Associated average charged particle multiplicities in K+p interactions at 32GeV/c

    International Nuclear Information System (INIS)

    Ajinenko, I.V.; Chliapnikov, P.V.; Gerdyukov, L.N.; Kubic, V.M.; Manyukov, B.A.; Minaev, N.G.; Rubin, A.M.; Ryadovikov, V.N.; Beer, M. de; Loret, M.; Saudraix, J.

    1975-01-01

    The average charged particle multiplicities, in the reactions K + p→K 0 X, K + p→π - X, K + p→pX and K + p→Δ ++ (1236)X at 32GeV/c are studied as functions of the mass squared Msub(X)sup(2) of the associated system X. A comparison with the corresponding results obtained at lower incident momenta and with other incident particles is presented [fr

  16. Thorium–phosphorus triamidoamine complexes containing Th–P single- and multiple-bond interactions

    Science.gov (United States)

    Wildman, Elizabeth P.; Balázs, Gábor; Wooles, Ashley J.; Scheer, Manfred; Liddle, Stephen T.

    2016-01-01

    Despite the burgeoning field of uranium-ligand multiple bonds, analogous complexes involving other actinides remain scarce. For thorium, under ambient conditions only a few multiple bonds to carbon, nitrogen, oxygen, sulfur, selenium and tellurium are reported, and no multiple bonds to phosphorus are known, reflecting a general paucity of synthetic methodologies and also problems associated with stabilising these linkages at the large thorium ion. Here we report structurally authenticated examples of a parent thorium(IV)–phosphanide (Th–PH2), a terminal thorium(IV)–phosphinidene (Th=PH), a parent dithorium(IV)–phosphinidiide (Th–P(H)-Th) and a discrete actinide–phosphido complex under ambient conditions (Th=P=Th). Although thorium is traditionally considered to have dominant 6d-orbital contributions to its bonding, contrasting to majority 5f-orbital character for uranium, computational analyses suggests that the bonding of thorium can be more nuanced, in terms of 5f- versus 6d-orbital composition and also significant involvement of the 7s-orbital and how this affects the balance of 5f- versus 6d-orbital bonding character. PMID:27682617

  17. GENIE: a software package for gene-gene interaction analysis in genetic association studies using multiple GPU or CPU cores

    Directory of Open Access Journals (Sweden)

    Wang Kai

    2011-05-01

    Full Text Available Abstract Background Gene-gene interaction in genetic association studies is computationally intensive when a large number of SNPs are involved. Most of the latest Central Processing Units (CPUs have multiple cores, whereas Graphics Processing Units (GPUs also have hundreds of cores and have been recently used to implement faster scientific software. However, currently there are no genetic analysis software packages that allow users to fully utilize the computing power of these multi-core devices for genetic interaction analysis for binary traits. Findings Here we present a novel software package GENIE, which utilizes the power of multiple GPU or CPU processor cores to parallelize the interaction analysis. GENIE reads an entire genetic association study dataset into memory and partitions the dataset into fragments with non-overlapping sets of SNPs. For each fragment, GENIE analyzes: 1 the interaction of SNPs within it in parallel, and 2 the interaction between the SNPs of the current fragment and other fragments in parallel. We tested GENIE on a large-scale candidate gene study on high-density lipoprotein cholesterol. Using an NVIDIA Tesla C1060 graphics card, the GPU mode of GENIE achieves a speedup of 27 times over its single-core CPU mode run. Conclusions GENIE is open-source, economical, user-friendly, and scalable. Since the computing power and memory capacity of graphics cards are increasing rapidly while their cost is going down, we anticipate that GENIE will achieve greater speedups with faster GPU cards. Documentation, source code, and precompiled binaries can be downloaded from http://www.cceb.upenn.edu/~mli/software/GENIE/.

  18. The interactive business case approach for multiple land use: more efficiency, less costs!

    NARCIS (Netherlands)

    Franssen, R.J.M.; Ellen, G.J.; van der Heijden, G.M.A.; van Lamoen, F.; Melisie, E.J.; Peerdeman, K.; Wind, M.H.A.; Paalman, M.

    2011-01-01

    This paper describes Interactive Business Case Approach (IBCA) in a participatory planning setting concerning multifunctional land use, as an instrument for climate adaptation strategies. Multifunctional land use is an solution to optimize the use of scare spatial resources, especially in densely

  19. Ecosystem services capacity across heterogeneous forest types: understanding the interactions and suggesting pathways for sustaining multiple ecosystem services.

    Science.gov (United States)

    Alamgir, Mohammed; Turton, Stephen M; Macgregor, Colin J; Pert, Petina L

    2016-10-01

    As ecosystem services supply from tropical forests is declining due to deforestation and forest degradation, much effort is essential to sustain ecosystem services supply from tropical forested landscapes, because tropical forests provide the largest flow of multiple ecosystem services among the terrestrial ecosystems. In order to sustain multiple ecosystem services, understanding ecosystem services capacity across heterogeneous forest types and identifying certain ecosystem services that could be managed to leverage positive effects across the wider bundle of ecosystem services are required. We sampled three forest types, tropical rainforests, sclerophyll forests, and rehabilitated plantation forests, over an area of 32,000m(2) from Wet Tropics bioregion, Australia, aiming to compare supply and evaluate interactions and patterns of eight ecosystem services (global climate regulation, air quality regulation, erosion regulation, nutrient regulation, cyclone protection, habitat provision, energy provision, and timber provision). On average, multiple ecosystem services were highest in the rainforests, lowest in sclerophyll forests, and intermediate in rehabilitated plantation forests. However, a wide variation was apparent among the plots across the three forest types. Global climate regulation service had a synergistic impact on the supply of multiple ecosystem services, while nutrient regulation service was found to have a trade-off impact. Considering multiple ecosystem services, most of the rehabilitated plantation forest plots shared the same ordination space with rainforest plots in the ordination analysis, indicating that rehabilitated plantation forests may supply certain ecosystem services nearly equivalent to rainforests. Two synergy groups and one trade-off group were identified. Apart from conserving rainforests and sclerophyll forests, our findings suggest two additional integrated pathways to sustain the supply of multiple ecosystem services from a

  20. The Red Queen lives: Epistasis between linked resistance loci.

    Science.gov (United States)

    Metzger, César M J A; Luijckx, Pepijn; Bento, Gilberto; Mariadassou, Mahendra; Ebert, Dieter

    2016-02-01

    A popular theory explaining the maintenance of genetic recombination (sex) is the Red Queen Theory. This theory revolves around the idea that time-lagged negative frequency-dependent selection by parasites favors rare host genotypes generated through recombination. Although the Red Queen has been studied for decades, one of its key assumptions has remained unsupported. The signature host-parasite specificity underlying the Red Queen, where infection depends on a match between host and parasite genotypes, relies on epistasis between linked resistance loci for which no empirical evidence exists. We performed 13 genetic crosses and tested over 7000 Daphnia magna genotypes for resistance to two strains of the bacterial pathogen Pasteuria ramosa. Results reveal the presence of strong epistasis between three closely linked resistance loci. One locus masks the expression of the other two, while these two interact to produce a single resistance phenotype. Changing a single allele on one of these interacting loci can reverse resistance against the tested parasites. Such a genetic mechanism is consistent with host and parasite specificity assumed by the Red Queen Theory. These results thus provide evidence for a fundamental assumption of this theory and provide a genetic basis for understanding the Red Queen dynamics in the Daphnia-Pasteuria system. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  1. Description of charged particle multiplicity distribution in high energy strong interaction

    International Nuclear Information System (INIS)

    Qin Keyu

    1994-01-01

    With the assumption that the probability for n-charged particles production in hadron-hadron collision is Pn and proper choice of 1 , 2 , k and x in Pn, the true multiplicity distribution in full phase space can be described successfully at the centre of mass energy √S GeV. Using the experimental data of non singe-diffractive collisions between proton and antiproton at centre of mass energies of 200 and 900 GeV, the supposition has been examined and confirmed: it is very good to describe the facts. The theoretical bases of supposition were discussed

  2. Quark jets from antineutrino interactions. 2. Inclusive particle spectra and multiplicities in the quark jets

    International Nuclear Information System (INIS)

    Ammosov, V.V.; Denisov, A.G.; Gapienko, G.S.

    1981-01-01

    The results on inclusive particle production in the antineutrino charged current induced hadron jets observed in the Fermilab 15- ft. bubble chamber are presented. Fractional energy distributions, particle ratios and average multiplicities of the hadrons in the jets are measured. Ratios between the inclusive production rates of different mesons in the jets are studied to seek evidence for the d-quark origin of the observed hadrons. Good over-all agreement with the hypothesis of d-quark fragmentation with universal fragmentation functions obeying isospin systematics is established [ru

  3. Charged particle multiplicity in e+e- interactions at $\\sqrt{s}$ = 130 GeV

    CERN Document Server

    Abreu, P; Adye, T; Agasi, E; Ajinenko, I; Aleksan, Roy; Alekseev, G D; Alemany, R; Allport, P P; Almehed, S; Amaldi, Ugo; Amato, S; Andreazza, A; Andrieux, M L; Antilogus, P; Apel, W D; Arnoud, Y; Åsman, B; Augustin, J E; Augustinus, A; Baillon, Paul; Bambade, P; Barão, F; Barate, R; Barbi, M S; Bardin, Dimitri Yuri; Baroncelli, A; Bärring, O; Barrio, J A; Bartl, Walter; Bates, M J; Battaglia, Marco; Baubillier, M; Baudot, J; Becks, K H; Begalli, M; Beillière, P; Belokopytov, Yu A; Belous, K S; Benvenuti, Alberto C; Berggren, M; Bertrand, D; Bianchi, F; Bigi, M; Bilenky, S M; Billoir, P; Bloch, D; Blume, M; Blyth, S; Bolognese, T; Bonesini, M; Bonivento, W; Booth, P S L; Borisov, G; Bosio, C; Bosworth, S; Botner, O; Boudinov, E; Bouquet, B; Bourdarios, C; Bowcock, T J V; Bozzo, M; Branchini, P; Brand, K D; Brenke, T; Brenner, R A; Bricman, C; Brillault, L; Brown, R C A; Brückman, P; Brunet, J M; Bugge, L; Buran, T; Burgsmüller, T; Buschmann, P; Buys, A; Cabrera, S; Caccia, M; Calvi, M; Camacho-Rozas, A J; Camporesi, T; Canale, V; Canepa, M; Cankocak, K; Cao, F; Carena, F; Carroll, L; Caso, Carlo; Castillo-Gimenez, M V; Cattai, A; Cavallo, F R; Cerrito, L; Chabaud, V; Charpentier, P; Chaussard, L; Chauveau, J; Checchia, P; Chelkov, G A; Chen, M; Chierici, R; Chliapnikov, P V; Chochula, P; Chorowicz, V; Cindro, V; Collins, P; Contreras, J L; Contri, R; Cortina, E; Cosme, G; Cossutti, F; Crawley, H B; Crennell, D J; Crosetti, G; Cuevas-Maestro, J; Czellar, S; Dahl-Jensen, Erik; Dahm, J; D'Almagne, B; Dam, M; Damgaard, G; Dauncey, P D; Davenport, Martyn; Da Silva, W; Defoix, C; Deghorain, A; Della Ricca, G; Delpierre, P A; Demaria, N; De Angelis, A; de Boer, Wim; De Brabandere, S; De Clercq, C; La Vaissière, C de; De Lotto, B; De Min, A; De Paula, L S; De Saint-Jean, C; Dijkstra, H; Di Ciaccio, Lucia; Djama, F; Dolbeau, J; Dönszelmann, M; Doroba, K; Dracos, M; Drees, J; Drees, K A; Dris, M; Dufour, Y; Edsall, D M; Ehret, R; Eigen, G; Ekelöf, T J C; Ekspong, Gösta; Elsing, M; Engel, J P; Ershaidat, N; Erzen, B; Espirito-Santo, M C; Falk, E; Fassouliotis, D; Feindt, Michael; Fenyuk, A; Ferrer, A; Filippas-Tassos, A; Firestone, A; Fischer, P A; Föth, H; Fokitis, E; Fontanelli, F; Formenti, F; Franek, B J; Frenkiel, P; Fries, D E C; Frodesen, A G; Frühwirth, R; Fulda-Quenzer, F; Fuster, J A; Galloni, A; Gamba, D; Gandelman, M; García, C; García, J; Gaspar, C; Gasparini, U; Gavillet, P; Gazis, E N; Gelé, D; Gerber, J P; Gerdyukov, L N; Gibbs, M; Gokieli, R; Golob, B; Gopal, Gian P; Gorn, L; Górski, M; Guz, Yu; Gracco, Valerio; Graziani, E; Grosdidier, G; Grzelak, K; Gumenyuk, S A; Gunnarsson, P; Günther, M; Guy, J; Hahn, F; Hahn, S; Hajduk, Z; Hallgren, A; Hamacher, K; Hao, W; Harris, F J; Hedberg, V; Henriques, R P; Hernández, J J; Herquet, P; Herr, H; Hessing, T L; Higón, E; Hilke, Hans Jürgen; Hill, T S; Holmgren, S O; Holt, P J; Holthuizen, D J; Hoorelbeke, S; Houlden, M A; Hrubec, Josef; Huet, K; Hultqvist, K; Jackson, J N; Jacobsson, R; Jalocha, P; Janik, R; Jarlskog, C; Jarlskog, G; Jarry, P; Jean-Marie, B; Johansson, E K; Jönsson, L B; Jönsson, P E; Joram, Christian; Juillot, P; Kaiser, M; Kapusta, F; Karafasoulis, K; Karlsson, M; Karvelas, E; Katsanevas, S; Katsoufis, E C; Keränen, R; Khokhlov, Yu A; Khomenko, B A; Khovanskii, N N; King, B J; Kjaer, N J; Klein, H; Klovning, A; Kluit, P M; Köne, B; Kokkinias, P; Koratzinos, M; Korcyl, K; Kourkoumelis, C; Kuznetsov, O; Kramer, P H; Krammer, Manfred; Kreuter, C; Kronkvist, I J; Krumshtein, Z; Krupinski, W; Kubinec, P; Kucewicz, W; Kurvinen, K L; Lacasta, C; Laktineh, I; Lamblot, S; Lamsa, J; Lanceri, L; Lane, D W; Langefeld, P; Last, I; Laugier, J P; Lauhakangas, R; Leder, Gerhard; Ledroit, F; Lefébure, V; Legan, C K; Leitner, R; Lemoigne, Y; Lemonne, J; Lenzen, Georg; Lepeltier, V; Lesiak, T; Liko, D; Lindner, R; Lipniacka, A; Lippi, I; Lörstad, B; Lokajícek, M; Loken, J G; López, J M; Loukas, D; Lutz, P; Lyons, L; MacNaughton, J N; Maehlum, G; Maio, A; Malychev, V; Mandl, F; Marco, J; Marco, R P; Maréchal, B; Margoni, M; Marin, J C; Mariotti, C; Markou, A; Maron, T; Martínez-Rivero, C; Martínez-Vidal, F; Martí i García, S; Matorras, F; Matteuzzi, C; Matthiae, Giorgio; Mazzucato, M; McCubbin, M L; McKay, R; McNulty, R; Medbo, J; Merk, M; Meroni, C; Meyer, S; Meyer, W T; Michelotto, M; Migliore, E; Mirabito, L; Mjörnmark, U; Moa, T; Møller, R; Mönig, K; Monge, M R; Morettini, P; Müller, H; Mundim, L M; Murray, W J; Muryn, B; Myatt, Gerald; Naraghi, F; Navarria, Francesco Luigi; Navas, S; Nawrocki, K; Negri, P; Némécek, S; Neumann, W; Neumeister, N; Nicolaidou, R; Nielsen, B S; Nieuwenhuizen, M; Nikolaenko, V; Niss, P; Nomerotski, A; Normand, Ainsley; Oberschulte-Beckmann, W; Obraztsov, V F; Olshevskii, A G; Onofre, A; Orava, Risto; Österberg, K; Ouraou, A; Paganini, P; Paganoni, M; Pagès, P; Palka, H; Papadopoulou, T D; Papageorgiou, K; Pape, L; Parkes, C; Parodi, F; Passeri, A; Pegoraro, M; Peralta, L; Pernegger, H; Pernicka, Manfred; Perrotta, A; Petridou, C; Petrolini, A; Petrovykh, M; Phillips, H T; Piana, G; Pierre, F; Pimenta, M; Pindo, M; Plaszczynski, S; Podobrin, O; Pol, M E; Polok, G; Poropat, P; Pozdnyakov, V; Prest, M; Privitera, P; Pukhaeva, N; Pullia, Antonio; Radojicic, D; Ragazzi, S; Rahmani, H; Rames, J; Ratoff, P N; Read, A L; Reale, M; Rebecchi, P; Redaelli, N G; Regler, Meinhard; Reid, D; Renton, P B; Resvanis, L K; Richard, F; Richardson, J; Rídky, J; Rinaudo, G; Ripp, I; Romero, A; Roncagliolo, I; Ronchese, P; Roos, L; Rosenberg, E I; Rosso, E; Roudeau, Patrick; Rovelli, T; Rückstuhl, W; Ruhlmann-Kleider, V; Ruiz, A; Rybicki, K; Saarikko, H; Sacquin, Yu; Sadovskii, A; Sajot, G; Salt, J; Sánchez, J; Sannino, M; Schimmelpfennig, M; Schneider, H; Schwickerath, U; Schyns, M A E; Sciolla, G; Scuri, F; Seager, P; Sedykh, Yu; Segar, A M; Seitz, A; Sekulin, R L; Shellard, R C; Siccama, I; Siegrist, P; Simonetti, S; Simonetto, F; Sissakian, A N; Sitár, B; Skaali, T B; Smadja, G; Smirnov, N; Smirnova, O G; Smith, G R; Solovyanov, O; Sosnowski, R; Souza-Santos, D; Spiriti, E; Sponholz, P; Squarcia, S; Stanescu, C; Stapnes, Steinar; Stavitski, I; Stichelbaut, F; Stocchi, A; Strauss, J; Strub, R; Stugu, B; Szczekowski, M; Szeptycka, M; Tabarelli de Fatis, T; Tavernet, J P; Chikilev, O G; Tilquin, A; Timmermans, J; Tkatchev, L G; Todorov, T; Toet, D Z; Tomaradze, A G; Tomé, B; Tonazzo, A; Tortora, L; Tranströmer, G; Treille, D; Trischuk, W; Tristram, G; Trombini, A; Troncon, C; Tsirou, A L; Turluer, M L; Tyapkin, I A; Tyndel, M; Tzamarias, S; Überschär, B; Ullaland, O; Uvarov, V; Valenti, G; Vallazza, E; Van der Velde, C; van Apeldoorn, G W; van Dam, P; Van Doninck, W K; Van Eldik, J; Vassilopoulos, N; Vegni, G; Ventura, L; Venus, W A; Verbeure, F; Verlato, M; Vertogradov, L S; Vilanova, D; Vincent, P; Vitale, L; Vlasov, E; Vodopyanov, A S; Vrba, V; Wahlen, H; Walck, C; Waldner, F; Weierstall, M; Weilhammer, Peter; Weiser, C; Wetherell, Alan M; Wicke, D; Wickens, J H; Wielers, M; Wilkinson, G R; Williams, W S C; Winter, M; Witek, M; Woschnagg, K; Yip, K; Yushchenko, O P; Zach, F; Zaitsev, A; Zalewska-Bak, A; Zalewski, Piotr; Zavrtanik, D; Zevgolatakos, E; Zimin, N I; Zito, M; Zontar, D; Zuberi, R; Zucchelli, G C; Zumerle, G; Charpentier, Ph; Gavillet, Ph; Jarlskog, Ch; Khohklov, Yu; Papadopoulou, Th D

    1996-01-01

    From the data collected by DELPHI at LEP in autumn 1995, the multiplicity of charged particles at a hadronic energy of 130 GeV has been measured to be = 23.84 \\pm 0.51 (stat) \\pm 0.52 (syst). When compared to lower energy data, the value measured is consistent with the evolution predicted by QCD with corrections at next-to-leading order, for a value \\alpha_s(130 {\\mathrm{GeV}}) = 0.105 \\pm 0.003 (stat) \\pm 0.008 (syst).

  4. Long-term tracking of multiple interacting pedestrians using a single camera

    CSIR Research Space (South Africa)

    Keaikitse, M

    2014-11-01

    Full Text Available interacting pedestrians using a single camera Mogomotsi Keaikitse∗, Willie Brink† and Natasha Govender∗ ∗Modelling and Digital Sciences, Council for Scientific and Industrial Research, Pretoria, South Africa †Department of Mathematical Sciences, Stellenbosch...-identified and their tracks extended. Standard, publicly available data sets are used to test the system. I. INTRODUCTION Closed circuit cameras are becoming widespread and preva- lent in cities and towns around the world, indicating that surveillance is an important issue...

  5. Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

    DEFF Research Database (Denmark)

    Christensen, Tove

    2005-01-01

    may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation...... and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS. Copyright (c) 2005 ...

  6. Fungible dynamics: There are only two types of entangling multiple-qubit interactions

    International Nuclear Information System (INIS)

    Bremner, Michael J.; Dodd, Jennifer L.; Nielsen, Michael A.; Bacon, Dave

    2004-01-01

    What interactions are sufficient to simulate arbitrary quantum dynamics in a composite quantum system? It has been shown that all two-body Hamiltonian evolutions can be simulated using any fixed two-body entangling n-qubit Hamiltonian and fast local unitaries. By entangling we mean that every qubit is coupled to every other qubit, if not directly, then indirectly via intermediate qubits. We extend this study to the case where interactions may involve more than two qubits at a time. We find necessary and sufficient conditions for an arbitrary n-qubit Hamiltonian to be dynamically universal, that is, able to simulate any other Hamiltonian acting on n qubits, possibly in an inefficient manner. We prove that an entangling Hamiltonian is dynamically universal if and only if it contains at least one coupling term involving an even number of interacting qubits. For odd entangling Hamiltonians, i.e., Hamiltonians with couplings that involve only an odd number of qubits, we prove that dynamic universality is possible on an encoded set of n-1 logical qubits. We further prove that an odd entangling Hamiltonian can simulate any other odd Hamiltonian and classify the algebras that such Hamiltonians generate. Thus, our results show that up to local unitary operations, there are only two fundamentally different types of entangling Hamiltonian on n qubits. We also demonstrate that, provided the number of qubits directly coupled by the Hamiltonian is bounded above by a constant, our techniques can be made efficient

  7. Another procedure for the preliminary ordering of loci based on two point lod scores.

    Science.gov (United States)

    Curtis, D

    1994-01-01

    Because of the difficulty of performing full likelihood analysis over multiple loci and the large numbers of possible orders, a number of methods have been proposed for quickly evaluating orders and, to a lesser extent, for generating good orders. A new method is proposed which uses a function which is moderately laborious to compute, the sum of lod scores between all pairs of loci. This function can be smoothly minimized by initially allowing the loci to be placed anywhere in space, and only subsequently constraining them to lie along a one-dimensional map. Application of this approach to sample data suggests that it has promise and might usefully be combined with other methods when loci need to be ordered.

  8. Cure of chronic hepatitis C virus infection in an HIV-coinfected patient with multiple comorbidities and drug interaction challenges.

    Science.gov (United States)

    Álvarez, Hortensia; Mariño, Ana; Valcarce, Nieves; Khoo, Saye; Bhagani, Sanjay; Schapiro, Jonathan; Llibre, Josep M

    2018-01-01

    Curing hepatitis C virus (HCV) infection in patients harbouring multiple severe comorbidities is a medical challenge. Evidence-based data are lacking regarding HCV treatment with direct-acting antiviral regimens in particular populations of HCV/HIV-coinfected patients with cirrhosis and chronic kidney disease on haemodialysis. Here, we present the HCV treatment challenges facing a patient with HIV coinfection, prior failure of both HIV-1 and HCV therapy, cirrhosis, end-stage renal failure on haemodialysis, as well as management of drug-drug interactions, especially given the need to receive long-term amiodarone therapy.

  9. Effects of multiple interacting disturbances and salvage logging on forest carbon stocks

    Science.gov (United States)

    Bradford, J.B.; Fraver, S.; Milo, A.M.; D'Amato, A.W.; Palik, B.; Shinneman, D.J.

    2012-01-01

    Climate change is anticipated to increase the frequency of disturbances, potentially impacting carbon stocks in terrestrial ecosystems. However, little is known about the implications of either multiple disturbances or post-disturbance forest management activities on ecosystem carbon stocks. This study quantified how forest carbon stocks responded to stand-replacing blowdown and wildfire, both individually and in combination with and without post-disturbance salvage operations, in a sub-boreal jack pine ecosystem. Individually, blowdown or fire caused similar decreases in live carbon and total ecosystem carbon. However, whereas blowdown increased carbon in down woody material and forest floor, fire increased carbon in standing snags, a difference that may have consequences for long-term carbon cycling patterns. Fire after the blowdown caused substantial additional reduction in ecosystem carbon stocks, suggesting that potential increases in multiple disturbance events may represent a challenge for sustaining ecosystem carbon stocks. Salvage logging, as examined here, decreased carbon stored in snags and down woody material but had no significant effect on total ecosystem carbon stocks.

  10. Mapping the genetic basis of symbiotic variation in legume-rhizobium interactions in Medicago truncatula.

    Science.gov (United States)

    Gorton, Amanda J; Heath, Katy D; Pilet-Nayel, Marie-Laure; Baranger, Alain; Stinchcombe, John R

    2012-11-01

    Mutualisms are known to be genetically variable, where the genotypes differ in the fitness benefits they gain from the interaction. To date, little is known about the loci that underlie such genetic variation in fitness or whether the loci influencing fitness are partner specific, and depend on the genotype of the interaction partner. In the legume-rhizobium mutualism, one set of potential candidate genes that may influence the fitness benefits of the symbiosis are the plant genes involved in the initiation of the signaling pathway between the two partners. Here we performed quantitative trait loci (QTL) mapping in Medicago truncatula in two different rhizobium strain treatments to locate regions of the genome influencing plant traits, assess whether such regions are dependent on the genotype of the rhizobial mutualist (QTL × rhizobium strain), and evaluate the contribution of sequence variation at known symbiosis signaling genes. Two of the symbiotic signaling genes, NFP and DMI3, colocalized with two QTL affecting average fruit weight and leaf number, suggesting that natural variation in nodulation genes may potentially influence plant fitness. In both rhizobium strain treatments, there were QTL that influenced multiple traits, indicative of either tight linkage between loci or pleiotropy, including one QTL with opposing effects on growth and reproduction. There was no evidence for QTL × rhizobium strain or genotype × genotype interactions, suggesting either that such interactions are due to small-effect loci or that more genotype-genotype combinations need to be tested in future mapping studies.

  11. Tuning of the PYTHIA 6.4 Multiple Parton Interaction model to Minimum Bias and Underlying Event data

    CERN Document Server

    Firdoua, Nameequa

    QCD has been quite successful in describing hadronic interactions at large transfer momenta, also known as hard interactions. However high energy pp and p p collisions are dominated by soft partonic collisions. Di erent phenomenological models are implemented in several Monte Carlo (MC) event generators such as PYTHIA, PHOJET and HERWIG etc., which attempt to simulate these interactions. These MC event generators have free parameters which need to be tuned to improve the agreement with the data. In this thesis the MC event generator PYTHIA6.424 is considered and the optimization of its model parameters have been presented. This work mainly focuses on tuning of multiple parton interaction parameters to Minimum Bias and Underlying event published data from ATLAS at 0.9 and 7TeV and from CDF II at 1.96 TeV. The method employed to tune the parameters is based on a linear and iterative approach and allows the simultaneous variation of many parameters. Six parameters are tuned, which are found to be...

  12. Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

    2016-01-15

    The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

  13. Multiple effects of S13 in modulating the strength of intersubunit interactions in the ribosome during translation.

    Science.gov (United States)

    Cukras, Anthony R; Green, Rachel

    2005-05-27

    The ribosomal protein S13 is found in the head region of the small subunit, where it interacts with the central protuberance of the large ribosomal subunit and with the P site-bound tRNA through its extended C terminus. The bridging interactions between the large and small subunits are dynamic, and are thought to be critical in orchestrating the molecular motions of the translation cycle. S13 provides a direct link between the tRNA-binding site and the movements in the head of the small subunit seen during translocation, thereby providing a possible pathway of signal transduction. We have created and characterized an rpsM(S13)-deficient strain of Escherichia coli and have found significant defects in subunit association, initiation and translocation through in vitro assays of S13-deficient ribosomes. Targeted mutagenesis of specific bridge and tRNA contact elements in S13 provides evidence that these two interaction domains play critical roles in maintaining the fidelity of translation. This ribosomal protein thus appears to play a non-essential, yet important role by modulating subunit interactions in multiple steps of the translation cycle.

  14. Genetic effects at pleiotropic loci are context-dependent with consequences for the maintenance of genetic variation in populations.

    Directory of Open Access Journals (Sweden)

    Heather A Lawson

    2011-09-01

    Full Text Available Context-dependent genetic effects, including genotype-by-environment and genotype-by-sex interactions, are a potential mechanism by which genetic variation of complex traits is maintained in populations. Pleiotropic genetic effects are also thought to play an important role in evolution, reflecting functional and developmental relationships among traits. We examine context-dependent genetic effects at pleiotropic loci associated with normal variation in multiple metabolic syndrome (MetS components (obesity, dyslipidemia, and diabetes-related traits. MetS prevalence is increasing in Western societies and, while environmental in origin, presents substantial variation in individual response. We identify 23 pleiotropic MetS quantitative trait loci (QTL in an F(16 advanced intercross between the LG/J and SM/J inbred mouse strains (Wustl:LG,SM-G16; n = 1002. Half of each family was fed a high-fat diet and half fed a low-fat diet; and additive, dominance, and parent-of-origin imprinting genotypic effects were examined in animals partitioned into sex, diet, and sex-by-diet cohorts. We examine the context-dependency of the underlying additive, dominance, and imprinting genetic effects of the traits associated with these pleiotropic QTL. Further, we examine sequence polymorphisms (SNPs between LG/J and SM/J as well as differential expression of positional candidate genes in these regions. We show that genetic associations are different in different sex, diet, and sex-by-diet settings. We also show that over- or underdominance and ecological cross-over interactions for single phenotypes may not be common, however multidimensional synthetic phenotypes at loci with pleiotropic effects can produce situations that favor the maintenance of genetic variation in populations. Our findings have important implications for evolution and the notion of personalized medicine.

  15. Integrative analysis of a cross-loci regulation network identifies App as a gene regulating insulin secretion from pancreatic islets.

    Directory of Open Access Journals (Sweden)

    Zhidong Tu

    Full Text Available Complex diseases result from molecular changes induced by multiple genetic factors and the environment. To derive a systems view of how genetic loci interact in the context of tissue-specific molecular networks, we constructed an F2 intercross comprised of >500 mice from diabetes-resistant (B6 and diabetes-susceptible (BTBR mouse strains made genetically obese by the Leptin(ob/ob mutation (Lep(ob. High-density genotypes, diabetes-related clinical traits, and whole-transcriptome expression profiling in five tissues (white adipose, liver, pancreatic islets, hypothalamus, and gastrocnemius muscle were determined for all mice. We performed an integrative analysis to investigate the inter-relationship among genetic factors, expression traits, and plasma insulin, a hallmark diabetes trait. Among five tissues under study, there are extensive protein-protein interactions between genes responding to different loci in adipose and pancreatic islets that potentially jointly participated in the regulation of plasma insulin. We developed a novel ranking scheme based on cross-loci protein-protein network topology and gene expression to assess each gene's potential to regulate plasma insulin. Unique candidate genes were identified in adipose tissue and islets. In islets, the Alzheimer's gene App was identified as a top candidate regulator. Islets from 17-week-old, but not 10-week-old, App knockout mice showed increased insulin secretion in response to glucose or a membrane-permeant cAMP analog, in agreement with the predictions of the network model. Our result provides a novel hypothesis on the mechanism for the connection between two aging-related diseases: Alzheimer's disease and type 2 diabetes.

  16. Quantitative trait loci mapping of heat tolerance in broccoli (Brassica oleracea var. italica) using genotyping-by-sequencing.

    Science.gov (United States)

    Branham, Sandra E; Stansell, Zachary J; Couillard, David M; Farnham, Mark W

    2017-03-01

    Five quantitative trait loci and one epistatic interaction were associated with heat tolerance in a doubled haploid population of broccoli evaluated in three summer field trials. Predicted rising global temperatures due to climate change have generated a demand for crops that are resistant to yield and quality losses from heat stress. Broccoli (Brassica oleracea var. italica) is a cool weather crop with high temperatures during production decreasing both head quality and yield. Breeding for heat tolerance in broccoli has potential to both expand viable production areas and extend the growing season but breeding efficiency is constrained by limited genetic information. A doubled haploid (DH) broccoli population segregating for heat tolerance was evaluated for head quality in three summer fields in Charleston, SC, USA. Multiple quantitative trait loci (QTL) mapping of 1,423 single nucleotide polymorphisms developed through genotyping-by-sequencing identified five QTL and one positive epistatic interaction that explained 62.1% of variation in heat tolerance. The QTL identified here can be used to develop markers for marker-assisted selection and to increase our understanding of the molecular mechanisms underlying plant response to heat stress.

  17. 8th International Workshop on Multiple Partonic Interactions at the LHC

    CERN Document Server

    2016-01-01

    MPI are experiencing a growing popularity and are widely invoked to account for observations that cannot be explained otherwise: the activity of the Underlying Event, the rates for multiple heavy flavour production, the survival probability of large rapidity gaps in hard diffraction, etc. At the same time, the implementation of MPI effects in Monte Carlo generators is quickly proceeding at an increasing level of sophistication and complexity, which can have far reaching implications for LHC physics. The ultimate ambition of this workshop is to promote MPI as a unifying concept between apparently distinct lines of research, to profit from experimental progress in order to constrain their implementation in models, and to evaluate their impact on the LHC physics program.

  18. Too many motives? The interactive effects of multiple motives on organizational citizenship behavior.

    Science.gov (United States)

    Takeuchi, Riki; Bolino, Mark C; Lin, Cheng-Chen

    2015-07-01

    Prior research indicates that employees engage in organizational citizenship behaviors (OCBs) because of prosocial values, organizational concern, and impression management motives. Building upon and extending prior research, we investigate all 3 OCB motives by developing a categorization scheme to differentiate their distinctiveness and by building a contextualized argument regarding their interactive effects on OCB in a more collectivistic culture. In a sample of 379 Chinese employee-supervisor dyads from Taiwan, we found that the relationship between prosocial values motives and OCBs directed at individuals was strengthened by organizational concern motives; likewise, the relationship between organizational concern and OCBs directed at the organization was strengthened by prosocial values motives. However, in contrast to prior research (Grant & Mayer, 2009), the relationship between prosocial values motives and OCBs directed at individuals was weakened by impression management motives. A 3-way interaction between all 3 motives further suggests that, in Asian cultures, impression management motives may undermine the positive effects of prosocial values and organizational concern motives on OCBs directed at individuals but not OCBs directed at the organization. (c) 2015 APA, all rights reserved).

  19. Assessing Interactions of Multiple Agrichemicals by Using Bacterial Assemblages in a Wetland Mesocosm System

    Directory of Open Access Journals (Sweden)

    Bruce Libman

    2005-08-01

    Full Text Available Agrichemicals may enter wetlands located adjacent to or downstream from agricultural fields. We investigated the individual and interactive effects of three agrichemicals [atrazine, chlorpyrifos, and monosodium acid methanearsonate (MSMA] and methyl mercury on abundance and heterotrophic potential of wetland heterotrophic bacteria assemblages. We used a factorial experimental design, in which chemicals were introduced in all possible combinations to 66 500-liter mesocosms at the Biological Field Station of the University of Mississippi. Methyl mercury was added to bring the total mercury (HG concentration to 0.4 mg/Kg wet weight at the sediment surface. Atrazine, chlorpyrifos, and MSMA were added at concentrations of 192, 51, and 219μg/L, respectively. Over 32 days of exposure, microbial heterotrophic activity was sensitive to only the interactive effect of HG*ATR*CPF in the sediments and only CPF in the water. Total bacterial numbers did not exhibit any significant treatment effects. Therefore, the effects of agrichemicals were reflected on cell-specific bacterial heterotrophic activity rather than bacterial population size.

  20. Probing the Unique Contributions of Self-Concept, Task Values, and Their Interactions Using Multiple Value Facets and Multiple Academic Outcomes

    Directory of Open Access Journals (Sweden)

    Jiesi Guo

    2016-01-01

    Full Text Available Drawing on expectancy-value theory, the present study examined the unique contributions of the four major value beliefs and self-concept on achievement, self-reported effort, and teacher-rated behavioral engagement in mathematics. In particular, we examined the multiplicative effects of self-concept and task values on educational outcomes using the latent moderated structural equation approach. Participants were 1,868 German ninth-grade students. The data analyses relied on a higher-order structure of value beliefs, which is suited to parsing the differential patterns of predictive relations for different value beliefs. The findings revealed that (a self-concept was more predictive of achievement, whereas value beliefs were more predictive of self-rated effort; (b self-concept and value beliefs emerged as equally important predictors of teacher-reported engagement; (c among the four value beliefs, achievement was more associated with low cost, whereas effort was more associated with attainment value; and (d latent interactions between self-concept and value beliefs predicted the three outcomes synergistically.

  1. Multiparticle Production Process in $pp$ Interaction with High Multiplicity at E_p=70 GeV. Proposal "Termalization"

    CERN Document Server

    Avdeichikov, V V; Balandin, V P; Vasendina, V A; Zhidkov, N K; Zolin, L S; Zulkarneev, R Ya; Kireev, V I; Kosarev, I G; Kuzmin, N A; Kuraev, E A; Mandjavidze, I D; Nikitin, V A; Petukhov, Yu P; Peshekhonov, V D; Rufanov, I A; Susakian, A N; Yukaev, A I; Basiladze, Sergei G; Volkov, V Yu; Ermolov, P F; Kramarenko, V A; Kubarovskii, A V; Leflat, A K; Merkin, M M; Popov, V V; Tikhonova, L A; Anikeev, A N; Vasilchenko, V G; Vorobev, A P; Lapshin, V G; Maiorov, S V; Melnik, Yu M; Meshchanin, A P; Ryadovikov, V N; Kholodenko, A G; Tsyupa, Yu P; Chikilev, O G; Yakutin, A E; Dremin, I M; Kokoulina, E S; Pankov, A A; Kuvshinov, V I

    2004-01-01

    The goal of the proposed experiment is the investigation of the collective behaviour of particles in the process of multiple hadron production in the $pp$ interaction $pp\\to n_\\pi\\pi+2N$ at the beam energy $E_{\\rm lab}=70$ GeV. The domain of high multiplicity $n_\\pi=20{-}35$ or $z=n/\\bar n=3{-}5$ will be studied. Near the threshold of the reaction $n_\\pi\\to 69$, all particles get a small relative momentum. As a consequence of the multiboson interference a number of collective effects may occur. In particular, drastic increase of the partial cross section $\\sigma(n)$ of the $n$ identical particles production, as compared with commonly accepted extrapolation, and increase of the rate of direct photons are expected. The experiment is carried out on the modernized installation SVD, a spectrometer with a vertex detector which is supplied with a trigger system for registration of rare events with high multiplicity, on extracted proton beam of the IHEP (Protvino) 70 GeV accelerator. Required beam intensity is $\\sim ...

  2. Dealing with Tight Couplings and Multiple Interactions in Complex Technological Systems

    DEFF Research Database (Denmark)

    Aanestad, M.; Jensen, Tina Blegind; Grisot, M.

    In this paper we discuss the challenges of dealing with interdependencies in complex assemblages of heterogeneous and interconnected information systems (IS), which we conceptualize as organizationwide information infrastructures. We draw on Perrow's studies of complex technological systems, where...... couplings between information systems, actors, and work practices in the hospital environment. The paper's main focus is on describing what it entails in practice to deal with these interdependencies during and after implementation. We emphasize the work of sorting out and dealing with various types...... interactions, mechanisms, and couplings are emphasized. We base our paper on an empirical case study from a Norwegian hospital, where a seemingly trivial project aimed at the introduction of scanners turned out to be more complex than expected. This we claim is partly due to the interdependencies and tight...

  3. Multiple interactions between maternally-activated signalling pathways control Xenopus nodal-related genes.

    Science.gov (United States)

    Rex, Maria; Hilton, Emma; Old, Robert

    2002-03-01

    We have investigated the induction of the six Xenopus nodal-related genes, Xnr1-Xnr6, by maternal determinants. The beta-catenin pathway was modelled by stimulation using Xwnt8, activin-like signalling was modelled by activin, and VegT action was studied by overexpression in animal cap explants. Combinations of factors were examined, and previously unrecognised interactions were revealed in animal caps and whole embryos. For the induction of Xnr5 and Xnr6 in whole embryos, using a beta-catenin antisense morpholino oligonucleotide or a dominant negative XTcf3, we have demonstrated an absolute permissive requirement for the beta-catenin/Tcf pathway, in addition to the requirement for VegT action. In animal caps Xnr5 and Xnr6 are induced in response to VegT overexpression, and this induction is dependent upon the concomitant activation of the beta-catenin pathway that VegT initiates in animal caps. For the induction of Xnr3, VegT interacts negatively so as to inhibit the induction otherwise observed with wnt-signalling alone. The negative effect of VegT is not the result of a general inhibition of wnt-signalling, and does not result from an inhibition of wnt-induced siamois expression. A 294 bp proximal promoter fragment of the Xnr3 gene is sufficient to mediate the negative effect of VegT. Further experiments, employing cycloheximide to examine the dependence of Xnr gene expression upon proteins translated after the mid-blastula stage, demonstrated that Xnrs 4, 5 and 6 are 'primary' Xnr genes whose expression in the late blastula is solely dependent upon factors present before the mid-blastula stage.

  4. A discrete model of Ostwald ripening based on multiple pairwise interactions

    Science.gov (United States)

    Di Nunzio, Paolo Emilio

    2018-06-01

    A discrete multi-particle model of Ostwald ripening based on direct pairwise interactions is developed for particles with incoherent interfaces as an alternative to the classical LSW mean field theory. The rate of matter exchange depends on the average surface-to-surface interparticle distance, a characteristic feature of the system which naturally incorporates the effect of volume fraction of second phase. The multi-particle diffusion is described through the definition of an interaction volume containing all the particles involved in the exchange of solute. At small volume fractions this is proportional to the size of the central particle, at higher volume fractions it gradually reduces as a consequence of diffusion screening described on a geometrical basis. The topological noise present in real systems is also included. For volume fractions below about 0.1 the model predicts broad and right-skewed stationary size distributions resembling a lognormal function. Above this value, a transition to sharper, more symmetrical but still right-skewed shapes occurs. An excellent agreement with experiments is obtained for 3D particle size distributions of solid-solid and solid-liquid systems with volume fraction 0.07, 0.30, 0.52 and 0.74. The kinetic constant of the model depends on the cube root of volume fraction up to about 0.1, then increases rapidly with an upward concavity. It is in good agreement with the available literature data on solid-liquid mixtures in the volume fraction range from 0.20 to about 0.75.

  5. Interactions of Multiple Atmospheric Circulation Drive the Drought in Tarim River Basin

    Science.gov (United States)

    Wu, Yong-Ping; Feng, Guo-Lin; Li, Bai-Lian

    2016-05-01

    Global warming is likely to cause overall drying of land surfaces and aridity increasing leading to expansion of dry climate zones. There is an increased risk of extremely arid environment and large deserts developed progressively in the central Asia. However, the key factors causing the drying in mid-Asia remain inconclusive. Here, we analyzed the relationship among precipitation, water vapor transportation in Tarim River Basin (TRB) and Multiple Atmospheric Circulation (MAC) to explore the mechanism of MAC driving the drying in TRB, through comparing MAC between abundant and scarce precipitation years. We found that Westerly Circulation (WC) and Asian Summer Monsoon (ASM) are likely to promote the precipitation respectively. Whereas, they not only have their own influence but also restrict each other and facilitate the forming of peculiar water vapor transport channel for TRB, which is probably to restrain the precipitation and its distribution pattern and accelerate the drying in this region. Our results enrich the findings on mechanisms of wet places becoming wetter while dry areas getting drier under the global warming.

  6. Transverse energy and multiplicity distributions of p-p and A+A interactions

    International Nuclear Information System (INIS)

    Tannenbaum, M.J.

    1990-01-01

    Data from AGS-E802 have been presented at the percent HIPAGS workshop at BNL, published in journals and in conference proceedings (St. Malo, Moriond), to which the reader is referred. Two results are mentioned here. The Lead Glass distribution dE T 0 /dn from central O + Au collisions can be compared to the spectrometer dn (π-)/dy from central Si + Au collisions. The agreement of the two distributions is excellent and confirms that the estimated position and value of the maximum in the distribution η|max, dE T /dη|max, and the width Δη FWHM , from the PbGl data are reasonable, and that nothing exceptional is occurring outside of the PbGl acceptance. Additionally, these data, and previous measurements of pseudorapidity distributions of multiplicity and Transverse Energy at both the AGS and CERN are analyzed in an acceptance-independent and model-independent method, with the conclusion that simple considerations of nuclear geometry do not provide an explanation of the different √ s NN dependences observed in 16 O + Au and p-p reactions. 13 refs., 2 figs

  7. Wide range of interacting partners of pea Gβ subunit of G-proteins suggests its multiple functions in cell signalling.

    Science.gov (United States)

    Bhardwaj, Deepak; Lakhanpaul, Suman; Tuteja, Narendra

    2012-09-01

    Climate change is a major concern especially in view of the increasing global population and food security. Plant scientists need to look for genetic tools whose appropriate usage can contribute to sustainable food availability. G-proteins have been identified as some of the potential genetic tools that could be useful for protecting plants from various stresses. Heterotrimeric G-proteins consisting of three subunits Gα, Gβ and Gγ are important components of a number of signalling pathways. Their structure and functions are already well studied in animals but their potential in plants is now gaining attention for their role in stress tolerance. Earlier we have reported that over expressing pea Gβ conferred heat tolerance in tobacco plants. Here we report the interacting partners (proteins) of Gβ subunit of Pisum sativum and their putative role in stress and development. Out of 90 transformants isolated from the yeast-two-hybrid (Y2H) screening, seven were chosen for further investigation due to their recurrence in multiple experiments. These interacting partners were confirmed using β-galactosidase colony filter lift and ONPG (O-nitrophenyl-β-D-galactopyranoside) assays. These partners include thioredoxin H, histidine-containing phosphotransfer protein 5-like, pathogenesis-related protein, glucan endo-beta-1, 3-glucosidase (acidic isoform), glycine rich RNA binding protein, cold and drought-regulated protein (corA gene) and soluble inorganic pyrophosphatase 1. This study suggests the role of pea Gβ subunit in stress signal transduction and development pathways owing to its capability to interact with a wide range of proteins of multiple functions. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  8. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    Energy Technology Data Exchange (ETDEWEB)

    Baattrup-Pedersen, Annette, E-mail: abp@bios.au.dk [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Göthe, Emma [Department of Bioscience, Aarhus University, Vejlsøvej 25, P.O. Box 314, DK-8600 Silkeborg (Denmark); Riis, Tenna [Department of Bioscience, Aarhus University, Ole Worms Allé 1, Building 1135, Room 217, DK-8000 Aarhus C (Denmark); O' Hare, Matthew T. [Centre for Ecology and Hydrology, Bush Estate, Penicuik EH26 0QB (United Kingdom)

    2016-02-01

    Historically, close attention has been paid to negative impacts associated with nutrient loads to streams and rivers, but today hydromorphological alterations are considered increasingly implicated when lowland streams do not achieve good ecological status. Here, we explore if trait-abundance patterns of aquatic plants change along gradients in hydromorphological degradation and eutrophication in lowland stream sites located in Denmark. Specifically, we hypothesised that: i) changes in trait-abundance patterns occur along gradients in hydromorphological degradation and ii) trait-abundance patterns can serve to disentangle effects of eutrophication and hydromorphological degradation in lowland streams reflecting that the mechanisms behind changes differ. We used monitoring data from a total of 147 stream reaches with combined data on aquatic plant species abundance, catchment land use, hydromorphological alterations (i.e. planform, cross section, weed cutting) and water chemistry parameters. Traits related to life form, dispersal, reproduction and survival together with ecological preference values for nutrients and light (Ellenberg N and L) were allocated to 41 species representing 79% of the total species pool. We found clear evidence that habitat degradation (hydromorphological alterations and eutrophication) mediated selective changes in the trait-abundance patterns of the plant community. Specific traits could distinguish hydromorphological degradation (free-floating, surface; anchored floating leaves; anchored heterophylly) from eutrophication (free-floating, submerged; leaf area). We provide a conceptual framework for interpretation of how eutrophication and hydromorphological degradation interact and how this is reflected in trait-abundance patterns in aquatic plant communities in lowland streams. Our findings support the merit of trait-based approaches in biomonitoring as they shed light on mechanisms controlling structural changes under environmental

  9. Functional trait composition of aquatic plants can serve to disentangle multiple interacting stressors in lowland streams

    International Nuclear Information System (INIS)

    Baattrup-Pedersen, Annette; Göthe, Emma; Riis, Tenna; O'Hare, Matthew T.

    2016-01-01

    Historically, close attention has been paid to negative impacts associated with nutrient loads to streams and rivers, but today hydromorphological alterations are considered increasingly implicated when lowland streams do not achieve good ecological status. Here, we explore if trait-abundance patterns of aquatic plants change along gradients in hydromorphological degradation and eutrophication in lowland stream sites located in Denmark. Specifically, we hypothesised that: i) changes in trait-abundance patterns occur along gradients in hydromorphological degradation and ii) trait-abundance patterns can serve to disentangle effects of eutrophication and hydromorphological degradation in lowland streams reflecting that the mechanisms behind changes differ. We used monitoring data from a total of 147 stream reaches with combined data on aquatic plant species abundance, catchment land use, hydromorphological alterations (i.e. planform, cross section, weed cutting) and water chemistry parameters. Traits related to life form, dispersal, reproduction and survival together with ecological preference values for nutrients and light (Ellenberg N and L) were allocated to 41 species representing 79% of the total species pool. We found clear evidence that habitat degradation (hydromorphological alterations and eutrophication) mediated selective changes in the trait-abundance patterns of the plant community. Specific traits could distinguish hydromorphological degradation (free-floating, surface; anchored floating leaves; anchored heterophylly) from eutrophication (free-floating, submerged; leaf area). We provide a conceptual framework for interpretation of how eutrophication and hydromorphological degradation interact and how this is reflected in trait-abundance patterns in aquatic plant communities in lowland streams. Our findings support the merit of trait-based approaches in biomonitoring as they shed light on mechanisms controlling structural changes under environmental

  10. Do multiple fires interact to affect vegetation structure in temperate eucalypt forests?

    Science.gov (United States)

    Haslem, Angie; Leonard, Steve W J; Bruce, Matthew J; Christie, Fiona; Holland, Greg J; Kelly, Luke T; MacHunter, Josephine; Bennett, Andrew F; Clarke, Michael F; York, Alan

    2016-12-01

    Fire plays an important role in structuring vegetation in fire-prone regions worldwide. Progress has been made towards documenting the effects of individual fire events and fire regimes on vegetation structure; less is known of how different fire history attributes (e.g., time since fire, fire frequency) interact to affect vegetation. Using the temperate eucalypt foothill forests of southeastern Australia as a case study system, we examine two hypotheses about such interactions: (1) post-fire vegetation succession (e.g., time-since-fire effects) is influenced by other fire regime attributes and (2) the severity of the most recent fire overrides the effect of preceding fires on vegetation structure. Empirical data on vegetation structure were collected from 540 sites distributed across central and eastern Victoria, Australia. Linear mixed models were used to examine these hypotheses and determine the relative influence of fire and environmental attributes on vegetation structure. Fire history measures, particularly time since fire, affected several vegetation attributes including ground and canopy strata; others such as low and sub-canopy vegetation were more strongly influenced by environmental characteristics like rainfall. There was little support for the hypothesis that post-fire succession is influenced by fire history attributes other than time since fire; only canopy regeneration was influenced by another variable (fire type, representing severity). Our capacity to detect an overriding effect of the severity of the most recent fire was limited by a consistently weak effect of preceding fires on vegetation structure. Overall, results suggest the primary way that fire affects vegetation structure in foothill forests is via attributes of the most recent fire, both its severity and time since its occurrence; other attributes of fire regimes (e.g., fire interval, frequency) have less influence. The strong effect of environmental drivers, such as rainfall and

  11. Charged particles multiplicity in interactions of 3.7 A GeV 28Si with light and heavy target nuclei in nuclear emulsions

    International Nuclear Information System (INIS)

    Singh, B.K.; Tuli, S.K.

    1998-01-01

    Results from measurement of multiplicity of different charged particles emitted from the interactions of 3.7 A GeV 28 Si with different target groups in nuclear emulsion and correlations among them are presented. The nature of the dependence of multiplicities of charged particles on the impact parameter is examined. Analysis of data in terms of specific multiplicity for different target groups is performed and the results are discussed in the light of superposition model. (author)

  12. Multiplicities of pions and slow protons in nuclear interactions at relativistic energies

    International Nuclear Information System (INIS)

    Idh, J.

    1993-02-01

    The distributions of the transverse energy and the multiplicity of charged particles in oxygen induced reactions are examined in the Fritiof Monte Carlo model. The shape of the distributions are found to be determined by the distribution of the number of particle-emitting sources, i.e. strings. The fluctuations in particle emission from each string is hidden by these much larger fluctuations. The fluctuations of these distributions when partial phase space coverage is used is well described by purely stochastic emission. Distributions of slow singly-charged fragments in the target region is measured for both hadron and oxygen induced reactions. The distributions extends to much larger values than simulated data from the Monte Carlo models Fritiof 1.7 and Venus 3.14. The hadron induced reactions give distributions that can be reproduced assuming that each participating target nucleon produced fragments according to a geometric distribution, where the average number of fragments per participating target nucleon is target dependent. The extracted average number of produced fragments are similar for proton and pion induced reactions. When the tails of the distributions are studied their extension can be parametrized, and for such an approach a target dependence of A 2/3 is found for all projectiles. The data for 60 and 200 A GeV are almost identical for distributions as well as angular and energy examined distributions. The angular distributions follow an exponential in cos(θ). If the slopes of the angular distributions are examined and target dependences as well as centrality dependences are extracted. For light targets there is a strong target dependence, but for targets heavier than copper there is not any great differences. The centrality dependence is almost negligible for a gold-target but for a copper-target the most central collisions have more forward peaked distributions. (62 refs.)

  13. Biology and applications of human minisatellite loci.

    Science.gov (United States)

    Armour, J A; Jeffreys, A J

    1992-12-01

    Highly repetitive minisatellites' include the most variable human loci described to date. They have proved invaluable in a wide variety of genetic analyses, and despite some controversies surrounding their practical implementation, have been extensively adopted in civil and forensic casework. Molecular analysis of internal allelic structure has provided detailed insights into the repeat-unit turnover mechanisms operating in germline mutations, which are ultimately responsible for the extreme variability seen at these loci.

  14. Interaction of multiple networks modulated by the working memory training based on real-time fMRI

    Science.gov (United States)

    Shen, Jiahui; Zhang, Gaoyan; Zhu, Chaozhe; Yao, Li; Zhao, Xiaojie

    2015-03-01

    Neuroimaging studies of working memory training have identified the alteration of brain activity as well as the regional interactions within the functional networks such as central executive network (CEN) and default mode network (DMN). However, how the interaction within and between these multiple networks is modulated by the training remains unclear. In this paper, we examined the interaction of three training-induced brain networks during working memory training based on real-time functional magnetic resonance imaging (rtfMRI). Thirty subjects assigned to the experimental and control group respectively participated in two times training separated by seven days. Three networks including silence network (SN), CEN and DMN were identified by the training data with the calculated function connections within each network. Structural equation modeling (SEM) approach was used to construct the directional connectivity patterns. The results showed that the causal influences from the percent signal changes of target ROI to the SN were positively changed in both two groups, as well as the causal influence from the SN to CEN was positively changed in experimental group but negatively changed in control group from the SN to DMN. Further correlation analysis of the changes in each network with the behavioral improvements showed that the changes in SN were stronger positively correlated with the behavioral improvement of letter memory task. These findings indicated that the SN was not only a switch between the target ROI and the other networks in the feedback training but also an essential factor to the behavioral improvement.

  15. Probabilistic assessment of the dynamic interaction between multiple pedestrians and vertical vibrations of footbridges

    Science.gov (United States)

    Tubino, Federica

    2018-03-01

    The effect of human-structure interaction in the vertical direction for footbridges is studied based on a probabilistic approach. The bridge is modeled as a continuous dynamic system, while pedestrians are schematized as moving single-degree-of-freedom systems with random dynamic properties. The non-dimensional form of the equations of motion allows us to obtain results that can be applied in a very wide set of cases. An extensive Monte Carlo simulation campaign is performed, varying the main non-dimensional parameters identified, and the mean values and coefficients of variation of the damping ratio and of the non-dimensional natural frequency of the coupled system are reported. The results obtained can be interpreted from two different points of view. If the characterization of pedestrians' equivalent dynamic parameters is assumed as uncertain, as revealed from a current literature review, then the paper provides a range of possible variations of the coupled system damping ratio and natural frequency as a function of pedestrians' parameters. Assuming that a reliable characterization of pedestrians' dynamic parameters is available (which is not the case at present, but could be in the future), the results presented can be adopted to estimate the damping ratio and natural frequency of the coupled footbridge-pedestrian system for a very wide range of real structures.

  16. Simultaneous analysis of multiple neurotransmitters by hydrophilic interaction liquid chromatography coupled to tandem mass spectrometry.

    Science.gov (United States)

    Tufi, Sara; Lamoree, Marja; de Boer, Jacob; Leonards, Pim

    2015-05-22

    Neurotransmitters are endogenous metabolites that allow the signal transmission across neuronal synapses. Their biological role is crucial for many physiological functions and their levels can be changed by several diseases. Because of their high polarity, hydrophilic interaction liquid chromatography (HILIC) is a promising tool for neurotransmitter analysis. Due to the large number of HILIC stationary phases available, an evaluation of the column performances and retention behaviors has been performed on five different commercial HILIC packing materials (silica, amino, amide and two zwitterionic stationary phases). Several parameters like the linear correlation between retention and the distribution coefficient (logD), the separation factor k and the column resolution Rs have been investigated and the column performances have been visualized with a heat map and hierarchical clustering analysis. An optimized and validated HILIC-MS/MS method based on the ZIC-cHILIC column is proposed for the simultaneous detection and quantification of twenty compounds consisting of neurotransmitters, precursors and metabolites: 3-methoxytyramine (3-MT), 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxy-L-tripthophan, acetylcholine, choline, L-3,4-dihydroxyphenylalanine (L-DOPA), dopamine, epinephrine, γ-aminobutyric acid (GABA), glutamate, glutamine, histamine, histidine, L-tryptophan, L-tyrosine, norepinephrine, normetanephrine, phenylalanine, serotonin and tyramine. The method was applied to neuronal metabolite profiling of the central nervous system of the freshwater snail Lymnaea stagnalis. This method is suitable to explore neuronal metabolism and its alteration in different biological matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  18. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    NARCIS (Netherlands)

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, Jose Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Terue, Maria; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; Lopez-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Angel Gonzalez-Gay, Miguel; Zhernakova, Alexandra; Padyukov, Leonid; Aarcon-Riquelme, Marta; Wijmenga, Cisca; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jorg H. W.; Voskuy, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airo, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic

  19. Lifestyle may modify the glucose-raising effect of genetic loci. A study in the Greek population.

    Science.gov (United States)

    Marouli, E; Kanoni, S; Dimitriou, M; Kolovou, G; Deloukas, P; Dedoussis, G

    2016-03-01

    Lifestyle habits including dietary intake and physical activity are closely associated with multiple body processes including glucose metabolism and are known to affect human health. Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with glucose levels. The hypothesis tested here is whether a healthy lifestyle assessed via a score is associated with glycaemic traits and whether there is an interaction between the lifestyle and known glucose-raising genetic variants in association with glycaemic traits. Participants of Greek descent from the THISEAS study were included in this analysis. We developed a glucose preventive score (GPS) including dietary and physical activity characteristics. We also modelled a weighted genetic risk score (wGRS), based on 20 known glucose-raising loci, in order to investigate the impact of lifestyle-gene interaction on glucose levels. The GPS was observed to be significantly associated with lower glucose concentrations (β ± SE: -0.083 ± 0.021 mmol/L, P = 1.6 × 10(-04)) and the wGRS, as expected, with increased glucose levels (β ± SE: 0.020 ± 0.007 mmol/L, P = 8.4 × 10(-3)). The association of the wGRS with glucose levels was attenuated after interaction with the GPS. A higher GPS indicated decreasing glucose levels in the presence of an increasing wGRS (β interaction ± SE: -0.019 ± 0.007 mmol/L, P = 0.014). Our results indicate that lower glucose levels underlie a healthier lifestyle and also support an interaction between the wGRS for known glycaemic loci and GPS associated with lower glucose levels. These scores could be useful tools for monitoring glucose metabolism. Copyright © 2016. Published by Elsevier B.V.

  20. Design and synthesis of an amphiphilic graft hydrogel having a hydrophobic domain formed by multiple interactions

    Energy Technology Data Exchange (ETDEWEB)

    Nitta, Kyohei [Department of Life and Functional Material Science, Graduate School of Natural Science, Konan University, 8-9-1 Okamoto, Higashinada, Kobe 658-8501 (Japan); Japan Society for the Promotion of Science (DC1), Ichibancho, Chiyoda, Tokyo 102-8471 (Japan); Kimoto, Atsushi [Department of Chemistry of Functional Molecules, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada, Kobe 658-8501 (Japan); Watanabe, Junji, E-mail: junjiknd@konan-u.ac.jp [Department of Chemistry of Functional Molecules, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada, Kobe 658-8501 (Japan)

    2016-11-01

    A novel hydrogel having hydrophobic oligo segments and hydrophilic poly(acrylamidoglycolic acid) (PAGA) as pH responsive polymer segments was designed and synthesized to be used as a soft biomaterial. Poly(trimethylene carbonate) (PTMC) as the side chain, for which the degrees of polymerization were 9, 19, and 49, and the composition ratios were 1, 5, and 10 mol%, was used as the oligo segment in the hydrogel. The swelling ratio of the hydrogel was investigated under various changes in conditions such as pH, temperature, and hydrogen bonding upon urea addition. Under pH 2–11 conditions, the graft gel reversibly swelled and shrank due to the effect of PAGA main chain. The interior morphology and skin layer of the hydrogel was observed by a scanning electron microscope. The hydrogel composed of PAGA as the hydrophilic polymer backbone had a sponge-like structure, with a pore size of approximately 100 μm. On the other hand, upon increasing the ratio of trimethylene carbonate (TMC) units in the hydrogel, the pores became smaller or disappeared. Moreover, thickness of the skin layer significantly increased with the swelling ratio depended on the incorporation ratios of the PTMC macromonomer. Molecular incorporation in the hydrogel was evaluated using a dye as a model drug molecule. These features would play an important role in drug loading. Increasing the ratio of TMC units favored the adsorption of the dye and activation of the incorporation behavior. - Highlights: • Hydrogen bonding and hydrophobic interaction are dominant factor for forming hydrogels. • Hydrogel properties were tuned by changing in graft length and macromonomer content in feed. • The resulting graft gel could encapsulate and retain organic dye in the hydrogel. • Poly(trimethylene carbonate) segment in the hydrogel was dominant unit for hydrogel.

  1. Quantifying Trophic Interactions and Carbon Flow in Louisiana Salt Marshes Using Multiple Biomarkers

    Science.gov (United States)

    Polito, M. J.; Lopez-Duarte, P. C.; Olin, J.; Johnson, J. J.; Able, K.; Martin, C. W.; Fodrie, J.; Hooper-Bui, L. M.; Taylor, S.; Stouffer, P.; Roberts, B. J.; Rabalais, N. N.; Jensen, O.

    2017-12-01

    Salt marshes are critical habitats for many species in the northern Gulf of Mexico. However, given their complex nature, quantifying trophic linkages and the flow of carbon through salt marsh food webs is challenging. This gap in our understanding of food web structure and function limits our ability to evaluate the impacts of natural and anthropogenic stressors on salt marsh ecosystems. For example, 2010 Deepwater Horizon (DWH) oil spill had the potential to alter trophic and energy pathways. Even so, our ability to evaluate its effects on Louisiana salt marsh food webs was limited by a poor basis for comparison of the pre-spill baseline food web. To be better equipped to measure significant alterations in salt marsh ecosystems in the future, we quantified trophic interactions at two marsh sites in Barataria Bay, LA in May and October of 2015. Trophic structure and carbon flow across 52 species of saltmarsh primary producers and consumers were examined through a combination of three approaches: bulk tissue stable isotope analysis (δ13C, δ15N, δ34S), dietary fatty acid analysis (FAA), and compound-specific stable isotope analysis of essential amino acids (δ13C EAA). Bulk stable isotope analysis indicated similar trophic diversity between sites and seasons with the use of aquatic resources increasing concomitantly with trophic level. FAA and δ13C EAA biomarkers revealed that marsh organisms were largely divided into two groups: those that primarily derive carbon from terrestrial C4 grasses, and those that predominately derive carbon from a combination of phytoplankton and benthic microalgal sources. Differences in trophic structure and carbon flow were minimal between seasons and sites that were variably impacted by the DWH spill. These data on salt marsh ecosystem structure will be useful to inform future injury assessments and restoration initiatives.

  2. Design and synthesis of an amphiphilic graft hydrogel having a hydrophobic domain formed by multiple interactions

    International Nuclear Information System (INIS)

    Nitta, Kyohei; Kimoto, Atsushi; Watanabe, Junji

    2016-01-01

    A novel hydrogel having hydrophobic oligo segments and hydrophilic poly(acrylamidoglycolic acid) (PAGA) as pH responsive polymer segments was designed and synthesized to be used as a soft biomaterial. Poly(trimethylene carbonate) (PTMC) as the side chain, for which the degrees of polymerization were 9, 19, and 49, and the composition ratios were 1, 5, and 10 mol%, was used as the oligo segment in the hydrogel. The swelling ratio of the hydrogel was investigated under various changes in conditions such as pH, temperature, and hydrogen bonding upon urea addition. Under pH 2–11 conditions, the graft gel reversibly swelled and shrank due to the effect of PAGA main chain. The interior morphology and skin layer of the hydrogel was observed by a scanning electron microscope. The hydrogel composed of PAGA as the hydrophilic polymer backbone had a sponge-like structure, with a pore size of approximately 100 μm. On the other hand, upon increasing the ratio of trimethylene carbonate (TMC) units in the hydrogel, the pores became smaller or disappeared. Moreover, thickness of the skin layer significantly increased with the swelling ratio depended on the incorporation ratios of the PTMC macromonomer. Molecular incorporation in the hydrogel was evaluated using a dye as a model drug molecule. These features would play an important role in drug loading. Increasing the ratio of TMC units favored the adsorption of the dye and activation of the incorporation behavior. - Highlights: • Hydrogen bonding and hydrophobic interaction are dominant factor for forming hydrogels. • Hydrogel properties were tuned by changing in graft length and macromonomer content in feed. • The resulting graft gel could encapsulate and retain organic dye in the hydrogel. • Poly(trimethylene carbonate) segment in the hydrogel was dominant unit for hydrogel.

  3. Interactions between multiple filaments and bacterial biofilms on the surface of an apple

    Science.gov (United States)

    He, CHENG; Maoyuan, XU; Shuhui, PAN; Xinpei, LU; Dawei, LIU

    2018-04-01

    In this paper, the interactions between two dielectric barrier discharge (DBD) filaments and three bacterial biofilms are simulated. The modeling of a DBD streamer is studied by means of 2D finite element calculation. The model is described by the proper governing equations of air DBD at atmospheric pressure and room temperature. The electric field in the computing domain and the self-consistent transportation of reactive species between a cathode and biofilms on the surface of an apple are realized by solving a Poisson equation and continuity equations. The electron temperature is solved by the electron energy conservation equation. The conductivity and permittivity of bacterial biofilms are considered, and the shapes of the bacterial biofilms are irregular in the uncertainty and randomness of colony growth. The distribution of the electrons suggests that two plasma channels divide into three plasma channels when the streamer are 1 mm from the biofilms. The toe-shapes of the biofilms and the simultaneous effect of two streamer heads result in a high electric field around the biofilms, therefore the stronger ionization facilitates the major part of two streamers combined into one streamer and three streamers arise. The distribution of the reactive oxygen species and the reactive nitrogen species captured by time fluences are non-uniform due to the toe-shaped bacterial biofilms. However, the plasma can intrude into the cavities in the adjacent biofilms due to the μm-scale mean free path. The two streamers case has a larger treatment area and realizes the simultaneous treatment of three biofilms compared with one streamer case.

  4. Multiple drivers, scales, and interactions influence southern Appalachian stream salamander occupancy

    Science.gov (United States)

    Cecala, Kristen K.; Maerz, John C.; Halstead, Brian J.; Frisch, John R.; Gragson, Ted L.; Hepinstall-Cymerman, Jeffrey; Leigh, David S.; Jackson, C. Rhett; Peterson, James T.; Pringle, Catherine M.

    2018-01-01

    Understanding how factors that vary in spatial scale relate to population abundance is vital to forecasting species responses to environmental change. Stream and river ecosystems are inherently hierarchical, potentially resulting in organismal responses to fine‐scale changes in patch characteristics that are conditional on the watershed context. Here, we address how populations of two salamander species are affected by interactions among hierarchical processes operating at different scales within a rapidly changing landscape of the southern Appalachian Mountains. We modeled reach‐level occupancy of larval and adult black‐bellied salamanders (Desmognathus quadramaculatus) and larval Blue Ridge two‐lined salamanders (Eurycea wilderae) as a function of 17 different terrestrial and aquatic predictor variables that varied in spatial extent. We found that salamander occurrence varied widely among streams within fully forested catchments, but also exhibited species‐specific responses to changes in local conditions. While D. quadramaculatus declined predictably in relation to losses in forest cover, larval occupancy exhibited the strongest negative response to forest loss as well as decreases in elevation. Conversely, occupancy of E. wilderae was unassociated with watershed conditions, only responding negatively to higher proportions of fast‐flowing stream habitat types. Evaluation of hierarchical relationships demonstrated that most fine‐scale variables were closely correlated with broad watershed‐scale variables, suggesting that local reach‐scale factors have relatively smaller effects within the context of the larger landscape. Our results imply that effective management of southern Appalachian stream salamanders must first focus on the larger scale condition of watersheds before management of local‐scale conditions should proceed. Our findings confirm the results of some studies while refuting the results of others, which may indicate that

  5. Multiple Gene-Environment Interactions on the Angiogenesis Gene-Pathway Impact Rectal Cancer Risk and Survival

    Directory of Open Access Journals (Sweden)

    Noha Sharafeldin

    2017-09-01

    Full Text Available Characterization of gene-environment interactions (GEIs in cancer is limited. We aimed at identifying GEIs in rectal cancer focusing on a relevant biologic process involving the angiogenesis pathway and relevant environmental exposures: cigarette smoking, alcohol consumption, and animal protein intake. We analyzed data from 747 rectal cancer cases and 956 controls from the Diet, Activity and Lifestyle as a Risk Factor for Rectal Cancer study. We applied a 3-step analysis approach: first, we searched for interactions among single nucleotide polymorphisms on the pathway genes; second, we searched for interactions among the genes, both steps using Logic regression; third, we examined the GEIs significant at the 5% level using logistic regression for cancer risk and Cox proportional hazards models for survival. Permutation-based test was used for multiple testing adjustment. We identified 8 significant GEIs associated with risk among 6 genes adjusting for multiple testing: TNF (OR = 1.85, 95% CI: 1.10, 3.11, TLR4 (OR = 2.34, 95% CI: 1.38, 3.98, and EGR2 (OR = 2.23, 95% CI: 1.04, 4.78 with smoking; IGF1R (OR = 1.69, 95% CI: 1.04, 2.72, TLR4 (OR = 2.10, 95% CI: 1.22, 3.60 and EGR2 (OR = 2.12, 95% CI: 1.01, 4.46 with alcohol; and PDGFB (OR = 1.75, 95% CI: 1.04, 2.92 and MMP1 (OR = 2.44, 95% CI: 1.24, 4.81 with protein. Five GEIs were associated with survival at the 5% significance level but not after multiple testing adjustment: CXCR1 (HR = 2.06, 95% CI: 1.13, 3.75 with smoking; and KDR (HR = 4.36, 95% CI: 1.62, 11.73, TLR2 (HR = 9.06, 95% CI: 1.14, 72.11, EGR2 (HR = 2.45, 95% CI: 1.42, 4.22, and EGFR (HR = 6.33, 95% CI: 1.95, 20.54 with protein. GEIs between angiogenesis genes and smoking, alcohol, and animal protein impact rectal cancer risk. Our results support the importance of considering the biologic hypothesis to characterize GEIs associated with cancer outcomes.

  6. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations

    Directory of Open Access Journals (Sweden)

    Rajani Rai

    2015-11-01

    Full Text Available Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR and Classification and Regression Tree Analysis (CRT to investigate the gene–gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634; FAS (rs2234767; FASL (rs763110; DCC (rs2229080, rs4078288, rs7504990, rs714; PSCA (rs2294008, rs2978974; ADRA2A (rs1801253; ADRB1 (rs1800544; ADRB3 (rs4994; CYP17 (rs2486758 involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634, DCC (rs714, rs2229080, rs4078288 and ADRB3 (rs4994 polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994 to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10 or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10. Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility.

  7. Three new loci for determining x chromosome inactivation patterns

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Tümer, Zeynep; Ravn, Kirstine

    2011-01-01

    . The reliability of the loci was validated by showing a high correlation between the results obtained by employing the new loci and the AR locus using DNA from 15 females who were informative for all four loci. Altogether, we show that these loci can be applied easily in molecular diagnostic laboratories, either...

  8. Characterization of interactions of simvastatin, pravastatin, fluvastatin, and pitavastatin with bovine serum albumin: multiple spectroscopic and molecular docking.

    Science.gov (United States)

    Shi, Jie-Hua; Wang, Qi; Pan, Dong-Qi; Liu, Ting-Ting; Jiang, Min

    2017-05-01

    The binding interactions of simvastatin (SIM), pravastatin (PRA), fluvastatin (FLU), and pitavastatin (PIT) with bovine serum albumin (BSA) were investigated for determining the affinity of four statins with BSA through multiple spectroscopic and molecular docking methods. The experimental results showed that SIM, PRA, FLU, and PIT statins quenched the intrinsic fluorescence of BSA through a static quenching process and the stable stains-BSA complexes with the binding constants in the order of 10 4  M -1 at 298 K were formed through intermolecular nonbond interaction. The values of ΔH 0 , ΔS 0 and ΔG 0 in the binding process of SIM, PRA, FLU, and PIT with BSA were negative at the studied temperature range, suggesting that the binding process of four statins and BSA was spontaneous and the main interaction forces were van der Waals force and hydrogen-bonding interactions. Moreover, the binding of four statins with BSA was enthalpy-driven process due to |ΔH°|>|TΔS°| under the studied temperature range. From the results of site marker competitive experiments and molecular docking, subdomain IIIA (site II) was the primary binding site for SIM, PRA, FLU, and PIT on BSA. The results of UV-vis absorption, synchronous fluorescence, 3D fluorescence and FT-IR spectra proved that the slight change in the conformation of BSA, while the significant changes in the conformation of SIM, PRA, FLU, and PIT drug in statin-BSA complexes, indicating that the flexibility of statin molecules plays an important role in increasing the stability of statin-BSA complexes.

  9. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

    DEFF Research Database (Denmark)

    Justice, Anne E; Winkler, Thomas W; Feitosa, Mary F

    2017-01-01

    Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87......% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent...... direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting...

  10. Amplification Biases and Consistent Recovery of Loci in a Double-Digest RAD-seq Protocol

    Science.gov (United States)

    DaCosta, Jeffrey M.; Sorenson, Michael D.

    2014-01-01

    A growing variety of “genotype-by-sequencing” (GBS) methods use restriction enzymes and high throughput DNA sequencing to generate data for a subset of genomic loci, allowing the simultaneous discovery and genotyping of thousands of polymorphisms in a set of multiplexed samples. We evaluated a “double-digest” restriction-site associated DNA sequencing (ddRAD-seq) protocol by 1) comparing results for a zebra finch (Taeniopygia guttata) sample with in silico predictions from the zebra finch reference genome; 2) assessing data quality for a population sample of indigobirds (Vidua spp.); and 3) testing for consistent recovery of loci across multiple samples and sequencing runs. Comparison with in silico predictions revealed that 1) over 90% of predicted, single-copy loci in our targeted size range (178–328 bp) were recovered; 2) short restriction fragments (38–178 bp) were carried through the size selection step and sequenced at appreciable depth, generating unexpected but nonetheless useful data; 3) amplification bias favored shorter, GC-rich fragments, contributing to among locus variation in sequencing depth that was strongly correlated across samples; 4) our use of restriction enzymes with a GC-rich recognition sequence resulted in an up to four-fold overrepresentation of GC-rich portions of the genome; and 5) star activity (i.e., non-specific cutting) resulted in thousands of “extra” loci sequenced at low depth. Results for three species of indigobirds show that a common set of thousands of loci can be consistently recovered across both individual samples and sequencing runs. In a run with 46 samples, we genotyped 5,996 loci in all individuals and 9,833 loci in 42 or more individuals, resulting in <1% missing data for the larger data set. We compare our approach to similar methods and discuss the range of factors (fragment library preparation, natural genetic variation, bioinformatics) influencing the recovery of a consistent set of loci among

  11. MRMer, an interactive open source and cross-platform system for data extraction and visualization of multiple reaction monitoring experiments.

    Science.gov (United States)

    Martin, Daniel B; Holzman, Ted; May, Damon; Peterson, Amelia; Eastham, Ashley; Eng, Jimmy; McIntosh, Martin

    2008-11-01

    Multiple reaction monitoring (MRM) mass spectrometry identifies and quantifies specific peptides in a complex mixture with very high sensitivity and speed and thus has promise for the high throughput screening of clinical samples for candidate biomarkers. We have developed an interactive software platform, called MRMer, for managing highly complex MRM-MS experiments, including quantitative analyses using heavy/light isotopic peptide pairs. MRMer parses and extracts information from MS files encoded in the platform-independent mzXML data format. It extracts and infers precursor-product ion transition pairings, computes integrated ion intensities, and permits rapid visual curation for analyses exceeding 1000 precursor-product pairs. Results can be easily output for quantitative comparison of consecutive runs. Additionally MRMer incorporates features that permit the quantitative analysis experiments including heavy and light isotopic peptide pairs. MRMer is open source and provided under the Apache 2.0 license.

  12. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    International Nuclear Information System (INIS)

    Manek, Aditya K.; Ferrari, Maud C.O.; Niyogi, Som; Chivers, Douglas P.

    2014-01-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors

  13. The interactive effects of multiple stressors on physiological stress responses and club cell investment in fathead minnows

    Energy Technology Data Exchange (ETDEWEB)

    Manek, Aditya K., E-mail: aditya.manek@usask.ca [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada); Ferrari, Maud C.O. [Department of Biomedical Sciences, WCVM, University of Saskatchewan, Saskatoon, SK S7N 5B4 (Canada); Niyogi, Som; Chivers, Douglas P. [Department of Biology, University of Saskatchewan, Saskatoon, S7N 5E2 SK (Canada)

    2014-04-01

    Anthropogenic activities have dramatically increased over the past decades, with the consequence that many organisms are simultaneously exposed to multiple stressors. Understanding how organisms respond to these stressors is a key focus for scientists from many disciplines. Here we investigated the interactive effects of two stressors, UV radiation (UVR) and cadmium (Cd) exposure on a common freshwater fish, fathead minnow (Pimephales promelas). UVR is known to influence the density of epidermal club cells (ECCs), which are not only a key component of the innate immune system of fishes, but are also the source of chemical alarm cues that serve to warn other fishes of nearby predators. In contrast, Cd impairs the physiological stress response and ability of fish to respond to alarm cues. We used an integrative approach to examine physiological stress response as well as investment in ECCs. Fish exposed to UVR had higher levels of cortisol than non-exposed controls, but Cd reduced cortisol levels substantially for fish exposed to UVR. Fish exposed to UVR, either in the presence or absence of Cd, showed consistent decreases in ECC investment compared to non-exposed controls. Despite differences in ECC number, there was no difference in the potency of alarm cues prepared from the skin of UVR and Cd exposed or non-exposed fish indicating that UVR and Cd exposure combined may have little influence on chemically-mediated predator–prey interactions. - Highlights: • UV radiation caused a physiological stress response (cortisol release) in fish. • Cd reduced cortisol levels substantially for fish exposed to UV. • Fish exposed to UV, with or without Cd, showed decreases in club cell investment. • There was no difference in alarm cues potency from UV and Cd exposed fish. • Our work highlights the difficulty of untangling effects of multiple stressors.

  14. Genome scan for nonadditive heterotic trait loci reveals mainly underdominant effects in Saccharomyces cerevisiae.

    Science.gov (United States)

    Laiba, Efrat; Glikaite, Ilana; Levy, Yael; Pasternak, Zohar; Fridman, Eyal

    2016-04-01

    The overdominant model of heterosis explains the superior phenotype of hybrids by synergistic allelic interaction within heterozygous loci. To map such genetic variation in yeast, we used a population doubling time dataset of Saccharomyces cerevisiae 16 × 16 diallel and searched for major contributing heterotic trait loci (HTL). Heterosis was observed for the majority of hybrids, as they surpassed their best parent growth rate. However, most of the local heterozygous loci identified by genome scan were surprisingly underdominant, i.e., reduced growth. We speculated that in these loci adverse effects on growth resulted from incompatible allelic interactions. To test this assumption, we eliminated these allelic interactions by creating hybrids with local hemizygosity for the underdominant HTLs, as well as for control random loci. Growth of hybrids was indeed elevated for most hemizygous to HTL genes but not for control genes, hence validating the results of our genome scan. Assessing the consequences of local heterozygosity by reciprocal hemizygosity and allele replacement assays revealed the influence of genetic background on the underdominant effects of HTLs. Overall, this genome-wide study on a multi-parental hybrid population provides a strong argument against single gene overdominance as a major contributor to heterosis, and favors the dominance complementation model.

  15. Multiple Forms and Settings of Exposure to Violence and Values: Unique and Interactive Relationships With Antisocial Behavior in Adolescence.

    Science.gov (United States)

    Bacchini, Dario; Affuso, Gaetana; Aquilar, Serena

    2015-10-01

    The general purpose of this study was to investigate the relationships between multiple forms and settings of exposure to violence (ETV) as well as personal values and antisocial behavior (ASB) in adolescence. The association of ETV as witness or victim in different contexts (family, school, or neighborhood) and the association of the selected values of power, universalism, and conformity with ASB were analyzed. In addition, the role of ETV in moderating the relationship between values and ASB was tested. A total of 369 adolescents participated in the study. Hierarchical multiple regression analysis was performed. Results revealed that ASB was independently affected by exposure to family violence as a victim, exposure to school violence as a witness, exposure to neighborhood violence as a witness, and by all three selected values. The associations of ASB with universalism and conformity were negative. Conversely, the association of ASB with power was positive. One interaction had statistically significant effects. Results revealed that exposure to school violence as a witness moderates the relationship between universalism and ASB. The results highlight a high percentage of explained variance by ETV and values on ASB and suggest the importance of adopting a socio-ecological framework in interpreting adolescent behavior. © The Author(s) 2014.

  16. Strange particle cross sections and