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Sample records for accelerating epistasis analysis

  1. Epistasis analysis using artificial intelligence.

    PubMed

    Moore, Jason H; Hill, Doug P

    2015-01-01

    Here we introduce artificial intelligence (AI) methodology for detecting and characterizing epistasis in genetic association studies. The ultimate goal of our AI strategy is to analyze genome-wide genetics data as a human would using sources of expert knowledge as a guide. The methodology presented here is based on computational evolution, which is a type of genetic programming. The ability to generate interesting solutions while at the same time learning how to solve the problem at hand distinguishes computational evolution from other genetic programming approaches. We provide a general overview of this approach and then present a few examples of its application to real data. PMID:25403541

  2. Dynamic Network-Based Epistasis Analysis: Boolean Examples

    PubMed Central

    Azpeitia, Eugenio; Benítez, Mariana; Padilla-Longoria, Pablo; Espinosa-Soto, Carlos; Alvarez-Buylla, Elena R.

    2011-01-01

    In this article we focus on how the hierarchical and single-path assumptions of epistasis analysis can bias the inference of gene regulatory networks. Here we emphasize the critical importance of dynamic analyses, and specifically illustrate the use of Boolean network models. Epistasis in a broad sense refers to gene interactions, however, as originally proposed by Bateson, epistasis is defined as the blocking of a particular allelic effect due to the effect of another allele at a different locus (herein, classical epistasis). Classical epistasis analysis has proven powerful and useful, allowing researchers to infer and assign directionality to gene interactions. As larger data sets are becoming available, the analysis of classical epistasis is being complemented with computer science tools and system biology approaches. We show that when the hierarchical and single-path assumptions are not met in classical epistasis analysis, the access to relevant information and the correct inference of gene interaction topologies is hindered, and it becomes necessary to consider the temporal dynamics of gene interactions. The use of dynamical networks can overcome these limitations. We particularly focus on the use of Boolean networks that, like classical epistasis analysis, relies on logical formalisms, and hence can complement classical epistasis analysis and relax its assumptions. We develop a couple of theoretical examples and analyze them from a dynamic Boolean network model perspective. Boolean networks could help to guide additional experiments and discern among alternative regulatory schemes that would be impossible or difficult to infer without the elimination of these assumption from the classical epistasis analysis. We also use examples from the literature to show how a Boolean network-based approach has resolved ambiguities and guided epistasis analysis. Our article complements previous accounts, not only by focusing on the implications of the hierarchical and

  3. Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits.

    PubMed

    Zhang, Futao; Xie, Dan; Liang, Meimei; Xiong, Momiao

    2016-04-01

    To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI's Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes. PMID:27104857

  4. Functional Regression Models for Epistasis Analysis of Multiple Quantitative Traits

    PubMed Central

    Xie, Dan; Liang, Meimei; Xiong, Momiao

    2016-01-01

    To date, most genetic analyses of phenotypes have focused on analyzing single traits or analyzing each phenotype independently. However, joint epistasis analysis of multiple complementary traits will increase statistical power and improve our understanding of the complicated genetic structure of the complex diseases. Despite their importance in uncovering the genetic structure of complex traits, the statistical methods for identifying epistasis in multiple phenotypes remains fundamentally unexplored. To fill this gap, we formulate a test for interaction between two genes in multiple quantitative trait analysis as a multiple functional regression (MFRG) in which the genotype functions (genetic variant profiles) are defined as a function of the genomic position of the genetic variants. We use large-scale simulations to calculate Type I error rates for testing interaction between two genes with multiple phenotypes and to compare the power with multivariate pairwise interaction analysis and single trait interaction analysis by a single variate functional regression model. To further evaluate performance, the MFRG for epistasis analysis is applied to five phenotypes of exome sequence data from the NHLBI’s Exome Sequencing Project (ESP) to detect pleiotropic epistasis. A total of 267 pairs of genes that formed a genetic interaction network showed significant evidence of epistasis influencing five traits. The results demonstrate that the joint interaction analysis of multiple phenotypes has a much higher power to detect interaction than the interaction analysis of a single trait and may open a new direction to fully uncovering the genetic structure of multiple phenotypes. PMID:27104857

  5. Identifiability and inference of pathway motifs by epistasis analysis.

    PubMed

    Phenix, Hilary; Perkins, Theodore; Kærn, Mads

    2013-06-01

    The accuracy of genetic network inference is limited by the assumptions used to determine if one hypothetical model is better than another in explaining experimental observations. Most previous work on epistasis analysis-in which one attempts to infer pathway relationships by determining equivalences among traits following mutations-has been based on Boolean or linear models. Here, we delineate the ultimate limits of epistasis-based inference by systematically surveying all two-gene network motifs and use symbolic algebra with arbitrary regulation functions to examine trait equivalences. Our analysis divides the motifs into equivalence classes, where different genetic perturbations result in indistinguishable experimental outcomes. We demonstrate that this partitioning can reveal important information about network architecture, and show, using simulated data, that it greatly improves the accuracy of genetic network inference methods. Because of the minimal assumptions involved, equivalence partitioning has broad applicability for gene network inference. PMID:23822501

  6. Identifiability and inference of pathway motifs by epistasis analysis

    NASA Astrophysics Data System (ADS)

    Phenix, Hilary; Perkins, Theodore; Kærn, Mads

    2013-06-01

    The accuracy of genetic network inference is limited by the assumptions used to determine if one hypothetical model is better than another in explaining experimental observations. Most previous work on epistasis analysis—in which one attempts to infer pathway relationships by determining equivalences among traits following mutations—has been based on Boolean or linear models. Here, we delineate the ultimate limits of epistasis-based inference by systematically surveying all two-gene network motifs and use symbolic algebra with arbitrary regulation functions to examine trait equivalences. Our analysis divides the motifs into equivalence classes, where different genetic perturbations result in indistinguishable experimental outcomes. We demonstrate that this partitioning can reveal important information about network architecture, and show, using simulated data, that it greatly improves the accuracy of genetic network inference methods. Because of the minimal assumptions involved, equivalence partitioning has broad applicability for gene network inference.

  7. Parallelizing Epistasis Detection in GWAS on FPGA and GPU-Accelerated Computing Systems.

    PubMed

    González-Domínguez, Jorge; Wienbrandt, Lars; Kässens, Jan Christian; Ellinghaus, David; Schimmler, Manfred; Schmidt, Bertil

    2015-01-01

    High-throughput genotyping technologies (such as SNP-arrays) allow the rapid collection of up to a few million genetic markers of an individual. Detecting epistasis (based on 2-SNP interactions) in Genome-Wide Association Studies is an important but time consuming operation since statistical computations have to be performed for each pair of measured markers. Computational methods to detect epistasis therefore suffer from prohibitively long runtimes; e.g., processing a moderately-sized dataset consisting of about 500,000 SNPs and 5,000 samples requires several days using state-of-the-art tools on a standard 3 GHz CPU. In this paper, we demonstrate how this task can be accelerated using a combination of fine-grained and coarse-grained parallelism on two different computing systems. The first architecture is based on reconfigurable hardware (FPGAs) while the second architecture uses multiple GPUs connected to the same host. We show that both systems can achieve speedups of around four orders-of-magnitude compared to the sequential implementation. This significantly reduces the runtimes for detecting epistasis to only a few minutes for moderately-sized datasets and to a few hours for large-scale datasets. PMID:26451813

  8. JBASE: Joint Bayesian Analysis of Subphenotypes and Epistasis

    PubMed Central

    Colak, Recep; Kim, TaeHyung; Kazan, Hilal; Oh, Yoomi; Cruz, Miguel; Valladares-Salgado, Adan; Peralta, Jesus; Escobedo, Jorge; Parra, Esteban J.; Kim, Philip M.; Goldenberg, Anna

    2016-01-01

    Motivation: Rapid advances in genotyping and genome-wide association studies have enabled the discovery of many new genotype–phenotype associations at the resolution of individual markers. However, these associations explain only a small proportion of theoretically estimated heritability of most diseases. In this work, we propose an integrative mixture model called JBASE: joint Bayesian analysis of subphenotypes and epistasis. JBASE explores two major reasons of missing heritability: interactions between genetic variants, a phenomenon known as epistasis and phenotypic heterogeneity, addressed via subphenotyping. Results: Our extensive simulations in a wide range of scenarios repeatedly demonstrate that JBASE can identify true underlying subphenotypes, including their associated variants and their interactions, with high precision. In the presence of phenotypic heterogeneity, JBASE has higher Power and lower Type 1 Error than five state-of-the-art approaches. We applied our method to a sample of individuals from Mexico with Type 2 diabetes and discovered two novel epistatic modules, including two loci each, that define two subphenotypes characterized by differences in body mass index and waist-to-hip ratio. We successfully replicated these subphenotypes and epistatic modules in an independent dataset from Mexico genotyped with a different platform. Availability and implementation: JBASE is implemented in C++, supported on Linux and is available at http://www.cs.toronto.edu/∼goldenberg/JBASE/jbase.tar.gz. The genotype data underlying this study are available upon approval by the ethics review board of the Medical Centre Siglo XXI. Please contact Dr Miguel Cruz at mcruzl@yahoo.com for assistance with the application. Contact: anna.goldenberg@utoronto.ca Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26411870

  9. Epistasis in Monkeyflowers

    PubMed Central

    Kelly, John K.

    2005-01-01

    Epistasis contributes significantly to intrapopulation variation in floral morphology, development time, and male fitness components of Mimulus guttatus. This is demonstrated with a replicated line-cross experiment involving slightly over 7000 plants. The line-cross methodology is based on estimates for means. It thus has greater power than the variance partitioning approaches historically used to estimate epistasis within populations. The replication of the breeding design across many pairs of randomly extracted, inbred lines is necessary given the diversity of multilocus genotypes residing within an outbred deme. Male fitness is shown to exhibit synergistic epistasis, an accelerating decline in fitness with inbreeding. Synergism is a necessary, but not sufficient, condition for a mutational deterministic hypothesis for the evolutionary maintenance of sexual reproduction. Unlike male fitness measures, flower morphology and development time yield positive evidence of epistasis but not of synergism. The results for these traits suggest that epistatic effects are variable across genetic backgrounds or sets of interacting loci. PMID:15944350

  10. Analysis of epistasis for diabetic nephropathy among type 2 diabetic patients.

    PubMed

    Hsieh, Chang-Hsun; Liang, Kung-Hao; Hung, Yi-Jen; Huang, Li-Chin; Pei, Dee; Liao, Ya-Tang; Kuo, Shi-Wen; Bey, Monica Shian-Jy; Chen, Jui-Lin; Chen, Ellson Y

    2006-09-15

    Diabetic nephropathy (DN) is one of the most serious complications of diabetes, accounting for the majority of patients with end-stage renal disease. The molecular pathogenesis of DN involves multiple pathways in a complex, partially resolved manner. The paper presents an exploratory epistatic study for DN. Association analysis were performed on 231 SNP loci in a cohort of 264 type 2 diabetes patients, followed by the epistasis analysis using the multifactor dimensionality reduction and the genetic algorithm with Boolean algebra. A two-locus epistatic effect of EGFR and RXRG was identified, with a cross-validation consistency of 91.7%. PMID:16893912

  11. Epistasis Test in Meta-Analysis: A Multi-Parameter Markov Chain Monte Carlo Model for Consistency of Evidence.

    PubMed

    Lin, Chin; Chu, Chi-Ming; Su, Sui-Lung

    2016-01-01

    Conventional genome-wide association studies (GWAS) have been proven to be a successful strategy for identifying genetic variants associated with complex human traits. However, there is still a large heritability gap between GWAS and transitional family studies. The "missing heritability" has been suggested to be due to lack of studies focused on epistasis, also called gene-gene interactions, because individual trials have often had insufficient sample size. Meta-analysis is a common method for increasing statistical power. However, sufficient detailed information is difficult to obtain. A previous study employed a meta-regression-based method to detect epistasis, but it faced the challenge of inconsistent estimates. Here, we describe a Markov chain Monte Carlo-based method, called "Epistasis Test in Meta-Analysis" (ETMA), which uses genotype summary data to obtain consistent estimates of epistasis effects in meta-analysis. We defined a series of conditions to generate simulation data and tested the power and type I error rates in ETMA, individual data analysis and conventional meta-regression-based method. ETMA not only successfully facilitated consistency of evidence but also yielded acceptable type I error and higher power than conventional meta-regression. We applied ETMA to three real meta-analysis data sets. We found significant gene-gene interactions in the renin-angiotensin system and the polycyclic aromatic hydrocarbon metabolism pathway, with strong supporting evidence. In addition, glutathione S-transferase (GST) mu 1 and theta 1 were confirmed to exert independent effects on cancer. We concluded that the application of ETMA to real meta-analysis data was successful. Finally, we developed an R package, etma, for the detection of epistasis in meta-analysis [etma is available via the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/etma/index.html]. PMID:27045371

  12. Epistasis Test in Meta-Analysis: A Multi-Parameter Markov Chain Monte Carlo Model for Consistency of Evidence

    PubMed Central

    Lin, Chin; Chu, Chi-Ming; Su, Sui-Lung

    2016-01-01

    Conventional genome-wide association studies (GWAS) have been proven to be a successful strategy for identifying genetic variants associated with complex human traits. However, there is still a large heritability gap between GWAS and transitional family studies. The “missing heritability” has been suggested to be due to lack of studies focused on epistasis, also called gene–gene interactions, because individual trials have often had insufficient sample size. Meta-analysis is a common method for increasing statistical power. However, sufficient detailed information is difficult to obtain. A previous study employed a meta-regression-based method to detect epistasis, but it faced the challenge of inconsistent estimates. Here, we describe a Markov chain Monte Carlo-based method, called “Epistasis Test in Meta-Analysis” (ETMA), which uses genotype summary data to obtain consistent estimates of epistasis effects in meta-analysis. We defined a series of conditions to generate simulation data and tested the power and type I error rates in ETMA, individual data analysis and conventional meta-regression-based method. ETMA not only successfully facilitated consistency of evidence but also yielded acceptable type I error and higher power than conventional meta-regression. We applied ETMA to three real meta-analysis data sets. We found significant gene–gene interactions in the renin–angiotensin system and the polycyclic aromatic hydrocarbon metabolism pathway, with strong supporting evidence. In addition, glutathione S-transferase (GST) mu 1 and theta 1 were confirmed to exert independent effects on cancer. We concluded that the application of ETMA to real meta-analysis data was successful. Finally, we developed an R package, etma, for the detection of epistasis in meta-analysis [etma is available via the Comprehensive R Archive Network (CRAN) at https://cran.r-project.org/web/packages/etma/index.html]. PMID:27045371

  13. Genome-wide analysis of epistasis in body mass index using multiple human populations

    PubMed Central

    Wei, Wen-Hua; Hemani, Gib; Gyenesei, Attila; Vitart, Veronique; Navarro, Pau; Hayward, Caroline; Cabrera, Claudia P; Huffman, Jennifer E; Knott, Sara A; Hicks, Andrew A; Rudan, Igor; Pramstaller, Peter P; Wild, Sarah H; Wilson, James F; Campbell, Harry; Hastie, Nicholas D; Wright, Alan F; Haley, Chris S

    2012-01-01

    We surveyed gene–gene interactions (epistasis) in human body mass index (BMI) in four European populations (n<1200) via exhaustive pair-wise genome scans where interactions were computed as F ratios by testing a linear regression model fitting two single-nucleotide polymorphisms (SNPs) with interactions against the one without. Before the association tests, BMI was corrected for sex and age, normalised and adjusted for relatedness. Neither single SNPs nor SNP interactions were genome-wide significant in either cohort based on the consensus threshold (P=5.0E−08) and a Bonferroni corrected threshold (P=1.1E−12), respectively. Next we compared sub genome-wide significant SNP interactions (P<5.0E−08) across cohorts to identify common epistatic signals, where SNPs were annotated to genes to test for gene ontology (GO) enrichment. Among the epistatic genes contributing to the commonly enriched GO terms, 19 were shared across study cohorts of which 15 are previously published genome-wide association loci, including CDH13 (cadherin 13) associated with height and SORCS2 (sortilin-related VPS10 domain containing receptor 2) associated with circulating insulin-like growth factor 1 and binding protein 3. Interactions between the 19 shared epistatic genes and those involving BMI candidate loci (P<5.0E−08) were tested across cohorts and found eight replicated at the SNP level (P<0.05) in at least one cohort, which were further tested and showed limited replication in a separate European population (n>5000). We conclude that genome-wide analysis of epistasis in multiple populations is an effective approach to provide new insights into the genetic regulation of BMI but requires additional efforts to confirm the findings. PMID:22333899

  14. Deep epistasis in human metabolism

    PubMed Central

    Imielinski, Marcin; Belta, Calin

    2010-01-01

    We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing “deep” epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets. PMID:20590333

  15. Deep epistasis in human metabolism

    NASA Astrophysics Data System (ADS)

    Imielinski, Marcin; Belta, Calin

    2010-06-01

    We extend and apply a method that we have developed for deriving high-order epistatic relationships in large biochemical networks to a published genome-scale model of human metabolism. In our analysis we compute 33 328 reaction sets whose knockout synergistically disables one or more of 43 important metabolic functions. We also design minimal knockouts that remove flux through fumarase, an enzyme that has previously been shown to play an important role in human cancer. Most of these knockout sets employ more than eight mutually buffering reactions, spanning multiple cellular compartments and metabolic subsystems. These reaction sets suggest that human metabolic pathways possess a striking degree of parallelism, inducing "deep" epistasis between diversely annotated genes. Our results prompt specific chemical and genetic perturbation follow-up experiments that could be used to query in vivo pathway redundancy. They also suggest directions for future statistical studies of epistasis in genetic variation data sets.

  16. Epistasis in protein evolution.

    PubMed

    Starr, Tyler N; Thornton, Joseph W

    2016-07-01

    The structure, function, and evolution of proteins depend on physical and genetic interactions among amino acids. Recent studies have used new strategies to explore the prevalence, biochemical mechanisms, and evolutionary implications of these interactions-called epistasis-within proteins. Here we describe an emerging picture of pervasive epistasis in which the physical and biological effects of mutations change over the course of evolution in a lineage-specific fashion. Epistasis can restrict the trajectories available to an evolving protein or open new paths to sequences and functions that would otherwise have been inaccessible. We describe two broad classes of epistatic interactions, which arise from different physical mechanisms and have different effects on evolutionary processes. Specific epistasis-in which one mutation influences the phenotypic effect of few other mutations-is caused by direct and indirect physical interactions between mutations, which nonadditively change the protein's physical properties, such as conformation, stability, or affinity for ligands. In contrast, nonspecific epistasis describes mutations that modify the effect of many others; these typically behave additively with respect to the physical properties of a protein but exhibit epistasis because of a nonlinear relationship between the physical properties and their biological effects, such as function or fitness. Both types of interaction are rampant, but specific epistasis has stronger effects on the rate and outcomes of evolution, because it imposes stricter constraints and modulates evolutionary potential more dramatically; it therefore makes evolution more contingent on low-probability historical events and leaves stronger marks on the sequences, structures, and functions of protein families. PMID:26833806

  17. Dynamic Epistasis under Varying Environmental Perturbations

    PubMed Central

    Barker, Brandon; Xu, Lin; Gu, Zhenglong

    2015-01-01

    Epistasis describes the phenomenon that mutations at different loci do not have independent effects with regard to certain phenotypes. Understanding the global epistatic landscape is vital for many genetic and evolutionary theories. Current knowledge for epistatic dynamics under multiple conditions is limited by the technological difficulties in experimentally screening epistatic relations among genes. We explored this issue by applying flux balance analysis to simulate epistatic landscapes under various environmental perturbations. Specifically, we looked at gene-gene epistatic interactions, where the mutations were assumed to occur in different genes. We predicted that epistasis tends to become more positive from glucose-abundant to nutrient-limiting conditions, indicating that selection might be less effective in removing deleterious mutations in the latter. We also observed a stable core of epistatic interactions in all tested conditions, as well as many epistatic interactions unique to each condition. Interestingly, genes in the stable epistatic interaction network are directly linked to most other genes whereas genes with condition-specific epistasis form a scale-free network. Furthermore, genes with stable epistasis tend to have similar evolutionary rates, whereas this co-evolving relationship does not hold for genes with condition-specific epistasis. Our findings provide a novel genome-wide picture about epistatic dynamics under environmental perturbations. PMID:25625594

  18. How mutational epistasis impairs predictability in protein evolution and design.

    PubMed

    Miton, Charlotte M; Tokuriki, Nobuhiko

    2016-07-01

    There has been much debate about the extent to which mutational epistasis, that is, the dependence of the outcome of a mutation on the genetic background, constrains evolutionary trajectories. The degree of unpredictability introduced by epistasis, due to the non-additivity of functional effects, strongly hinders the strategies developed in protein design and engineering. While many studies have addressed this issue through systematic characterization of evolutionary trajectories within individual enzymes, the field lacks a consensus view on this matter. In this work, we performed a comprehensive analysis of epistasis by analyzing the mutational effects from nine adaptive trajectories toward new enzymatic functions. We quantified epistasis by comparing the effect of mutations occurring between two genetic backgrounds: the starting enzyme (for example, wild type) and the intermediate variant on which the mutation occurred during the trajectory. We found that most trajectories exhibit positive epistasis, in which the mutational effect is more beneficial when it occurs later in the evolutionary trajectory. Approximately half (49%) of functional mutations were neutral or negative on the wild-type background, but became beneficial at a later stage in the trajectory, indicating that these functional mutations were not predictable from the initial starting point. While some cases of strong epistasis were associated with direct interaction between residues, many others were caused by long-range indirect interactions between mutations. Our work highlights the prevalence of epistasis in enzyme adaptive evolution, in particular positive epistasis, and suggests the necessity of incorporating mutational epistasis in protein engineering and design to create highly efficient catalysts. PMID:26757214

  19. Integrated pathway and epistasis analysis reveals interactive effect of genetic variants at TERF1 and AFAP1L2 loci on melanoma risk.

    PubMed

    Brossard, Myriam; Fang, Shenying; Vaysse, Amaury; Wei, Qingyi; Chen, Wei V; Mohamdi, Hamida; Maubec, Eve; Lavielle, Nolwenn; Galan, Pilar; Lathrop, Mark; Avril, Marie-Françoise; Lee, Jeffrey E; Amos, Christopher I; Demenais, Florence

    2015-10-15

    Genome-wide association studies (GWASs) have characterized 13 loci associated with melanoma, which only account for a small part of melanoma risk. To identify new genes with too small an effect to be detected individually but which collectively influence melanoma risk and/or show interactive effects, we used a two-step analysis strategy including pathway analysis of genome-wide SNP data, in a first step, and epistasis analysis within significant pathways, in a second step. Pathway analysis, using the gene-set enrichment analysis (GSEA) approach and the gene ontology (GO) database, was applied to the outcomes of MELARISK (3,976 subjects) and MDACC (2,827 subjects) GWASs. Cross-gene SNP-SNP interaction analysis within melanoma-associated GOs was performed using the INTERSNP software. Five GO categories were significantly enriched in genes associated with melanoma (false discovery rate ≤ 5% in both studies): response to light stimulus, regulation of mitotic cell cycle, induction of programmed cell death, cytokine activity and oxidative phosphorylation. Epistasis analysis, within each of the five significant GOs, showed significant evidence for interaction for one SNP pair at TERF1 and AFAP1L2 loci (pmeta-int  = 2.0 × 10(-7) , which met both the pathway and overall multiple-testing corrected thresholds that are equal to 9.8 × 10(-7) and 2.0 × 10(-7) , respectively) and suggestive evidence for another pair involving correlated SNPs at the same loci (pmeta-int  = 3.6 × 10(-6) ). This interaction has important biological relevance given the key role of TERF1 in telomere biology and the reported physical interaction between TERF1 and AFAP1L2 proteins. This finding brings a novel piece of evidence for the emerging role of telomere dysfunction into melanoma development. PMID:25892537

  20. The decline in fitness with inbreeding: evidence for negative dominance-by-dominance epistasis in Drosophila melanogaster.

    PubMed

    Sharp, N P; Agrawal, A F

    2016-04-01

    Genetic interactions can play an important role in the evolution of reproductive strategies. In particular, negative dominance-by-dominance epistasis for fitness can theoretically favour sex and recombination. This form of epistasis can be detected statistically because it generates nonlinearity in the relationship between fitness and inbreeding coefficient. Measures of fitness in progressively inbred lines tend to show limited evidence for epistasis. However, tests of this kind can be biased against detecting an accelerating decline due to line losses at higher inbreeding levels. We tested for dominance-by-dominance epistasis in Drosophila melanogaster by examining viability at five inbreeding levels that were generated simultaneously, avoiding the bias against detecting nonlinearity that has affected previous studies. We find an accelerating rate of fitness decline with inbreeding, indicating that dominance-by-dominance epistasis is negative on average, which should favour sex and recombination. PMID:26709722

  1. Experimental evolution and epistasis in variable environments

    NASA Astrophysics Data System (ADS)

    Tans, Sander

    2014-03-01

    Environmental changes trigger cellular responses, but also impose selective pressures on the underlying regulatory systems. To disentangle this complex interplay we follow a synthetic biology approach. By linking the output of regulatory systems to bacterial growth, quantified temporally variable selective pressures can be applied to regulatory systems. This approach allows one to explore how networks evolve in complex variable environments. Epistatic interactions that underlie evolutionary constraint have mainly been studied for constant external conditions. However, environmental changes may modulate epistasis and hence affect genetic constraints. We investigate genetic constraints in the adaptive evolution of a novel regulatory function in variable environments, using the lac repressor, LacI, as a model system. We systematically reconstructed mutational trajectories from wild type LacI to three different variants that each exhibit an inverse response to the inducing ligand IPTG, and analyzed the higher-order interactions between genetic and environmental changes. We find epistasis to depend strongly on the environment. As a result, mutational steps essential to inversion but inaccessible by positive selection in one environment, become accessible in another. We present a graphical method to analyze the observed complex higher-order interactions between multiple mutations and environmental change, and show how they can be explained by a combination of mutational effects on allostery and thermodynamic stability. This dependency of genetic constraint on the environment should fundamentally affect evolutionary dynamics and phylogenetic analysis. NWO-FOM

  2. Weak Epistasis Generally Stabilizes Phenotypes in a Mouse Intercross

    PubMed Central

    Tyler, Anna L.; Donahue, Leah Rae; Churchill, Gary A.; Carter, Gregory W.

    2016-01-01

    The extent and strength of epistasis is commonly unresolved in genetic studies, and observed epistasis is often difficult to interpret in terms of biological consequences or overall genetic architecture. We investigated the prevalence and consequences of epistasis by analyzing four body composition phenotypes—body weight, body fat percentage, femoral density, and femoral circumference—in a large F2 intercross of B6-lit/lit and C3.B6-lit/lit mice. We used Combined Analysis of Pleiotropy and Epistasis (CAPE) to examine interactions for the four phenotypes simultaneously, which revealed an extensive directed network of genetic loci interacting with each other, circulating IGF1, and sex to influence these phenotypes. The majority of epistatic interactions had small effects relative to additive effects of individual loci, and tended to stabilize phenotypes towards the mean of the population rather than extremes. Interactive effects of two alleles inherited from one parental strain commonly resulted in phenotypes closer to the population mean than the additive effects from the two loci, and often much closer to the mean than either single-locus model. Alternatively, combinations of alleles inherited from different parent strains contribute to more extreme phenotypes not observed in either parental strain. This class of phenotype-stabilizing interactions has effects that are close to additive and are thus difficult to detect except in very large intercrosses. Nevertheless, we found these interactions to be useful in generating hypotheses for functional relationships between genetic loci. Our findings suggest that while epistasis is often weak and unlikely to account for a large proportion of heritable variance, even small-effect genetic interactions can facilitate hypotheses of underlying biology in well-powered studies. PMID:26828925

  3. Accelerating pulsar timing data analysis

    NASA Astrophysics Data System (ADS)

    van Haasteren, Rutger

    2013-02-01

    The analysis of pulsar timing data, especially in pulsar timing array (PTA) projects, has encountered practical difficulties: evaluating the likelihood and/or correlation-based statistics can become prohibitively computationally expensive for large data sets. In situations where a stochastic signal of interest has a power spectral density that dominates the noise in a limited bandwidth of the total frequency domain (e.g. the isotropic background of gravitational waves), a linear transformation exists that transforms the timing residuals to a basis in which virtually all the information about the stochastic signal of interest is contained in a small fraction of basis vectors. By only considering such a small subset of these `generalized residuals', the dimensionality of the data analysis problem is greatly reduced, which can cause a large speedup in the evaluation of the likelihood: the ABC-method (Acceleration By Compression). The compression fidelity, calculable with crude estimates of the signal and noise, can be used to determine how far a data set can be compressed without significant loss of information. Both direct tests on the likelihood, and Bayesian analysis of mock data, show that the signal can be recovered as well as with an analysis of uncompressed data. In the analysis of International PTA Mock Data Challenge data sets, speedups of a factor of 3 orders of magnitude are demonstrated. For realistic PTA data sets the acceleration may become greater than six orders of magnitude due to the low signal-to-noise ratio.

  4. Confronting the missing epistasis problem: on the reproducibility of gene-gene interactions.

    PubMed

    Murk, William; Bracken, Michael B; DeWan, Andrew T

    2015-08-01

    Epistasis (gene-gene interaction) is thought to play an integral role in the genetic basis of complex traits, and a significant amount of research has been invested into identifying this phenomenon in human disease. However, the overall success of empirical studies of epistasis in humans is unclear, as such studies are rarely systematically evaluated. Here, we have selected asthma as an example of a well-studied, complex human disease, and provide a critical analysis and replication attempt of nearly all prior reports of epistasis for this disease. Of 191 previously reported interactions, we find that 39.8% were not originally identified using an explicit test for interaction and thus may not have been true epistatic effects to begin with. Moreover, directions of effect were not described for 46.1% of the interactions, which prevents their rigorous replication. In the original studies, attempts at replication were made for 15.2% of the interactions, and 7.3% were actually replicated. In the current study, we were able to evaluate 85.9% of the interactions using a large asthma dataset from the GABRIEL Consortium. None of these interactions could be replicated based on strict criteria. However, we found nominally significant (p < 0.05) evidence in support of 23.8% of the evaluated interactions. Although many reports of epistasis are not robustly supported in the published literature, our results suggest that at least some of these reports may have been true-positive examples of epistasis. In general, improvements in empirical studies of epistasis are called for, in order to better understand the importance of this phenomenon in human disease. PMID:25998948

  5. A survey about methods dedicated to epistasis detection

    PubMed Central

    Niel, Clément; Sinoquet, Christine; Dina, Christian; Rocheleau, Ghislain

    2015-01-01

    During the past decade, findings of genome-wide association studies (GWAS) improved our knowledge and understanding of disease genetics. To date, thousands of SNPs have been associated with diseases and other complex traits. Statistical analysis typically looks for association between a phenotype and a SNP taken individually via single-locus tests. However, geneticists admit this is an oversimplified approach to tackle the complexity of underlying biological mechanisms. Interaction between SNPs, namely epistasis, must be considered. Unfortunately, epistasis detection gives rise to analytic challenges since analyzing every SNP combination is at present impractical at a genome-wide scale. In this review, we will present the main strategies recently proposed to detect epistatic interactions, along with their operating principle. Some of these methods are exhaustive, such as multifactor dimensionality reduction, likelihood ratio-based tests or receiver operating characteristic curve analysis; some are non-exhaustive, such as machine learning techniques (random forests, Bayesian networks) or combinatorial optimization approaches (ant colony optimization, computational evolution system). PMID:26442103

  6. A survey about methods dedicated to epistasis detection.

    PubMed

    Niel, Clément; Sinoquet, Christine; Dina, Christian; Rocheleau, Ghislain

    2015-01-01

    During the past decade, findings of genome-wide association studies (GWAS) improved our knowledge and understanding of disease genetics. To date, thousands of SNPs have been associated with diseases and other complex traits. Statistical analysis typically looks for association between a phenotype and a SNP taken individually via single-locus tests. However, geneticists admit this is an oversimplified approach to tackle the complexity of underlying biological mechanisms. Interaction between SNPs, namely epistasis, must be considered. Unfortunately, epistasis detection gives rise to analytic challenges since analyzing every SNP combination is at present impractical at a genome-wide scale. In this review, we will present the main strategies recently proposed to detect epistatic interactions, along with their operating principle. Some of these methods are exhaustive, such as multifactor dimensionality reduction, likelihood ratio-based tests or receiver operating characteristic curve analysis; some are non-exhaustive, such as machine learning techniques (random forests, Bayesian networks) or combinatorial optimization approaches (ant colony optimization, computational evolution system). PMID:26442103

  7. Hugoniot analysis of the ram accelerator

    NASA Astrophysics Data System (ADS)

    Knowlen, C.; Bruckner, A. P.

    The thermodynamic properties of a combustible propellant gas, after it has been processed by a ram accelerator propulsive mode, are related by a 'ram accelerator Hugoniot' expression. These end states are determined from the 1-D conservation equations in a manner similar to that used for detonation waves, but with the addition of a force term in the momentum equation. Establishment of a region of potentially accessible thermodynamic end states that are consistent with ram accelerator operation at and above the Chapman-Jouguet detonation speed indicates that there are no fundamental constraints on accelerating projectiles over a wide range of Mach numbers in a single propellant mixture. Interpreting experimental data in the context of a generalized ram accelerator process leads to relatively simple propulsive models which can predict the projectile acceleration of any propulsive mode. The projectile velocity and acceleration histories determined by the Hugoniot analysis for the thermally choked ram accelerator mode are in excellent agreement with experiments.

  8. Epistasis and its consequences for the evolution of natural populations.

    PubMed

    Fenster, C B; Galloway, L F; Chao, L

    1997-07-01

    Throughout the neodarwinian synthesis, theorists have debated the role of gene interactions, or epistasis, in the evolutionary process. Unfortunately, empirical measurement of the role of epistasis in the evolution of natural populations has, until now, been difficult. Two developments in empirical approaches have occurred: (1) application of theory to the evolution of natural populations, and (2) the concurrent development of molecular marker-assisted techniques to understand the architecture of quantitative genetic variation. Thus, exciting developments in both theory and empirical data collection provide the stimulus for documenting the role of epistasis in the evolutionary process. PMID:21238076

  9. Rapid appearance of epistasis during adaptive divergence following colonization.

    PubMed Central

    Carroll, Scott P; Dingle, Hugh; Famula, Thomas R

    2003-01-01

    Theory predicts that short-term adaptation within populations depends on additive (A) genetic effects, while gene-gene interactions 'epistasis (E)' are important only in long-term evolution. However, few data exist on the genetic architecture of adaptive variation, and the relative importance of A versus non-additive genetic effects continues to be a central controversy of evolutionary biology after more than 70 years of debate. To examine this issue directly, we conducted hybridization experiments between two populations of wild soapberry bugs that have strongly differentiated in 100 or fewer generations following a host plant shift. Contrary to expectation, we found that between-population E and dominance (D) have appeared quickly in the evolution of new phenotypes. Rather than thousands of generations, adaptive gene differences between populations have evolved in tens. Such complex genetic variation could underlie the seemingly extreme rates of evolution that are increasingly reported in many taxa. In the case of the soapberry bug, extraordinary ecological opportunity, rather than mortality, may have created hard selection for genetic variants. Because ultimate division of populations into genetic species depends on epistatic loss of hybrid compatibility, local adaptation based on E may accelerate macro-evolutionary diversification. PMID:12952643

  10. Protein evolution. Pervasive degeneracy and epistasis in a protein-protein interface.

    PubMed

    Podgornaia, Anna I; Laub, Michael T

    2015-02-01

    Mapping protein sequence space is a difficult problem that necessitates the analysis of 20(N) combinations for sequences of length N. We systematically mapped the sequence space of four key residues in the Escherichia coli protein kinase PhoQ that drive recognition of its substrate PhoP. We generated a library containing all 160,000 variants of PhoQ at these positions and used a two-step selection coupled to next-generation sequencing to identify 1659 functional variants. Our results reveal extensive degeneracy in the PhoQ-PhoP interface and epistasis, with the effect of individual substitutions often highly dependent on context. Together, epistasis and the genetic code create a pattern of connectivity of functional variants in sequence space that likely constrains PhoQ evolution. Consequently, the diversity of PhoQ orthologs is substantially lower than that of functional PhoQ variants. PMID:25657251

  11. A pharmaco-epistasis strategy reveals a new cell size controlling pathway in yeast

    PubMed Central

    Moretto, Fabien; Sagot, Isabelle; Daignan-Fornier, Bertrand; Pinson, Benoît

    2013-01-01

    Cell size is a complex quantitative trait resulting from interactions between intricate genetic networks and environmental conditions. Here, taking advantage of previous studies that uncovered hundreds of genes affecting budding yeast cell size homeostasis, we performed a wide pharmaco-epistasis analysis using drugs mimicking cell size mutations. Simple epistasis relationship emerging from this approach allowed us to characterize a new cell size homeostasis pathway comprising the sirtuin Sir2, downstream effectors including the large ribosomal subunit (60S) and the transcriptional regulators Swi4 and Swi6. We showed that this Sir2/60S signaling route acts independently of other previously described cell size controlling pathways and may integrate the metabolic status of the cell through NAD+ intracellular concentration. Finally, although Sir2 and the 60S subunits regulate both cell size and replicative aging, we found that there is no clear causal relationship between these two complex traits. This study sheds light on a pathway of >50 genes and illustrates how pharmaco-epistasis applied to yeast offers a potent experimental framework to explore complex genotype/phenotype relationships. PMID:24217298

  12. Naturally segregating loci exhibit epistasis for fitness

    PubMed Central

    Monnahan, Patrick J.; Kelly, John K.

    2015-01-01

    The extent to which gene interaction or epistasis contributes to fitness variation within populations remains poorly understood, despite its importance to a myriad of evolutionary questions. Here, we report a multi-year field study estimating fitness of Mimulus guttatus genetic lines in which pairs of naturally segregating loci exist in an otherwise uniform background. An allele at QTL x5b—a locus originally mapped for its effect on flower size—positively affects survival if combined with one genotype at quantitative trait locus x10a (aa) but has negative effects when combined with the other genotypes (Aa and AA). The viability differences between genotypes parallel phenotypic differences for the time and node at which a plant flowers. Viability is negatively correlated with fecundity across genotypes, indicating antagonistic pleiotropy for fitness components. This trade-off reduces the genetic variance for total fitness relative to the individual fitness components and thus may serve to maintain variation. Additionally, we find that the effects of each locus and their interaction often vary with the environment. PMID:26246336

  13. The effect of epistasis on sexually antagonistic genetic variation

    PubMed Central

    Arnqvist, Göran; Vellnow, Nikolas; Rowe, Locke

    2014-01-01

    There is increasing evidence of segregating sexually antagonistic (SA) genetic variation for fitness in laboratory and wild populations, yet the conditions for the maintenance of such variation can be restrictive. Epistatic interactions between genes can contribute to the maintenance of genetic variance in fitness and we suggest that epistasis between SA genes should be pervasive. Here, we explore its effect on SA genetic variation in fitness using a two locus model with negative epistasis. Our results demonstrate that epistasis often increases the parameter space showing polymorphism for SA loci. This is because selection in one locus is affected by allele frequencies at the other, which can act to balance net selection in males and females. Increased linkage between SA loci had more marginal effects. We also show that under some conditions, large portions of the parameter space evolve to a state where male benefit alleles are fixed at one locus and female benefit alleles at the other. This novel effect of epistasis on SA loci, which we term the ‘equity effect’, may have important effects on population differentiation and may contribute to speciation. More generally, these results support the suggestion that epistasis contributes to population divergence. PMID:24870040

  14. Genotypic Context and Epistasis in Individuals and Populations.

    PubMed

    Sackton, Timothy B; Hartl, Daniel L

    2016-07-14

    Genes encode components of coevolved and interconnected networks. The effect of genotype on phenotype therefore depends on genotypic context through gene interactions known as epistasis. Epistasis is important in predicting phenotype from genotype for an individual. It is also examined in population studies to identify genetic risk factors in complex traits and to predict evolution under selection. Paradoxically, the effects of genotypic context in individuals and populations are distinct and sometimes contradictory. We argue that predicting genotype from phenotype for individuals based on population studies is difficult and, especially in human genetics, likely to result in underestimating the effects of genotypic context. PMID:27419868

  15. An efficient algorithm to perform multiple testing in epistasis screening

    PubMed Central

    2013-01-01

    Background Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP

  16. Accelerator physics analysis with an integrated toolkit

    SciTech Connect

    Holt, J.A.; Michelotti, L.; Satogata, T.

    1992-08-01

    Work is in progress on an integrated software toolkit for linear and nonlinear accelerator design, analysis, and simulation. As a first application, ``beamline`` and ``MXYZPTLK`` (differential algebra) class libraries, were used with an X Windows graphics library to build an user-friendly, interactive phase space tracker which, additionally, finds periodic orbits. This program was used to analyse a theoretical lattice which contains octupoles and decapoles to find the 20th order, stable and unstable periodic orbits and to explore the local phase space structure.

  17. Acceleration of Data Analysis Applications using GPUs

    NASA Astrophysics Data System (ADS)

    Fillmore, D.; Messmer, P.; Mullowney, P.; Amyx, K.

    2008-12-01

    The vast amount of data collected by present and future scientific instruments, sensors and numerical models requires a significant increase in computing power for analysis. In many cases, processing time on a single workstation becomes impractical. While clusters of commodity processors can be utilized to accelerate some of these tasks, the relatively high software development cost, as well as acquisition and operational costs, make them less attractive for broad use. Over the past few years, another class of architectures has gained some popularity, namely heterogeneous architectures, which consist of general purpose processors connected to specialized processors. One of the most prominent examples are Graphics Processing Units (GPUs), which offer a tremendous amount of floating-point processing power due to demand for high-quality graphics in the computer game market. However, in order to harness this processing power, software developers have to develop with a detailed understanding of the underlying hardware. This burden on the developer is often hardly justifiable considering the rapid evolution of the hardware. In this talk, we will introduce GPULib, an open source library that enables scientists to accelerate their data analysis tasks using the GPUs already installed in their system from within high-level languages like IDL or MATLAB, and present examples and possible speedup from real-world data analysis applications. This work is funded through NASA Phase II SBIR Grant NNG06CA13C.

  18. Accelerating DNA analysis applications on GPU clusters

    SciTech Connect

    Tumeo, Antonino; Villa, Oreste

    2010-06-13

    DNA analysis is an emerging application of high performance bioinformatic. Modern sequencing machinery are able to provide, in few hours, large input streams of data which needs to be matched against exponentially growing databases known fragments. The ability to recognize these patterns effectively and fastly may allow extending the scale and the reach of the investigations performed by biology scientists. Aho-Corasick is an exact, multiple pattern matching algorithm often at the base of this application. High performance systems are a promising platform to accelerate this algorithm, which is computationally intensive but also inherently parallel. Nowadays, high performance systems also include heterogeneous processing elements, such as Graphic Processing Units (GPUs), to further accelerate parallel algorithms. Unfortunately, the Aho-Corasick algorithm exhibits large performance variabilities, depending on the size of the input streams, on the number of patterns to search and on the number of matches, and poses significant challenges on current high performance software and hardware implementations. An adequate mapping of the algorithm on the target architecture, coping with the limit of the underlining hardware, is required to reach the desired high throughputs. Load balancing also plays a crucial role when considering the limited bandwidth among the nodes of these systems. In this paper we present an efficient implementation of the Aho-Corasick algorithm for high performance clusters accelerated with GPUs. We discuss how we partitioned and adapted the algorithm to fit the Tesla C1060 GPU and then present a MPI based implementation for a heterogeneous high performance cluster. We compare this implementation to MPI and MPI with pthreads based implementations for a homogeneous cluster of x86 processors, discussing the stability vs. the performance and the scaling of the solutions, taking into consideration aspects such as the bandwidth among the different nodes.

  19. Epistasis and the selective advantage of sex and recombination

    NASA Astrophysics Data System (ADS)

    de Oliveira, Viviane M.; da Silva, Juliana K.; Campos, Paulo R. A.

    2008-09-01

    The understanding of the central mechanisms favoring sex and recombination in real populations is one of the fundamental issues in evolutionary biology. Based on a previous stochastic formulation for the study of sex, here we aim to investigate the conditions under which epistasis favors the fixation of the sexual mode of reproduction in a given population. In addition, we try to identify the evolutionary forces which contribute to this process. One considers a finite population model which assumes the existence of a recombination modifier allele that can activate the recombination mechanism. We have found that sex is very little favored in a scenario of antagonistic epistasis, and this advantage only occurs in a narrow range of values of the selection coefficient sd . On the other hand, synergistic epistasis favors recombination in a very broad domain. However, the major mechanism contributing to the spreading of the modifier allele depends on the range of values of sd . At large sd , background selection favors recombination since it increases the efficacy of selection, while at low sd Muller’s ratchet is the leading mechanism.

  20. Epistasis between mutations is host-dependent for an RNA virus

    PubMed Central

    Lalić, Jasna; Elena, Santiago F.

    2013-01-01

    How, and to what extent, does the environment influence the way mutations interact? Do environmental changes affect both the sign and the magnitude of epistasis? Are there any correlations between environments in the variability, sign or magnitude of epistasis? Very few studies have tackled these questions. Here, we addressed them in the context of viral emergence. Most emerging viruses are RNA viruses with small genomes, overlapping reading frames and multifunctional proteins for which epistasis is abundant. Understanding the effect of host species in the sign and magnitude of epistasis will provide insights into the evolutionary ecology of infectious diseases and the predictability of viral emergence. PMID:22809724

  1. Accelerating Large Data Analysis By Exploiting Regularities

    NASA Technical Reports Server (NTRS)

    Moran, Patrick J.; Ellsworth, David

    2003-01-01

    We present techniques for discovering and exploiting regularity in large curvilinear data sets. The data can be based on a single mesh or a mesh composed of multiple submeshes (also known as zones). Multi-zone data are typical to Computational Fluid Dynamics (CFD) simulations. Regularities include axis-aligned rectilinear and cylindrical meshes as well as cases where one zone is equivalent to a rigid-body transformation of another. Our algorithms can also discover rigid-body motion of meshes in time-series data. Next, we describe a data model where we can utilize the results from the discovery process in order to accelerate large data visualizations. Where possible, we replace general curvilinear zones with rectilinear or cylindrical zones. In rigid-body motion cases we replace a time-series of meshes with a transformed mesh object where a reference mesh is dynamically transformed based on a given time value in order to satisfy geometry requests, on demand. The data model enables us to make these substitutions and dynamic transformations transparently with respect to the visualization algorithms. We present results with large data sets where we combine our mesh replacement and transformation techniques with out-of-core paging in order to achieve significant speed-ups in analysis.

  2. Dispersion Analysis of the Pulseline Accelerator

    SciTech Connect

    Caporaso, G J; Briggs, R J; Poole, B R; Nelson, S D

    2005-05-10

    The authors analyze the sheath helix model of the pulseline accelerator. They find the dispersion relation for a shielded helix with a dielectric material between the shield and the helix and compare it against the results from 3-D electromagnetic simulations. Expressions for the fields near the beam axis are obtained. A scheme to taper the properties of the helix to maintain synchronism with the accelerated ions is described. An approximate circuit model of the system that includes beam loading is derived.

  3. Gait analysis using gravitational acceleration measured by wearable sensors.

    PubMed

    Takeda, Ryo; Tadano, Shigeru; Todoh, Masahiro; Morikawa, Manabu; Nakayasu, Minoru; Yoshinari, Satoshi

    2009-02-01

    A novel method for measuring human gait posture using wearable sensor units is proposed. The sensor units consist of a tri-axial acceleration sensor and three gyro sensors aligned on three axes. The acceleration and angular velocity during walking were measured with seven sensor units worn on the abdomen and the lower limb segments (both thighs, shanks and feet). The three-dimensional positions of each joint are calculated from each segment length and joint angle. Joint angle can be estimated mechanically from the gravitational acceleration along the anterior axis of the segment. However, the acceleration data during walking includes three major components; translational acceleration, gravitational acceleration and external noise. Therefore, an optimization analysis was represented to separate only the gravitational acceleration from the acceleration data. Because the cyclic patterns of acceleration data can be found during constant walking, a FFT analysis was applied to obtain some characteristic frequencies in it. A pattern of gravitational acceleration was assumed using some parts of these characteristic frequencies. Every joint position was calculated from the pattern under the condition of physiological motion range of each joint. An optimized pattern of the gravitational acceleration was selected as a solution of an inverse problem. Gaits of three healthy volunteers were measured by walking for 20s on a flat floor. As a result, the acceleration data of every segment was measured simultaneously. The characteristic three-dimensional walking could be shown by the expression using a stick figure model. In addition, the trajectories of the knee joint in the horizontal plane could be checked by visual imaging on a PC. Therefore, this method provides important quantitive information for gait diagnosis. PMID:19121522

  4. Simple genomes, complex interactions: Epistasis in RNA virus

    NASA Astrophysics Data System (ADS)

    Elena, Santiago F.; Solé, Ricard V.; Sardanyés, Josep

    2010-06-01

    Owed to their reduced size and low number of proteins encoded, RNA viruses and other subviral pathogens are often considered as being genetically too simple. However, this structural simplicity also creates the necessity for viral RNA sequences to encode for more than one protein and for proteins to carry out multiple functions, all together resulting in complex patterns of genetic interactions. In this work we will first review the experimental studies revealing that the architecture of viral genomes is dominated by antagonistic interactions among loci. Second, we will also review mathematical models and provide a description of computational tools for the study of RNA virus dynamics and evolution. As an application of these tools, we will finish this review article by analyzing a stochastic bit-string model of in silico virus replication. This model analyzes the interplay between epistasis and the mode of replication on determining the population load of deleterious mutations. The model suggests that, for a given mutation rate, the deleterious mutational load is always larger when epistasis is predominantly antagonistic than when synergism is the rule. However, the magnitude of this effect is larger if replication occurs geometrically than if it proceeds linearly.

  5. The Red Queen lives: Epistasis between linked resistance loci.

    PubMed

    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. PMID:26763092

  6. Impact of epistasis and pleiotropy on evolutionary adaptation

    PubMed Central

    Østman, Bjørn; Hintze, Arend; Adami, Christoph

    2012-01-01

    Evolutionary adaptation is often likened to climbing a hill or peak. While this process is simple for fitness landscapes where mutations are independent, the interaction between mutations (epistasis) as well as mutations at loci that affect more than one trait (pleiotropy) are crucial in complex and realistic fitness landscapes. We investigate the impact of epistasis and pleiotropy on adaptive evolution by studying the evolution of a population of asexual haploid organisms (haplotypes) in a model of N interacting loci, where each locus interacts with K other loci. We use a quantitative measure of the magnitude of epistatic interactions between substitutions, and find that it is an increasing function of K. When haplotypes adapt at high mutation rates, more epistatic pairs of substitutions are observed on the line of descent than expected. The highest fitness is attained in landscapes with an intermediate amount of ruggedness that balance the higher fitness potential of interacting genes with their concomitant decreased evolvability. Our findings imply that the synergism between loci that interact epistatically is crucial for evolving genetic modules with high fitness, while too much ruggedness stalls the adaptive process. PMID:21697174

  7. Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus.

    PubMed

    Schoustra, Sijmen; Hwang, Sungmin; Krug, Joachim; de Visser, J Arjan G M

    2016-08-31

    Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization. PMID:27559062

  8. Analysis of accelerated motion in the theory of relativity

    NASA Technical Reports Server (NTRS)

    Jones, R. T.

    1976-01-01

    Conventional treatments of accelerated motion in the theory of relativity have led to certain difficulties of interpretation. Certain reversals in the apparent gravitational field of an accelerated body may be avoided by simpler analysis based on the use of restricted conformal transformations. In the conformal theory the velocity of light remains constant even for experimenters in accelerated motion. The problem considered is that of rectilinear motion with a variable velocity. The motion takes place along the x or x' axis of two coordinate systems.

  9. A new tool for accelerator system modeling and analysis

    SciTech Connect

    Gillespie, G.H.; Hill, B.W.; Jameson, R.A.

    1994-09-01

    A novel computer code is being developed to generate system level designs of radiofrequency ion accelerators. The goal of the Accelerator System Model (ASM) code is to create a modeling and analysis tool that is easy to use, automates many of the initial design calculations, supports trade studies used in assessing alternate designs and yet is flexible enough to incorporate new technology concepts as they emerge. Hardware engineering parameters and beam dynamics are modeled at comparable levels of fidelity. Existing scaling models of accelerator subsystems were sued to produce a prototype of ASM (version 1.0) working within the Shell for Particle Accelerator Related Codes (SPARC) graphical user interface. A small user group has been testing and evaluating the prototype for about a year. Several enhancements and improvements are now being developed. The current version (1.1) of ASM is briefly described and an example of the modeling and analysis capabilities is illustrated.

  10. Failure Mode Effects Analysis for an Accelerator Control System

    SciTech Connect

    Hartman, Steven M

    2009-01-01

    Failure mode effects analysis (FMEA) has been used in industry for design, manufacturing and assembly process quality control. It describes a formal approach for categorizing how a process may fail and for prioritizing failures based on their severity, frequency and likelihood of detection. Experience conducting a partial FMEA of an accelerator subsystem and its related control system will be reviewed. The applicability of the FMEA process to an operational accelerator control system will be discussed.

  11. Statistical modeling of interlocus interactions in a complex disease: rejection of the multiplicative model of epistasis in type 1 diabetes.

    PubMed Central

    Cordell, H J; Todd, J A; Hill, N J; Lord, C J; Lyons, P A; Peterson, L B; Wicker, L S; Clayton, D G

    2001-01-01

    In general, common diseases do not follow a Mendelian inheritance pattern. To identify disease mechanisms and etiology, their genetic dissection may be assisted by evaluation of linkage in mouse models of human disease. Statistical modeling of multiple-locus linkage data from the nonobese diabetic (NOD) mouse model of type 1 diabetes has previously provided evidence for epistasis between alleles of several Idd (insulin-dependent diabetes) loci. The construction of NOD congenic strains containing selected segments of the diabetes-resistant strain genome allows analysis of the joint effects of alleles of different loci in isolation, without the complication of other segregating Idd loci. In this article, we analyze data from congenic strains carrying two chromosome intervals (a double congenic strain) for two pairs of loci: Idd3 and Idd10 and Idd3 and Idd5. The joint action of both pairs is consistent with models of additivity on either the log odds of the penetrance, or the liability scale, rather than with the previously proposed multiplicative model of epistasis. For Idd3 and Idd5 we would also not reject a model of additivity on the penetrance scale, which might indicate a disease model mediated by more than one pathway leading to beta-cell destruction and development of diabetes. However, there has been confusion between different definitions of interaction or epistasis as used in the biological, statistical, epidemiological, and quantitative and human genetics fields. The degree to which statistical analyses can elucidate underlying biologic mechanisms may be limited and may require prior knowledge of the underlying etiology. PMID:11333244

  12. Dominant-and-recessive epistasis in a homeotic mosquito mutant.

    PubMed

    Bhalla, S C

    1976-12-01

    Following selection for 15 generations a pure strain of a homeotic mutant spur was isolated from a Brazilian population of the mosquito Culex pipiens fatigans. Monohybrid crosses showed a 13:3 segregation indicating dominant-and-recessive epistasis for wild-type vs. spur. This implies that a dominant allele at one locus and a recessive at the other interact to produce the mutant phenotype. Dihybrid crosses with linkage group II markers yellow and ruby gave 39:13:9:3 ratios indicating independent segregation. However, the dihybrid cross with linkage group I marker maroon showed a highly significant departure from 39:13:9:3 ratio. Data available indicate that the phenotype spur is controlled by a dominant epistat in linkage group III and a recessive epistat (approximately 31.9 crossover units from maroon) in linkage group I. PMID:1022329

  13. A robustness study of parametric and non-parametric tests in model-based multifactor dimensionality reduction for epistasis detection

    PubMed Central

    2013-01-01

    Background Applying a statistical method implies identifying underlying (model) assumptions and checking their validity in the particular context. One of these contexts is association modeling for epistasis detection. Here, depending on the technique used, violation of model assumptions may result in increased type I error, power loss, or biased parameter estimates. Remedial measures for violated underlying conditions or assumptions include data transformation or selecting a more relaxed modeling or testing strategy. Model-Based Multifactor Dimensionality Reduction (MB-MDR) for epistasis detection relies on association testing between a trait and a factor consisting of multilocus genotype information. For quantitative traits, the framework is essentially Analysis of Variance (ANOVA) that decomposes the variability in the trait amongst the different factors. In this study, we assess through simulations, the cumulative effect of deviations from normality and homoscedasticity on the overall performance of quantitative Model-Based Multifactor Dimensionality Reduction (MB-MDR) to detect 2-locus epistasis signals in the absence of main effects. Methodology Our simulation study focuses on pure epistasis models with varying degrees of genetic influence on a quantitative trait. Conditional on a multilocus genotype, we consider quantitative trait distributions that are normal, chi-square or Student’s t with constant or non-constant phenotypic variances. All data are analyzed with MB-MDR using the built-in Student’s t-test for association, as well as a novel MB-MDR implementation based on Welch’s t-test. Traits are either left untransformed or are transformed into new traits via logarithmic, standardization or rank-based transformations, prior to MB-MDR modeling. Results Our simulation results show that MB-MDR controls type I error and false positive rates irrespective of the association test considered. Empirically-based MB-MDR power estimates for MB-MDR with Welch

  14. Acceleration of reverse analysis method using hyperbolic activation function

    NASA Astrophysics Data System (ADS)

    Pwasong, Augustine; Sathasivam, Saratha

    2015-10-01

    Hyperbolic activation function is examined for its ability to accelerate the performance of doing data mining by using a technique named as Reverse Analysis method. In this paper, we describe how Hopfield network perform better with hyperbolic activation function and able to induce logical rules from large database by using reverse analysis method: given the values of the connections of a network, we can hope to know what logical rules are entrenched in the database. We limit our analysis to Horn clauses.

  15. Further analysis of MHD acceleration for a hypersonic wind tunnel

    SciTech Connect

    Christiansen, M.J.; Schmidt, H.J.; Chapman, J.N.

    1995-12-31

    A previously completed MHD study of the use of an MHD accelerator with seeded air from a state-of-the-art arc heater, was generally hailed as showing that the system studied has some promise of meeting the most critical hypersonic testing requirements. However, some concerns existed about certain aspects of the results. This paper discusses some of these problems and presents analysis of potential solutions. Specifically the problems addressed are; reducing the amount of seed in the flow, reducing test chamber temperatures, and reducing the oxygen dissociation. Modeling techniques are used to study three design variables of the MHD accelerator. The accelerator channel inlet Mach number, the accelerator channel divergence angle, and the magnetic field strength are all studied. These variables are all optimized to meet the goals for seed, temperature, and dissociated oxygen reduction. The results of this paper are encouraging, showing that all three goals can be met. General relationships are observed as to how the design variables affect the performance of the MHD accelerator facility. This paper expands on the results presented in the UTSI report and further supports the feasibility of MHD acceleration as a means to provide hypersonic flight simulation.

  16. Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus

    PubMed Central

    Lalić, J; Elena, S F

    2012-01-01

    How epistatic interactions between mutations determine the genetic architecture of fitness is of central importance in evolution. The study of epistasis is particularly interesting for RNA viruses because of their genomic compactness, lack of genetic redundancy, and apparent low complexity. Moreover, interactions between mutations in viral genomes determine traits such as resistance to antiviral drugs, virulence and host range. In this study we generated 53 Tobacco etch potyvirus genotypes carrying pairs of single-nucleotide substitutions and measured their separated and combined deleterious fitness effects. We found that up to 38% of pairs had significant epistasis for fitness, including both positive and negative deviations from the null hypothesis of multiplicative effects. Interestingly, the sign of epistasis was correlated with viral protein–protein interactions in a model network, being predominantly positive between linked pairs of proteins and negative between unlinked ones. Furthermore, 55% of significant interactions were cases of reciprocal sign epistasis (RSE), indicating that adaptive landscapes for RNA viruses maybe highly rugged. Finally, we found that the magnitude of epistasis correlated negatively with the average effect of mutations. Overall, our results are in good agreement to those previously reported for other viruses and further consolidate the view that positive epistasis is the norm for small and compact genomes that lack genetic robustness. PMID:22491062

  17. Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types

    PubMed Central

    Park, Solip; Lehner, Ben

    2015-01-01

    Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. PMID:26227665

  18. Cancer type-dependent genetic interactions between cancer driver alterations indicate plasticity of epistasis across cell types.

    PubMed

    Park, Solip; Lehner, Ben

    2015-07-01

    Cancers, like many diseases, are normally caused by combinations of genetic alterations rather than by changes affecting single genes. It is well established that the genetic alterations that drive cancer often interact epistatically, having greater or weaker consequences in combination than expected from their individual effects. In a stringent statistical analysis of data from > 3,000 tumors, we find that the co-occurrence and mutual exclusivity relationships between cancer driver alterations change quite extensively in different types of cancer. This cannot be accounted for by variation in tumor heterogeneity or unrecognized cancer subtypes. Rather, it suggests that how genomic alterations interact cooperatively or partially redundantly to driver cancer changes in different types of cancers. This re-wiring of epistasis across cell types is likely to be a basic feature of genetic architecture, with important implications for understanding the evolution of multicellularity and human genetic diseases. In addition, if this plasticity of epistasis across cell types is also true for synthetic lethal interactions, a synthetic lethal strategy to kill cancer cells may frequently work in one type of cancer but prove ineffective in another. PMID:26227665

  19. New accelerators for femtosecond beam pump-and-probe analysis

    NASA Astrophysics Data System (ADS)

    Uesaka, Mitsuru; Sakumi, Akira; Hosokai, Tomonao; Kinoshita, Kenichi; Yamaoka, Nobuaki; Zhidkov, Alexei; Ohkubo, Takeru; Ueda, Toru; Muroya, Yusa; Katsumura, Yosuke; Iijima, Hokuto; Tomizawa, Hiromitsu; Kumagai, Noritaka

    2005-12-01

    Femtosecond electron beams are novel tool for pump-probe analysis of condensed matter. Progress in developing femtosecond electron beams with the use of both conventional accelerators and laser-plasma accelerators is discussed. In conventional accelerators, the critical issue is timing jitter and drift of the linac-laser synchronization system. Sophisticated electronic devices are developed to reduce the jitter to 330 fs (rms); the precise control of temperature at several parts of the accelerator lessens the drift to 1 ps (rms). We also report on a full-optical X-ray and e-beam system based on the laser-plasma cathode by using a 12 TW 50 fs laser, which enables 40 MeV (at maximum), 40 fs (cal.), 100 pC and quasi-monochromatic single electron bunches. Since the synchronization is done by a passive optical beam-splitter, this system intrinsically has no jitter and drift. It could achieve tens of femtoseconds time-resolved analysis in the near future.

  20. RATES OF FITNESS DECLINE AND REBOUND SUGGEST PERVASIVE EPISTASIS

    PubMed Central

    Perfeito, L; Sousa, A; Bataillon, T; Gordo, I

    2014-01-01

    Unraveling the factors that determine the rate of adaptation is a major question in evolutionary biology. One key parameter is the effect of a new mutation on fitness, which invariably depends on the environment and genetic background. The fate of a mutation also depends on population size, which determines the amount of drift it will experience. Here, we manipulate both population size and genotype composition and follow adaptation of 23 distinct Escherichia coli genotypes. These have previously accumulated mutations under intense genetic drift and encompass a substantial fitness variation. A simple rule is uncovered: the net fitness change is negatively correlated with the fitness of the genotype in which new mutations appear—a signature of epistasis. We find that Fisher's geometrical model can account for the observed patterns of fitness change and infer the parameters of this model that best fit the data, using Approximate Bayesian Computation. We estimate a genomic mutation rate of 0.01 per generation for fitness altering mutations, albeit with a large confidence interval, a mean fitness effect of mutations of −0.01, and an effective number of traits nine in mutS− E. coli. This framework can be extended to confront a broader range of models with data and test different classes of fitness landscape models. PMID:24372601

  1. Epistasis and the Dynamics of Reversion in Molecular Evolution.

    PubMed

    McCandlish, David M; Shah, Premal; Plotkin, Joshua B

    2016-07-01

    Recent studies of protein evolution contend that the longer an amino acid substitution is present at a site, the less likely it is to revert to the amino acid previously occupying that site. Here we study this phenomenon of decreasing reversion rates rigorously and in a much more general context. We show that, under weak mutation and for arbitrary fitness landscapes, reversion rates decrease with time for any site that is involved in at least one epistatic interaction. Specifically, we prove that, at stationarity, the hazard function of the distribution of waiting times until reversion is strictly decreasing for any such site. Thus, in the presence of epistasis, the longer a particular character has been absent from a site, the less likely the site will revert to its prior state. We also explore several examples of this general result, which share a common pattern whereby the probability of having reverted increases rapidly at short times to some substantial value before becoming almost flat after a few substitutions at other sites. This pattern indicates a characteristic tendency for reversion to occur either almost immediately after the initial substitution or only after a very long time. PMID:27194749

  2. Automatic Beam Path Analysis of Laser Wakefield Particle Acceleration Data

    SciTech Connect

    Rubel, Oliver; Geddes, Cameron G.R.; Cormier-Michel, Estelle; Wu, Kesheng; Prabhat,; Weber, Gunther H.; Ushizima, Daniela M.; Messmer, Peter; Hagen, Hans; Hamann, Bernd; Bethel, E. Wes

    2009-10-19

    Numerical simulations of laser wakefield particle accelerators play a key role in the understanding of the complex acceleration process and in the design of expensive experimental facilities. As the size and complexity of simulation output grows, an increasingly acute challenge is the practical need for computational techniques that aid in scientific knowledge discovery. To that end, we present a set of data-understanding algorithms that work in concert in a pipeline fashion to automatically locate and analyze high energy particle bunches undergoing acceleration in very large simulation datasets. These techniques work cooperatively by first identifying features of interest in individual timesteps, then integrating features across timesteps, and based on the information derived perform analysis of temporally dynamic features. This combination of techniques supports accurate detection of particle beams enabling a deeper level of scientific understanding of physical phenomena than hasbeen possible before. By combining efficient data analysis algorithms and state-of-the-art data management we enable high-performance analysis of extremely large particle datasets in 3D. We demonstrate the usefulness of our methods for a variety of 2D and 3D datasets and discuss the performance of our analysis pipeline.

  3. The Impact of Macroscopic Epistasis on Long-Term Evolutionary Dynamics

    PubMed Central

    Good, Benjamin H.; Desai, Michael M.

    2015-01-01

    Genetic interactions can strongly influence the fitness effects of individual mutations, yet the impact of these epistatic interactions on evolutionary dynamics remains poorly understood. Here we investigate the evolutionary role of epistasis over 50,000 generations in a well-studied laboratory evolution experiment in Escherichia coli. The extensive duration of this experiment provides a unique window into the effects of epistasis during long-term adaptation to a constant environment. Guided by analytical results in the weak-mutation limit, we develop a computational framework to assess the compatibility of a given epistatic model with the observed patterns of fitness gain and mutation accumulation through time. We find that a decelerating fitness trajectory alone provides little power to distinguish between competing models, including those that lack any direct epistatic interactions between mutations. However, when combined with the mutation trajectory, these observables place strong constraints on the set of possible models of epistasis, ruling out many existing explanations of the data. Instead, we find that the data are consistent with a “two-epoch” model of adaptation, in which an initial burst of diminishing-returns epistasis is followed by a steady accumulation of mutations under a constant distribution of fitness effects. Our results highlight the need for additional DNA sequencing of these populations, as well as for more sophisticated models of epistasis that are compatible with all of the experimental data. PMID:25395665

  4. Epistasis in intra- and inter-gene pool crosses of the common bean.

    PubMed

    Borel, J C; Ramalho, M A P; Abreu, A F B

    2016-01-01

    Epistasis has been shown to have an important role in the genetic control of several quantitative traits in the common bean. This study aimed to investigate the occurrence of epistasis in intra- and inter-pool gene crosses of the common bean. Four elite lines adapted to Brazilian conditions were used as parents, two from the Andean gene pool (ESAL 686; BRS Radiante) and two from the Mesoamerican gene pool (BRSMG Majestoso; BRS Valente). Four F2 populations were obtained: "A" (ESAL 686 x BRS Radiante), "B" (BRSMG Majestoso x BRS Valente), "C" (BRS Radiante x BRSMG Majestoso), and "D" (BRS Valente x ESAL 686). A random sample of F2 plants from each population was backcrossed to parents and F1 individuals, according to the triple test cross. Three types of progenies from each population were evaluated in contiguous trials. Seed yield and 100-seed weight were evaluated. Dominance genetic variance was predominant in most cases. However, the estimates of genetic variance may be biased by the occurrence of linkage disequilibrium and epistasis. Epistasis was detected for both traits; however, the occurrence differed among the populations and between the two traits. The results of this study reinforce the hypothesis that epistasis is present in the genetic control of traits in the common bean and suggest that the phenomenon is more frequent in inter-gene pool crosses than in intra-gene pool crosses. PMID:26985920

  5. Measuring epistasis in fitness landscapes: The correlation of fitness effects of mutations.

    PubMed

    Ferretti, Luca; Schmiegelt, Benjamin; Weinreich, Daniel; Yamauchi, Atsushi; Kobayashi, Yutaka; Tajima, Fumio; Achaz, Guillaume

    2016-05-01

    Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models. PMID:26854875

  6. Review: High-performance computing to detect epistasis in genome scale data sets.

    PubMed

    Upton, Alex; Trelles, Oswaldo; Cornejo-García, José Antonio; Perkins, James Richard

    2016-05-01

    It is becoming clear that most human diseases have a complex etiology that cannot be explained by single nucleotide polymorphisms (SNPs) or simple additive combinations; the general consensus is that they are caused by combinations of multiple genetic variations. The limited success of some genome-wide association studies is partly a result of this focus on single genetic markers. A more promising approach is to take into account epistasis, by considering the association of multiple SNP interactions with disease. However, as genomic data continues to grow in resolution, and genome and exome sequencing become more established, the number of combinations of variants to consider increases rapidly. Two potential solutions should be considered: the use of high-performance computing, which allows us to consider a larger number of variables, and heuristics to make the solution more tractable, essential in the case of genome sequencing. In this review, we look at different computational methods to analyse epistatic interactions within disease-related genetic data sets created by microarray technology. We also review efforts to use epistatic analysis results to produce biomarkers for diagnostic tests and give our views on future directions in this field in light of advances in sequencing technology and variants in non-coding regions. PMID:26272945

  7. Mitochondrial–Nuclear Epistasis Impacts Fitness and Mitochondrial Physiology of Interpopulation Caenorhabditis briggsae Hybrids

    PubMed Central

    Chang, Chih-Chiun; Rodriguez, Joel; Ross, Joseph

    2015-01-01

    In order to identify the earliest genetic changes that precipitate species formation, it is useful to study genetic incompatibilities that cause only mild dysfunction when incompatible alleles are combined in an interpopulation hybrid. Such hybridization within the nematode species Caenorhabditis briggsae has been suggested to result in selection against certain combinations of nuclear and mitochondrial alleles, raising the possibility that mitochondrial–nuclear (mitonuclear) epistasis reduces hybrid fitness. To test this hypothesis, cytoplasmic–nuclear hybrids (cybrids) were created to purposefully disrupt any epistatic interactions. Experimental analysis of the cybrids suggests that mitonuclear discord can result in decreased fecundity, increased lipid content, and increased mitochondrial reactive oxygen species levels. Many of these effects were asymmetric with respect to cross direction, as expected if cytoplasmic–nuclear Dobzhansky-Muller incompatibilities exist. One such effect is consistent with the interpretation that disrupting coevolved mitochondrial and nuclear loci impacts mitochondrial function and organismal fitness. These findings enhance efforts to study the genesis, identity, and maintenance of genetic incompatibilities that precipitate the speciation process. PMID:26585825

  8. Shadows of complexity: what biological networks reveal about epistasis and pleiotropy.

    PubMed

    Tyler, Anna L; Asselbergs, Folkert W; Williams, Scott M; Moore, Jason H

    2009-02-01

    Pleiotropy, in which one mutation causes multiple phenotypes, has traditionally been seen as a deviation from the conventional observation in which one gene affects one phenotype. Epistasis, or gene-gene interaction, has also been treated as an exception to the Mendelian one gene-one phenotype paradigm. This simplified perspective belies the pervasive complexity of biology and hinders progress toward a deeper understanding of biological systems. We assert that epistasis and pleiotropy are not isolated occurrences, but ubiquitous and inherent properties of biomolecular networks. These phenomena should not be treated as exceptions, but rather as fundamental components of genetic analyses. A systems level understanding of epistasis and pleiotropy is, therefore, critical to furthering our understanding of human genetics and its contribution to common human disease. Finally, graph theory offers an intuitive and powerful set of tools with which to study the network bases of these important genetic phenomena. PMID:19204994

  9. Accelerated Gibbs Sampling for Infinite Sparse Factor Analysis

    SciTech Connect

    Andrzejewski, D M

    2011-09-12

    The Indian Buffet Process (IBP) gives a probabilistic model of sparse binary matrices with an unbounded number of columns. This construct can be used, for example, to model a fixed numer of observed data points (rows) associated with an unknown number of latent features (columns). Markov Chain Monte Carlo (MCMC) methods are often used for IBP inference, and in this technical note, we provide a detailed review of the derivations of collapsed and accelerated Gibbs samplers for the linear-Gaussian infinite latent feature model. We also discuss and explain update equations for hyperparameter resampling in a 'full Bayesian' treatment and present a novel slice sampler capable of extending the accelerated Gibbs sampler to the case of infinite sparse factor analysis by allowing the use of real-valued latent features.

  10. Analysis of accelerants and fire debris using aroma detection technology

    SciTech Connect

    Barshick, S.A.

    1997-01-17

    The purpose of this work was to investigate the utility of electronic aroma detection technologies for the detection and identification of accelerant residues in suspected arson debris. Through the analysis of known accelerant residues, a trained neural network was developed for classifying suspected arson samples. Three unknown fire debris samples were classified using this neural network. The item corresponding to diesel fuel was correctly identified every time. For the other two items, wide variations in sample concentration and excessive water content, producing high sample humidities, were shown to influence the sensor response. Sorbent sampling prior to aroma detection was demonstrated to reduce these problems and to allow proper neural network classification of the remaining items corresponding to kerosene and gasoline.

  11. Analysis of Cultural Heritage by Accelerator Techniques and Analytical Imaging

    NASA Astrophysics Data System (ADS)

    Ide-Ektessabi, Ari; Toque, Jay Arre; Murayama, Yusuke

    2011-12-01

    In this paper we present the result of experimental investigation using two very important accelerator techniques: (1) synchrotron radiation XRF and XAFS; and (2) accelerator mass spectrometry and multispectral analytical imaging for the investigation of cultural heritage. We also want to introduce a complementary approach to the investigation of artworks which is noninvasive and nondestructive that can be applied in situ. Four major projects will be discussed to illustrate the potential applications of these accelerator and analytical imaging techniques: (1) investigation of Mongolian Textile (Genghis Khan and Kublai Khan Period) using XRF, AMS and electron microscopy; (2) XRF studies of pigments collected from Korean Buddhist paintings; (3) creating a database of elemental composition and spectral reflectance of more than 1000 Japanese pigments which have been used for traditional Japanese paintings; and (4) visible light-near infrared spectroscopy and multispectral imaging of degraded malachite and azurite. The XRF measurements of the Japanese and Korean pigments could be used to complement the results of pigment identification by analytical imaging through spectral reflectance reconstruction. On the other hand, analysis of the Mongolian textiles revealed that they were produced between 12th and 13th century. Elemental analysis of the samples showed that they contained traces of gold, copper, iron and titanium. Based on the age and trace elements in the samples, it was concluded that the textiles were produced during the height of power of the Mongol empire, which makes them a valuable cultural heritage. Finally, the analysis of the degraded and discolored malachite and azurite demonstrates how multispectral analytical imaging could be used to complement the results of high energy-based techniques.

  12. GPU accelerated dynamic functional connectivity analysis for functional MRI data.

    PubMed

    Akgün, Devrim; Sakoğlu, Ünal; Esquivel, Johnny; Adinoff, Bryon; Mete, Mutlu

    2015-07-01

    Recent advances in multi-core processors and graphics card based computational technologies have paved the way for an improved and dynamic utilization of parallel computing techniques. Numerous applications have been implemented for the acceleration of computationally-intensive problems in various computational science fields including bioinformatics, in which big data problems are prevalent. In neuroimaging, dynamic functional connectivity (DFC) analysis is a computationally demanding method used to investigate dynamic functional interactions among different brain regions or networks identified with functional magnetic resonance imaging (fMRI) data. In this study, we implemented and analyzed a parallel DFC algorithm based on thread-based and block-based approaches. The thread-based approach was designed to parallelize DFC computations and was implemented in both Open Multi-Processing (OpenMP) and Compute Unified Device Architecture (CUDA) programming platforms. Another approach developed in this study to better utilize CUDA architecture is the block-based approach, where parallelization involves smaller parts of fMRI time-courses obtained by sliding-windows. Experimental results showed that the proposed parallel design solutions enabled by the GPUs significantly reduce the computation time for DFC analysis. Multicore implementation using OpenMP on 8-core processor provides up to 7.7× speed-up. GPU implementation using CUDA yielded substantial accelerations ranging from 18.5× to 157× speed-up once thread-based and block-based approaches were combined in the analysis. Proposed parallel programming solutions showed that multi-core processor and CUDA-supported GPU implementations accelerated the DFC analyses significantly. Developed algorithms make the DFC analyses more practical for multi-subject studies with more dynamic analyses. PMID:25805449

  13. A multi-beamlet analysis of the MITICA accelerator

    SciTech Connect

    Fonnesu, N. Agostinetti, P.; Serianni, G.; Veltri, P.; Kisaki, M.

    2015-04-08

    The thermo-mechanical analysis and the mechanical design of the accelerator of MITICA (i.e. the full size prototype of the ITER neutral beam injector under construction at RFX [1]) are based on the calculation of the power deposition induced by particle impacts. This calculation is performed by EAMCC [2], a relativistic particle tracking code based on the Monte-Carlo method for describing collisions inside the accelerator, under prescribed electric and magnetic fields. The magnetic field maps are produced by 3D codes, while the electric field maps come from the 2D axi-symmetric code SLACCAD [3]. In order to perform a multi-beamlet analysis, which allows to take into account the beamlet-beamlet repulsion, and to consider other effects neglected under the hypothesis of axi-symmetric beam, a fully 3D version of the code is required. In this paper, a modified version of EAMCC, fully 3D, capable of modifying the mesh of the 3D maps and of dealing with uneven meshes is presented. A finer mesh is used just in the regions where a more detailed description of the fields is required, for a more realistic simulation. A comparison between the original code and the modified version is presented at first, as a validation of the modifications introduced in the latter. Subsequently, the main results of a single-beamlet analysis performed with the two versions of the code are shown and the differences between the 2D and the 3D simulations discussed. The last part is dedicated to the multi-beamlet simulation of the accelerator.

  14. [Analysis of human tissue samples for volatile fire accelerants].

    PubMed

    Treibs, Rudolf

    2014-01-01

    In police investigations of fires, the cause of a fire and the fire debris analysis regarding traces of fire accelerants are important aspects for forensic scientists. Established analytical procedures were recently applied to the remains of fire victims. When examining lung tissue samples, vapors inhaled from volatile ignitable liquids could be identified and differentiated from products of pyrolysis caused by the fire. In addition to the medico-legal results this evidence allowed to draw conclusions as to whether the fire victim was still alive when the fire started. PMID:24855737

  15. The Benefits of Acceleration: An Outcomes Analysis of Dual Enrollment

    ERIC Educational Resources Information Center

    Morrison, Michael C.

    2007-01-01

    This study adds to the growing body of research with a focus on (1) the characteristics of accelerated (dual enrolled) students versus their counterparts who did not participate in accelerated programs; (2) differences in academic outcomes of accelerated and non-accelerated students; and (3) differences in days to complete the associate degree for…

  16. Direct and indirect genetic effects of sex-specific mitonuclear epistasis on reproductive ageing.

    PubMed

    Immonen, E; Collet, M; Goenaga, J; Arnqvist, G

    2016-03-01

    Mitochondria are involved in ageing and their function requires coordinated action of both mitochondrial and nuclear genes. Epistasis between the two genomes can influence lifespan but whether this also holds for reproductive senescence is unclear. Maternal inheritance of mitochondria predicts sex differences in the efficacy of selection on mitonuclear genotypes that should result in differences between females and males in mitochondrial genetic effects. Mitonuclear genotype of a focal individual may also indirectly affect trait expression in the mating partner. We tested these predictions in the seed beetle Callosobruchus maculatus, using introgression lines harbouring distinct mitonuclear genotypes. Our results reveal both direct and indirect sex-specific effects of mitonuclear epistasis on reproductive ageing. Females harbouring coadapted mitonuclear genotypes showed higher lifetime fecundity due to slower senescence relative to novel mitonuclear combinations. We found no evidence for mitonuclear coadaptation in males. Mitonuclear epistasis not only affected age-specific ejaculate weight, but also influenced male age-dependent indirect effects on traits expressed by their female partners (fecundity, egg size, longevity). These results demonstrate important consequences of sex-specific mitonuclear epistasis for both mating partners, consistent with a role for mitonuclear genetic constraints upon sex-specific adaptive evolution. PMID:26732015

  17. Ant Species Differences Determined by Epistasis between Brood and Worker Genomes

    PubMed Central

    Linksvayer, Timothy A.

    2007-01-01

    Epistasis arising from physiological interactions between gene products often contributes to species differences, particularly those involved in reproductive isolation. In social organisms, phenotypes are influenced by the genotypes of multiple interacting individuals. In theory, social interactions can give rise to an additional type of epistasis between the genomes of social partners that can contribute to species differences. Using a full-factorial cross-fostering design with three species of closely related Temnothorax ants, I found that adult worker size was determined by an interaction between the genotypes of developing brood and care-giving workers, i.e. intergenomic epistasis. Such intergenomic social epistasis provides a strong signature of coevolution between social partners. These results demonstrate that just as physiologically interacting genes coevolve, diverge, and contribute to species differences, so do socially interacting genes. Coevolution and conflict between social partners, especially relatives such as parents and offspring, has long been recognized as having widespread evolutionary effects. This coevolutionary process may often result in coevolved socially-interacting gene complexes that contribute to species differences. PMID:17912371

  18. Evolution and polymorphism in the multilocus Levene model with no or weak epistasis

    PubMed Central

    Bürger, Reinhard

    2010-01-01

    Evolution and the maintenance of polymorphism under the multilocus Levene model with soft selection are studied. The number of loci and alleles, the number of demes, the linkage map, and the degree of dominance are arbitrary, but epistasis is absent or weak. We prove that, without epistasis and under mild, generic conditions, every trajectory converges to a stationary point in linkage equilibrium. Consequently, the equilibrium and stability structure can be determined by investigating the much simpler gene-frequency dynamics on the linkage-equilibrium manifold. For a haploid species an analogous result is shown. For weak epistasis, global convergence to quasi-linkage equilibrium is established. As an application, the maintenance of multilocus polymorphism is explored if the degree of dominance is intermediate at every locus and epistasis is absent or weak. If there are at least two demes, then arbitrarily many multiallelic loci can be maintained polymorphic at a globally asymptotically stable equilibrium. Because this holds for an open set of parameters, such equilibria are structurally stable. If the degree of dominance is not only intermediate but also deme independent, and loci are diallelic, an open set of parameters yielding an internal equilibrium exists only if the number of loci is strictly less than the number of demes. Otherwise, a fully polymorphic equilibrium exists only nongenerically, and if it exists, it consists of a manifold of equilibria. Its dimension is determined. In the absence of genotype-by-environment interaction, however, a manifold of equilibria occurs for an open set of parameters. In this case, the equilibrium structure is not robust to small deviations from no genotype-by-environment interaction. In a quantitative-genetic setting, the assumptions of no epistasis and intermediate dominance are equivalent to assuming that in every deme directional selection acts on a trait that is determined additively, i.e., by nonepistatic loci with

  19. Cosmic acceleration without dark energy: background tests and thermodynamic analysis

    SciTech Connect

    Lima, J.A.S.; Graef, L.L.; Pavón, D.; Basilakos, Spyros E-mail: leilagraef@usp.br E-mail: svasil@academyofathens.gr

    2014-10-01

    A cosmic scenario with gravitationally induced particle creation is proposed. In this model the Universe evolves from an early to a late time de Sitter era, with the recent accelerating phase driven only by the negative creation pressure associated with the cold dark matter component. The model can be interpreted as an attempt to reduce the so-called cosmic sector (dark matter plus dark energy) and relate the two cosmic accelerating phases (early and late time de Sitter expansions). A detailed thermodynamic analysis including possible quantum corrections is also carried out. For a very wide range of the free parameters, it is found that the model presents the expected behavior of an ordinary macroscopic system in the sense that it approaches thermodynamic equilibrium in the long run (i.e., as it nears the second de Sitter phase). Moreover, an upper bound is found for the Gibbons–Hawking temperature of the primordial de Sitter phase. Finally, when confronted with the recent observational data, the current 'quasi'-de Sitter era, as predicted by the model, is seen to pass very comfortably the cosmic background tests.

  20. Cosmic acceleration without dark energy: background tests and thermodynamic analysis

    NASA Astrophysics Data System (ADS)

    Lima, J. A. S.; Graef, L. L.; Pavón, D.; Basilakos, Spyros

    2014-10-01

    A cosmic scenario with gravitationally induced particle creation is proposed. In this model the Universe evolves from an early to a late time de Sitter era, with the recent accelerating phase driven only by the negative creation pressure associated with the cold dark matter component. The model can be interpreted as an attempt to reduce the so-called cosmic sector (dark matter plus dark energy) and relate the two cosmic accelerating phases (early and late time de Sitter expansions). A detailed thermodynamic analysis including possible quantum corrections is also carried out. For a very wide range of the free parameters, it is found that the model presents the expected behavior of an ordinary macroscopic system in the sense that it approaches thermodynamic equilibrium in the long run (i.e., as it nears the second de Sitter phase). Moreover, an upper bound is found for the Gibbons-Hawking temperature of the primordial de Sitter phase. Finally, when confronted with the recent observational data, the current `quasi'-de Sitter era, as predicted by the model, is seen to pass very comfortably the cosmic background tests.

  1. Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy.

    PubMed

    Luizon, Marcelo R; Sandrim, Valeria C; Palei, Ana Ct; Lacchini, Riccardo; Cavalli, Ricardo C; Duarte, Geraldo; Tanus-Santos, Jose E

    2012-09-01

    Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)₁₃-₂₅, rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. PMID:22573202

  2. Discovering epistasis in large scale genetic association studies by exploiting graphics cards

    PubMed Central

    Chen, Gary K.; Guo, Yunfei

    2013-01-01

    Despite the enormous investments made in collecting DNA samples and generating germline variation data across thousands of individuals in modern genome-wide association studies (GWAS), progress has been frustratingly slow in explaining much of the heritability in common disease. Today's paradigm of testing independent hypotheses on each single nucleotide polymorphism (SNP) marker is unlikely to adequately reflect the complex biological processes in disease risk. Alternatively, modeling risk as an ensemble of SNPs that act in concert in a pathway, and/or interact non-additively on log risk for example, may be a more sensible way to approach gene mapping in modern studies. Implementing such analyzes genome-wide can quickly become intractable due to the fact that even modest size SNP panels on modern genotype arrays (500k markers) pose a combinatorial nightmare, require tens of billions of models to be tested for evidence of interaction. In this article, we provide an in-depth analysis of programs that have been developed to explicitly overcome these enormous computational barriers through the use of processors on graphics cards known as Graphics Processing Units (GPU). We include tutorials on GPU technology, which will convey why they are growing in appeal with today's numerical scientists. One obvious advantage is the impressive density of microprocessor cores that are available on only a single GPU. Whereas high end servers feature up to 24 Intel or AMD CPU cores, the latest GPU offerings from nVidia feature over 2600 cores. Each compute node may be outfitted with up to 4 GPU devices. Success on GPUs varies across problems. However, epistasis screens fare well due to the high degree of parallelism exposed in these problems. Papers that we review routinely report GPU speedups of over two orders of magnitude (>100x) over standard CPU implementations. PMID:24348518

  3. Discovering epistasis in large scale genetic association studies by exploiting graphics cards.

    PubMed

    Chen, Gary K; Guo, Yunfei

    2013-01-01

    Despite the enormous investments made in collecting DNA samples and generating germline variation data across thousands of individuals in modern genome-wide association studies (GWAS), progress has been frustratingly slow in explaining much of the heritability in common disease. Today's paradigm of testing independent hypotheses on each single nucleotide polymorphism (SNP) marker is unlikely to adequately reflect the complex biological processes in disease risk. Alternatively, modeling risk as an ensemble of SNPs that act in concert in a pathway, and/or interact non-additively on log risk for example, may be a more sensible way to approach gene mapping in modern studies. Implementing such analyzes genome-wide can quickly become intractable due to the fact that even modest size SNP panels on modern genotype arrays (500k markers) pose a combinatorial nightmare, require tens of billions of models to be tested for evidence of interaction. In this article, we provide an in-depth analysis of programs that have been developed to explicitly overcome these enormous computational barriers through the use of processors on graphics cards known as Graphics Processing Units (GPU). We include tutorials on GPU technology, which will convey why they are growing in appeal with today's numerical scientists. One obvious advantage is the impressive density of microprocessor cores that are available on only a single GPU. Whereas high end servers feature up to 24 Intel or AMD CPU cores, the latest GPU offerings from nVidia feature over 2600 cores. Each compute node may be outfitted with up to 4 GPU devices. Success on GPUs varies across problems. However, epistasis screens fare well due to the high degree of parallelism exposed in these problems. Papers that we review routinely report GPU speedups of over two orders of magnitude (>100x) over standard CPU implementations. PMID:24348518

  4. Bayesian Analysis of Peak Ground Acceleration Attenuation Relationship

    SciTech Connect

    Mu Heqing; Yuen Kaveng

    2010-05-21

    Estimation of peak ground acceleration is one of the main issues in civil and earthquake engineering practice. The Boore-Joyner-Fumal empirical formula is well known for this purpose. In this paper we propose to use the Bayesian probabilistic model class selection approach to obtain the most suitable prediction model class for the seismic attenuation formula. The optimal model class is robust in the sense that it has balance between the data fitting capability and the sensitivity to noise. A database of strong-motion records is utilized for the analysis. It turns out that the optimal model class is simpler than the full order attenuation model suggested by Boore, Joyner and Fumal (1993).

  5. SIMS analysis of high-performance accelerator niobium

    SciTech Connect

    Maheshwari, P.; Stevie, F. A.; Myneni, Ganapati Rao; Rigsbee, J, M.; Dhakal, Pashupati; Ciovati, Gianluigi; Griffis, D. P.

    2014-11-01

    Niobium is used to fabricate superconducting radio frequency accelerator modules because of its high critical temperature, high critical magnetic field, and easy formability. Recent experiments have shown a very significant improvement in performance (over 100%) after a high-temperature bake at 1400 degrees C for 3h. SIMS analysis of this material showed the oxygen profile was significantly deeper than the native oxide with a shape that is indicative of diffusion. Positive secondary ion mass spectra showed the presence of Ti with a depth profile similar to that of O. It is suspected that Ti is associated with the performance improvement. The source of Ti contamination in the anneal furnace has been identified, and a new furnace was constructed without Ti. Initial results from the new furnace do not show the yield improvement. Further analyses should determine the relationship of Ti to cavity performance.

  6. Transition of Iodine Analysis to Accelerator Mass Spectrometry

    SciTech Connect

    Watrous, Matthew George; Adamic, Mary Louise; Olson, John Eric; Baeck, D. L.; Fox, R. V.; Hahn, P. A.; Jenson, D. D.; Lister, T. E.

    2015-09-01

    The goal of the project, New Paradigms for Isotope Ratio Mass Spectrometry: Raising the Scientific Profile and Improved Performance for Accelerator Mass Spectrometry (AMS) and Thermal Ionization Mass Spectrometry (TIMS), is to ensure that the ongoing isotope ratio determination capability within the U.S. Department of Energy complex is the world’s best for application to nonproliferation. This report spells out the progress of Task 4, Transition of TIMS to AMS for Iodine Analysis, of the larger project. The subtasks under Task 4 and the accomplishments throughout the three year project life cycle are presented in this report. Progress was made in optimization of chemical extraction, determination of a detection limit for 127Iodine, production of standard materials for AMS analysis quality assurance, facilitation of knowledge exchange with respect to analyzing iodine on an AMS, cross comparison with a world-leading AMS laboratory, supercritical fluid extraction of iodine for AMS analysis and electrodeposition of seawater as a direct method of preparation for iodine analysis by AMS--all with the goal of minimizing the time required to stand up an AMS capability for iodine analysis of exposed air filters at INL. An effective extraction method has been developed and demonstrated for iodine analysis of exposed air filters. Innovative techniques to accomplish the cathode preparation for AMS analysis were developed and demonstrated and published. The known gap of a lack of available materials for reference standards in the analysis of iodine by AMS was filled by the preparation of homogenous materials that were calibrated against NIST materials. A minimum limit on the amount of abundant isotope in a sample was determined for AMS analysis. The knowledge exchange occurred with fantastic success. Scientists engaged the international AMS community at conferences, as well as in their laboratories for collaborative work. The supercritical fluid extraction work has positive

  7. Transition of Iodine Analysis to Accelerator Mass Spectrometry

    SciTech Connect

    M. L. Adamic; J. E. Olson; D. D. Jenson; J. G. Eisenmenger; M. G. Watrous

    2012-09-01

    This NA 22 funded research project investigated the transition of iodine isotopic analyses from thermal ionization mass spectrometry (TIMS) to an accelerator mass spectrometry (AMS) system. Previous work (Fiscal Year 2010) had demonstrated comparable data from TIMS and AMS. With AMS providing comparable data with improved background levels and vastly superior sample throughput, improvement in the sample extraction from environmental sample matrices was needed to bring sample preparation throughput closer to the operation level of the instrument. Previous research used an extraction chemistry that was not optimized for yield or refined for reduced labor to prove the principle. This research was done to find an extraction with better yield using less labor per sample to produce a sample ready for the AMS instrument. An extraction method using tetramethyl ammonium hydroxide (TMAH) was developed for removal of iodine species from high volume air filters. The TMAH with gentle heating was superior to the following three extraction methods: ammonium hydroxide aided by sonication, acidic and basic extraction aided by microwave, and ethanol mixed with sodium hydroxide. Taking the iodine from the extraction solvent to being ready for AMS analysis was accomplished by a direct precipitation, as well as, using silver wool to harvest the iodine from the TMAH. Portions of the same filters processed in FY 2010 were processed again with the improved extraction scheme followed by successful analysis by AMS at the Swiss Federal Institute of Technology. The data favorably matched the data obtained in 2010. The time required for analysis has been reduced over the aqueous extraction/AMS approach developed in FY 2010. For a hypothetical batch of 30 samples, the AMS methodology is about 10 times faster than the traditional gas phase chemistry and TIMS analysis. As an additional benefit, background levels for the AMS method are about 1000 times lower than TIMS. This results from the

  8. Statistical analysis of accelerated temperature aging of semiconductor devices

    NASA Astrophysics Data System (ADS)

    Johnson, W. A.; Milles, M. F.

    1981-05-01

    A number of semiconductor devices taken from a distribution were operated at several elevated temperatures to induce failure in all devices within a reasonable time. Assuming general characteristics of the device failure probability density function (pdf) and its temperature dependence, the expected cumulative failure function (cff) for devices in normal operation were estimated based on statistical inference, taking the average probability of a random device (from the same distribution but operated at a normal temperature) failing as a function of time. A review of the mathematical formalism employed in semiconductor reliability discussions is included. Three failure pdf's at particular usefulness to this analysis--exponential, normal, and lognormal - are discussed. The cff, at times orders of magnitude loss then, at times comparable to the desired system useful, life (*10 to the 4th power to 10 to the 5th power hr) is considered. A review of accelerated temperature aging is presented, and the assumption concerning the general characteristics of the failure pdf, which are fundamental to this analysis, are emphasized.

  9. Accelerated Sensitivity Analysis in High-Dimensional Stochastic Reaction Networks

    PubMed Central

    Arampatzis, Georgios; Katsoulakis, Markos A.; Pantazis, Yannis

    2015-01-01

    Existing sensitivity analysis approaches are not able to handle efficiently stochastic reaction networks with a large number of parameters and species, which are typical in the modeling and simulation of complex biochemical phenomena. In this paper, a two-step strategy for parametric sensitivity analysis for such systems is proposed, exploiting advantages and synergies between two recently proposed sensitivity analysis methodologies for stochastic dynamics. The first method performs sensitivity analysis of the stochastic dynamics by means of the Fisher Information Matrix on the underlying distribution of the trajectories; the second method is a reduced-variance, finite-difference, gradient-type sensitivity approach relying on stochastic coupling techniques for variance reduction. Here we demonstrate that these two methods can be combined and deployed together by means of a new sensitivity bound which incorporates the variance of the quantity of interest as well as the Fisher Information Matrix estimated from the first method. The first step of the proposed strategy labels sensitivities using the bound and screens out the insensitive parameters in a controlled manner. In the second step of the proposed strategy, a finite-difference method is applied only for the sensitivity estimation of the (potentially) sensitive parameters that have not been screened out in the first step. Results on an epidermal growth factor network with fifty parameters and on a protein homeostasis with eighty parameters demonstrate that the proposed strategy is able to quickly discover and discard the insensitive parameters and in the remaining potentially sensitive parameters it accurately estimates the sensitivities. The new sensitivity strategy can be several times faster than current state-of-the-art approaches that test all parameters, especially in “sloppy” systems. In particular, the computational acceleration is quantified by the ratio between the total number of parameters over

  10. Durability analysis of composite structures using the accelerated testing methodology

    NASA Astrophysics Data System (ADS)

    Kuraishi, Akira

    The applications of composite materials are increasing significantly due to their excellent properties and design flexibility, and composite materials have completely replaced conventional metals in several applications. However, much larger opportunities will be likely to occur when physical bases for durability characterization become established. Polymeric composite materials are in general viscoelastic, and their stiffness and strength depend on temperature and loading rate. These effects play an important role in the long-term durability of the composite materials, and therefore it is important to develop a durability analysis method for composite structures that considers these effects. The present approach is based on three components, a new accelerated material characterization methodology, statistical analysis of this methodology, and conventional design tools tailored for the temperature and loading rate dependence. The material characterization methodology uses series of short-term tests at elevated temperatures to predict life for wide ranges of temperature and loading conditions. This methodology is based on the empirical relation between the effects of temperature and loading rate on the stiffness and strength of polymeric composite materials. The statistical analysis allows us to create the confidence interval of the prediction, which is essential in generating the design allowables. Common design tools such as failure criteria and cumulative damage laws can be tailored to consider the temperature and loading rate dependence. These components are integrated into the proposed durability analysis and design method for composite structures. The durability design of a composite rotor for the flywheel energy storage system is shown as an example. This example demonstrates that the proposed design method is not significantly different from conventional designs in terms of complexity and required effort.

  11. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine

    PubMed Central

    McKinney, Brett A.; Lareau, Caleb; Oberg, Ann L.; Kennedy, Richard B.; Ovsyannikova, Inna G.; Poland, Gregory A.

    2016-01-01

    Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine. PMID:27513748

  12. The Integration of Epistasis Network and Functional Interactions in a GWAS Implicates RXR Pathway Genes in the Immune Response to Smallpox Vaccine.

    PubMed

    McKinney, Brett A; Lareau, Caleb; Oberg, Ann L; Kennedy, Richard B; Ovsyannikova, Inna G; Poland, Gregory A

    2016-01-01

    Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine. PMID:27513748

  13. Solar wind conditions leading to efficient radiation belt electron acceleration: A superposed epoch analysis

    SciTech Connect

    Li, W.; Thorne, R. M.; Bortnik, J.; Baker, D. N.; Reeves, G. D.; Kanekal, S. G.; Spence, H. E.; Green, J. C.

    2015-09-07

    In this study by determining preferential solar wind conditions leading to efficient radiation belt electron acceleration is crucial for predicting radiation belt electron dynamics. Using Van Allen Probes electron observations (>1 MeV) from 2012 to 2015, we identify a number of efficient and inefficient acceleration events separately to perform a superposed epoch analysis of the corresponding solar wind parameters and geomagnetic indices. By directly comparing efficient and inefficient acceleration events, we clearly show that prolonged southward Bz, high solar wind speed, and low dynamic pressure are critical for electron acceleration to >1 MeV energies in the heart of the outer radiation belt. We also evaluate chorus wave evolution using the superposed epoch analysis for the identified efficient and inefficient acceleration events and find that chorus wave intensity is much stronger and lasts longer during efficient electron acceleration events, supporting the scenario that chorus waves play a key role in MeV electron acceleration.

  14. ViSEN: methodology and software for visualization of statistical epistasis networks.

    PubMed

    Hu, Ting; Chen, Yuanzhu; Kiralis, Jeff W; Moore, Jason H

    2013-04-01

    The nonlinear interaction effect among multiple genetic factors, i.e. epistasis, has been recognized as a key component in understanding the underlying genetic basis of complex human diseases and phenotypic traits. Due to the statistical and computational complexity, most epistasis studies are limited to interactions with an order of two. We developed ViSEN to analyze and visualize epistatic interactions of both two-way and three-way. ViSEN not only identifies strong interactions among pairs or trios of genetic attributes, but also provides a global interaction map that shows neighborhood and clustering structures. This visualized information could be very helpful to infer the underlying genetic architecture of complex diseases and to generate plausible hypotheses for further biological validations. ViSEN is implemented in Java and freely available at https://sourceforge.net/projects/visen/. PMID:23468157

  15. Epistasis between adults and larvae underlies caste fate and fitness in a clonal ant.

    PubMed

    Teseo, Serafino; Châline, Nicolas; Jaisson, Pierre; Kronauer, Daniel J C

    2014-01-01

    In social species, the phenotype and fitness of an individual depend in part on the genotype of its social partners. However, how these indirect genetic effects affect genotype fitness in competitive situations is poorly understood in animal societies. We therefore studied phenotypic plasticity and fitness of two clones of the ant Cerapachys biroi in monoclonal and chimeric colonies. Here we show that, while clone B has lower fitness in isolation, surprisingly, it consistently outcompetes clone A in chimeras. The reason is that, in chimeras, clone B produces more individuals specializing in reproduction rather than cooperative tasks, behaving like a facultative social parasite. A cross-fostering experiment shows that the proportion of these individuals depends on intergenomic epistasis between larvae and nursing adults, explaining the flexible allocation strategy of clone B. Our results suggest that intergenomic epistasis can be the proximate mechanism for social parasitism in ants, revealing striking analogies between social insects and social microbes. PMID:24561920

  16. Estimation and interpretation of genetic effects with epistasis using the NOIA model.

    PubMed

    Alvarez-Castro, José M; Carlborg, Orjan; Rönnegård, Lars

    2012-01-01

    We introduce this communication with a brief outline of the historical landmarks in genetic modeling, especially concerning epistasis. Then, we present methods for the use of genetic modeling in QTL analyses. In particular, we summarize the essential expressions of the natural and orthogonal interactions (NOIA) model of genetic effects. Our motivation for reviewing that theory here is twofold. First, this review presents a digest of the expressions for the application of the NOIA model, which are often mixed with intermediate and additional formulae in the original articles. Second, we make the required theory handy for the reader to relate the genetic concepts to the particular mathematical expressions underlying them. We illustrate those relations by providing graphical interpretations and a diagram summarizing the key features for applying genetic modeling with epistasis in comprehensive QTL analyses. Finally, we briefly review some examples of the application of NOIA to real data and the way it improves the interpretability of the results. PMID:22565838

  17. Lorentz Force Detuning Analysis of the SNS Accelerating Cavities

    SciTech Connect

    R. Mitchell; K. Matsumoto; G. Ciovati; K. Davis; K. Macha; R. Sundelin

    2001-09-01

    The Spallation Neutron Source (SNS) project incorporates a superconducting radio-frequency (SRF) accelerator for the final section of the pulsed mode linac Cavities with geometrical {beta} values of {beta} = 0.61 and {beta} = 0.81 are utilized in the SRF section, and are constructed out of thin-walled niobium with stiffener rings welded between the cells near the iris. The welded titanium helium vessel and tuner assembly restrains the cavity beam tubes Cavities with {beta} values less than one have relatively steep and flat side-walls making the cavities susceptible to Ised RF induces cyclic Lorentz pressures that mechanically excite the cavities, producing a dynamic Lorentz force detuning different from a continuous RF system. The amplitude of the dynamic detuning for a given cavity design is a function of the mechanical damping, stiffness of the tuner/helium vessel assembly, RF pulse profile, and the RF pulse rate. This paper presents analysis and testing results to date, and indicates areas where more investigation is required.

  18. Plasticity and epistasis strongly affect bacterial fitness after losing multiple metabolic genes.

    PubMed

    D'Souza, Glen; Waschina, Silvio; Kaleta, Christoph; Kost, Christian

    2015-05-01

    Many bacterial lineages lack seemingly essential metabolic genes. Previous work suggested selective benefits could drive the loss of biosynthetic functions from bacterial genomes when the corresponding metabolites are sufficiently available in the environment. However, the factors that govern this "genome streamlining" remain poorly understood. Here we determine the effect of plasticity and epistasis on the fitness of Escherichia coli genotypes from whose genome biosynthetic genes for one, two, or three different amino acids have been deleted. Competitive fitness experiments between auxotrophic mutants and prototrophic wild-type cells in one of two carbon environments revealed that plasticity and epistasis strongly affected the mutants' fitness individually and interactively. Positive and negative epistatic interactions were prevalent, yet on average cancelled each other out. Moreover, epistasis correlated negatively with the expected effects of combined auxotrophy-causing mutations, thus producing a pattern of diminishing returns. Moreover, computationally analyzing 1,432 eubacterial metabolic networks revealed that most pairs of auxotrophies co-occurred significantly more often than expected by chance, suggesting epistatic interactions and/or environmental factors favored these combinations. Our results demonstrate that both the genetic background and environmental conditions determine the adaptive value of a loss-of-biochemical-function mutation and that fitness gains decelerate, as more biochemical functions are lost. PMID:25765095

  19. Genetic control of soybean seed isoflavone content: importance of statistical model and epistasis in complex traits.

    PubMed

    Gutierrez-Gonzalez, Juan Jose; Wu, Xiaolei; Zhang, Juan; Lee, Jeong-Dong; Ellersieck, Mark; Shannon, J Grover; Yu, Oliver; Nguyen, Henry T; Sleper, David A

    2009-10-01

    A major objective for geneticists is to decipher genetic architecture of traits associated with agronomic importance. However, a majority of such traits are complex, and their genetic dissection has been traditionally hampered not only by the number of minor-effect quantitative trait loci (QTL) but also by genome-wide interacting loci with little or no individual effect. Soybean (Glycine max [L.] Merr.) seed isoflavonoids display a broad range of variation, even in genetically stabilized lines that grow in a fixed environment, because their synthesis and accumulation are affected by many biotic and abiotic factors. Due to this complexity, isoflavone QTL mapping has often produced conflicting results especially with variable growing conditions. Herein, we comparatively mapped soybean seed isoflavones genistein, daidzein, and glycitein by using several of the most commonly used mapping approaches: interval mapping, composite interval mapping, multiple interval mapping and a mixed-model based composite interval mapping. In total, 26 QTLs, including many novel regions, were found bearing additive main effects in a population of RILs derived from the cross between Essex and PI 437654. Our comparative approach demonstrates that statistical mapping methodologies are crucial for QTL discovery in complex traits. Despite a previous understanding of the influence of additive QTL on isoflavone production, the role of epistasis is not well established. Results indicate that epistasis, although largely dependent on the environment, is a very important genetic component underlying seed isoflavone content, and suggest epistasis as a key factor causing the observed phenotypic variability of these traits in diverse environments. PMID:19626310

  20. Epistasis Constrains Mutational Pathways of Hemoglobin Adaptation in High-Altitude Pikas

    PubMed Central

    Tufts, Danielle M.; Natarajan, Chandrasekhar; Revsbech, Inge G.; Projecto-Garcia, Joana; Hoffmann, Federico G.; Weber, Roy E.; Fago, Angela; Moriyama, Hideaki; Storz, Jay F.

    2015-01-01

    A fundamental question in evolutionary genetics concerns the roles of mutational pleiotropy and epistasis in shaping trajectories of protein evolution. This question can be addressed most directly by using site-directed mutagenesis to explore the mutational landscape of protein function in experimentally defined regions of sequence space. Here, we evaluate how pleiotropic trade-offs and epistatic interactions influence the accessibility of alternative mutational pathways during the adaptive evolution of hemoglobin (Hb) function in high-altitude pikas (Mammalia: Lagomorpha). By combining ancestral protein resurrection with a combinatorial protein-engineering approach, we examined the functional effects of sequential mutational steps in all possible pathways that produced an increased Hb–O2 affinity. These experiments revealed that the effects of mutations on Hb–O2 affinity are highly dependent on the temporal order in which they occur: Each of three β-chain substitutions produced a significant increase in Hb–O2 affinity on the ancestral genetic background, but two of these substitutions produced opposite effects when they occurred as later steps in the pathway. The experiments revealed pervasive epistasis for Hb–O2 affinity, but affinity-altering mutations produced no significant pleiotropic trade-offs. These results provide insights into the properties of adaptive substitutions in naturally evolved proteins and suggest that the accessibility of alternative mutational pathways may be more strongly constrained by sign epistasis for positively selected biochemical phenotypes than by antagonistic pleiotropy. PMID:25415962

  1. Systemic properties of metabolic networks lead to an epistasis-based model for heterosis.

    PubMed

    Fiévet, Julie B; Dillmann, Christine; de Vienne, Dominique

    2010-01-01

    The genetic and molecular approaches to heterosis usually do not rely on any model of the genotype-phenotype relationship. From the generalization of Kacser and Burns' biochemical model for dominance and epistasis to networks with several variable enzymes, we hypothesized that metabolic heterosis could be observed because the response of the flux towards enzyme activities and/or concentrations follows a multi-dimensional hyperbolic-like relationship. To corroborate this, we used the values of systemic parameters accounting for the kinetic behaviour of four enzymes of the upstream part of glycolysis, and simulated genetic variability by varying in silico enzyme concentrations. Then we "crossed" virtual parents to get 1,000 hybrids, and showed that best-parent heterosis was frequently observed. The decomposition of the flux value into genetic effects, with the help of a novel multilocus epistasis index, revealed that antagonistic additive-by-additive epistasis effects play the major role in this framework of the genotype-phenotype relationship. This result is consistent with various observations in quantitative and evolutionary genetics, and provides a model unifying the genetic effects underlying heterosis. PMID:19916003

  2. Transition of Iodine Analysis to Accelerator Mass Spectrometry

    SciTech Connect

    J. E. Delmore

    2010-09-01

    Funding was received from NA-22 to investigate transitioning iodine isotopic analyses to an accelerator mass spectrometry (AMS) system. The present method uses gas-phase chemistry followed by thermal ionization mass spectrometry (TIMS). It was anticipated that the AMS approach could provide comparable data, with improved background levels and superior sample throughput. An aqueous extraction method was developed for removal of iodine species from high-volume air filters. Ethanol and sodium hydroxide, plus heating and ultrasonic treatment, were used to successfully extract iodine from loaded high-volume air filters. Portions of the same filters were also processed in the traditional method and analyzed by TIMS for comparison. Aliquot parts of the aqueous extracts were analyzed by AMS at the Swiss Federal Institute of Technology. Idaho National Laboratory (INL) personnel visited several AMS laboratories in the US, Spain, and Switzerland. Experience with AMS systems from several manufacturers was gained, and relationships were developed with key personnel at the laboratories. Three batches of samples were analyzed in Switzerland, and one in Spain. Results show that the INL extraction method successfully extracted enough iodine from high-volume air filters to allow AMS analysis. Comparison of the AMS and TIMS data is very encouraging; while the TIMS showed about forty percent more atoms of 129I, the 129/127 ratios tracked each other very well between the two methods. The time required for analysis is greatly reduced for the aqueous extraction/AMS approach. For a hypothetical batch of thirty samples, the AMS methodology is about five times faster than the traditional gas-phase chemistry and TIMS analysis. As an additional benefit, background levels for the AMS method are about 1000 times lower than for TIMS. This results from the fundamental mechanisms of ionization in the AMS system and cleanup of molecular interferences. We showed that an aqueous extraction of high

  3. Feature-based analysis of plasma-based particle acceleration data.

    PubMed

    Rübel, Oliver; Geddes, Cameron G R; Chen, Min; Cormier-Michel, Estelle; Bethel, E Wes

    2014-02-01

    Plasma-based particle accelerators can produce and sustain thousands of times stronger acceleration fields than conventional particle accelerators, providing a potential solution to the problem of the growing size and cost of conventional particle accelerators. To facilitate scientific knowledge discovery from the ever growing collections of accelerator simulation data generated by accelerator physicists to investigate next-generation plasma-based particle accelerator designs, we describe a novel approach for automatic detection and classification of particle beams and beam substructures due to temporal differences in the acceleration process, here called acceleration features. The automatic feature detection in combination with a novel visualization tool for fast, intuitive, query-based exploration of acceleration features enables an effective top-down data exploration process, starting from a high-level, feature-based view down to the level of individual particles. We describe the application of our analysis in practice to analyze simulations of single pulse and dual and triple colliding pulse accelerator designs, and to study the formation and evolution of particle beams, to compare substructures of a beam, and to investigate transverse particle loss. PMID:24356363

  4. Feature-based Analysis of Plasma-based Particle Acceleration Data

    SciTech Connect

    Ruebel, Oliver; Geddes, Cameron G.R.; Chen, Min; Cormier-Michel, Estelle; Bethel, E. Wes

    2013-07-05

    Plasma-based particle accelerators can produce and sustain thousands of times stronger acceleration fields than conventional particle accelerators, providing a potential solution to the problem of the growing size and cost of conventional particle accelerators. To facilitate scientific knowledge discovery from the ever growing collections of accelerator simulation data generated by accelerator physicists to investigate next-generation plasma-based particle accelerator designs, we describe a novel approach for automatic detection and classification of particle beams and beam substructures due to temporal differences in the acceleration process, here called acceleration features. The automatic feature detection in combination with a novel visualization tool for fast, intuitive, query-based exploration of acceleration features enables an effective top-down data exploration process, starting from a high-level, feature-based view down to the level of individual particles. We describe the application of our analysis in practice to analyze simulations of single pulse and dual and triple colliding pulse accelerator designs, and to study the formation and evolution of particle beams, to compare substructures of a beam and to investigate transverse particle loss.

  5. Using Biological Knowledge to Uncover the Mystery in the Search for Epistasis in Genome-Wide Association Studies

    PubMed Central

    Ritchie, Marylyn D.

    2011-01-01

    The search for the missing heritability in genome-wide association studies (GWAS) has become an important focus for the human genetics community. One suspected location of these genetic effects is in gene-gene interactions, or epistasis. The computational burden of exploring gene-gene interactions in the wealth of data generated in GWAS, along with small to moderate sample sizes, have led to epistasis being an afterthought, rather than a primary focus of GWAS analyses. In this review, we discuss some potential approaches to filter a GWAS dataset to a smaller, more manageable dataset where searching for epistasis is considerably more feasible. We describe a number of alternative approaches, but primarily focus on the use of prior biological knowledge from databases in the public domain to guide the search for epistasis. The manner in which prior knowledge is incorporated into a GWA study can be many and these data can be extracted from a variety of database sources. We discuss a number of these approaches and propose that a comprehensive approach will likely be most fruitful for searching for epistasis in large-scale genomic studies of the current state-of-the-art and into the future. PMID:21158748

  6. X Chromosome SNPs Were Heavily Involved In Epistasis Effects Of Net Merit Component Traits In Contemporary U.S. Holstein Cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Pairwise epistasis effects of net merit and its eight component traits were tested in 1654 contemporary U.S. Holstein cows using the BovineSNP50 (45,878 SNPs). A large number of epistasis effects exceeded the genome-wide significance of 5% type-I error with the Bonferroni correction and a QTL map of...

  7. A Massively Parallel Solver for the Mechanical Harmonic Analysis of Accelerator Cavities

    SciTech Connect

    O. Kononenko

    2015-02-17

    ACE3P is a 3D massively parallel simulation suite that developed at SLAC National Accelerator Laboratory that can perform coupled electromagnetic, thermal and mechanical study. Effectively utilizing supercomputer resources, ACE3P has become a key simulation tool for particle accelerator R and D. A new frequency domain solver to perform mechanical harmonic response analysis of accelerator components is developed within the existing parallel framework. This solver is designed to determine the frequency response of the mechanical system to external harmonic excitations for time-efficient accurate analysis of the large-scale problems. Coupled with the ACE3P electromagnetic modules, this capability complements a set of multi-physics tools for a comprehensive study of microphonics in superconducting accelerating cavities in order to understand the RF response and feedback requirements for the operational reliability of a particle accelerator. (auth)

  8. Association Mapping for Epistasis and Environmental Interaction of Yield Traits in 323 Cotton Cultivars under 9 Different Environments

    PubMed Central

    Pan, Zhaoe; Wang, Xiwen; He, Shoupu; Xiao, Songhua; Shi, Weijun; Zhou, Zhongli; Pang, Baoyin; Wang, Liru; Liu, Jianguang; Ma, Jun; Du, Xiongming; Zhu, Jun

    2014-01-01

    Improving yield is a major objective for cotton breeding schemes, and lint yield and its three component traits (boll number, boll weight and lint percentage) are complex traits controlled by multiple genes and various environments. Association mapping was performed to detect markers associated with these four traits using 651 simple sequence repeats (SSRs). A mixed linear model including epistasis and environmental interaction was used to screen the loci associated with these four yield traits by 323 accessions of Gossypium hirsutum L. evaluated in nine different environments. 251 significant loci were detected to be associated with lint yield and its three components, including 69 loci with individual effects and all involved in epistasis interactions. These significant loci explain ∼ 62.05% of the phenotypic variance (ranging from 49.06% ∼ 72.29% for these four traits). It was indicated by high contribution of environmental interaction to the phenotypic variance for lint yield and boll numbers, that genetic effects of SSR loci were susceptible to environment factors. Shared loci were also observed among these four traits, which may be used for simultaneous improvement in cotton breeding for yield traits. Furthermore, consistent and elite loci were screened with −Log10 (P-value) >8.0 based on predicted effects of loci detected in different environments. There was one locus and 6 pairs of epistasis for lint yield, 4 loci and 10 epistasis for boll number, 15 loci and 2 epistasis for boll weight, and 2 loci and 5 epistasis for lint percentage, respectively. These results provided insights into the genetic basis of lint yield and its components and may be useful for marker-assisted breeding to improve cotton production. PMID:24810754

  9. TRI-SERVICE SITE CHARACTERIZATION AND ANALYSIS PENETROMETER SYSTEM (SCAPS) ACCELERATED SENSOR DEVELOPMENT PROJECT

    EPA Science Inventory

    In 1994, the Strategic Environmental Research and Development Program (SERDP) funded a Tri-Service effort to accelerate the development and fielding of environmental sensing technologies to extend the capabilities of the Site Characterization and Analysis Penetrometer System (SCA...

  10. Analysis and Design of Optical Bragg Acceleration Structures

    SciTech Connect

    Mizrahi, Amit; Schaechter, Levi

    2004-12-07

    It is demonstrated that a Bragg waveguide consisting of a series of dielectric layers may form an excellent optical acceleration structure. Confinement of the accelerating fields is achieved for both planar and cylindrical configurations by adjusting the first dielectric layer width. A typical structure made of Silica and Zirconia may support gradients of the order of 1 GV/m with an interaction impedance of a few hundreds of Ohms and with an energy velocity of less than 0.5c. An interaction impedance of about one thousand Ohms may be obtained by replacing the Zirconia with a (fictitious) material of {epsilon} = 25. Special attention is paid to the wake-field developing in such a structure. In case of a relatively small number of layers, a qualitative approach shows that the emitted power is inversely proportional to the number of micro-bunches. Quantitative results are given for a higher number of dielectric layers, showing that in comparison to a structure bounded by metallic walls, the emitted power is significantly smaller due to propagation bands allowing electromagnetic energy to escape. The efficiency of the acceleration structures is investigated and shown to have an optimum as a function of the vacuum core dimension.

  11. Analysis of Capillary Guided Laser Plasma Accelerator Experiments at LBNL

    SciTech Connect

    Nakamura, K.; Esarey, E.; Leemans, W. P.; Gonsalves, A. J.; Panasenko, D.; Toth, Cs.; Geddes, C. G. R.; Schroeder, C. B.; Lin, C.

    2009-01-22

    Laser wakefield acceleration experiments were carried out by using a hydrogen-filled capillary discharge waveguide. For a 15 mm long, 200 {mu}m diameter capillary, quasi-monoenergetic e-beams up to 300 MeV were observed. By de-tuning discharge delay from optimum guiding performance, self-trapping was found to be stabilized. For a 33 mm long, 300 {mu}m capillary, a parameter regime with high energy electron beams, up to 1 GeV, was found. In this regime, the electron beam peak energy was correlated with the amount of trapped electrons.

  12. Analysis of Capillary Guided Laser Plasma Accelerator Experiments at LBNL

    SciTech Connect

    Advanced Light Source; Nakamura, Kei; Gonsalves, Anthony; Panasenko, Dmitriy; Lin, Chen; Toth, Csaba; Geddes, Cameron; Schroeder, Carl; Esarey, Eric; Leemans, Wim

    2008-09-29

    Laser wakefield acceleration experiments were carried out by using a hydrogen-filledcapillary discharge waveguide. For a 15 mm long, 200 mu m diameter capillary, quasi-monoenergetic e-beams up to 300 MeV were observed. By de-tuning discharge delay from optimum guiding performance, self-trapping was found to be stabilized. For a 33 mm long, 300 mu m capillary, a parameter regime with high energy electron beams, up to 1 GeV, was found. In this regime, the electron beam peak energy was correlated with the amount of trapped electrons.

  13. Use of Tritium Accelerator Mass Spectrometry for Tree Ring Analysis

    PubMed Central

    LOVE, ADAM H.; HUNT, JAMES R.; ROBERTS, MARK L.; SOUTHON, JOHN R.; CHIARAPPA - ZUCCA, MARINA L.; DINGLEY, KAREN H.

    2010-01-01

    Public concerns over the health effects associated with low-level and long-term exposure to tritium released from industrial point sources have generated the demand for better methods to evaluate historical tritium exposure levels for these communities. The cellulose of trees accurately reflects the tritium concentration in the source water and may contain the only historical record of tritium exposure. The tritium activity in the annual rings of a tree was measured using accelerator mass spectrometry to reconstruct historical annual averages of tritium exposure. Milligram-sized samples of the annual tree rings from a Tamarix located at the Nevada Test Site are used for validation of this methodology. The salt cedar was chosen since it had a single source of tritiated water that was well-characterized as it varied over time. The decay-corrected tritium activity of the water in which the salt cedar grew closely agrees with the organically bound tritium activity in its annual rings. This demonstrates that the milligram-sized samples used in tritium accelerator mass spectrometry are suited for reconstructing anthropogenic tritium levels in the environment. PMID:12144257

  14. Use of tritium accelerator mass spectrometry for tree ring analysis.

    PubMed

    Love, Adam H; Hunt, James R; Roberts, Mark L; Southon, John R; Chiarapp-Zucca, Marina L; Dingley, Karen H

    2002-07-01

    Public concerns over the health effects associated with low-level and long-term exposure to tritium released from industrial point sources have generated the demand for better methods to evaluate historical tritium exposure levels for these communities. The cellulose of trees accurately reflects the tritium concentration in the source water and may contain the only historical record of tritium exposure. The tritium activity in the annual rings of a tree was measured using accelerator mass spectrometry to reconstruct historical annual averages of tritium exposure. Milligram-sized samples of the annual tree rings from a Tamarix located at the Nevada Test Site are used for validation of this methodology. The salt cedar was chosen since it had a single source of tritiated water that was well-characterized as it varied over time. The decay-corrected tritium activity of the water in which the salt cedar grew closely agrees with the organically bound tritium activity in its annual rings. This demonstrates that the milligram-sized samples used in tritium accelerator mass spectrometry are suited for reconstructing anthropogenic tritium levels in the environment. PMID:12144257

  15. Environmental Interactions and Epistasis Are Revealed in the Proteomic Responses to Complex Stimuli

    PubMed Central

    Samir, Parimal; Rahul; Slaughter, James C.; Link, Andrew J.

    2015-01-01

    Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well. PMID:26247773

  16. A fast and powerful W-test for pairwise epistasis testing

    PubMed Central

    Wang, Maggie Haitian; Sun, Rui; Guo, Junfeng; Weng, Haoyi; Lee, Jack; Hu, Inchi; Sham, Pak Chung; Zee, Benny Chung-Ying

    2016-01-01

    Epistasis plays an essential role in the development of complex diseases. Interaction methods face common challenge of seeking a balance between persistent power, model complexity, computation efficiency, and validity of identified bio-markers. We introduce a novel W-test to identify pairwise epistasis effect, which measures the distributional difference between cases and controls through a combined log odds ratio. The test is model-free, fast, and inherits a Chi-squared distribution with data adaptive degrees of freedom. No permutation is needed to obtain the P-values. Simulation studies demonstrated that the W-test is more powerful in low frequency variants environment than alternative methods, which are the Chi-squared test, logistic regression and multifactor-dimensionality reduction (MDR). In two independent real bipolar disorder genome-wide associations (GWAS) datasets, the W-test identified significant interactions pairs that can be replicated, including SLIT3-CENPN, SLIT3-TMEM132D, CNTNAP2-NDST4 and CNTCAP2-RTN4R. The genes in the pairs play central roles in neurotransmission and synapse formation. A majority of the identified loci are undiscoverable by main effect and are low frequency variants. The proposed method offers a powerful alternative tool for mapping the genetic puzzle underlying complex disorders. PMID:27112568

  17. Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis.

    PubMed

    Wilkins, Jon F; McHale, Peter T; Gervin, Joshua; Lander, Arthur D

    2016-04-01

    A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.e. unfit phenotypes with frequencies on the order of 1%) can, under the right circumstances, be expected to be driven primarily by synergistic epistatic interactions. Conditions that are necessary, collectively, for this outcome include a strongly non-linear phenotypic landscape, strong (but not too strong) selection against the disease phenotype, and "noise" in the genotype-phenotype map that is both environmental (extrinsic, time-correlated) and developmental (intrinsic, uncorrelated) and, in both cases, neither too little nor too great. These results suggest ways in which geneticists might identify, a priori, those disease traits for which an "epistatic explanation" should be sought, and in the process better focus ongoing searches for risk alleles. PMID:27123867

  18. A fast and powerful W-test for pairwise epistasis testing.

    PubMed

    Wang, Maggie Haitian; Sun, Rui; Guo, Junfeng; Weng, Haoyi; Lee, Jack; Hu, Inchi; Sham, Pak Chung; Zee, Benny Chung-Ying

    2016-07-01

    Epistasis plays an essential role in the development of complex diseases. Interaction methods face common challenge of seeking a balance between persistent power, model complexity, computation efficiency, and validity of identified bio-markers. We introduce a novel W-test to identify pairwise epistasis effect, which measures the distributional difference between cases and controls through a combined log odds ratio. The test is model-free, fast, and inherits a Chi-squared distribution with data adaptive degrees of freedom. No permutation is needed to obtain the P-values. Simulation studies demonstrated that the W-test is more powerful in low frequency variants environment than alternative methods, which are the Chi-squared test, logistic regression and multifactor-dimensionality reduction (MDR). In two independent real bipolar disorder genome-wide associations (GWAS) datasets, the W-test identified significant interactions pairs that can be replicated, including SLIT3-CENPN, SLIT3-TMEM132D, CNTNAP2-NDST4 and CNTCAP2-RTN4R The genes in the pairs play central roles in neurotransmission and synapse formation. A majority of the identified loci are undiscoverable by main effect and are low frequency variants. The proposed method offers a powerful alternative tool for mapping the genetic puzzle underlying complex disorders. PMID:27112568

  19. Cuckoo search epistasis: a new method for exploring significant genetic interactions.

    PubMed

    Aflakparast, M; Salimi, H; Gerami, A; Dubé, M-P; Visweswaran, S; Masoudi-Nejad, A

    2014-06-01

    The advent of high-throughput sequencing technology has resulted in the ability to measure millions of single-nucleotide polymorphisms (SNPs) from thousands of individuals. Although these high-dimensional data have paved the way for better understanding of the genetic architecture of common diseases, they have also given rise to challenges in developing computational methods for learning epistatic relationships among genetic markers. We propose a new method, named cuckoo search epistasis (CSE) for identifying significant epistatic interactions in population-based association studies with a case-control design. This method combines a computationally efficient Bayesian scoring function with an evolutionary-based heuristic search algorithm, and can be efficiently applied to high-dimensional genome-wide SNP data. The experimental results from synthetic data sets show that CSE outperforms existing methods including multifactorial dimensionality reduction and Bayesian epistasis association mapping. In addition, on a real genome-wide data set related to Alzheimer's disease, CSE identified SNPs that are consistent with previously reported results, and show the utility of CSE for application to genome-wide data. PMID:24549111

  20. Epistasis and the Structure of Fitness Landscapes: Are Experimental Fitness Landscapes Compatible with Fisher's Geometric Model?

    PubMed

    Blanquart, François; Bataillon, Thomas

    2016-06-01

    The fitness landscape defines the relationship between genotypes and fitness in a given environment and underlies fundamental quantities such as the distribution of selection coefficient and the magnitude and type of epistasis. A better understanding of variation in landscape structure across species and environments is thus necessary to understand and predict how populations will adapt. An increasing number of experiments investigate the properties of fitness landscapes by identifying mutations, constructing genotypes with combinations of these mutations, and measuring the fitness of these genotypes. Yet these empirical landscapes represent a very small sample of the vast space of all possible genotypes, and this sample is often biased by the protocol used to identify mutations. Here we develop a rigorous statistical framework based on Approximate Bayesian Computation to address these concerns and use this flexible framework to fit a broad class of phenotypic fitness models (including Fisher's model) to 26 empirical landscapes representing nine diverse biological systems. Despite uncertainty owing to the small size of most published empirical landscapes, the inferred landscapes have similar structure in similar biological systems. Surprisingly, goodness-of-fit tests reveal that this class of phenotypic models, which has been successful so far in interpreting experimental data, is a plausible in only three of nine biological systems. More precisely, although Fisher's model was able to explain several statistical properties of the landscapes-including the mean and SD of selection and epistasis coefficients-it was often unable to explain the full structure of fitness landscapes. PMID:27052568

  1. Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis

    PubMed Central

    Gervin, Joshua; Lander, Arthur D.

    2016-01-01

    A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.e. unfit phenotypes with frequencies on the order of 1%) can, under the right circumstances, be expected to be driven primarily by synergistic epistatic interactions. Conditions that are necessary, collectively, for this outcome include a strongly non-linear phenotypic landscape, strong (but not too strong) selection against the disease phenotype, and “noise” in the genotype-phenotype map that is both environmental (extrinsic, time-correlated) and developmental (intrinsic, uncorrelated) and, in both cases, neither too little nor too great. These results suggest ways in which geneticists might identify, a priori, those disease traits for which an “epistatic explanation” should be sought, and in the process better focus ongoing searches for risk alleles. PMID:27123867

  2. Physical analysis of the radiation shielding for the medical accelerators

    NASA Astrophysics Data System (ADS)

    Li, Q. F.; Xing, Q. Z.; Kong, C. C.

    2009-02-01

    Radiation safety standards today require comprehensive shielding protection schemes for all particle accelerators. The original shielding system of BJ-20 (BeiJing-20 MeV), the high-energy medical electron linac, was designed only for the 18 MeV level. And the dose caused by the lost electrons in the 270° bending magnet system was neglected. In this paper, the leakage dose of BJ-20 is carefully analyzed. The radiation leakage dose distribution of the photons coming from the accelerator head is obtained for energy levels of 6, 12, 14, and 18 MeV. The dose of the photoneutrons is especially analyzed for the 18 MeV level. The result gives that even neglecting the dose from the 270° bending magnet system, the shielding system is still not enough for the energy levels lower than 18 MeV. The radiation leakage produced by electrons that are lost in the 270° bending magnet system has been particularly studied. Using beam transport theory and Monte Carlo sampling methods, which have been combined in calculations, we have obtained the distribution of the energy, position, and direction of the lost electrons. These data were then further processed by the Monte Carlo N-particle (MCNP) code as input data. The results show that when the electron loss rate in the 270° bending magnet system is 13.5%, the radiation leakage dose of the photons generated by the lost electrons is 0.1% higher than that at the isocenter, and the corresponding relative leakage dose of the photoneutrons reaches 0.045% around an angle of 170° at 18 MeV level. Both of these parameters exceed radioprotection safety standards for medical accelerators. The original shielding design is therefore not suitable and is also incomplete since the radiation produced by the electrons being lost in the 270° bending magnet system was neglected and the leakage dose for the low-energy levels was not considered in the original design. Our calculations provide a very useful tool for further optimization and design

  3. Solar wind conditions leading to efficient radiation belt electron acceleration: A superposed epoch analysis

    DOE PAGESBeta

    Li, W.; Thorne, R. M.; Bortnik, J.; Baker, D. N.; Reeves, G. D.; Kanekal, S. G.; Spence, H. E.; Green, J. C.

    2015-09-07

    In this study by determining preferential solar wind conditions leading to efficient radiation belt electron acceleration is crucial for predicting radiation belt electron dynamics. Using Van Allen Probes electron observations (>1 MeV) from 2012 to 2015, we identify a number of efficient and inefficient acceleration events separately to perform a superposed epoch analysis of the corresponding solar wind parameters and geomagnetic indices. By directly comparing efficient and inefficient acceleration events, we clearly show that prolonged southward Bz, high solar wind speed, and low dynamic pressure are critical for electron acceleration to >1 MeV energies in the heart of the outermore » radiation belt. We also evaluate chorus wave evolution using the superposed epoch analysis for the identified efficient and inefficient acceleration events and find that chorus wave intensity is much stronger and lasts longer during efficient electron acceleration events, supporting the scenario that chorus waves play a key role in MeV electron acceleration.« less

  4. Analysis of ICRF-Accelerated Ions in ASDEX Upgrade

    SciTech Connect

    Mantsinen, M. J.; Eriksson, L.-G.; Noterdaeme, J.-M.

    2007-09-28

    MHD-induced losses of fast ions with energy in the MeV range have been observed during high-power ICRF heating of hydrogen minority ions in the ASDEX Upgrade tokamak (R{sub 0}{approx_equal}1.65 m, a{approx_equal}0.5 m). ICRF heating and ICRF-driven fast ions in discharges exhibiting fast ion losses due to toroidal Alfven eigenmodes and a new core-localised MHD instability are analysed. It is found that the lost ions are ICRF-accelerated trapped protons with energy in the range of 0.3-1.6 MeV, orbit widths of 20-35 cm, and turning points at r/a>0.5 and at major radii close to the cyclotron resonance {omega} = {omega}{sub cH}(R). The presence of such protons is consistent with ICRF modelling.

  5. RAPID COMMUNICATION: Analysis of photoneutron spectra produced in medical accelerators

    NASA Astrophysics Data System (ADS)

    Ongaro, Carla; Zanini, Alba; Nastasi, U.; Ródenas, José; Ottaviano, Giuseppe; Manfredotti, Claudio

    2000-12-01

    A complete method is presented for the evaluation of photoneutron spectra produced in linear accelerators for cancer radiotherapy. It consists of a computer simulation code based on the MCNP4B Monte Carlo code, in which the new routine GAMMAN was implemented, allowing the accurate study of photoneutron production in high Z elements. In addition an experimental method based on a passive bubble spectrometer allows direct measurements of the photoneutron spectrum at the patient plane, also under the photon beam. The results are presented both for a 15 MeV linac with a traditional collimator system and for an 18 MeV linac equipped with a multileaf collimator, used in conformational radiotherapy.

  6. Omega3P: A Parallel Finite-Element Eigenmode Analysis Code for Accelerator Cavities

    SciTech Connect

    Lee, Lie-Quan; Li, Zenghai; Ng, Cho; Ko, Kwok; /SLAC

    2009-03-04

    Omega3P is a parallel eigenmode calculation code for accelerator cavities in frequency domain analysis using finite-element methods. In this report, we will present detailed finite-element formulations and resulting eigenvalue problems for lossless cavities, cavities with lossy materials, cavities with imperfectly conducting surfaces, and cavities with waveguide coupling. We will discuss the parallel algorithms for solving those eigenvalue problems and demonstrate modeling of accelerator cavities through different examples.

  7. Hamiltonian analysis for linearly acceleration-dependent Lagrangians

    NASA Astrophysics Data System (ADS)

    Cruz, Miguel; Gómez-Cortés, Rosario; Molgado, Alberto; Rojas, Efraín

    2016-06-01

    We study the constrained Ostrogradski-Hamilton framework for the equations of motion provided by mechanical systems described by second-order derivative actions with a linear dependence in the accelerations. We stress out the peculiar features provided by the surface terms arising for this type of theories and we discuss some important properties for this kind of actions in order to pave the way for the construction of a well defined quantum counterpart by means of canonical methods. In particular, we analyse in detail the constraint structure for these theories and its relation to the inherent conserved quantities where the associated energies together with a Noether charge may be identified. The constraint structure is fully analyzed without the introduction of auxiliary variables, as proposed in recent works involving higher order Lagrangians. Finally, we also provide some examples where our approach is explicitly applied and emphasize the way in which our original arrangement results in propitious for the Hamiltonian formulation of covariant field theories.

  8. Comprehensive identification and analysis of human accelerated regulatory DNA

    PubMed Central

    Gittelman, Rachel M.; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S.; Hawkins, R. David; Akey, Joshua M.

    2015-01-01

    It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

  9. Comprehensive identification and analysis of human accelerated regulatory DNA.

    PubMed

    Gittelman, Rachel M; Hun, Enna; Ay, Ferhat; Madeoy, Jennifer; Pennacchio, Len; Noble, William S; Hawkins, R David; Akey, Joshua M

    2015-09-01

    It has long been hypothesized that changes in gene regulation have played an important role in human evolution, but regulatory DNA has been much more difficult to study compared with protein-coding regions. Recent large-scale studies have created genome-scale catalogs of DNase I hypersensitive sites (DHSs), which demark potentially functional regulatory DNA. To better define regulatory DNA that has been subject to human-specific adaptive evolution, we performed comprehensive evolutionary and population genetics analyses on over 18 million DHSs discovered in 130 cell types. We identified 524 DHSs that are conserved in nonhuman primates but accelerated in the human lineage (haDHS), and estimate that 70% of substitutions in haDHSs are attributable to positive selection. Through extensive computational and experimental analyses, we demonstrate that haDHSs are often active in brain or neuronal cell types; play an important role in regulating the expression of developmentally important genes, including many transcription factors such as SOX6, POU3F2, and HOX genes; and identify striking examples of adaptive regulatory evolution that may have contributed to human-specific phenotypes. More generally, our results reveal new insights into conserved and adaptive regulatory DNA in humans and refine the set of genomic substrates that distinguish humans from their closest living primate relatives. PMID:26104583

  10. Analysis of Human Accelerated DNA Regions Using Archaic Hominin Genomes

    PubMed Central

    Burbano, Hernán A.; Green, Richard E.; Maricic, Tomislav; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Kelso, Janet; Pollard, Katherine S.; Lachmann, Michael; Pääbo, Svante

    2012-01-01

    Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations. PMID:22412940

  11. [Preparation of Rubber Accelerator Zinc Diethyldithiocarbamate and Its Spectral Analysis].

    PubMed

    Zhang, Zhi-liang; Jia, Tai-xuan; Jiang, Yue-hua; Peng, Hong-yan; Xu, Guang-pu; Li, Hong-liang

    2015-08-01

    In the study, rubber accelerator Zinc diethyldithiocarbamate (EZ) was synthesized firstly. Complex EZ of single crystal was cultivated by solvent evaporation method. EZ was detected and characterized by XRD single crystal diffraction, FTIR and TG-DSC. The micro-structure and intrinsic regularity were revealed. Its highly efficient performance of rubber vulcanization promotion was decided due to its orientation structure? and high order. The result of TG-DSC showed that complex EZ was possessed with a little CS2. The chemical bond types in EZ were revealed by FTIR, the same as single crystal? diffraction testing by different way. The decomposition temperature of EZ was very high. It could provided reference with research on rubber vulcanizing properties by EZ on rubber vulcanizing machine. This study can help the enterprises to designate the working standard tracing detection of EZ industrialized production. Performance index of EZ was judged. The project of EZ industry standard can be declared by the enterprises, written a draft standard on the basis experimental data. PMID:26672276

  12. Analysis of human accelerated DNA regions using archaic hominin genomes.

    PubMed

    Burbano, Hernán A; Green, Richard E; Maricic, Tomislav; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Kelso, Janet; Pollard, Katherine S; Lachmann, Michael; Pääbo, Svante

    2012-01-01

    Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations. PMID:22412940

  13. Superconducting Accelerating Cavity Pressure Sensitivity Analysis and Stiffening

    SciTech Connect

    Rodnizki, J; Ben Aliz, Y; Grin, A; Horvitz, Z; Perry, A; Weissman, L; Davis, G Kirk; Delayen, Jean R.

    2014-12-01

    The Soreq Applied Research Accelerator Facility (SARAF) design is based on a 40 MeV 5 mA light ions superconducting RF linac. Phase-I of SARAF delivers up to 2 mA CW proton beams in an energy range of 1.5 - 4.0 MeV. The maximum beam power that we have reached is 5.7 kW. Today, the main limiting factor to reach higher ion energy and beam power is related to the HWR sensitivity to the liquid helium coolant pressure fluctuations. The HWR sensitivity to helium pressure is about 60 Hz/mbar. The cavities had been designed, a decade ago, to be soft in order to enable tuning of their novel shape. However, the cavities turned out to be too soft. In this work we found that increasing the rigidity of the cavities in the vicinity of the external drift tubes may reduce the cavity sensitivity by a factor of three. A preliminary design to increase the cavity rigidity is presented.

  14. Data acquisition, control, and analysis for the Argonne Advanced Accelerator Test Facility (AATF)

    SciTech Connect

    Schoessow, P.

    1989-01-01

    The AATF has been used to study wakefield acceleration and focusing in plasmas and rf structures. A PC-based system is described which incorporates the functions of beamline control and acquisition, storage, and preliminary analysis of video images from luminescent screen beam diagnostics. General features of the offline analysis of wakefield data are also discussed. 4 refs., 3 figs.

  15. Analysis of Voltage Signals from Superconducting Accelerator Magnets

    SciTech Connect

    Lizarazo, J.; Caspi, S.; Ferracin, P.; Joseph, J.; Lietzke, A. F.; Sabbi, G. L.; Wang, X.

    2009-10-30

    We present two techniques used in the analysis of voltage tap data collected during recent tests of superconducting magnets developed by the Superconducting Magnet Program at Lawrence Berkeley National Laboratory. The first technique was used on a quadrupole to provide information about quench origins that could not be obtained using the time-of-flight method. The second technique illustrates the use of data from transient flux imbalances occurring during magnet ramping to diagnose changes in the current-temperature margin of a superconducting cable. In both cases, the results of this analysis contributed to make improvements on subsequent magnets.

  16. Metabolic epistasis among apoptosis-inducing factor and the mitochondrial import factor CHCHD4

    PubMed Central

    Modjtahedi, Nazanine; Hangen, Emilie; Gonin, Patrick; Kroemer, Guido

    2015-01-01

    Abstract Hypomorphic mutation of apoptosis-inducing factor (AIF) in the whole body or organ-specific knockout of AIF compromises the activity of respiratory chain complexes I and IV, as it confers resistance to obesity and diabetes induced by high-fat diet. The mitochondrial defect induced by AIF deficiency can be explained by reduced AIF-dependent mitochondrial import of CHCHD4, which in turn is required for optimal import and assembly of respiratory chain complexes. Here we show that, as compared to wild type control littermates, mice with a heterozygous knockout of CHCHD4 exhibit reduced weight gain when fed with a Western style high-fat diet. This finding suggests widespread metabolic epistasis among AIF and CHCHD4. Targeting either of these proteins or their functional interaction might constitute a novel strategy to combat obesity. PMID:26178476

  17. Incorporating epistasis interaction of genetic susceptibility single nucleotide polymorphisms in a lung cancer risk prediction model

    PubMed Central

    MARCUS, MICHAEL W.; RAJI, OLAIDE Y.; DUFFY, STEPHEN W.; YOUNG, ROBERT P.; HOPKINS, RAEWYN J.; FIELD, JOHN K.

    2016-01-01

    Incorporation of genetic variants such as single nucleotide polymorphisms (SNPs) into risk prediction models may account for a substantial fraction of attributable disease risk. Genetic data, from 2385 subjects recruited into the Liverpool Lung Project (LLP) between 2000 and 2008, consisting of 20 SNPs independently validated in a candidate-gene discovery study was used. Multifactor dimensionality reduction (MDR) and random forest (RF) were used to explore evidence of epistasis among 20 replicated SNPs. Multivariable logistic regression was used to identify similar risk predictors for lung cancer in the LLP risk model for the epidemiological model and extended model with SNPs. Both models were internally validated using the bootstrap method and model performance was assessed using area under the curve (AUC) and net reclassification improvement (NRI). Using MDR and RF, the overall best classifier of lung cancer status were SNPs rs1799732 (DRD2), rs5744256 (IL-18), rs2306022 (ITGA11) with training accuracy of 0.6592 and a testing accuracy of 0.6572 and a cross-validation consistency of 10/10 with permutation testing P<0.0001. The apparent AUC of the epidemiological model was 0.75 (95% CI 0.73–0.77). When epistatic data were incorporated in the extended model, the AUC increased to 0.81 (95% CI 0.79–0.83) which corresponds to 8% increase in AUC (DeLong's test P=2.2e-16); 17.5% by NRI. After correction for optimism, the AUC was 0.73 for the epidemiological model and 0.79 for the extended model. Our results showed modest improvement in lung cancer risk prediction when the SNP epistasis factor was added. PMID:27121382

  18. Genecentric: a package to uncover graph-theoretic structure in high-throughput epistasis data

    PubMed Central

    2013-01-01

    Background New technology has resulted in high-throughput screens for pairwise genetic interactions in yeast and other model organisms. For each pair in a collection of non-essential genes, an epistasis score is obtained, representing how much sicker (or healthier) the double-knockout organism will be compared to what would be expected from the sickness of the component single knockouts. Recent algorithmic work has identified graph-theoretic patterns in this data that can indicate functional modules, and even sets of genes that may occur in compensatory pathways, such as a BPM-type schema first introduced by Kelley and Ideker. However, to date, any algorithms for finding such patterns in the data were implemented internally, with no software being made publically available. Results Genecentric is a new package that implements a parallelized version of the Leiserson et al. algorithm (J Comput Biol 18:1399-1409, 2011) for generating generalized BPMs from high-throughput genetic interaction data. Given a matrix of weighted epistasis values for a set of double knock-outs, Genecentric returns a list of generalized BPMs that may represent compensatory pathways. Genecentric also has an extension, GenecentricGO, to query FuncAssociate (Bioinformatics 25:3043-3044, 2009) to retrieve GO enrichment statistics on generated BPMs. Python is the only dependency, and our web site provides working examples and documentation. Conclusion We find that Genecentric can be used to find coherent functional and perhaps compensatory gene sets from high throughput genetic interaction data. Genecentric is made freely available for download under the GPLv2 from http://bcb.cs.tufts.edu/genecentric. PMID:23331614

  19. Incorporating epistasis interaction of genetic susceptibility single nucleotide polymorphisms in a lung cancer risk prediction model.

    PubMed

    Marcus, Michael W; Raji, Olaide Y; Duffy, Stephen W; Young, Robert P; Hopkins, Raewyn J; Field, John K

    2016-07-01

    Incorporation of genetic variants such as single nucleotide polymorphisms (SNPs) into risk prediction models may account for a substantial fraction of attributable disease risk. Genetic data, from 2385 subjects recruited into the Liverpool Lung Project (LLP) between 2000 and 2008, consisting of 20 SNPs independently validated in a candidate-gene discovery study was used. Multifactor dimensionality reduction (MDR) and random forest (RF) were used to explore evidence of epistasis among 20 replicated SNPs. Multivariable logistic regression was used to identify similar risk predictors for lung cancer in the LLP risk model for the epidemiological model and extended model with SNPs. Both models were internally validated using the bootstrap method and model performance was assessed using area under the curve (AUC) and net reclassification improvement (NRI). Using MDR and RF, the overall best classifier of lung cancer status were SNPs rs1799732 (DRD2), rs5744256 (IL-18), rs2306022 (ITGA11) with training accuracy of 0.6592 and a testing accuracy of 0.6572 and a cross-validation consistency of 10/10 with permutation testing P<0.0001. The apparent AUC of the epidemiological model was 0.75 (95% CI 0.73-0.77). When epistatic data were incorporated in the extended model, the AUC increased to 0.81 (95% CI 0.79-0.83) which corresponds to 8% increase in AUC (DeLong's test P=2.2e-16); 17.5% by NRI. After correction for optimism, the AUC was 0.73 for the epidemiological model and 0.79 for the extended model. Our results showed modest improvement in lung cancer risk prediction when the SNP epistasis factor was added. PMID:27121382

  20. Enabling More than Moore: Accelerated Reliability Testing and Risk Analysis for Advanced Electronics Packaging

    NASA Technical Reports Server (NTRS)

    Ghaffarian, Reza; Evans, John W.

    2014-01-01

    For five decades, the semiconductor industry has distinguished itself by the rapid pace of improvement in miniaturization of electronics products-Moore's Law. Now, scaling hits a brick wall, a paradigm shift. The industry roadmaps recognized the scaling limitation and project that packaging technologies will meet further miniaturization needs or ak.a "More than Moore". This paper presents packaging technology trends and accelerated reliability testing methods currently being practiced. Then, it presents industry status on key advanced electronic packages, factors affecting accelerated solder joint reliability of area array packages, and IPC/JEDEC/Mil specifications for characterizations of assemblies under accelerated thermal and mechanical loading. Finally, it presents an examples demonstrating how Accelerated Testing and Analysis have been effectively employed in the development of complex spacecraft thereby reducing risk. Quantitative assessments necessarily involve the mathematics of probability and statistics. In addition, accelerated tests need to be designed which consider the desired risk posture and schedule for particular project. Such assessments relieve risks without imposing additional costs. and constraints that are not value added for a particular mission. Furthermore, in the course of development of complex systems, variances and defects will inevitably present themselves and require a decision concerning their disposition, necessitating quantitative assessments. In summary, this paper presents a comprehensive view point, from technology to systems, including the benefits and impact of accelerated testing in offsetting risk.

  1. Detecting chaos in particle accelerators through the frequency map analysis method

    SciTech Connect

    Papaphilippou, Yannis

    2014-06-01

    The motion of beams in particle accelerators is dominated by a plethora of non-linear effects, which can enhance chaotic motion and limit their performance. The application of advanced non-linear dynamics methods for detecting and correcting these effects and thereby increasing the region of beam stability plays an essential role during the accelerator design phase but also their operation. After describing the nature of non-linear effects and their impact on performance parameters of different particle accelerator categories, the theory of non-linear particle motion is outlined. The recent developments on the methods employed for the analysis of chaotic beam motion are detailed. In particular, the ability of the frequency map analysis method to detect chaotic motion and guide the correction of non-linear effects is demonstrated in particle tracking simulations but also experimental data.

  2. Automated detection and analysis of particle beams in laser-plasma accelerator simulations

    SciTech Connect

    Ushizima, Daniela Mayumi; Geddes, C.G.; Cormier-Michel, E.; Bethel, E. Wes; Jacobsen, J.; Prabhat, ,; R.ubel, O.; Weber, G,; Hamann, B.

    2010-05-21

    Numerical simulations of laser-plasma wakefield (particle) accelerators model the acceleration of electrons trapped in plasma oscillations (wakes) left behind when an intense laser pulse propagates through the plasma. The goal of these simulations is to better understand the process involved in plasma wake generation and how electrons are trapped and accelerated by the wake. Understanding of such accelerators, and their development, offer high accelerating gradients, potentially reducing size and cost of new accelerators. One operating regime of interest is where a trapped subset of electrons loads the wake and forms an isolated group of accelerated particles with low spread in momentum and position, desirable characteristics for many applications. The electrons trapped in the wake may be accelerated to high energies, the plasma gradient in the wake reaching up to a gigaelectronvolt per centimeter. High-energy electron accelerators power intense X-ray radiation to terahertz sources, and are used in many applications including medical radiotherapy and imaging. To extract information from the simulation about the quality of the beam, a typical approach is to examine plots of the entire dataset, visually determining the adequate parameters necessary to select a subset of particles, which is then further analyzed. This procedure requires laborious examination of massive data sets over many time steps using several plots, a routine that is unfeasible for large data collections. Demand for automated analysis is growing along with the volume and size of simulations. Current 2D LWFA simulation datasets are typically between 1GB and 100GB in size, but simulations in 3D are of the order of TBs. The increase in the number of datasets and dataset sizes leads to a need for automatic routines to recognize particle patterns as particle bunches (beam of electrons) for subsequent analysis. Because of the growth in dataset size, the application of machine learning techniques for

  3. Accelerating Climate Data Analysis and Visualization with Parallel Scripting

    NASA Astrophysics Data System (ADS)

    Mickelson, S. A.; Jacob, R. L.; Wilde, M.; Wozniak, J.; Dennis, J.

    2011-12-01

    Climate models are continuing to increase both in their resolution and the number of variables used, resulting in multi-terabyte model outputs. This large volume of data overwhelms the series of processing steps used to derive climate averages and produce visualizations. Since many of the tasks in the post- processing sequence are independent, we have applied task-parallel scripting to speed up the post-processing. We have re-written portions of the complex shell script that processes output from the Community Atmosphere Model in Swift, a high-level implicitly-parallel scripting language that uses data dependencies to automatically parallelize a workflow. This has resulted in valuable speedups in model analysis for this heavily-used procedure. We describe the structure, usage, performance, and our experiences with the resulting script.

  4. Beam Based HOM Analysis of Accelerating Structures at the TESLA Test Facility Linac

    SciTech Connect

    Wendt, M.; Schreiber, S.; Castro, P.; Gossel, A.; Huning, M.; Devanz, G.; Jablonka, M.; Magne, C.; Napoly, O.; Baboi, N.; /SLAC

    2005-08-09

    The beam emittance in future linear accelerators for high energy physics and SASE-FEL applications depends highly on the field performance in the accelerating structures, i.e. the damping of higher order modes (HOM). Besides theoretical and laboratory analysis, a beam based analysis technique was established [1] at the TESLA Test Facility (TTF) linac. It uses a charge modulated beam of variable modulation frequency to excite dipole modes. This causes a modulation of the transverse beam displacement, which is observed at a downstream BPM and associated with a direct analysis of the modes at the HOM-couplers. A brief introduction of eigenmodes of a resonator and the concept of the wake potential is given. Emphasis is put on beam instrumentation and signal analysis aspects, required for this beam based HOM measurement technique.

  5. Design and Analysis of a Micro-Optical Position Readout for Acceleration Sensing

    SciTech Connect

    Dickey, Fred M.; Holswade, Scott C.; Shagam, Richard N.

    1999-07-08

    Sandia National Laboratories is developing a MEMS-based trajectory safety subsystem, which allows enablement of critical functions only after a particular acceleration environment has been achieved. The device, known as an Environmental Sensing Device (ESD), consists of a suspended moving shuttle that translates a given distance when exposed to an appropriate acceleration environment. The shuttle contains an embedded code, consisting of grating structures, that is illuminated and optically read using a semiconductor laser and detector integrated together in a GaAs-based Photonic Integrated Circuit (PIC) flip-chip bonded to the assembly. This paper will describe the optical design and performance analysis of the embedded code features in the shuttle.

  6. An improved method for statistical analysis of raw accelerator mass spectrometry data

    SciTech Connect

    Gutjahr, A.; Phillips, F.; Kubik, P.W.; Elmore, D.

    1987-01-01

    Hierarchical statistical analysis is an appropriate method for statistical treatment of raw accelerator mass spectrometry (AMS) data. Using Monte Carlo simulations we show that this method yields more accurate estimates of isotope ratios and analytical uncertainty than the generally used propagation of errors approach. The hierarchical analysis is also useful in design of experiments because it can be used to identify sources of variability. 8 refs., 2 figs.

  7. Interjoint dynamic interaction during constrained human quiet standing examined by induced acceleration analysis.

    PubMed

    Sasagawa, Shun; Shinya, Masahiro; Nakazawa, Kimitaka

    2014-01-01

    Recent studies have demonstrated that human quiet standing is a multijoint movement, whereby the central nervous system (CNS) is required to deal with dynamic interactions among the joints to achieve optimal motor performance. The purpose of this study was to investigate how the CNS deals with such interjoint interaction during quiet standing by examining the relationship between the kinetics (torque) and kinematics (angular acceleration) within the multi-degree of freedom system. We modeled quiet standing as a double-link inverted pendulum involving both ankle and hip joints and conducted an "induced acceleration analysis." We found that the net ankle and hip torques induced angular accelerations of comparable magnitudes to the ankle (3.8 ± 1.4°/s(2) and 3.3 ± 1.2°/s(2)) and hip (9.1 ± 3.2°/s(2) and 10.5 ± 3.5°/s(2)) joints, respectively. Angular accelerations induced by the net ankle and hip torques were modulated in a temporally antiphase pattern to one another in each of the two joints. These quantitative and temporal relationships allowed the angular accelerations induced by the two net torques to countercompensate one another, thereby substantially (∼70%) reducing the resultant angular accelerations of the individual joints. These results suggest that, by taking advantage of the interjoint interaction, the CNS prevents the net torques from producing large amplitudes of the resultant angular accelerations when combined with the kinematic effects of all other torques in the chain. PMID:24089399

  8. DEVELOPMENT OF ACCELERATOR DATA REPORTING SYSTEM AND ITS APPLICATION TO TREND ANALYSIS OF BEAM CURRENT DATA

    SciTech Connect

    Padilla, M.J.; Blokland, W.

    2009-01-01

    Detailed ongoing information about the ion beam quality is crucial to the successful operation of the Spallation Neutron Source at Oak Ridge National Laboratory. In order to provide the highest possible neutron production time, ion beam quality is monitored to isolate possible problems or performance-related issues throughout the accelerator and accumulator ring. For example, beam current monitor (BCM) data is used to determine the quality of the beam transport through the accelerator. In this study, a reporting system infrastructure was implemented and used to generate a trend analysis report of the BCM data. The BCM data was analyzed to facilitate the identifi cation of monitor calibration issues, beam trends, beam abnormalities, beam deviations and overall beam quality. A comparison between transformed BCM report data and accelerator log entries shows promising results which represent correlations between the data and changes made within the accelerator. The BCM analysis report is one of many reports within a system that assist in providing overall beam quality information to facilitate successful beam operation. In future reports, additional data manipulation functions and analysis can be implemented and applied. Built-in and user-defi ned analytic functions are available throughout the reporting system and can be reused with new data.

  9. Interface for the rapid analysis of liquid samples by accelerator mass spectrometry

    SciTech Connect

    Turteltaub, Kenneth; Ognibene, Ted; Thomas, Avi; Daley, Paul F; Salazar Quintero, Gary A; Bench, Graham

    2014-02-04

    An interface for the analysis of liquid sample having carbon content by an accelerator mass spectrometer including a wire, defects on the wire, a system for moving the wire, a droplet maker for producing droplets of the liquid sample and placing the droplets of the liquid sample on the wire in the defects, a system that converts the carbon content of the droplets of the liquid sample to carbon dioxide gas in a helium stream, and a gas-accepting ion source connected to the accelerator mass spectrometer that receives the carbon dioxide gas of the sample in a helium stream and introduces the carbon dioxide gas of the sample into the accelerator mass spectrometer.

  10. Sensitivity Analysis of the Off-Normal Conditions of the SPIDER Accelerator

    SciTech Connect

    Veltri, P.; Agostinetti, P.; Antoni, V.; Chitarin, G.; Marconato, N.; Pilan, N.; Sartori, E.; Serianni, G.; Cavenago, M.

    2011-09-26

    In the context of the development of the 1 MV neutral beam injector for the ITER tokamak, the study on beam formation and acceleration has considerable importance. This effort includes the ion source and accelerator SPIDER (Source for Production of Ions of Deuterium Extracted from an Rf plasma) ion source, planned to be built in Padova, and designed to extract and accelerate a 355 A/m{sup 2} current of H{sup -}(or 285 A/m{sup 2} D{sup -}) up to 100 kV. Exhaustive simulations were already carried out during the accelerator optimization leading to the present design. However, as it is expected that the accelerator shall operate also in case of pre-programmed or undesired off-normal conditions, the investigation of a large set of off-normal scenarios is necessary. These analyses will also be useful for the evaluation of the real performances of the machine, and should help in interpreting experimental results, or in identifying dangerous operating conditions.The present contribution offers an overview of the results obtained during the investigation of these off-normal conditions, by means of different modeling tools and codes. The results, showed a good flexibility of the device in different operating conditions. Where the consequences of the abnormalities appeared to be problematic further analysis were addressed.

  11. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

    PubMed Central

    Kojadinovic, M.; MacLean, R. C.

    2016-01-01

    Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds. PMID:27170722

  12. A novel two-stage approach for epistasis detection in genome-wide case-control studies.

    PubMed

    Liao, Zhongli; Zeng, Qingguang; Liao, Bo; Li, Xiong

    2014-10-01

    A significant challenge in epistasis detection is the huge amount of data, which leads to combinatorial explosion. This study focuses on a two-stage approach for detecting epistasis only among single nucleotide polymorphisms (SNPs) that show some marginal effect. We present this two-stage approach based on the fusion of two criteria (TwoFC) to detect epistatic interactions. We fuse the G (2) test and absolute probability difference function as a scoring function to measure the strength of association between SNPs and disease status. The fused scoring function is an excellent measure of the strength of such an association. The two-stage strategy greatly reduces the computation load on epistasis detection. We use both simulated data sets and a real disease data set to evaluate our method. The results of an experiment on the simulated data sets show that TwoFC exhibits high power and sample efficiency. The results of an experiment on the real disease data set show that our method performs well even with large-scale data sets. PMID:24880910

  13. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas.

    PubMed

    Vogwill, T; Kojadinovic, M; MacLean, R C

    2016-05-11

    Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds. PMID:27170722

  14. Rapid analysis of scattering from periodic dielectric structures using accelerated Cartesian expansions

    SciTech Connect

    Baczewski, Andrew David; Miller, Nicholas C.; Shanker, Balasubramaniam

    2012-03-22

    Here, the analysis of fields in periodic dielectric structures arise in numerous applications of recent interest, ranging from photonic bandgap structures and plasmonically active nanostructures to metamaterials. To achieve an accurate representation of the fields in these structures using numerical methods, dense spatial discretization is required. This, in turn, affects the cost of analysis, particularly for integral-equation-based methods, for which traditional iterative methods require Ο(Ν2) operations, Ν being the number of spatial degrees of freedom. In this paper, we introduce a method for the rapid solution of volumetric electric field integral equations used in the analysis of doubly periodic dielectric structures. The crux of our method is the accelerated Cartesian expansion algorithm, which is used to evaluate the requisite potentials in Ο(Ν) cost. Results are provided that corroborate our claims of acceleration without compromising accuracy, as well as the application of our method to a number of compelling photonics applications.

  15. Thermal performance analysis and measurements of the prototype cryomodules of European XFEL accelerator - part I

    NASA Astrophysics Data System (ADS)

    Wang, X. L.; Barbanotti, S.; Eschke, J.; Jensch, K.; Klos, R.; Maschmann, W.; Petersen, B.; Sawlanski, O.

    2014-11-01

    The European X-Ray Free Electron Laser (XFEL), the research facility currently under construction in the Hamburg area, Germany, is based on a superconducting linear accelerator that brings electrons to almost the speed of light. The linear accelerator consists of 100 accelerating cryomodules (CMs) operating at the temperature of 2 K. The thermal performances of the accelerator CMs are a key element to determine the heat load budget, the required capacity and the cost of the XFEL refrigerating system and to guarantee its efficient operation. The measurement of the thermal performances of the CMs is also an important step in the qualification of the CMs during the series production. This paper describes the thermal performance analysis of the European XFEL prototype cryomodules. The analysis takes into account all the main contributors (multilayer insulation, current leads, power couplers, support posts, and cavities) to the static and dynamic heat loads at various cryogenic temperature levels. Existing empirical databases are reviewed and used to evaluate the heat transfer through the multilayer insulation and numerical simulations are developed to investigate the heat loads generated from the different CM components.

  16. Analysis of the acceleration region in a circulating fluidized bed riser operating above fast fluidization velocities

    SciTech Connect

    Monazam, E.R.; Shadle, L.J.

    2008-11-05

    In commercial circulating fluidized bed (CFB) processes the acceleration zone greatly contributes to solids mixing, gas and solids dispersion, and particle residence times. A new analysis was developed to describe the relative gas-solids concentration in the acceleration region of a transport system with air as the fluidizing agent for Geldart-type B particles. A theoretical expression was derived from a drag relationship and momentum and continuity equations to describe the evolution of the gas-solids profile along the axial direction. The acceleration zone was characterized using nondimensional analysis of the continuum equations (balances of masses and momenta) that described multiphase flows. In addition to acceleration length, the boundary condition for the solids fraction at the bottom of the riser and the fully developed regions were measured using an industrial scale CFB of 0.3 m diameter and 15 m tall. The operating factors affecting the flow development in the acceleration region were determined for three materials of various sizes and densities in core annular and dilute regimes of the riser. Performance data were taken from statistically designed experiments over a wide range of Fr (0.5-39), Re (8-600), Ar (29-3600), load ratio (0.2-28), riser to particle diameter ratio (375-5000), and gas to solids density ratio (138-1381). In this one-dimensional system of equations, velocities and solid fractions were assumed to be constant over any cross section. The model and engineering correlations were compared with literature expressions to assess their validity and range of applicability. These expressions can be used as tools for simulation and design of a CFB riser and can also be easily coupled to a kinetics model for process simulation.

  17. Epistasis and genotype-by-environment interaction of grain protein content in durum wheat

    PubMed Central

    2010-01-01

    Parental, F1 , F 2 , BC 1 and BC 2 generations of four crosses involving four cultivars of durum wheat (Triticum durum Desf.) were evaluated at two sites in Tunisia. A three-parameter model was found inadequate for all cases except crosses Chili x Cocorit 71 at site Sidi Thabet and Inrat 69 x Karim at both sites. In most cases a digenic epistatic model was sufficient to explain variation in generation means. Dominance effects (h) and additive x additive epistasis (i) (when significant) were more important than additive (d) effects and other epistatic components. Considering the genotype-by-environment interaction, the non-interactive model (m, d, h, e) was found adequate. Additive variance was higher than environmental variance in three crosses at both sites. The estimated values of narrow-sense heritability were dependent upon the cross and the sites and were 0%-85%. The results indicate that appropriate choice of environment and selection in later generations would increase grain protein content in durum wheat. PMID:21637615

  18. Relationship between leaf stages and epistasis for resistance to Stagonospora nodorum in durum wheat

    PubMed Central

    Bnejdi, Fethi; Saadoun, Mourad; Naouari, Mouna; El Gazzah, Mohamed

    2012-01-01

    Ten varieties and eight generations (2F1, 2F2, 2B1 and 2B2) of durum wheat derived from two crosses were evaluated for resistance to natural infection by Stagonospora nodorum blotch (SNB) at the 2–3 and 6–7 leaf stages at two sites over two years. There were significant differences in the incidence of SNB between leaf stages in most of the wheat varieties, with resistance being most evident at the 6–7 leaf stage. Separate analyses of the mean values for each generation showed that the genetic mechanism of defense against the pathogen depended upon the leaf stage. At the 2–3 leaf stage, only additive and dominance effects were implicated in the control of SNB for the two crosses at the two sites and for the two replications. For the 6–7 leaf stage, inheritance was more complicated and an epistatic effect was involved. Narrow-sense heritability values (range: 0.63–0.67) were consistent between crosses and leaf stages. These findings indicate a lack of resistance to SNB at the 2–3 leaf stage whereas resistance was observed at the 6–7 leaf stage and involved the genetic mechanisms of plant defense such as epistasis. PMID:22888293

  19. The metabolic background is a global player in Saccharomyces gene expression epistasis.

    PubMed

    Alam, Mohammad Tauqeer; Zelezniak, Aleksej; Mülleder, Michael; Shliaha, Pavel; Schwarz, Roland; Capuano, Floriana; Vowinckel, Jakob; Radmaneshfar, Elahe; Krüger, Antje; Calvani, Enrica; Michel, Steve; Börno, Stefan; Christen, Stefan; Patil, Kiran Raosaheb; Timmermann, Bernd; Lilley, Kathryn S; Ralser, Markus

    2016-01-01

    The regulation of gene expression in response to nutrient availability is fundamental to the genotype-phenotype relationship. The metabolic-genetic make-up of the cell, as reflected in auxotrophy, is hence likely to be a determinant of gene expression. Here, we address the importance of the metabolic-genetic background by monitoring transcriptome, proteome and metabolome in a repertoire of 16 Saccharomyces cerevisiae laboratory backgrounds, combinatorially perturbed in histidine, leucine, methionine and uracil biosynthesis. The metabolic background affected up to 85% of the coding genome. Suggesting widespread confounding, these transcriptional changes show, on average, 83% overlap between unrelated auxotrophs and 35% with previously published transcriptomes generated for non-metabolic gene knockouts. Background-dependent gene expression correlated with metabolic flux and acted, predominantly through masking or suppression, on 88% of transcriptional interactions epistatically. As a consequence, the deletion of the same metabolic gene in a different background could provoke an entirely different transcriptional response. Propagating to the proteome and scaling up at the metabolome, metabolic background dependencies reveal the prevalence of metabolism-dependent epistasis at all regulatory levels. Urging a fundamental change of the prevailing laboratory practice of using auxotrophs and nutrient supplemented media, these results reveal epistatic intertwining of metabolism with gene expression on the genomic scale. PMID:27572163

  20. Fluorescence2D: Software for Accelerated Acquisition and Analysis of Two-Dimensional Fluorescence Spectra

    PubMed Central

    Kovrigin, Evgenii L.

    2014-01-01

    The Fluorescence2D is free software that allows analysis of two-dimensional fluorescence spectra obtained using the accelerated “triangular” acquisition schemes. The software is a combination of Python and MATLAB-based programs that perform conversion of the triangular data, display of the two-dimensional spectra, extraction of 1D slices at different wavelengths, and output in various graphic formats. PMID:24984078

  1. Stability analysis of multigrid acceleration methods for the solution of partial differential equations

    NASA Technical Reports Server (NTRS)

    Fay, John F.

    1990-01-01

    A calculation is made of the stability of various relaxation schemes for the numerical solution of partial differential equations. A multigrid acceleration method is introduced, and its effects on stability are explored. A detailed stability analysis of a simple case is carried out and verified by numerical experiment. It is shown that the use of multigrids can speed convergence by several orders of magnitude without adversely affecting stability.

  2. Wavelet Analysis of Acceleration Response of Beam Under the Moving Mass for Damage Assessment

    NASA Astrophysics Data System (ADS)

    Vaidya, Tanuja; Chatterjee, Animesh

    2016-04-01

    In the present study, acceleration response of cracked beam is analyzed by using the wavelet transform to detect the crack presence, its location and also to predict the crack severity. The equation of motion of beam under the moving mass is solved by using the fourth order Runge-Kutta method. A code is written by expanding the equation for first three vibration modes. Acceleration signal of the damaged beam under the moving mass contains the discontinuity at the crack location. This discontinuity contained in the acceleration signal is sufficiently visible but it is very small for some signals. Therefore, the acceleration signals are transformed using the wavelet analysis. A wavelet coefficient peak occurs at the location of discontinuity, so that we can identify the crack presence and its location. From the value of wavelet coefficient peak, we can also predict the crack effect with respect to the change in velocity of moving mass and change in crack depth. The main advantage of this method is that the wavelet coefficient peak is sufficiently higher even for the higher velocities and small size crack.

  3. Three dimensional gait analysis using wearable acceleration and gyro sensors based on quaternion calculations.

    PubMed

    Tadano, Shigeru; Takeda, Ryo; Miyagawa, Hiroaki

    2013-01-01

    This paper proposes a method for three dimensional gait analysis using wearable sensors and quaternion calculations. Seven sensor units consisting of a tri-axial acceleration and gyro sensors, were fixed to the lower limbs. The acceleration and angular velocity data of each sensor unit were measured during level walking. The initial orientations of the sensor units were estimated using acceleration data during upright standing position and the angular displacements were estimated afterwards using angular velocity data during gait. Here, an algorithm based on quaternion calculation was implemented for orientation estimation of the sensor units. The orientations of the sensor units were converted to the orientations of the body segments by a rotation matrix obtained from a calibration trial. Body segment orientations were then used for constructing a three dimensional wire frame animation of the volunteers during the gait. Gait analysis was conducted on five volunteers, and results were compared with those from a camera-based motion analysis system. Comparisons were made for the joint trajectory in the horizontal and sagittal plane. The average RMSE and correlation coefficient (CC) were 10.14 deg and 0.98, 7.88 deg and 0.97, 9.75 deg and 0.78 for the hip, knee and ankle flexion angles, respectively. PMID:23877128

  4. Three Dimensional Gait Analysis Using Wearable Acceleration and Gyro Sensors Based on Quaternion Calculations

    PubMed Central

    Tadano, Shigeru; Takeda, Ryo; Miyagawa, Hiroaki

    2013-01-01

    This paper proposes a method for three dimensional gait analysis using wearable sensors and quaternion calculations. Seven sensor units consisting of a tri-axial acceleration and gyro sensors, were fixed to the lower limbs. The acceleration and angular velocity data of each sensor unit were measured during level walking. The initial orientations of the sensor units were estimated using acceleration data during upright standing position and the angular displacements were estimated afterwards using angular velocity data during gait. Here, an algorithm based on quaternion calculation was implemented for orientation estimation of the sensor units. The orientations of the sensor units were converted to the orientations of the body segments by a rotation matrix obtained from a calibration trial. Body segment orientations were then used for constructing a three dimensional wire frame animation of the volunteers during the gait. Gait analysis was conducted on five volunteers, and results were compared with those from a camera-based motion analysis system. Comparisons were made for the joint trajectory in the horizontal and sagittal plane. The average RMSE and correlation coefficient (CC) were 10.14 deg and 0.98, 7.88 deg and 0.97, 9.75 deg and 0.78 for the hip, knee and ankle flexion angles, respectively. PMID:23877128

  5. Acceleration Studies

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.

    1993-01-01

    Work to support the NASA MSFC Acceleration Characterization and Analysis Project (ACAP) was performed. Four tasks (analysis development, analysis research, analysis documentation, and acceleration analysis) were addressed by parallel projects. Work concentrated on preparation for and implementation of near real-time SAMS data analysis during the USMP-1 mission. User support documents and case specific software documentation and tutorials were developed. Information and results were presented to microgravity users. ACAP computer facilities need to be fully implemented and networked, data resources must be cataloged and accessible, future microgravity missions must be coordinated, and continued Orbiter characterization is necessary.

  6. Experimental design and analysis for accelerated degradation tests with Li-ion cells.

    SciTech Connect

    Doughty, Daniel Harvey; Thomas, Edward Victor; Jungst, Rudolph George; Roth, Emanuel Peter

    2003-08-01

    This document describes a general protocol (involving both experimental and data analytic aspects) that is designed to be a roadmap for rapidly obtaining a useful assessment of the average lifetime (at some specified use conditions) that might be expected from cells of a particular design. The proposed experimental protocol involves a series of accelerated degradation experiments. Through the acquisition of degradation data over time specified by the experimental protocol, an unambiguous assessment of the effects of accelerating factors (e.g., temperature and state of charge) on various measures of the health of a cell (e.g., power fade and capacity fade) will result. In order to assess cell lifetime, it is necessary to develop a model that accurately predicts degradation over a range of the experimental factors. In general, it is difficult to specify an appropriate model form without some preliminary analysis of the data. Nevertheless, assuming that the aging phenomenon relates to a chemical reaction with simple first-order rate kinetics, a data analysis protocol is also provided to construct a useful model that relates performance degradation to the levels of the accelerating factors. This model can then be used to make an accurate assessment of the average cell lifetime. The proposed experimental and data analysis protocols are illustrated with a case study involving the effects of accelerated aging on the power output from Gen-2 cells. For this case study, inadequacies of the simple first-order kinetics model were observed. However, a more complex model allowing for the effects of two concurrent mechanisms provided an accurate representation of the experimental data.

  7. Fourier analysis of parallel inexact Block-Jacobi splitting with transport synthetic acceleration in slab geometry

    SciTech Connect

    Rosa, M.; Warsa, J. S.; Chang, J. H.

    2006-07-01

    A Fourier analysis is conducted for the discrete-ordinates (SN) approximation of the neutron transport problem solved with Richardson iteration (Source Iteration) and Richardson iteration preconditioned with Transport Synthetic Acceleration (TSA), using the Parallel Block-Jacobi (PBJ) algorithm. Both 'traditional' TSA (TTSA) and a 'modified' TSA (MTSA), in which only the scattering in the low order equations is reduced by some non-negative factor {beta} and < 1, are considered. The results for the un-accelerated algorithm show that convergence of the PBJ algorithm can degrade. The PBJ algorithm with TTSA can be effective provided the {beta} parameter is properly tuned for a given scattering ratio c, but is potentially unstable. Compared to TTSA, MTSA is less sensitive to the choice of {beta}, more effective for the same computational effort (c'), and it is unconditionally stable. (authors)

  8. Analysis of ballistic transport in nanoscale devices by using an accelerated finite element contact block reduction approach

    NASA Astrophysics Data System (ADS)

    Li, H.; Li, G.

    2014-08-01

    An accelerated Finite Element Contact Block Reduction (FECBR) approach is presented for computational analysis of ballistic transport in nanoscale electronic devices with arbitrary geometry and unstructured mesh. Finite element formulation is developed for the theoretical CBR/Poisson model. The FECBR approach is accelerated through eigen-pair reduction, lead mode space projection, and component mode synthesis techniques. The accelerated FECBR is applied to perform quantum mechanical ballistic transport analysis of a DG-MOSFET with taper-shaped extensions and a DG-MOSFET with Si/SiO2 interface roughness. The computed electrical transport properties of the devices obtained from the accelerated FECBR approach and associated computational cost as a function of system degrees of freedom are compared with those obtained from the original CBR and direct inversion methods. The performance of the accelerated FECBR in both its accuracy and efficiency is demonstrated.

  9. Analysis of ballistic transport in nanoscale devices by using an accelerated finite element contact block reduction approach

    SciTech Connect

    Li, H.; Li, G.

    2014-08-28

    An accelerated Finite Element Contact Block Reduction (FECBR) approach is presented for computational analysis of ballistic transport in nanoscale electronic devices with arbitrary geometry and unstructured mesh. Finite element formulation is developed for the theoretical CBR/Poisson model. The FECBR approach is accelerated through eigen-pair reduction, lead mode space projection, and component mode synthesis techniques. The accelerated FECBR is applied to perform quantum mechanical ballistic transport analysis of a DG-MOSFET with taper-shaped extensions and a DG-MOSFET with Si/SiO{sub 2} interface roughness. The computed electrical transport properties of the devices obtained from the accelerated FECBR approach and associated computational cost as a function of system degrees of freedom are compared with those obtained from the original CBR and direct inversion methods. The performance of the accelerated FECBR in both its accuracy and efficiency is demonstrated.

  10. A Domestic cat X Chromosome Linkage Map and the Sex-Linked orange Locus: Mapping of orange, Multiple Origins and Epistasis Over nonagouti

    PubMed Central

    Schmidt-Küntzel, Anne; Nelson, George; David, Victor A.; Schäffer, Alejandro A.; Eizirik, Eduardo; Roelke, Melody E.; Kehler, James S.; Hannah, Steven S.; O'Brien, Stephen J.; Menotti-Raymond, Marilyn

    2009-01-01

    A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9× whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9×-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. PMID:19189955

  11. A domestic cat X chromosome linkage map and the sex-linked orange locus: mapping of orange, multiple origins and epistasis over nonagouti.

    PubMed

    Schmidt-Küntzel, Anne; Nelson, George; David, Victor A; Schäffer, Alejandro A; Eizirik, Eduardo; Roelke, Melody E; Kehler, James S; Hannah, Steven S; O'Brien, Stephen J; Menotti-Raymond, Marilyn

    2009-04-01

    A comprehensive genetic linkage map of the domestic cat X chromosome was generated with the goal of localizing the genomic position of the classic X-linked orange (O) locus. Microsatellite markers with an average spacing of 3 Mb were selected from sequence traces of the cat 1.9x whole genome sequence (WGS), including the pseudoautosomal region 1 (PAR1). Extreme variation in recombination rates (centimorgans per megabase) was observed along the X chromosome, ranging from a virtual absence of recombination events in a region estimated to be >30 Mb to recombination frequencies of 15.7 cM/Mb in a segment estimated to be <0.3 Mb. This detailed linkage map was applied to position the X-linked orange gene, placing this locus on the q arm of the X chromosome, as opposed to a previously reported location on the p arm. Fine mapping placed the locus between markers at positions 106 and 116.8 Mb in the current 1.9x-coverage sequence assembly of the cat genome. Haplotype analysis revealed potential recombination events that could reduce the size of the candidate region to 3.5 Mb and suggested multiple origins for the orange phenotype in the domestic cat. Furthermore, epistasis of orange over nonagouti was demonstrated at the genetic level. PMID:19189955

  12. Failure modes and effects criticality analysis and accelerated life testing of LEDs for medical applications

    NASA Astrophysics Data System (ADS)

    Sawant, M.; Christou, A.

    2012-12-01

    While use of LEDs in Fiber Optics and lighting applications is common, their use in medical diagnostic applications is not very extensive. Since the precise value of light intensity will be used to interpret patient results, understanding failure modes [1-4] is very important. We used the Failure Modes and Effects Criticality Analysis (FMECA) tool to identify the critical failure modes of the LEDs. FMECA involves identification of various failure modes, their effects on the system (LED optical output in this context), their frequency of occurrence, severity and the criticality of the failure modes. The competing failure modes/mechanisms were degradation of: active layer (where electron-hole recombination occurs to emit light), electrodes (provides electrical contact to the semiconductor chip), Indium Tin Oxide (ITO) surface layer (used to improve current spreading and light extraction), plastic encapsulation (protective polymer layer) and packaging failures (bond wires, heat sink separation). A FMECA table is constructed and the criticality is calculated by estimating the failure effect probability (β), failure mode ratio (α), failure rate (λ) and the operating time. Once the critical failure modes were identified, the next steps were generation of prior time to failure distribution and comparing with our accelerated life test data. To generate the prior distributions, data and results from previous investigations were utilized [5-33] where reliability test results of similar LEDs were reported. From the graphs or tabular data, we extracted the time required for the optical power output to reach 80% of its initial value. This is our failure criterion for the medical diagnostic application. Analysis of published data for different LED materials (AlGaInP, GaN, AlGaAs), the Semiconductor Structures (DH, MQW) and the mode of testing (DC, Pulsed) was carried out. The data was categorized according to the materials system and LED structure such as AlGaInP-DH-DC, Al

  13. Will solid-state drives accelerate your bioinformatics? In-depth profiling, performance analysis and beyond.

    PubMed

    Lee, Sungmin; Min, Hyeyoung; Yoon, Sungroh

    2016-07-01

    A wide variety of large-scale data have been produced in bioinformatics. In response, the need for efficient handling of biomedical big data has been partly met by parallel computing. However, the time demand of many bioinformatics programs still remains high for large-scale practical uses because of factors that hinder acceleration by parallelization. Recently, new generations of storage devices have emerged, such as NAND flash-based solid-state drives (SSDs), and with the renewed interest in near-data processing, they are increasingly becoming acceleration methods that can accompany parallel processing. In certain cases, a simple drop-in replacement of hard disk drives by SSDs results in dramatic speedup. Despite the various advantages and continuous cost reduction of SSDs, there has been little review of SSD-based profiling and performance exploration of important but time-consuming bioinformatics programs. For an informative review, we perform in-depth profiling and analysis of 23 key bioinformatics programs using multiple types of devices. Based on the insight we obtain from this research, we further discuss issues related to design and optimize bioinformatics algorithms and pipelines to fully exploit SSDs. The programs we profile cover traditional and emerging areas of importance, such as alignment, assembly, mapping, expression analysis, variant calling and metagenomics. We explain how acceleration by parallelization can be combined with SSDs for improved performance and also how using SSDs can expedite important bioinformatics pipelines, such as variant calling by the Genome Analysis Toolkit and transcriptome analysis using RNA sequencing. We hope that this review can provide useful directions and tips to accompany future bioinformatics algorithm design procedures that properly consider new generations of powerful storage devices. PMID:26330577

  14. Mitonuclear Epistasis for Development Time and Its Modification by Diet in Drosophila.

    PubMed

    Mossman, Jim A; Biancani, Leann M; Zhu, Chen-Tseh; Rand, David M

    2016-05-01

    Mitochondrial (mtDNA) and nuclear genes have to operate in a coordinated manner to maintain organismal function, and the regulation of this homeostasis presents a substantial source of potential epistatic (G × G) interactions. How these interactions shape the fitness landscape is poorly understood. Here we developed a novel mitonuclear epistasis model, using selected strains of the Drosophila Genetic Reference Panel (DGRP) and mitochondrial genomes from within Drosophila melanogaster and D. simulans to test the hypothesis that mtDNA × nDNA interactions influence fitness. In total we built 72 genotypes (12 nuclear backgrounds × 6 mtDNA haplotypes, with 3 from each species) to dissect the relationship between genotype and phenotype. Each genotype was assayed on four food environments. We found considerable variation in several phenotypes, including development time and egg-to-adult viability, and this variation was partitioned into genetic (G), environmental (E), and higher-order (G × G, G × E, and G × G × E) components. Food type had a significant impact on development time and also modified mitonuclear epistases, evidencing a broad spectrum of G × G × E across these genotypes. Nuclear background effects were substantial, followed by mtDNA effects and their G × G interaction. The species of mtDNA haplotype had negligible effects on phenotypic variation and there was no evidence that mtDNA variation has different effects on male and female fitness traits. Our results demonstrate that mitonuclear epistases are context dependent, suggesting the selective pressure acting on mitonuclear genotypes may vary with food environment in a genotype-specific manner. PMID:26966258

  15. Converging Evidence for Epistasis between ANK3 and Potassium Channel Gene KCNQ2 in Bipolar Disorder

    PubMed Central

    Judy, Jennifer Toolan; Seifuddin, Fayaz; Pirooznia, Mehdi; Mahon, Pamela Belmonte; Jancic, Dubravka; Goes, Fernando S.; Schulze, Thomas; Cichon, Sven; Noethen, Markus; Rietschel, Marcella; DePaulo, J. Raymond; Potash, James B.; Zandi, Peter P.

    2013-01-01

    Genome-wide association studies (GWAS) have implicated ANK3 as a susceptibility gene for bipolar disorder (BP). We examined whether epistasis with ANK3 may contribute to the “missing heritability” in BP. We first identified via the STRING database 14 genes encoding proteins with prior biological evidence that they interact molecularly with ANK3. We then tested for statistical evidence of interactions between SNPs in these genes in association with BP in a discovery GWAS dataset and two replication GWAS datasets. The most significant interaction in the discovery GWAS was between SNPs in ANK3 and KCNQ2 (p = 3.18 × 10−8). A total of 31 pair-wise interactions involving combinations between two SNPs from KCNQ2 and 16 different SNPs in ANK3 were significant after permutation. Of these, 28 pair-wise interactions were significant in the first replication GWAS. None were significant in the second replication GWAS, but the two SNPs from KCNQ2 were found to significantly interact with five other SNPs in ANK3, suggesting possible allelic heterogeneity. KCNQ2 forms homo- and hetero-meric complexes with KCNQ3 that constitute voltage-gated potassium channels in neurons. ANK3 is an adaptor protein that, through its interaction with KCNQ2 and KCNQ3, directs the localization of this channel in the axon initial segment (AIS). At the AIS, the KCNQ2/3 complex gives rise to the M-current, which stabilizes the neuronal resting potential and inhibits repetitive firing of action potentials. Thus, these channels act as “dampening” components and prevent neuronal hyperactivity. The interactions between ANK3 and KCNQ2 merit further investigation, and if confirmed, may motivate a new line of research into a novel therapeutic target for BP. PMID:23730306

  16. Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

    SciTech Connect

    Melero, Cristina; Ollikainen, Noah; Harwood, Ian; Karpiak, Joel; Kortemme, Tanja

    2014-10-13

    Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test this strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.

  17. Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

    DOE PAGESBeta

    Melero, Cristina; Ollikainen, Noah; Harwood, Ian; Karpiak, Joel; Kortemme, Tanja

    2014-10-13

    Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

  18. Mitonuclear Epistasis for Development Time and Its Modification by Diet in Drosophila

    PubMed Central

    Biancani, Leann M.; Zhu, Chen-Tseh

    2016-01-01

    Mitochondrial (mtDNA) and nuclear genes have to operate in a coordinated manner to maintain organismal function, and the regulation of this homeostasis presents a substantial source of potential epistatic (G × G) interactions. How these interactions shape the fitness landscape is poorly understood. Here we developed a novel mitonuclear epistasis model, using selected strains of the Drosophila Genetic Reference Panel (DGRP) and mitochondrial genomes from within Drosophila melanogaster and D. simulans to test the hypothesis that mtDNA × nDNA interactions influence fitness. In total we built 72 genotypes (12 nuclear backgrounds × 6 mtDNA haplotypes, with 3 from each species) to dissect the relationship between genotype and phenotype. Each genotype was assayed on four food environments. We found considerable variation in several phenotypes, including development time and egg-to-adult viability, and this variation was partitioned into genetic (G), environmental (E), and higher-order (G × G, G × E, and G × G × E) components. Food type had a significant impact on development time and also modified mitonuclear epistases, evidencing a broad spectrum of G × G × E across these genotypes. Nuclear background effects were substantial, followed by mtDNA effects and their G × G interaction. The species of mtDNA haplotype had negligible effects on phenotypic variation and there was no evidence that mtDNA variation has different effects on male and female fitness traits. Our results demonstrate that mitonuclear epistases are context dependent, suggesting the selective pressure acting on mitonuclear genotypes may vary with food environment in a genotype-specific manner. PMID:26966258

  19. FAM-MDR: A Flexible Family-Based Multifactor Dimensionality Reduction Technique to Detect Epistasis Using Related Individuals

    PubMed Central

    Cattaert, Tom; Urrea, Víctor; Naj, Adam C.; De Lobel, Lizzy; De Wit, Vanessa; Fu, Mao; Mahachie John, Jestinah M.; Shen, Haiqing; Calle, M. Luz; Ritchie, Marylyn D.; Edwards, Todd L.; Van Steen, Kristel

    2010-01-01

    We propose a novel multifactor dimensionality reduction method for epistasis detection in small or extended pedigrees, FAM-MDR. It combines features of the Genome-wide Rapid Association using Mixed Model And Regression approach (GRAMMAR) with Model-Based MDR (MB-MDR). We focus on continuous traits, although the method is general and can be used for outcomes of any type, including binary and censored traits. When comparing FAM-MDR with Pedigree-based Generalized MDR (PGMDR), which is a generalization of Multifactor Dimensionality Reduction (MDR) to continuous traits and related individuals, FAM-MDR was found to outperform PGMDR in terms of power, in most of the considered simulated scenarios. Additional simulations revealed that PGMDR does not appropriately deal with multiple testing and consequently gives rise to overly optimistic results. FAM-MDR adequately deals with multiple testing in epistasis screens and is in contrast rather conservative, by construction. Furthermore, simulations show that correcting for lower order (main) effects is of utmost importance when claiming epistasis. As Type 2 Diabetes Mellitus (T2DM) is a complex phenotype likely influenced by gene-gene interactions, we applied FAM-MDR to examine data on glucose area-under-the-curve (GAUC), an endophenotype of T2DM for which multiple independent genetic associations have been observed, in the Amish Family Diabetes Study (AFDS). This application reveals that FAM-MDR makes more efficient use of the available data than PGMDR and can deal with multi-generational pedigrees more easily. In conclusion, we have validated FAM-MDR and compared it to PGMDR, the current state-of-the-art MDR method for family data, using both simulations and a practical dataset. FAM-MDR is found to outperform PGMDR in that it handles the multiple testing issue more correctly, has increased power, and efficiently uses all available information. PMID:20421984

  20. Dynamic analysis of an accelerator-driven fluid-fueled subcritical radioactive waste burning system

    SciTech Connect

    Woosley, M.L. Jr.; Rydin, R.A.

    1998-05-01

    The recent revival of interest in accelerator-driven subcritical fluid-fueled systems is documented. Several important applications of these systems are mentioned, and this is used to motivate the need for dynamic analysis of the nuclear kinetics of such systems. A physical description of the Los alamos National Laboratory accelerator-based conversion (ABC) concept is provided. This system is used as the basis for the kinetics study in this research. The current approach to the dynamic simulation of an accelerator-driven subcritical fluid-fueled system includes four functional elements: a discrete ordinates model is used to calculate the flux distribution for the source-driven system; a nodal convection model is used to calculate time-dependent isotope and temperature distributions that impact reactivity; a nodal importance weighting model is used to calculate the reactivity impact of temperature and isotope distributions and to feed this information back to the time-dependent nodal convection model; and a transient driver is used to simulate transients, model the balance of plant, and record simulation data. Specific transients that have been analyzed with the current modeling system are discussed. These transients include loss-of-flow and loss-of-cooling accidents, xenon and samarium transients, and cold-plug and overfueling events. The results of various transients have uncovered unpredictable behavior, unresolved design issues, and the need for active control. The need for the development of a nodal-coupling spatial kinetics model is mentioned.

  1. Preliminary Safety Analysis Report (PSAR), The NSLS 200 MeV Linear Electron Accelerator

    SciTech Connect

    Blumberg, L.N.; Ackerman, A.I.; Dickinson, T.; Heese, R.N.; Larson, R.A.; Neuls, C.W.; Pjerov, S.; Sheehan, J.F.

    1993-06-15

    The radiological, fire and electrical hazards posed by a 200 MeV electron Linear Accelerator, which the NSLS Department will install and commission within a newly assembled structure, are addressed in this Preliminary Safety Analysis Report. Although it is clear that this accelerator is intended to be the injector for a future experimental facility, we address only the Linac in the present PSAR since neither the final design nor the operating characteristics of the experimental facility are known at the present time. The fire detection and control system to be installed in the building is judged to be completely adequate in terms of the marginal hazard presented - no combustible materials other than the usual cabling associated with such a facility have been identified. Likewise, electrical hazards associated with power supplies for the beam transport magnets and accelerator components such as the accelerator klystrons and electron gun are classified as marginal in terms of potential personnel injury, cost of equipment lost, program downtime and public impact perceptions as defined in the BNL Environmental Safety and Health Manual and the probability of occurrence is deemed to be remote. No unusual features have been identified for the power supplies or electrical distribution system, and normal and customary electrical safety standards as practiced throughout the NSLS complex and the Laboratory are specified in this report. The radiation safety hazards are similarly judged to be marginal in terms of probability of occurrence and potential injury consequences since, for the low intensity operation proposed - a factor of 25 less than the maximum Linac capability specified by the vendor - the average beam power is only 0.4 watts. The shielding specifications given in this report will give adequate protection to both the general public and nonradiation workers in areas adjacent to the building as well as radiation workers within the controlled access building.

  2. Analysis of damaging effects of laser-plasma accelerated shrapnels on protecting glass shield

    NASA Astrophysics Data System (ADS)

    Martinkova, Michaela; Kalal, Milan; Shmatov, Mikhail L.

    2013-11-01

    Analysis of the damage caused by laser plasma accelerated fragments of metal target was performed. Measured as well as calculated parameters of craters and shrapnel found in BK7 glass blastshield are presented. Method applied for the measurement of parameters of craters is described. Potential damage of optical elements by the so-called striking cores (high-velocity stable objects arising due to collapse of cones or some other target parts toward their axes) that can be generated in IFE related experiments is evaluated.

  3. The relevance of particle flux monitors in accelerator-based activation analysis

    NASA Astrophysics Data System (ADS)

    Segebade, Chr.; Maimaitimin, M.; Zaijing, Sun

    2013-04-01

    One of the most critical parameters in activation analysis is the flux density of the activating radiation, its spatial distribution in particular. The validity of the basic equation for calculating the activity induced to the exposed item depends upon the fulfilment of several conditions, the most relevant of them being equal doses of incident activating radiation received by the unknown sample, the calibration material and the reference material, respectively. This requirement is most problematic if accelerator-produced radiation is used for activation. Whilst nuclear research reactors usually are equipped with exposure positions that provide fairly homogenous activation fields for thermal neutron activation analysis accelerator-generated particle beams (neutrons, photons, charged particles) usually exhibit axial and, in particular, sharp radial flux gradients. Different experimental procedures have been developed to fulfil the condition mentioned above. In this paper, three variants of the application of flux monitors in photon activation analysis are discussed (external monitor, additive and inherent internal monitor). Experiments have indicated that the latter technique yields highest quality of the analytical results.

  4. Rapid analysis of scattering from periodic dielectric structures using accelerated Cartesian expansions

    DOE PAGESBeta

    Baczewski, Andrew David; Miller, Nicholas C.; Shanker, Balasubramaniam

    2012-03-22

    Here, the analysis of fields in periodic dielectric structures arise in numerous applications of recent interest, ranging from photonic bandgap structures and plasmonically active nanostructures to metamaterials. To achieve an accurate representation of the fields in these structures using numerical methods, dense spatial discretization is required. This, in turn, affects the cost of analysis, particularly for integral-equation-based methods, for which traditional iterative methods require Ο(Ν2) operations, Ν being the number of spatial degrees of freedom. In this paper, we introduce a method for the rapid solution of volumetric electric field integral equations used in the analysis of doubly periodic dielectricmore » structures. The crux of our method is the accelerated Cartesian expansion algorithm, which is used to evaluate the requisite potentials in Ο(Ν) cost. Results are provided that corroborate our claims of acceleration without compromising accuracy, as well as the application of our method to a number of compelling photonics applications.« less

  5. Elemental analysis of concrete samples using an accelerator-based PGNAA setup

    NASA Astrophysics Data System (ADS)

    Naqvi, A. A.; Nagadi, M. M.; Baghabra Al-Amoudi, Omar S.

    2004-09-01

    Elemental analysis of concrete samples was carried out using an accelerator-based prompt gamma ray neutron activation analysis (PGNAA) setup. The gamma rays were produced via the capture of thermal neutron in the concrete sample. The prompt gamma ray yield was measured for 12 cm long concrete samples as a function of sample radius over a range of 6-11.5 cm radii. The optimum yield of the prompt gamma rays from the concrete sample was measured from a sample with 11.5 cm radius. The gamma ray yield was also calculated for 12 cm long concrete samples with 6-11.5 cm radius using Monte Carlo simulations. The experimental results were in excellent agreement with the calculated yield of the prompt gamma rays from the samples. Result of this study has shown the useful application of an accelerator-based PGNAA setup in elemental analysis of concrete sample. The facility can be further used to determine the chloride and sulfate concentrations in concrete samples for corrosion studies of reinforcement steel in concrete structures.

  6. The relevance of particle flux monitors in accelerator-based activation analysis

    SciTech Connect

    Segebade, Chr.; Maimaitimin, M.; Sun Zaijing

    2013-04-19

    One of the most critical parameters in activation analysis is the flux density of the activating radiation, its spatial distribution in particular. The validity of the basic equation for calculating the activity induced to the exposed item depends upon the fulfilment of several conditions, the most relevant of them being equal doses of incident activating radiation received by the unknown sample, the calibration material and the reference material, respectively. This requirement is most problematic if accelerator-produced radiation is used for activation. Whilst nuclear research reactors usually are equipped with exposure positions that provide fairly homogenous activation fields for thermal neutron activation analysis accelerator-generated particle beams (neutrons, photons, charged particles) usually exhibit axial and, in particular, sharp radial flux gradients. Different experimental procedures have been developed to fulfil the condition mentioned above. In this paper, three variants of the application of flux monitors in photon activation analysis are discussed (external monitor, additive and inherent internal monitor). Experiments have indicated that the latter technique yields highest quality of the analytical results.

  7. Uncertainty in the estimates of peak ground acceleration in seismic hazard analysis

    NASA Astrophysics Data System (ADS)

    Pavlenko, V. A.

    2015-11-01

    Probabilistic seismic hazard analysis has become a standard procedure preceding the antiseismic construction. An important component of the relevant calculations is the allowance for the uncertainty in the strong motion parameters (e.g., peak ground acceleration (PGA)). In the present-day approaches of probabilistic analysis, this uncertainty is modeled by a random variable (a residual) which has a lognormal distribution. With this model, the extrapolation into the area of long return periods yields nonzero probabilities of unrealistically high PGA. In the present work, the distribution of the logarithmic PGA residuals is modeled by different parametric distributions. From the set of these distributions, the one which provides the closest approximation of the empirical data is selected by the statistical criteria. The analysis shows that the generalized extreme value distribution (GEVD) most accurately reproduces the residuals of the logarithmic PGA, and the tail of the distribution is approximated by the generalized Pareto distribution (GPD).

  8. Shielding analysis at the upper section of the accelerator-driven system.

    PubMed

    Sasa, Toshinobu; Yang, Jin An; Oigawa, Hiroyuki

    2005-01-01

    The proton beam duct of the accelerator-driven system (ADS) acts as a streaming path for spallation neutrons and photons and causes the activation of the magnets and other devices above the subcritical core. We have performed a streaming analysis at the upper section of the lead-bismuth target/cooled ADS (800 MWth). MCNPX was used to calculate the radiation dose from streamed neutrons and photons through the beam duct. For the secondary photon production calculation, cross sections for several actinides were substituted with plutonium because of the lack of gamma production cross section. From the results of this analysis, the neutron dose from the beam duct is seen to be about 20 orders higher than that of the bulk shield. The magnets and shield plug are heavily irradiated by streaming neutrons according to the DCHAIN-SP analysis. PMID:16604639

  9. Using Uncertainty Analysis to Guide the Development of Accelerated Stress Tests (Presentation)

    SciTech Connect

    Kempe, M.

    2014-03-01

    Extrapolation of accelerated testing to the long-term results expected in the field has uncertainty associated with the acceleration factors and the range of possible stresses in the field. When multiple stresses (such as temperature and humidity) can be used to increase the acceleration, the uncertainty may be reduced according to which stress factors are used to accelerate the degradation.

  10. Analysis of walking variability through simultaneous evaluation of the head, lumbar, and lower-extremity acceleration in healthy youth

    PubMed Central

    Toda, Haruki; Nagano, Akinori; Luo, Zhiwei

    2016-01-01

    [Purpose] The purpose of this study was to clarify whether walking speed affects acceleration variability of the head, lumbar, and lower extremity by simultaneously evaluating of acceleration. [Subjects and Methods] Twenty young individuals recruited from among the staff at Kurashiki Heisei Hospital participated in this study. Eight accelerometers were used to measure the head, lumbar and lower extremity accelerations. The participants were instructed to walk at five walking speeds prescribed by a metronome. Acceleration variability was assessed by a cross-correlation analysis normalized using z-transform in order to evaluate stride-to-stride variability. [Results] Vertical acceleration variability was the smallest in all body parts, and walking speed effect had laterality. Antero-posterior acceleration variability was significantly associated with walking speed at sites other than the head. Medio-lateral acceleration variability of the bilateral hip alone was smaller than the antero-posterior variability. [Conclusion] The findings of this study suggest that the effect of walking speed changes on the stride-to-stride acceleration variability was individual for each body parts, and differs among directions. PMID:27390419

  11. GPU-Accelerated Analysis and Visualization of Large Structures Solved by Molecular Dynamics Flexible Fitting

    PubMed Central

    McGreevy, Ryan; Isralewitz, Barry

    2014-01-01

    Hybrid structure fitting methods combine data from cryo-electron microscopy and X-ray crystallography with molecular dynamics simulations for the determination of all-atom structures of large biomolecular complexes. Evaluating the quality-of-fit obtained from hybrid fitting is computationally demanding, particularly in the context of a multiplicity of structural conformations that must be evaluated. Existing tools for quality-of-fit analysis and visualization have previously targeted small structures and are too slow to be used interactively for large biomolecular complexes of particular interest today such as viruses or for long molecular dynamics trajectories as they arise in protein folding. We present new data-parallel and GPU-accelerated algorithms for rapid interactive computation of quality-of-fit metrics linking all-atom structures and molecular dynamics trajectories to experimentally determined density maps obtained from cryo-electron microscopy or X-ray crystallography. We evaluate the performance and accuracy of the new quality-of-fit analysis algorithms vis-a-vis existing tools, examine algorithm performance on GPU-accelerated desktop workstations and supercomputers, and describe new visualization techniques for results of hybrid structure fitting methods. PMID:25340325

  12. Problems and Pit-Falls in Testing for G × E and Epistasis in Candidate Gene Studies of Human Behavior

    PubMed Central

    Verhulst, Brad

    2014-01-01

    Conclusions about the genetic architecture of a phenotype relating to the contributions of genetic additivity, dominance, epistasis or genotype × environment interaction, depend upon the statistical and distributional properties of the measured trait. This dependence is frequently ignored in contemporary genetic studies and can radically change the conclusions that may be drawn from the data. The interdependence of the conclusions about genetic architecture and instruments used for behavioral measurement is explored by simulated studies of the interaction between candidate genes and measured environment in psychiatric genetics. Trait values are simulated (N = 100,000) under several commonly encountered scenarios and subjected to two simulated 20-item psychological tests each comprising items with different patterns of difficulty and sensitivity to variation (discriminating power) in the latent trait. Test scores are generated for each test by summing the binary responses across all items. The full model for digenic additive and non-additive genetic effects and G × E is fitted to the trait values and test scores under a range of different simulated genetic architectures. Untransformed test scores show complex patterns of epistasis and G × E even when the underlying effects of genes and environment are purely additive and the transformation of symptom counts does not fully recover the simulated underlying genetic architecture. Accordingly, failing to allow for the theory of measurement when analyzing details of genetic architecture may frequently lead to replicable over-reporting of interactions and mislead potential investigators and funding agencies. PMID:25195167

  13. Partial Dominance, Overdominance, Epistasis and QTL by Environment Interactions Contribute to Heterosis in Two Upland Cotton Hybrids.

    PubMed

    Shang, Lianguang; Wang, Yumei; Cai, Shihu; Wang, Xiaocui; Li, Yuhua; Abduweli, Abdugheni; Hua, Jinping

    2016-03-01

    Based on two recombinant inbred line (RIL) populations, two corresponding backcross (BC) populations were constructed to elucidate the genetic basis of heterosis in Upland cotton (Gossypium hirsutum L.). The yield, and yield components, of these populations were evaluated in three environments. At the single-locus level, 78 and 66 quantitative trait loci (QTL) were detected using composite interval mapping in RIL and BC populations, respectively, and 29 QTL were identified based on mid-parental heterosis (MPH) data of two hybrids. Considering all traits together, a total of 50 (64.9%) QTL with partial dominance effect, and 27 (35.1%) QTL for overdominance effect were identified in two BC populations. At the two-locus level, 120 and 88 QTL with main effects (M-QTL), and 335 and 99 QTL involved in digenic interactions (E-QTL), were detected by inclusive composite interval mapping in RIL and BC populations, respectively. A large number of QTL by environment interactions (QEs) for M-QTL and E-QTL were detected in three environments. For most traits, average E-QTL explained a larger proportion of phenotypic variation than did M-QTL in two RIL populations and two BC populations. It was concluded that partial dominance, overdominance, epistasis, and QEs all contribute to heterosis in Upland cotton, and that partial dominance resulting from single loci and epistasis play a relatively more important role than other genetic effects in heterosis in Upland cotton. PMID:26715091

  14. Epistasis and the Structure of Fitness Landscapes: Are Experimental Fitness Landscapes Compatible with Fisher’s Geometric Model?

    PubMed Central

    Blanquart, François; Bataillon, Thomas

    2016-01-01

    The fitness landscape defines the relationship between genotypes and fitness in a given environment and underlies fundamental quantities such as the distribution of selection coefficient and the magnitude and type of epistasis. A better understanding of variation in landscape structure across species and environments is thus necessary to understand and predict how populations will adapt. An increasing number of experiments investigate the properties of fitness landscapes by identifying mutations, constructing genotypes with combinations of these mutations, and measuring the fitness of these genotypes. Yet these empirical landscapes represent a very small sample of the vast space of all possible genotypes, and this sample is often biased by the protocol used to identify mutations. Here we develop a rigorous statistical framework based on Approximate Bayesian Computation to address these concerns and use this flexible framework to fit a broad class of phenotypic fitness models (including Fisher’s model) to 26 empirical landscapes representing nine diverse biological systems. Despite uncertainty owing to the small size of most published empirical landscapes, the inferred landscapes have similar structure in similar biological systems. Surprisingly, goodness-of-fit tests reveal that this class of phenotypic models, which has been successful so far in interpreting experimental data, is a plausible in only three of nine biological systems. More precisely, although Fisher’s model was able to explain several statistical properties of the landscapes—including the mean and SD of selection and epistasis coefficients—it was often unable to explain the full structure of fitness landscapes. PMID:27052568

  15. Accelerating Policy Decisions to Adopt Haemophilus influenzae Type b Vaccine: A Global, Multivariable Analysis

    PubMed Central

    Shearer, Jessica C.; Stack, Meghan L.; Richmond, Marcie R.; Bear, Allyson P.; Hajjeh, Rana A.; Bishai, David M.

    2010-01-01

    Background Adoption of new and underutilized vaccines by national immunization programs is an essential step towards reducing child mortality. Policy decisions to adopt new vaccines in high mortality countries often lag behind decisions in high-income countries. Using the case of Haemophilus influenzae type b (Hib) vaccine, this paper endeavors to explain these delays through the analysis of country-level economic, epidemiological, programmatic and policy-related factors, as well as the role of the Global Alliance for Vaccines and Immunisation (GAVI Alliance). Methods and Findings Data for 147 countries from 1990 to 2007 were analyzed in accelerated failure time models to identify factors that are associated with the time to decision to adopt Hib vaccine. In multivariable models that control for Gross National Income, region, and burden of Hib disease, the receipt of GAVI support speeded the time to decision by a factor of 0.37 (95% CI 0.18–0.76), or 63%. The presence of two or more neighboring country adopters accelerated decisions to adopt by a factor of 0.50 (95% CI 0.33–0.75). For each 1% increase in vaccine price, decisions to adopt are delayed by a factor of 1.02 (95% CI 1.00–1.04). Global recommendations and local studies were not associated with time to decision. Conclusions This study substantiates previous findings related to vaccine price and presents new evidence to suggest that GAVI eligibility is associated with accelerated decisions to adopt Hib vaccine. The influence of neighboring country decisions was also highly significant, suggesting that approaches to support the adoption of new vaccines should consider supply- and demand-side factors. Please see later in the article for the Editors' Summary PMID:20305714

  16. Species-wide Genetic Incompatibility Analysis Identifies Immune Genes as Hotspots of Deleterious Epistasis

    PubMed Central

    Chae, Eunyoung; Bomblies, Kirsten; Kim, Sang-Tae; Karelina, Darya; Zaidem, Maricris; Ossowski, Stephan; Martín-Pizarro, Carmen; Laitinen, Roosa A. E.; Rowan, Beth A.; Tenenboim, Hezi; Lechner, Sarah; Demar, Monika; Habring-Müller, Anette; Lanz, Christa; Rätsch, Gunnar; Weigel, Detlef

    2014-01-01

    Summary Intraspecific genetic incompatibilities prevent the assembly of specific alleles into single genotypes and influence genome- and species-wide patterns of sequence variation. A common incompatibility in plants is hybrid necrosis, characterized by autoimmune responses due to epistatic interactions between natural genetic variants. By systematically testing thousands of F1 hybrids of Arabidopsis thaliana strains, we identified a small number of incompatibility hotspots in the genome, often in regions densely populated by NLR immune receptor genes. In several cases, these immune receptor loci interact with each other, suggestive of conflict within the immune system. A particularly dangerous locus is a highly variable cluster of NLR genes, DANGEROUS MIX2 (DM2), which causes multiple, independent incompatibilities with genes that encode a range of biochemical functions, including NLRs. Our findings suggest that deleterious interactions of immune receptors at the front lines of host-pathogen co-evolution limit the combinations of favorable disease resistance alleles accessible to plant genomes. PMID:25467443

  17. Waveband Analysis of Track Irregularities in High-Speed Railway from On-Board Acceleration Measurement

    NASA Astrophysics Data System (ADS)

    Lee, Jun Seok; Choi, Sunghoon; Kim, Sang-Soo; Kim, Young Guk; Kim, Seog Won; Park, Choonsoo

    This paper is focused on waveband analysis of the lateral and vertical track irregularities from the on-board acceleration measurement of in-service high-speed trains. The track irregularities play important roles to determine dynamic stability of vehicles and ride quality of passengers, so that their amplitude and wavelength should be monitored continuously and carefully. Measuring acceleration at the axle-box or bogie of the trains has been under consideration for low-cost implementation and robust to a harsh railway environment. To estimate the track irregularities, lateral and vertical vibration caused by the wheel/track interaction is measured by the axle-box and bogie mounted accelerometers of an in-service high-speed train. A Kalman filter is used to prevent unrealistic drifts in the estimation. By applying the waveband-pass and compensation filters to the estimated displacement, it is possible to estimate the track irregularities. A distance-wavelength representation is used to identify their waveband in an intuitive way. It is verified by comparing with a commercial track geometry measurement system. From their comparison, it confirms that the representation can produce a satisfactory result.

  18. Analysis of secondary particle behavior in multiaperture, multigrid accelerator for the ITER neutral beam injector.

    PubMed

    Mizuno, T; Taniguchi, M; Kashiwagi, M; Umeda, N; Tobari, H; Watanabe, K; Dairaku, M; Sakamoto, K; Inoue, T

    2010-02-01

    Heat load on acceleration grids by secondary particles such as electrons, neutrals, and positive ions, is a key issue for long pulse acceleration of negative ion beams. Complicated behaviors of the secondary particles in multiaperture, multigrid (MAMuG) accelerator have been analyzed using electrostatic accelerator Monte Carlo code. The analytical result is compared to experimental one obtained in a long pulse operation of a MeV accelerator, of which second acceleration grid (A2G) was removed for simplification of structure. The analytical results show that relatively high heat load on the third acceleration grid (A3G) since stripped electrons were deposited mainly on A3G. This heat load on the A3G can be suppressed by installing the A2G. Thus, capability of MAMuG accelerator is demonstrated for suppression of heat load due to secondary particles by the intermediate grids. PMID:20192410

  19. Analysis of secondary particle behavior in multiaperture, multigrid accelerator for the ITER neutral beam injector

    SciTech Connect

    Mizuno, T.; Taniguchi, M.; Kashiwagi, M.; Umeda, N.; Tobari, H.; Watanabe, K.; Dairaku, M.; Sakamoto, K.; Inoue, T.

    2010-02-15

    Heat load on acceleration grids by secondary particles such as electrons, neutrals, and positive ions, is a key issue for long pulse acceleration of negative ion beams. Complicated behaviors of the secondary particles in multiaperture, multigrid (MAMuG) accelerator have been analyzed using electrostatic accelerator Monte Carlo code. The analytical result is compared to experimental one obtained in a long pulse operation of a MeV accelerator, of which second acceleration grid (A2G) was removed for simplification of structure. The analytical results show that relatively high heat load on the third acceleration grid (A3G) since stripped electrons were deposited mainly on A3G. This heat load on the A3G can be suppressed by installing the A2G. Thus, capability of MAMuG accelerator is demonstrated for suppression of heat load due to secondary particles by the intermediate grids.

  20. On the Impact of a Quadratic Acceleration Term in the Analysis of Position Time Series

    NASA Astrophysics Data System (ADS)

    Bogusz, Janusz; Klos, Anna; Bos, Machiel Simon; Hunegnaw, Addisu; Teferle, Felix Norman

    2016-04-01

    The analysis of Global Navigation Satellite System (GNSS) position time series generally assumes that each of the coordinate component series is described by the sum of a linear rate (velocity) and various periodic terms. The residuals, the deviations between the fitted model and the observations, are then a measure of the epoch-to-epoch scatter and have been used for the analysis of the stochastic character (noise) of the time series. Often the parameters of interest in GNSS position time series are the velocities and their associated uncertainties, which have to be determined with the highest reliability. It is clear that not all GNSS position time series follow this simple linear behaviour. Therefore, we have added an acceleration term in the form of a quadratic polynomial function to the model in order to better describe the non-linear motion in the position time series. This non-linear motion could be a response to purely geophysical processes, for example, elastic rebound of the Earth's crust due to ice mass loss in Greenland, artefacts due to deficiencies in bias mitigation models, for example, of the GNSS satellite and receiver antenna phase centres, or any combination thereof. In this study we have simulated 20 time series with different stochastic characteristics such as white, flicker or random walk noise of length of 23 years. The noise amplitude was assumed at 1 mm/y-/4. Then, we added the deterministic part consisting of a linear trend of 20 mm/y (that represents the averaged horizontal velocity) and accelerations ranging from minus 0.6 to plus 0.6 mm/y2. For all these data we estimated the noise parameters with Maximum Likelihood Estimation (MLE) using the Hector software package without taken into account the non-linear term. In this way we set the benchmark to then investigate how the noise properties and velocity uncertainty may be affected by any un-modelled, non-linear term. The velocities and their uncertainties versus the accelerations for

  1. Mapa-an object oriented code with a graphical user interface for accelerator design and analysis

    SciTech Connect

    Shasharina, S.G.; Cary, J.R.

    1997-02-01

    We developed a code for accelerator modeling which will allow users to create and analyze accelerators through a graphical user interface (GUI). The GUI can read an accelerator from files or create it by adding, removing and changing elements. It also creates 4D orbits and lifetime plots. The code includes a set of accelerator elements classes, C++ utility and GUI libraries. Due to the GUI, the code is easy to use and expand. {copyright} {ital 1997 American Institute of Physics.}

  2. Mapa-an object oriented code with a graphical user interface for accelerator design and analysis

    SciTech Connect

    Shasharina, Svetlana G.; Cary, John R.

    1997-02-01

    We developed a code for accelerator modeling which will allow users to create and analyze accelerators through a graphical user interface (GUI). The GUI can read an accelerator from files or create it by adding, removing and changing elements. It also creates 4D orbits and lifetime plots. The code includes a set of accelerator elements classes, C++ utility and GUI libraries. Due to the GUI, the code is easy to use and expand.

  3. Accelerated Monte Carlo Simulation for Safety Analysis of the Advanced Airspace Concept

    NASA Technical Reports Server (NTRS)

    Thipphavong, David

    2010-01-01

    Safe separation of aircraft is a primary objective of any air traffic control system. An accelerated Monte Carlo approach was developed to assess the level of safety provided by a proposed next-generation air traffic control system. It combines features of fault tree and standard Monte Carlo methods. It runs more than one order of magnitude faster than the standard Monte Carlo method while providing risk estimates that only differ by about 10%. It also preserves component-level model fidelity that is difficult to maintain using the standard fault tree method. This balance of speed and fidelity allows sensitivity analysis to be completed in days instead of weeks or months with the standard Monte Carlo method. Results indicate that risk estimates are sensitive to transponder, pilot visual avoidance, and conflict detection failure probabilities.

  4. Final safety analysis report for the Ground Test Accelerator (GTA), Phase 2

    SciTech Connect

    1994-10-01

    This document is the third volume of a 3 volume safety analysis report on the Ground Test Accelerator (GTA). The GTA program at the Los Alamos National Laboratory (LANL) is the major element of the national Neutral Particle Beam (NPB) program, which is supported by the Strategic Defense Initiative Office (SDIO). A principal goal of the national NPB program is to assess the feasibility of using hydrogen and deuterium neutral particle beams outside the Earth`s atmosphere. The main effort of the NPB program at Los Alamos concentrates on developing the GTA. The GTA is classified as a low-hazard facility, except for the cryogenic-cooling system, which is classified as a moderate-hazard facility. This volume consists of appendices C through U of the report

  5. On a thermal analysis of a second stripper for rare isotope accelerator.

    SciTech Connect

    Momozaki, Y.; Nolen, J.; Nuclear Engineering Division

    2008-08-04

    This memo summarizes simple calculations and results of the thermal analysis on the second stripper to be used in the driver linac of Rare Isotope Accelerator (RIA). Both liquid (Sodium) and solid (Titanium and Vanadium) stripper concepts were considered. These calculations were intended to provide basic information to evaluate the feasibility of liquid (thick film) and solid (rotating wheel) second strippers. Nuclear physics calculations to estimate the volumetric heat generation in the stripper material were performed by 'LISE for Excel'. In the thermal calculations, the strippers were modeled as a thin 2D plate with uniform heat generation within the beam spot. Then, temperature distributions were computed by assuming that the heat spreads conductively in the plate in radial direction without radiative heat losses to surroundings.

  6. Final safety analysis report for the Ground Test Accelerator (GTA), Phase 2

    SciTech Connect

    1994-10-01

    This document is the first volume of a 3 volume safety analysis report on the Ground Test Accelerator (GTA). The GTA program at the Los Alamos National Laboratory (LANL) is the major element of the national Neutral Particle Beam (NPB) program, which is supported by the Strategic Defense Initiative Office (SDIO). A principal goal of the national NPB program is to assess the feasibility of using hydrogen and deuterium neutral particle beams outside the Earth`s atmosphere. The main effort of the NPB program at Los Alamos concentrates on developing the GTA. The GTA is classified as a low-hazard facility, except for the cryogenic-cooling system, which is classified as a moderate-hazard facility. This volume consists of an introduction, summary/conclusion, site description and assessment, description of facility, and description of operation.

  7. Accelerator-Based PIXE and STIM Analysis of Candidate Solar Sail Materials

    SciTech Connect

    Hollerman, W.A.; Stanaland, T.L.; Boudreaux, P.; Elberson, L.; Fontenot, J.; Gates, E.; Greco, R.; McBride, M.; Woodward, A.; Edwards, D.

    2003-08-26

    Solar sailing is a unique form of propulsion where a spacecraft gains momentum from incident photons. A totally reflective sail experiences a pressure of 9.1 {mu}Pa at a distance of 1 AU from the Sun. Since sails are not limited by reaction mass, they provide continual acceleration, reduced only by the lifetime of the lightweight film in the space environment and the distance to the Sun. Practical solar sails can expand the number of possible missions, enabling new concepts that are difficult by conventional means. One of the current challenges is to develop strong, lightweight, and radiation resistant sail materials. This paper will discuss initial results from a Particle Induced X-Ray Emission (PIXE) and Scanning Transmission Ion Microscopy (STIM) analysis of candidate solar sail materials.

  8. Detailed analysis of Honeywell In-Space Accelerometer data - STS-32. [crystal microstructure response to different types of residual acceleration

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. I. D.; Schoess, Jeff

    1993-01-01

    The Honeywell In-Space Accelerometer (HISA) system collected data in the mid-deck area of the Shuttle Columbia during the flight of STS-32, January 1990. The resulting data were to be used to investigate the response of crystal microstructure to different types of residual acceleration. The HISA is designed to detect and record transient and oscillatory accelerations. The sampling and electronics package stored averaged accelerations over two sampling periods; two sampling rates were available: 1 Hz and 50 Hz. Analysis of the HISA data followed the CMMR Acceleration Data Processing Guide, considering in-house computer modelling of a float-zone indium crystal growth experiment. Characteristic examples of HISA data showing the response to the primary reaction control system, Orbiter Maneuvering System operations, and crew treadmill activity are presented. Various orbiter structural modes are excited by these and other activities.

  9. Groundwater modelling: Towards an estimation of the acceleration factors of iterative methods via an analysis of the transmissivity spatial variability

    NASA Astrophysics Data System (ADS)

    Benali, Abdelmajid

    2013-01-01

    When running a groundwater flow model, a recurrent and seemingly subsidiary question arises at the starting step of computations: what value of acceleration parameter do we need to optimize the numerical solver? A method is proposed to provide a practical estimate of the optimal acceleration parameter via a geostatistical analysis of the spatial variability of the logarithm of the transmissivity field Y. The background of the approach is illustrated on the successive over-relaxation method (SOR) used, either as a stand-alone solver, or as a symmetric preconditioner (SSOR) to the gradient conjugate method, or as a smoother in multigrid methods. It shows that this optimum acceleration factor is a function of the standard deviation and the correlation length of Y. This provides an easy-to-use heuristic procedure to estimate the acceleration factors, which could even be incorporated in the software package. A case study illustrates the steps needed to perform this estimation.

  10. Variability in Working Memory Performance Explained by Epistasis versus Polygenic Scores in the ZNF804A Pathway

    PubMed Central

    Morris, Derek; Anney, Richard; Gill, Michael; Corvin, Aiden; Donohoe, Gary

    2015-01-01

    Importance We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic score and epistatic analyses. Of particular importance was the relative contribution of the polygenic score versus epistasis in variation explained. Objective The objectives were twofold: first, to assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis. The second was to assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. Design, Setting and Participants Patients with psychosis (N = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention and social cognition. We used the Psychiatric GWAS Consortium (PGC1) schizophrenia GWAS to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (N = 170), which was used to develop linear regression models containing the polygenic score and two-SNP interactions. The best-fitting models were tested for replication in two independent test sets of cases: 1) 170 individuals with schizophrenia or schizoaffective disorder and 2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder and other psychosis). Results Higher polygenic scores were associated with poorer performance amongst patients on IQ, memory and social cognition, explaining 1-3% of variation on these scores (p-values ranged from 0.012-0.034). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and controls (N = 89) respectively, the

  11. Soil dynamics and accelerated erosion: a sensitivity analysis of the LPJ Dynamic vegetation model

    NASA Astrophysics Data System (ADS)

    Bouchoms, Samuel; Van Oost, Kristof; Vanacker, Veerle; Kaplan, Jed O.; Vanwalleghem, Tom

    2013-04-01

    It is widely accepted that humans have become a major geomorphic force by disturbing natural vegetation patterns. Land conversion for agriculture purposes removes the protection of soils by the natural vegetation and leads to increased soil erosion by one to two orders of magnitude, breaking the balance that exists between the loss of soils and its production. Accelerated erosion and deposition have a strong influence on evolution and heterogeneity of basic soil characteristics (soil thickness, hydrology, horizon development,…) as well as on organic matter storage and cycling. Yet, since they are operating at a long time scale, those processes are not represented in state-of-art Dynamic Global Vegetation Models, which is a clear lack when exploring vegetation dynamics over past centuries. The main objectives of this paper are (i) to test the sensitivity of a Dynamic Global Vegetation Model, in terms of NPP and organic matter turnover, variations in state variables in response to accelerated erosion and (ii) to assess the performance of the model under the impact of erosion for a case-study in Central Spain. We evaluated the Lund-Postdam-Jena Dynamic Vegetation Model (LPJ DVGM) (Sitch et al, 2003) which simulates vegetation growth and carbon pools at the surface and in the soil based on climatic, pedologic and topographic variables. We assessed its reactions to changes in key soil properties that are affected by erosion such as texture and soil depth. We present the results of where we manipulated soil texture and bulk density while keeping the environmental drivers of climate, slope and altitude constant. For parameters exhibiting a strong control on NPP or SOM, a factorial analysis was conducted to test for interaction effects. The simulations show an important dependence on the clay content, especially for the slow cycling carbon pools and the biomass production, though the underground litter seems to be mostly influenced by the silt content. The fast cycling C

  12. Final safety analysis report for the Ground Test Accelerator (GTA), Phase 2

    SciTech Connect

    1994-10-01

    This document is the second volume of a 3 volume safety analysis report on the Ground Test Accelerator (GTA). The GTA program at the Los Alamos National Laboratory (LANL) is the major element of the national Neutral Particle Beam (NPB) program, which is supported by the Strategic Defense Initiative Office (SDIO). A principal goal of the national NPB program is to assess the feasibility of using hydrogen and deuterium neutral particle beams outside the Earth`s atmosphere. The main effort of the NPB program at Los Alamos concentrates on developing the GTA. The GTA is classified as a low-hazard facility, except for the cryogenic-cooling system, which is classified as a moderate-hazard facility. This volume consists of failure modes and effects analysis; accident analysis; operational safety requirements; quality assurance program; ES&H management program; environmental, safety, and health systems critical to safety; summary of waste-management program; environmental monitoring program; facility expansion, decontamination, and decommissioning; summary of emergency response plan; summary plan for employee training; summary plan for operating procedures; glossary; and appendices A and B.

  13. Analysis of graduates' perceptions of an accelerated bachelor of science program in nursing.

    PubMed

    Kemsley, Martha; McCausland, Linda; Feigenbaum, Janice; Riegle, Elizabeth

    2011-01-01

    Rapid expansion of second-degree programs as one approach to addressing the nursing shortage by increasing the number of graduates in shorter periods of time prompted the need for program evaluation to identify the outcomes, strengths, and best practices of these programs. This study used both quantitative and qualitative methods of inquiry to analyze the responses of 28 of 56 recent graduates of an accelerated baccalaureate program. Respondents rated components of the program from preadmission to graduation on a Likert scale and responded to open-ended questions regarding strengths and weaknesses of the program. Analysis included descriptive statistics for quantitative data and content analysis for qualitative data. The analysis showed a high degree of similarity between the quantitative and qualitative data. Highly rated program components, that is, opportunity for graduate course work and integration with graduate students, clinical skill practice and experiences, variety of teaching methodologies, peer and faculty support, were reflected in the themes of cohort bonding, variety of clinical experiences, and supportive faculty and staff. Outcomes of program satisfaction, National Council Licensure Examination pass rates, successful nursing employment, and graduate school attendance were supported by the data. PMID:21272836

  14. Accelerating Data Acquisition, Reduction, and Analysis at the Spallation Neutron Source

    SciTech Connect

    Campbell, Stuart I; Kohl, James Arthur; Granroth, Garrett E; Miller, Ross G; Doucet, Mathieu; Stansberry, Dale V; Proffen, Thomas E; Taylor, Russell J; Dillow, David

    2014-01-01

    ORNL operates the world's brightest neutron source, the Spallation Neutron Source (SNS). Funded by the US DOE Office of Basic Energy Science, this national user facility hosts hundreds of scientists from around the world, providing a platform to enable break-through research in materials science, sustainable energy, and basic science. While the SNS provides scientists with advanced experimental instruments, the deluge of data generated from these instruments represents both a big data challenge and a big data opportunity. For example, instruments at the SNS can now generate multiple millions of neutron events per second providing unprecedented experiment fidelity but leaving the user with a dataset that cannot be processed and analyzed in a timely fashion using legacy techniques. To address this big data challenge, ORNL has developed a near real-time streaming data reduction and analysis infrastructure. The Accelerating Data Acquisition, Reduction, and Analysis (ADARA) system provides a live streaming data infrastructure based on a high-performance publish subscribe system, in situ data reduction, visualization, and analysis tools, and integration with a high-performance computing and data storage infrastructure. ADARA allows users of the SNS instruments to analyze their experiment as it is run and make changes to the experiment in real-time and visualize the results of these changes. In this paper we describe ADARA, provide a high-level architectural overview of the system, and present a set of use-cases and real-world demonstrations of the technology.

  15. The Valley-of-Death: reciprocal sign epistasis constrains adaptive trajectories in a constant, nutrient limiting environment.

    PubMed

    Chiotti, Kami E; Kvitek, Daniel J; Schmidt, Karen H; Koniges, Gregory; Schwartz, Katja; Donckels, Elizabeth A; Rosenzweig, Frank; Sherlock, Gavin

    2014-12-01

    The fitness landscape is a powerful metaphor for describing the relationship between genotype and phenotype for a population under selection. However, empirical data as to the topography of fitness landscapes are limited, owing to difficulties in measuring fitness for large numbers of genotypes under any condition. We previously reported a case of reciprocal sign epistasis (RSE), where two mutations individually increased yeast fitness in a glucose-limited environment, but reduced fitness when combined, suggesting the existence of two peaks on the fitness landscape. We sought to determine whether a ridge connected these peaks so that populations founded by one mutant could reach the peak created by the other, avoiding the low-fitness "Valley-of-Death" between them. Sequencing clones after 250 generations of further evolution provided no evidence for such a ridge, but did reveal many presumptive beneficial mutations, adding to a growing body of evidence that clonal interference pervades evolving microbial populations. PMID:25449178

  16. Sociocultural epistasis and cultural exaptation in footbinding, marriage form, and religious practices in early 20th-century Taiwan.

    PubMed

    Brown, Melissa J; Feldman, Marcus W

    2009-12-29

    Social theorists have long recognized that changes in social order have cultural consequences but have not been able to provide an individual-level mechanism of such effects. Explanations of human behavior have only just begun to explore the different evolutionary dynamics of social and cultural inheritance. Here we provide ethnographic evidence of how cultural evolution, at the level of individuals, can be influenced by social evolution. Sociocultural epistasis--association of cultural ideas with the hierarchical structure of social roles--influences cultural change in unexpected ways. We document the existence of cultural exaptation, where a custom's origin was not due to acceptance of the later associated ideas. A cultural exaptation can develop in the absence of a cultural idea favoring it, or even in the presence of a cultural idea against it. Such associations indicate a potentially larger role for social evolutionary dynamics in explaining individual human behavior than previously anticipated. PMID:20080786

  17. Epistasis and the Genetic Divergence of Photoperiodism between Populations of the Pitcher-Plant Mosquito, Wyeomyia Smithii

    PubMed Central

    Hard, J. J.; Bradshaw, W. E.; Holzapfel, C. M.

    1992-01-01

    Parallel crosses between each of two southern (ancestral) and one northern (derived) population of the pitcher-plant mosquito, Wyeomyia smithii, were made to determine the genetic components of population divergence in critical photoperiod, a phenological trait that measures adaptation to seasonality along a climatic gradient. Joint scaling tests were used to analyze means and variances of first- and second-generation hybrids in order to determine whether nonadditive genetic variance, especially epistatic variance, contributed to divergence in critical photoperiod. In both crosses, digenic epistatic effects were highly significant, indicating that genetic divergence cannot have resulted solely from differences in additively acting loci. For one cross that could be tested directly for such effects, higher order epistasis and/or linkage did not contribute to the divergence of critical photoperiod between the constituent populations. PMID:1353737

  18. Epistasis and the genetic divergence of photoperiodism between populations of the pitcher-plant mosquito, Wyeomyia smithii.

    PubMed

    Hard, J J; Bradshaw, W E; Holzapfel, C M

    1992-06-01

    Parallel crosses between each of two southern (ancestral) and one northern (derived) population of the pitcher-plant mosquito, Wyeomyia smithii, were made to determine the genetic components of population divergence in critical photoperiod, a phenological trait that measures adaptation to seasonality along a climatic gradient. Joint scaling tests were used to analyze means and variances of first- and second-generation hybrids in order to determine whether nonadditive genetic variance, especially epistatic variance, contributed to divergence in critical photoperiod. In both crosses, digenic epistatic effects were highly significant, indicating that genetic divergence cannot have resulted solely from differences in additively acting loci. For one cross that could be tested directly for such effects, higher order epistasis and/or linkage did not contribute to the divergence of critical photoperiod between the constituent populations. PMID:1353737

  19. Partial Dominance, Overdominance and Epistasis as the Genetic Basis of Heterosis in Upland Cotton (Gossypium hirsutum L.)

    PubMed Central

    Wang, Yumei; Hua, Jinping

    2015-01-01

    Determination of genetic basis of heterosis may promote hybrid production in Upland cotton (Gossypium hirsutum L.). This study was designed to explore the genetic mechanism of heterosis for yield and yield components in F2: 3 and F2: 4 populations derived from a hybrid ‘Xinza No. 1’. Replicated yield field trials of the progenies were conducted in 2008 and 2009. Phenotypic data analyses indicated overdominance in F1 for yield and yield components. Additive and dominance effects at single-locus level and digenic epistatic interactions at two-locus level were analyzed by 421 marker loci spanning 3814 cM of the genome. A total of 38 and 49 QTLs controlling yield and yield components were identified in F2: 3 and F2: 4 populations, respectively. Analyses of these QTLs indicated that the effects of partial dominance and overdominance contributed to heterosis in Upland cotton simultaneously. Most of the QTLs showed partial dominance whereas 13 QTLs showing overdominance in F2:3 population, and 19 QTLs showed overdominance in F2:4. Among them, 21 QTLs were common in both F2: 3 and F2: 4 populations. A large number of two-locus interactions for yield and yield components were detected in both generations. AA (additive × additive) epistasis accounted for majority portion of epistatic effects. Thirty three complementary two-locus homozygotes (11/22 and 22/11) were the best genotypes for AA interactions in terms of bolls per plant. Genotypes of double homozygotes, 11/22, 22/11 and 22/22, performed best for AD/DA interactions, while genotype of 11/12 performed best for DD interactions. These results indicated that (1) partial dominance and overdominance effects at single-locus level and (2) epistasis at two-locus level elucidated the genetic basis of heterosis in Upland cotton. PMID:26618635

  20. Epistasis for Fitness-Related Quantitative Traits in Arabidopsis thaliana Grown in the Field and in the Greenhouse

    PubMed Central

    Malmberg, Russell L.; Held, Stephanie; Waits, Ashleigh; Mauricio, Rodney

    2005-01-01

    The extent to which epistasis contributes to adaptation, population differentiation, and speciation is a long-standing and important problem in evolutionary genetics. Using recombinant inbred (RI) lines of Arabidopsis thaliana grown under natural field conditions, we have examined the genetic architecture of fitness-correlated traits with respect to epistasis; we identified both single-locus additive and two-locus epistatic QTL for natural variation in fruit number, germination, and seed length and width. For fruit number, we found seven significant epistatic interactions, but only two additive QTL. For seed germination, length, and width, there were from two to four additive QTL and from five to eight epistatic interactions. The epistatic interactions were both positive and negative. In each case, the magnitude of the epistatic effects was roughly double that of the effects of the additive QTL, varying from −41% to +29% for fruit number and from −5% to +4% for seed germination, length, and width. A number of the QTL that we describe participate in more than one epistatic interaction, and some loci identified as additive also may participate in an epistatic interaction; the genetic architecture for fitness traits may be a network of additive and epistatic effects. We compared the map positions of the additive and epistatic QTL for germination, seed width, and seed length from plants grown in both the field and the greenhouse. While the total number of significant additive and epistatic QTL was similar under the two growth conditions, the map locations were largely different. We found a small number of significant epistatic QTL × environment effects when we tested directly for them. Our results support the idea that epistatic interactions are an important part of natural genetic variation and reinforce the need for caution in comparing results from greenhouse-grown and field-grown plants. PMID:16157670

  1. Rift strength controls rapid plate accelerations: A global analysis of Pangea fragmentation

    NASA Astrophysics Data System (ADS)

    Brune, S.; Williams, S.; Butterworth, N. P.; Müller, D.

    2015-12-01

    Motions of Earth's plates are thought to be driven by slab pull, basal drag, and ridge push. Here we propose that plate motions during supercontinental fragmentation are decisively controlled by the non-linear decay of a resistive force: rift strength. We use state-of-the-art global tectonic reconstructions and the new geotectonic analysis tool pyGPlates to analyze the transition from rifting to sea-floor spreading of well-studied post-Pangea rift systems (Central Atlantic, South Atlantic, Iberia/Newfoundland, Australia/Antarctica, North Atlantic, South China Sea, Gulf of California). In all cases, continental extension starts with a slow phase (< 10 mm/yr, full extension velocity) followed by a rapid acceleration over periods of a few My that introduces a fast rift phase (> 10 mm/yr). The transition from slow to fast extension takes place long before crustal break-up. In fact, we find that approximately half of the present day rifted margin area was created during the slow, and the other half during the fast phase. We reproduce the transition from slow to fast rifting using numerical forward models with force boundary conditions, such that rift velocities are not imposed but instead evolve naturally in response to changing strength of the rift. These models show that the two-phase velocity behavior during rifting and the rapid speed-up are intrinsic features of continental rupture that can be robustly inferred for different crust and mantle rheologies.It has been proposed that abrupt plate accelerations can be caused by plume-lithosphere interaction, subduction initiation, and slab detachment. However, none of these mechanisms explains our result that plate speed-up systematically precedes continental break-up. We therefore propose dynamic rift weakening as a new mechanism for rapid plate motion changes.

  2. Effect of acceleration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Kitamura, K.; Nemoto, N.; Shimizu, S.; Wada, W.; Kondo, K.; Tabata, T.; Sodeyama, S.; Ijiri, I.; Hattori, H.

    It is well known that hypo-gravity and hyper-gravity influence bone metabolism However basic data concerning the mechanism are a few because no in vitro model system of human bone is available Human bone consists of osteoblasts osteoclasts and the bone matrix No technique for the co-culture of these components has ever been developed Fish scale is a calcified tissue that contains osteoblasts osteoclasts and bone matrix all of which are similar to those found in human bone Recently we developed a new in vitro model system using goldfish scale This system can simultaneously detect the activities of both scale osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers Using this system we analyzed the bone metabolism under acceleration with a custom-made G-load apparatus Osteoclastic activity in the goldfish scales was suppressed under low-acceleration 0 5-G while osteoblastic activity did not change under this acceleration Under high-acceleration 6-G however the osteoblastic activity of the scales increased In addition the osteoclastic activity of the scales decreased These results suggest that both osteoblastic and osteoclastic activities are regulated by the strength of acceleration Therefore we strongly believe that our in vitro system is useful for analysis of bone metabolism under acceleration

  3. Genome-wide association interaction analysis for Alzheimer's disease

    PubMed Central

    Gusareva, Elena S.; Carrasquillo, Minerva M.; Bellenguez, Céline; Cuyvers, Elise; Colon, Samuel; Graff-Radford, Neill R.; Petersen, Ronald C.; Dickson, Dennis W.; Mahachie Johna, Jestinah M.; Bessonov, Kyrylo; Van Broeckhoven, Christine; Williams, Julie; Amouyel, Philippe; Sleegers, Kristel; Ertekin-Taner, Nilüfer; Lambert, Jean-Charles; Van Steen, Kristel

    2015-01-01

    We propose a minimal protocol for exhaustive genome-wide association interaction analysis that involves screening for epistasis over large-scale genomic data combining strengths of different methods and statistical tools. The different steps of this protocol are illustrated on a real-life data application for Alzheimer's disease (AD) (2259 patients and 6017 controls from France). Particularly, in the exhaustive genome-wide epistasis screening we identified AD-associated interacting SNPs-pair from chromosome 6q11.1 (rs6455128, the KHDRBS2 gene) and 13q12.11 (rs7989332, the CRYL1 gene) (p = 0.006, corrected for multiple testing). A replication analysis in the independent AD cohort from Germany (555 patients and 824 controls) confirmed the discovered epistasis signal (p = 0.036). This signal was also supported by a meta-analysis approach in 5 independent AD cohorts that was applied in the context of epistasis for the first time. Transcriptome analysis revealed negative correlation between expression levels of KHDRBS2 and CRYL1 in both the temporal cortex (β = −0.19, p = 0.0006) and cerebellum (β = −0.23, p < 0.0001) brain regions. This is the first time a replicable epistasis associated with AD was identified using a hypothesis free screening approach. PMID:24958192

  4. Spectral reconstruction by scatter analysis for a linear accelerator photon beam.

    PubMed

    Jalbout, Wassim T; Spyrou, Nicholas M

    2006-05-01

    Pre-existing methods for photon beam spectral reconstruction are briefly reviewed. An alternative reconstruction method by scatter analysis for linear accelerators is introduced. The method consists in irradiating a small plastic phantom at standard 100 cm SSD and inferring primary beam energy spectral information based on the measurement with a standard Farmer chamber of scatter around the phantom at several specific scatter angles: a scatter curve is measured which is indicative of the primary spectrum at hand. A Monte Carlo code is used to simulate the scatter measurement set-up and predict the relative magnitude of scatter measurements for mono-energetic primary beams. Based on mono-energetic primary scatter data, measured scatter curves are analysed and the spectrum unfolded as the sum of mono-energetic individual energy bins using the Schiff bremsstrahlung model. The method is applied to an Elekta/SL18 6 MV photon beam. The reconstructed spectrum matches the Monte Carlo calculated spectrum for the same beam within 6.2% (average error when spectra are compared bin by bin). Depth dose values calculated for the reconstructed spectrum agree with physically measured depth dose data to within 1%. Scatter analysis is preliminarily shown to have potential as a practical spectral reconstruction method requiring few measurements under standard 100 cm SSD and feasible in any radiotherapy department using a phantom and a Farmer chamber. PMID:16625037

  5. Foreign exchange market data analysis reveals statistical features that predict price movement acceleration.

    PubMed

    Nacher, Jose C; Ochiai, Tomoshiro

    2012-05-01

    Increasingly accessible financial data allow researchers to infer market-dynamics-based laws and to propose models that are able to reproduce them. In recent years, several stylized facts have been uncovered. Here we perform an extensive analysis of foreign exchange data that leads to the unveiling of a statistical financial law. First, our findings show that, on average, volatility increases more when the price exceeds the highest (or lowest) value, i.e., breaks the resistance line. We call this the breaking-acceleration effect. Second, our results show that the probability P(T) to break the resistance line in the past time T follows power law in both real data and theoretically simulated data. However, the probability calculated using real data is rather lower than the one obtained using a traditional Black-Scholes (BS) model. Taken together, the present analysis characterizes a different stylized fact of financial markets and shows that the market exceeds a past (historical) extreme price fewer times than expected by the BS model (the resistance effect). However, when the market does, we predict that the average volatility at that time point will be much higher. These findings indicate that any Markovian model does not faithfully capture the market dynamics. PMID:23004832

  6. Foreign exchange market data analysis reveals statistical features that predict price movement acceleration

    NASA Astrophysics Data System (ADS)

    Nacher, Jose C.; Ochiai, Tomoshiro

    2012-05-01

    Increasingly accessible financial data allow researchers to infer market-dynamics-based laws and to propose models that are able to reproduce them. In recent years, several stylized facts have been uncovered. Here we perform an extensive analysis of foreign exchange data that leads to the unveiling of a statistical financial law. First, our findings show that, on average, volatility increases more when the price exceeds the highest (or lowest) value, i.e., breaks the resistance line. We call this the breaking-acceleration effect. Second, our results show that the probability P(T) to break the resistance line in the past time T follows power law in both real data and theoretically simulated data. However, the probability calculated using real data is rather lower than the one obtained using a traditional Black-Scholes (BS) model. Taken together, the present analysis characterizes a different stylized fact of financial markets and shows that the market exceeds a past (historical) extreme price fewer times than expected by the BS model (the resistance effect). However, when the market does, we predict that the average volatility at that time point will be much higher. These findings indicate that any Markovian model does not faithfully capture the market dynamics.

  7. Hyperfractionated or Accelerated Radiotherapy in Lung Cancer: An Individual Patient Data Meta-Analysis

    PubMed Central

    Mauguen, Audrey; Le Péchoux, Cécile; Saunders, Michele I.; Schild, Steven E.; Turrisi, Andrew T.; Baumann, Michael; Sause, William T.; Ball, David; Belani, Chandra P.; Bonner, James A.; Zajusz, Aleksander; Dahlberg, Suzanne E.; Nankivell, Matthew; Mandrekar, Sumithra J.; Paulus, Rebecca; Behrendt, Katarzyna; Koch, Rainer; Bishop, James F.; Dische, Stanley; Arriagada, Rodrigo; De Ruysscher, Dirk; Pignon, Jean-Pierre

    2012-01-01

    Purpose In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation. Material and Methods We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy. Results In non–small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non–lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities. Conclusion Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity. PMID:22753901

  8. Analysis of transmitted optical spectrum enabling accelerated testing of multijunction concentrating photovoltaic designs

    NASA Astrophysics Data System (ADS)

    Miller, David C.; Kempe, Michael D.; Kennedy, Cheryl E.; Kurtz, Sarah R.

    2011-01-01

    Concentrating photovoltaic (CPV) technology has recently gained interest based on its scalability and expected low levelized cost of electricity. The reliability of encapsulation materials used in CPV systems, however, is not well established. For example, the present qualification test for CPV modules includes only real-time ultraviolet (UV) exposure, i.e., methods for accelerated UV testing have not yet been developed. To better define the stress inherent to CPV systems, the UV and infrared spectra transmitted through representative optical systems were evaluated. Measurements of optical components are used to assess expected optical performance and quantify damaging optical exposure. Optical properties (transmittance, refractive index, reflectance, and absorptance) of candidate materials (including PMMA, soda-lime glass, borosilicate glass, and quartz refractors), components (including Ag- and Al-enabled reflectors), and encapsulants (including EVA, ionomer, PDMS, PPMS, polyolefin, and PVB) were identified. The activation spectrum was calculated for the representative optical systems using an assumed action spectrum to compare the expected damaging dose of UV radiation delivered to the cell encapsulation. The dose and flux analysis identifies the significance of IR relative to UV exposure for CPV systems. Because UV light is typically more highly attenuated, the UV dose within the encapsulation may not greatly exceed the unconcentrated global solar condition, but the thermal load scales nearly directly with the geometric concentration. Relative to a previous analysis for crystalline silicon cell technology, the analysis here is performed for III-V multijunction technology. Novel aspects here also include additional materials (such as TPU encapsulation) and additional components (transmission through silicone on glass lenses, antireflective coatings, and the front glass used with reflective systems, as well as reflection off of the cell).

  9. Evaluation and analysis of the residual radioactivity for the 15UD Pelletron accelerator facility

    SciTech Connect

    Sonkawade, R. G.

    2007-07-01

    For the assessment of radiological impact of the accelerators, it will be better to have the documented information on activation of metal parts of the accelerator components. It is very much essential to get reliable data on these subjects. During acceleration of light ion, the residual radioactivity in the accelerator facility was found near the Analyzing Magnet, single slit, Beam Profile Monitors (BPM), Faraday Cups (FC), bellows, beginning of switching magnet bellows, at the target and the ladder. Study with HPGE detector gives an insight of the formation of the short or long lived radionuclides. The different targets used in the light ion experiment were also monitored and proper decommissioning and decontamination steps were followed. This paper presents the data of residual radioactivity in the 15UD Pelletron accelerator infrastructure. (author)

  10. Numerical Analysis of MHD Accelerator with Non-Equilibrium Air Plasma

    NASA Astrophysics Data System (ADS)

    Anwari, M.; H. Qazi, H.; Sukarsan; Harada, N.

    2012-12-01

    Magnetohydrodynamic (MHD) accelerator is proposed as a next generation propulsion system. It can be used to increase the performance of a propulsion system. The objective of this study is to investigate the performance of MHD accelerator using non-equilibrium air plasma as working gas. In this study, the fundamental performance of MHD accelerator such as flow performance and electrical performance is evaluated at different levels of applied magnetic field using 1-D numerical simulation. The numerical simulation is developed based on a set of differential equations with MHD approximation. To solve this set of differential equations the MacCormack scheme is used. A specified channel designed and developed at NASA Marshall Space Flight Centre is used in the numerical simulation. The composition of the simulated air plasma consists of seven species, namely, N2, N, O2, O, NO, NO+, and e-. The performance of the non-equilibrium MHD accelerator is also compared with the equilibrium MHD accelerator.

  11. Masking Epistasis Between MYC and TGF-β Pathways in Antiangiogenesis-Mediated Colon Cancer Suppression

    PubMed Central

    2014-01-01

    Background The c-Myc oncoprotein is activated in the majority of colorectal cancers (CRCs), whereas the TGF-β pathway is frequently affected by loss-of-function mutations, for example in SMAD2/3/4 genes. The canonical model places Myc downstream of inhibitory TGF-β signaling. However, we previously demonstrated that Myc also inhibits TGF-β signaling through the miR-17~92 microRNA cluster, raising the question about functional relationships between these two pathways. Methods We engineered a series of genetically complex murine and human CRC cell lines in which Myc and TGF-β activities could be manipulated simultaneously. This was achieved through retroviral expression of the Myc–estrogen receptor fusion protein and through Smad4 short hairpin RNA knockdown. Cell lines thus modified were injected subcutaneously in immunocompromised mice, and the resultant tumors (n = 5–10 per treatment group) were analyzed for overall growth and neovascularization. Additionally, the distribution of MYC and TGF-β pathway mutations was analyzed in previously profiled human CRC samples. Results In kras-mutated/trp53-deleted murine colonocytes, either Myc activation or TGF-β inactivation increased tumor sizes and microvascular densities approximately 1.5- to 2.5-fold, chiefly through downregulation of thrombospondin-1 and related type I repeat–containing proteins. Combining Myc activation with TGF-β inactivation did not further accelerate tumorigenesis. This redundancy and the negative effect of TGF-β signaling on angiogenesis were also demonstrated using xenografts of human CRC cell lines. Furthermore, the analysis of the Cancer Genome Atlas data revealed that in CRC without microsatellite instability, overexpression of Myc and inactivation of Smads (including acquired mutations in SMAD2) are mutually exclusive, with odds ratio less than 0.1. Conclusions In human CRC, gain-of-function alterations in Myc and loss-of-function alterations in TGF-β exhibit a masking

  12. Large scale neural circuit mapping data analysis accelerated with the graphical processing unit (GPU)

    PubMed Central

    Shi, Yulin; Veidenbaum, Alexander V.; Nicolau, Alex; Xu, Xiangmin

    2014-01-01

    Background Modern neuroscience research demands computing power. Neural circuit mapping studies such as those using laser scanning photostimulation (LSPS) produce large amounts of data and require intensive computation for post-hoc processing and analysis. New Method Here we report on the design and implementation of a cost-effective desktop computer system for accelerated experimental data processing with recent GPU computing technology. A new version of Matlab software with GPU enabled functions is used to develop programs that run on Nvidia GPUs to harness their parallel computing power. Results We evaluated both the central processing unit (CPU) and GPU-enabled computational performance of our system in benchmark testing and practical applications. The experimental results show that the GPU-CPU co-processing of simulated data and actual LSPS experimental data clearly outperformed the multi-core CPU with up to a 22x speedup, depending on computational tasks. Further, we present a comparison of numerical accuracy between GPU and CPU computation to verify the precision of GPU computation. In addition, we show how GPUs can be effectively adapted to improve the performance of commercial image processing software such as Adobe Photoshop. Comparison with Existing Method(s) To our best knowledge, this is the first demonstration of GPU application in neural circuit mapping and electrophysiology-based data processing. Conclusions Together, GPU enabled computation enhances our ability to process large-scale data sets derived from neural circuit mapping studies, allowing for increased processing speeds while retaining data precision. PMID:25277633

  13. Sample distillation/graphitization system for carbon pool analysis by accelerator mass spectrometry (AMS)

    NASA Astrophysics Data System (ADS)

    Pohlman, J. W.; Knies, D. L.; Grabowski, K. S.; DeTurck, T. M.; Treacy, D. J.; Coffin, R. B.

    2000-10-01

    A facility at the Naval Research Laboratory (NRL), Washington, DC, has been developed to extract, trap, cryogenically distill and graphitize carbon from a suite of organic and inorganic carbon pools for analysis by accelerator mass spectrometry (AMS). The system was developed to investigate carbon pools associated with the formation and stability of methane hydrates. However, since the carbon compounds found in hydrate fields are ubiquitous in aquatic ecosystems, this apparatus is applicable to a number of oceanographic and environmental sample types. Targeted pools are dissolved methane, dissolved organic carbon (DOC), dissolved inorganic carbon (DIC), solid organic matrices (e.g., seston, tissue and sediments), biomarkers and short chained (C 1-C 5) hydrocarbons from methane hydrates. In most instances, the extraction, distillation and graphitization events are continuous within the system, thus, minimizing the possibility of fractionation or contamination during sample processing. A variety of methods are employed to extract carbon compounds and convert them to CO 2 for graphitization. Dissolved methane and DIC from the same sample are sparged and cryogenically separated before the methane is oxidized in a high temperature oxygen stream. DOC is oxidized to CO 2 by 1200 W ultraviolet photo-oxidation lamp, and solids oxidized in sealed, evacuated tubes. Hydrocarbons liberated from the disassociation of gas hydrates are cryogenically separated with a cryogenic temperature control unit, and biomarkers separated and concentrated by preparative capillary gas chromatography (PCGC). With this system, up to 20 samples, standards or blanks can be processed per day.

  14. Cost Based Failure Modes and Effects Analysis (FMEA) for Systems of Accelerator Magnets.

    SciTech Connect

    Spencer, Cherrill M

    2003-06-02

    The proposed Next Linear Collider (NLC) has a proposed 85% overall availability goal, the availability specifications for all its 7200 magnets and their 6167 power supplies are 97.5% each. Thus all of the electromagnets and their power supplies must be highly reliable or quickly repairable. Improved reliability or repairability comes at a higher cost. We have developed a set of analysis procedures for magnet designers to use as they decide how much effort to exert, i.e. how much money to spend, to improve the reliability of a particular style of magnet. We show these procedures being applied to a standard SLAC electromagnet design in order to make it reliable enough to meet the NLC availability specs. First, empirical data from SLAC's accelerator failure database plus design experience are used to calculate MTBF for failure modes identified through a FMEA. Availability for one particular magnet can be calculated. Next, labor and material costs to repair magnet failures are used in a Monte Carlo simulation to calculate the total cost of all failures over a 30-year lifetime. Opportunity costs are included. Engineers choose from amongst various designs by comparing lifecycle costs.

  15. [Preparation of Rubber Accelerator Tetramethyl Thiuram Monosulfide and Its Spectral Analysis].

    PubMed

    Wang, Zhen-xiang; Li, Hong-liang; Jia, Tai-xuan; Zhang, Nan; Jin, Xin

    2015-07-01

    In the study, rubber accelerator tetramethyl thiuram monosulfide (TMTM) was synthesized firstly. Single crystal TMTM was cultivated by solvent evaporation method. TMTM was detected and characterized by XRD single crystal diffraction, FTIR, TG-DSC. The micro-structure and intrinsic regularity were revealed. The TMTM microstructure was revealed by XRD single crystal diffraction from the diffraction data, part of bond length and bond angle. Its highly efficient performance of rubber vulcanization promotion was decided due to its orientation structure and high order. Properties of TMTM was disclosed by TG-DSC analysis from the heat effect. The results of TG-DSC and FTIR showed that single crystal TMTM possessed with little CS2. The chemical bond types in TMTM were revealed by FTIR the same as single crystal diffraction testing by different way. The decomposition temperature of TMTM was very high. It could provided reference with research on rubber vulcanizing properties by TMTM on rubber vulcanizing machine. This study can help the enterprises to designate the working standard tracing detection of TMTM industrialized production. Performance index of TMTM was judged. The project of TMTM industry standard can be declared by the enterprises, written a draft standard. It can provide the basis experimental data on completing the revision of the national ministry of industry and information technology standard system project plan. PMID:26717743

  16. Dosimetric characterization of the irradiation cavity for accelerator-based in vivo neutron activation analysis.

    PubMed

    Byun, S H; Pejović-Milić, A; McMaster, S; Matysiak, W; Aslam; Liu, Z; Watters, L M; Prestwich, W V; McNeill, F E; Chettle, D R

    2007-03-21

    A neutron irradiation cavity for in vivo activation analysis has been characterized to estimate its dosimetric specifications. The cavity is defined to confine irradiation to the hand and modifies the neutron spectrum produced by a low energy accelerator neutron source to optimize activation per dose. Neutron and gamma-ray dose rates were measured with the microdosimetric technique using a tissue-equivalent proportional counter at the hand irradiation site and inside the hand access hole. For the outside of the cavity, a spherical neutron dose equivalent meter and a Farmer dosemeter were employed instead due to the low intensity of the radiation field. The maximum dose equivalent rate at the outside of the cavity was 2.94 microSv/100 microA min, which is lower by a factor of 1/2260 than the dose rate at the hand irradiation position. The local dose contributions from a hand, an arm and the rest of a body to the effective dose rate were estimated to be 1.73, 0.782 and 2.94 microSv/100 microA min, respectively. For the standard irradiation protocol of the in vivo hand activation, 300 microA min, an effective dose of 16.3 microSv would be delivered. PMID:17455391

  17. Lorentz force detuning analysis of the Spallation Neutron Source (SNS) accelerating cavities.

    SciTech Connect

    Mitchell, R.R.; Matsumoto, K. Y.; Ciovati, G.; Davis, K.; Macha, K.; Sundelin, R. M.

    2001-01-01

    The Spallation Neutron Source (SNS) project incorporates a superconducting radio-frequency (SRF) accelerator for the final section of the pulsed mode linac. Cavities with geometrical {beta} values of {beta}=0.61 and {beta}=0.81 are utilized in the SRF section, and are constructed out of thin-walled niobium with stiffener rings welded between the cells near the iris. The welded titanium helium vessel and tuner assembly restrains the cavity beam tubes. Cavities with {beta} values less than one have relatively steep and flat side-walls making the cavities susceptible to Lorentz force detuning. In addition, the pulsed RF induces cyclic Lorentz pressures that mechanically excite the cavities, producing a dynamic Lorentz force detuning different from a continuous RF system. The amplitude of the dynamic detuning for a given cavity design is a function of the mechanical damping, stiffness of the tuner/helium vessel assembly, RF pulse profile, and the RF pulse rate. This paper presents analysis and testing results to date, and indicates areas where more investigation is required.

  18. Accelerator-based trace element analysis of foods and agriculture products

    NASA Astrophysics Data System (ADS)

    Lagunas-Solar, Manuel C.; Piña U, Cecilia; Solís, Corina; Mireles, Alibech

    2008-05-01

    An accelerator-based analytical method for measuring trace elements in foods and agricultural products was developed, optimized, validated and compared using reference standards. The method's initial phase is a new, rapid and effective digestion process of a small mass analyte in an aqueous media containing H2O2. Digestion is initiated by radicals formed in water with pulsed UV (PUV) induced (laser) photolysis, which rapidly react with organic matter. After digestion, trace metals are pre-concentrated as carbamates and deposited as thin targets onto Teflon filters. Conventional particle induced X-ray emission (PIXE) or X-ray fluorescence (XRF) methods are then used to analyze elements in the sample. When foods and other agricultural commodities (i.e., soils, feeds) are analyzed, the combined method named pulsed UV (PUV)/PIXE results in enhanced detection of trace elements such as Fe, Co, Ni, Cu, Zn and Pb at ∼1 mg/kg (1 ppm) levels, without lengthy, acid-based digestions. It provides improvements in digestion kinetics and processing time enhancing analytical sensitivity and element recovery. Precision and recovery yields were confirmed with food reference standards. The analysis of edible foods from contaminated agricultural areas is also reported.

  19. Linear Accelerators

    SciTech Connect

    Sidorin, Anatoly

    2010-01-05

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  20. Linear Accelerators

    NASA Astrophysics Data System (ADS)

    Sidorin, Anatoly

    2010-01-01

    In linear accelerators the particles are accelerated by either electrostatic fields or oscillating Radio Frequency (RF) fields. Accordingly the linear accelerators are divided in three large groups: electrostatic, induction and RF accelerators. Overview of the different types of accelerators is given. Stability of longitudinal and transverse motion in the RF linear accelerators is briefly discussed. The methods of beam focusing in linacs are described.

  1. Molecular and functional analysis of mouse decay accelerating factor (CD55).

    PubMed Central

    Harris, C L; Rushmere, N K; Morgan, B P

    1999-01-01

    Molecular cloning of mouse decay accelerating factor (DAF; CD55) predicted two forms of the molecule, one transmembrane (TM) and the other glycosylphosphatidylinositol (GPI)-anchored; these are encoded by separate genes termed Daf-GPI and Daf-TM. In the present study several additional isoforms of mouse DAF, generated by alternative splicing from these genes, are described. Northern-blot analysis of RNA and reverse transcriptase-PCR from various tissues indicated that spleen and testis expressed high levels of DAF, which comprised several species. These species were cloned and sequence analysis revealed various novel forms in addition to those previously reported. Two novel forms were derived from the Daf-TM gene but the transmembrane sequence defined previously was replaced by a unique GPI-anchor addition sequence; one clone also had part of the serine/threonine/proline (STP) region deleted. A third clone, encoding a transmembrane protein, was also derived from this gene but the entire STP region was deleted. A fourth clone, derived from the Daf-GPI gene, contained a novel C-terminal sequence, suggestive of a secreted form of the protein. Two DAF cDNAs (TM and GPI-anchored) were stably expressed in Chinese hamster ovary cells. When these cells were attacked with mouse or rat complement and analysed for C3b deposition, DAF-transfected cells had greatly reduced C3b deposition compared with controls. Transfection with DAF also conferred protection from complement in a cell-lysis assay, and a soluble, recombinant form of mouse DAF inhibited complement in a haemolytic assay. PMID:10417349

  2. Analysis and design of nonlocal spin devices with electric-field-induced spin-transport acceleration

    SciTech Connect

    Takamura, Yota; Akushichi, Taiju; Shuto, Yusuke; Sugahara, Satoshi

    2015-05-07

    We apply electric-field-induced acceleration for spin transport to a four-terminal nonlocal device and theoretically analyze its Hanle-effect signals. The effect of the ferromagnetic contact widths of the spin injector and detector on the signals is carefully discussed. Although Hanle-effect signals are randomized owing to the effect of the contact widths, this can be excluded by selecting an appropriate electric field for acceleration of spin transport. Spin lifetime can be correctly extracted by nonlocal devices with electric-field acceleration even using the spin injector and detector with finite contact widths.

  3. Accelerated leukocyte telomere erosion in schizophrenia: Evidence from the present study and a meta-analysis.

    PubMed

    Rao, Shuquan; Kota, Lakshmi Narayanan; Li, Zongchang; Yao, Yao; Tang, Jinsong; Mao, Canquan; Jain, Sanjeev; Xu, Yong; Xu, Qi

    2016-08-01

    Human telomeres consist of tandem nucleotide repeats (TTAGGG) and associated proteins, and telomere length (TL) is reduced progressively with cell division over the lifespan. Telomere erosion might be accelerated or prevented to varying degrees when exposure to serious medical illnesses. In previous studies, an association between TL decrease and schizophrenia has been extensively reported; however, the results remain largely controversial. To further investigate TL in schizophrenia patients and reconcile this controversy, we first measured leucocyte TL (LTL) in our samples (52 paranoid schizophrenia, 89 non-paranoid patients and 120 controls), and then conducted a comprehensive meta-analysis of the existing results of LTL in patients of schizophrenia compared to healthy subjects. Totally, 11 studies encompassing 1243 patients of schizophrenia and 1274 controls were included in the final meta-analysis model. In our samples, significant reduction of LTL in paranoid schizophrenia was observed compared to controls (F = 50.88, P < 0.001); whereas there was no significant difference in LTL between non-paranoid schizophrenia and controls (F = 0.842, P = 0.360). For meta-analysis, random-effects model showed significant LTL decrease in patients of schizophrenia when compared to controls (Z = 2.07, P = 0.039, SMD = -0.48, 95% CI = -0.94 to -0.03). Moreover, a marginal decrease in LTL was observed in medicated patients (Z = 1.92, P = 0.055, SMD = -0.58, 95% CI = -1.18-0.01) and those patients with poor response to antipsychotics (Z = 1.76, P = 0.078, SMD = -0.60, 95% CI = -1.27-0.07). In conclusion, we observed significant reduction of LTL in individuals with schizophrenia compared with controls. However, all the studies included in the meta-analysis were cross-sectional, and better controlled long-term studies are needed to replicate this result. PMID:27174400

  4. Analysis of Transmitted Optical Spectrum Enabling Accelerated Testing of CPV Designs: Preprint

    SciTech Connect

    Miller, D. C.; Kempe, M. D.; Kennedy, C. E.; Kurtz, S. R.

    2009-07-01

    Reliability of CPV systems' materials is not well known; methods for accelerated UV testing have not been developed. UV and IR spectra transmitted through representative optical systems are evaluated.

  5. Extending PowerPack for Profiling and Analysis of High Performance Accelerator-Based Systems

    SciTech Connect

    Li, Bo; Chang, Hung-Ching; Song, Shuaiwen; Su, Chun-Yi; Meyer, Timmy; Mooring, John; Cameron, Kirk

    2014-12-01

    Accelerators offer a substantial increase in efficiency for high-performance systems offering speedups for computational applications that leverage hardware support for highly-parallel codes. However, the power use of some accelerators exceeds 200 watts at idle which means use at exascale comes at a significant increase in power at a time when we face a power ceiling of about 20 megawatts. Despite the growing domination of accelerator-based systems in the Top500 and Green500 lists of fastest and most efficient supercomputers, there are few detailed studies comparing the power and energy use of common accelerators. In this work, we conduct detailed experimental studies of the power usage and distribution of Xeon-Phi-based systems in comparison to the NVIDIA Tesla and at SandyBridge.

  6. Analysis of the behavior of a discharge in a coaxial plasma jet accelerator

    NASA Astrophysics Data System (ADS)

    Voronin, A. V.; Gusev, V. K.; Gerasimenko, Ya. A.

    2013-03-01

    We analyze the behavior of the discharge in a coaxial plasma jet accelerator with a pulsed supply of the working gas released by an electric discharge from titanium hydride powder. Radiation (varying with time) from the discharge in the accelerator was detected using an optical method through a narrow slit cut along the outer electrode by a Bifo Company K008 streak camera. Stable operation of the source with the highest kinetic energy of a pure hydrogen plasma jet was attained for a relatively uniform glow of the discharge along the accelerator during the entire current pulse. Conversely, local glow of the discharge at the outlet or inlet of the accelerator considerably contaminated the discharge with impurities, and the kinetic energy of the plasma jet decreased by an order of magnitude. The highest energy of the plasma jet was attained when the polarity of the electrodes was the same as at the plasma focus.

  7. Three-dimensional simulation analysis of the standing-wave free- electron laser two beam accelerator

    SciTech Connect

    Wang, C.; Sessler, A.

    1993-01-01

    We have modified a two-dimensional relativistic klystron code, developed by Ryne and Yu, to simulate both the standing-wave free- electron laser two-beam accelerator and the relativistic klystron two- beam accelerator. In this paper, the code is used to study a standing-wave free-electron laser with three cavities. The effect of the radius of the electron beam on the RF output power; namely, a three-dimensional effect is examined.

  8. Sensitivity analysis of an asymmetric Monte Carlo beam model of a Siemens Primus accelerator.

    PubMed

    Schreiber, Eric C; Sawkey, Daren L; Faddegon, Bruce A

    2012-01-01

    The assumption of cylindrical symmetry in radiotherapy accelerator models can pose a challenge for precise Monte Carlo modeling. This assumption makes it difficult to account for measured asymmetries in clinical dose distributions. We have performed a sensitivity study examining the effect of varying symmetric and asymmetric beam and geometric parameters of a Monte Carlo model for a Siemens PRIMUS accelerator. The accelerator and dose output were simulated using modified versions of BEAMnrc and DOSXYZnrc that allow lateral offsets of accelerator components and lateral and angular offsets for the incident electron beam. Dose distributions were studied for 40 × 40 cm² fields. The resulting dose distributions were analyzed for changes in flatness, symmetry, and off-axis ratio (OAR). The electron beam parameters having the greatest effect on the resulting dose distributions were found to be electron energy and angle of incidence, as high as 5% for a 0.25° deflection. Electron spot size and lateral offset of the electron beam were found to have a smaller impact. Variations in photon target thickness were found to have a small effect. Small lateral offsets of the flattening filter caused significant variation to the OAR. In general, the greatest sensitivity to accelerator parameters could be observed for higher energies and off-axis ratios closer to the central axis. Lateral and angular offsets of beam and accelerator components have strong effects on dose distributions, and should be included in any high-accuracy beam model. PMID:22402376

  9. Evidence of statistical epistasis between DISC1, CIT and NDEL1 impacting risk for schizophrenia: biological validation with functional neuroimaging.

    PubMed

    Nicodemus, Kristin K; Callicott, Joseph H; Higier, Rachel G; Luna, Augustin; Nixon, Devon C; Lipska, Barbara K; Vakkalanka, Radhakrishna; Giegling, Ina; Rujescu, Dan; St Clair, David; Muglia, Pierandrea; Shugart, Yin Yao; Weinberger, Daniel R

    2010-04-01

    The etiology of schizophrenia likely involves genetic interactions. DISC1, a promising candidate susceptibility gene, encodes a protein which interacts with many other proteins, including CIT, NDEL1, NDE1, FEZ1 and PAFAH1B1, some of which also have been associated with psychosis. We tested for epistasis between these genes in a schizophrenia case-control study using machine learning algorithms (MLAs: random forest, generalized boosted regression andMonteCarlo logic regression). Convergence of MLAs revealed a subset of seven SNPs that were subjected to 2-SNP interaction modeling using likelihood ratio tests for nested unconditional logistic regression models. Of the 7C2 = 21 interactions, four were significant at the α = 0.05 level: DISC1 rs1411771-CIT rs10744743 OR = 3.07 (1.37, 6.98) p = 0.007; CIT rs3847960-CIT rs203332 OR = 2.90 (1.45, 5.79) p = 0.003; CIT rs3847960-CIT rs440299 OR = 2.16 (1.04, 4.46) p = 0.038; one survived Bonferroni correction (NDEL1 rs4791707-CIT rs10744743 OR = 4.44 (2.22, 8.88) p = 0.00013). Three of four interactions were validated via functional magnetic resonance imaging (fMRI) in an independent sample of healthy controls; risk associated alleles at both SNPs predicted prefrontal cortical inefficiency during the N-back task, a schizophrenia-linked intermediate biological phenotype: rs3847960-rs440299; rs1411771-rs10744743, rs4791707-rs10744743 (SPM5 p < 0.05, corrected), although we were unable to statistically replicate the interactions in other clinical samples. Interestingly, the CIT SNPs are proximal to exons that encode theDISC1 interaction domain. In addition, the 3' UTR DISC1 rs1411771 is predicted to be an exonic splicing enhancer and the NDEL1 SNP is ~3,000 bp from the exon encoding the region of NDEL1 that interacts with the DISC1 protein, giving a plausible biological basis for epistasis signals validated by fMRI. PMID:20084519

  10. A Tandem Repeat in Decay Accelerating Factor 1 Is Associated with Severity of Murine Mercury-Induced Autoimmunity

    PubMed Central

    Gabriel, Rodney; Kono, Dwight H.; Hultman, Per; Pollard, K. Michael

    2014-01-01

    Decay accelerating factor (DAF), a complement-regulatory protein, protects cells from bystander complement-mediated lysis and negatively regulates T cells. Reduced expression of DAF occurs in several systemic autoimmune diseases including systemic lupus erythematosus, and DAF deficiency exacerbates disease in several autoimmune models, including murine mercury-induced autoimmunity (mHgIA). Daf1, located within Hmr1, a chromosome 1 locus associated in DBA/2 mice with resistance to mHgIA, could be a candidate. Here we show that reduced Daf1 transcription in lupus-prone mice was not associated with a reduction in the Daf1 transcription factor SP1. Studies of NZB mice congenic for the mHgIA-resistant DBA/2 Hmr1 locus suggested that Daf1 expression was controlled by the host genome and not the Hmr1 locus. A unique pentanucleotide repeat variant in the second intron of Daf1 in DBA/2 mice was identified and shown in F2 intercrosses to be associated with less severe disease; however, analysis of Hmr1 congenics indicated that this most likely reflected the presence of autoimmunity-predisposing genetic variants within the Hmr1 locus or that Daf1 expression is mediated by the tandem repeat in epistasis with other genetic variants present in autoimmune-prone mice. These studies argue that the effect of DAF on autoimmunity is complex and may require multiple genetic elements. PMID:24818014