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Sample records for accelerating epistasis analysis

  1. Accelerating epistasis analysis in human genetics with consumer graphics hardware

    PubMed Central

    2009-01-01

    Background Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR) is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs) have more memory bandwidth and computational capability than Central Processing Units (CPUs) and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. Findings We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective performance while leaving the CPU

  2. Accelerating epistasis analysis in human genetics with consumer graphics hardware.

    PubMed

    Sinnott-Armstrong, Nicholas A; Greene, Casey S; Cancare, Fabio; Moore, Jason H

    2009-07-24

    Human geneticists are now capable of measuring more than one million DNA sequence variations from across the human genome. The new challenge is to develop computationally feasible methods capable of analyzing these data for associations with common human disease, particularly in the context of epistasis. Epistasis describes the situation where multiple genes interact in a complex non-linear manner to determine an individual's disease risk and is thought to be ubiquitous for common diseases. Multifactor Dimensionality Reduction (MDR) is an algorithm capable of detecting epistasis. An exhaustive analysis with MDR is often computationally expensive, particularly for high order interactions. This challenge has previously been met with parallel computation and expensive hardware. The option we examine here exploits commodity hardware designed for computer graphics. In modern computers Graphics Processing Units (GPUs) have more memory bandwidth and computational capability than Central Processing Units (CPUs) and are well suited to this problem. Advances in the video game industry have led to an economy of scale creating a situation where these powerful components are readily available at very low cost. Here we implement and evaluate the performance of the MDR algorithm on GPUs. Of primary interest are the time required for an epistasis analysis and the price to performance ratio of available solutions. We found that using MDR on GPUs consistently increased performance per machine over both a feature rich Java software package and a C++ cluster implementation. The performance of a GPU workstation running a GPU implementation reduces computation time by a factor of 160 compared to an 8-core workstation running the Java implementation on CPUs. This GPU workstation performs similarly to 150 cores running an optimized C++ implementation on a Beowulf cluster. Furthermore this GPU system provides extremely cost effective performance while leaving the CPU available for other

  3. Dynamics in Epistasis Analysis.

    PubMed

    Awdeh, Aseel; Phenix, Hilary; Kaern, Mads; Perkins, Theodore

    2017-01-16

    Finding regulatory relationships between genes, including the direction and nature of influence between them, is a fundamental challenge in the field of molecular genetics. One classical approach to this problem is epistasis analysis. Broadly speaking, epistasis analysis infers the regulatory relationships between a pair of genes in a genetic pathway by considering the patterns of change in an observable trait resulting from single and double deletion of genes. While classical epistasis analysis has yielded deep insights on numerous genetic pathways, it is not without limitations. Here, we explore the possibility of dynamic epistasis analysis, in which, in addition to performing genetic perturbations of a pathway, we drive the pathway by a time-varying upstream signal. We explore the theoretical power of dynamical epistasis analysis by conducting an identifiability analysis of Boolean models of genetic pathways, comparing static and dynamic approaches. We find that even relatively simple input dynamics greatly increases the power of epistasis analysis to discriminate alternative network structures. Further, we explore the question of experiment design, and show that a subset of short time-varying signals, which we call dynamic primitives, allow maximum discriminative power with a reduced number of experiments.

  4. Reconstructability analysis of epistasis.

    PubMed

    Zwick, Martin

    2011-01-01

    The literature on epistasis describes various methods to detect epistatic interactions and to classify different types of epistasis. Reconstructability analysis (RA) has recently been used to detect epistasis in genomic data. This paper shows that RA offers a classification of types of epistasis at three levels of resolution (variable-based models without loops, variable-based models with loops, state-based models). These types can be defined by the simplest RA structures that model the data without information loss; a more detailed classification can be defined by the information content of multiple candidate structures. The RA classification can be augmented with structures from related graphical modeling approaches. RA can analyze epistatic interactions involving an arbitrary number of genes or SNPs and constitutes a flexible and effective methodology for genomic analysis.

  5. Epistasis analysis using information theory.

    PubMed

    Moore, Jason H; Hu, Ting

    2015-01-01

    Here we introduce entropy-based measures derived from information theory for detecting and characterizing epistasis in genetic association studies. We provide a general overview of the methods and highlight some of the modifications that have greatly improved its power for genetic analysis. We end with a few published studies of complex human diseases that have used these measures.

  6. Epistasis can accelerate adaptive diversification in haploid asexual populations.

    PubMed

    Griswold, Cortland K

    2015-03-07

    A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification.

  7. 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.

  8. 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

  9. 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.

  10. Epistasis analysis using multifactor dimensionality reduction.

    PubMed

    Moore, Jason H; Andrews, Peter C

    2015-01-01

    Here we introduce the multifactor dimensionality reduction (MDR) methodology and software package for detecting and characterizing epistasis in genetic association studies. We provide a general overview of the method and then highlight some of the key functions of the open-source MDR software package that is freely distributed. We end with a few examples of published studies of complex human diseases that have used MDR.

  11. A fast and exhaustive method for heterogeneity and epistasis analysis based on multi-objective optimization.

    PubMed

    Li, Xiong

    2017-09-15

    The existing epistasis analysis approaches have been criticized mainly for their: (i) ignoring heterogeneity during epistasis analysis; (ii) high computational costs; and (iii) volatility of performances and results. Therefore, they will not perform well in general, leading to lack of reproducibility and low power in complex disease association studies. In this work, a fast scheme is proposed to accelerate exhaustive searching based on multi-objective optimization named ESMO for concurrently analyzing heterogeneity and epistasis phenomena. In ESMO, mutual entropy and Bayesian network approaches are combined for evaluating epistatic SNP combinations. In order to be compatible with heterogeneity of complex diseases, we designed an adaptive framework based on non-dominant sort and top k selection algorithm with improved time complexity O(k*M*N) . Moreover, ESMO is accelerated by strategies such as trading space for time, calculation sharing and parallel computing. Finally, ESMO is nonparametric and model-free. We compared ESMO with other recent or classic methods using different evaluating measures. The experimental results show that our method not only can quickly handle epistasis, but also can effectively detect heterogeneity of complex population structures. https://github.com/XiongLi2016/ESMO/tree/master/ESMO-common-master . lx_hncs@163.com.

  12. A strategy to apply quantitative epistasis analysis on developmental traits.

    PubMed

    Labocha, Marta K; Yuan, Wang; Aleman-Meza, Boanerges; Zhong, Weiwei

    2017-05-15

    Genetic interactions are keys to understand complex traits and evolution. Epistasis analysis is an effective method to map genetic interactions. Large-scale quantitative epistasis analysis has been well established for single cells. However, there is a substantial lack of such studies in multicellular organisms and their complex phenotypes such as development. Here we present a method to extend quantitative epistasis analysis to developmental traits. In the nematode Caenorhabditis elegans, we applied RNA interference on mutants to inactivate two genes, used an imaging system to quantitatively measure phenotypes, and developed a set of statistical methods to extract genetic interactions from phenotypic measurement. Using two different C. elegans developmental phenotypes, body length and sex ratio, as examples, we showed that this method could accommodate various metazoan phenotypes with performances comparable to those methods in single cell growth studies. Comparing with qualitative observations, this method of quantitative epistasis enabled detection of new interactions involving subtle phenotypes. For example, several sex-ratio genes were found to interact with brc-1 and brd-1, the orthologs of the human breast cancer genes BRCA1 and BARD1, respectively. We confirmed the brc-1 interactions with the following genes in DNA damage response: C34F6.1, him-3 (ortholog of HORMAD1, HORMAD2), sdc-1, and set-2 (ortholog of SETD1A, SETD1B, KMT2C, KMT2D), validating the effectiveness of our method in detecting genetic interactions. We developed a reliable, high-throughput method for quantitative epistasis analysis of developmental phenotypes.

  13. 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.

  14. Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast

    PubMed Central

    Jasmin, Jean-Nicolas; Lenormand, Thomas

    2016-01-01

    Much of our knowledge about the fitness effects of new mutations has been gained from mutation accumulation (MA) experiments. Yet the fitness effect of single mutations is rarely measured in MA experiments. This raises several issues, notably for inferring epistasis for fitness. The acceleration of fitness decline in MA lines has been taken as evidence for synergistic epistasis, but establishing the role of epistasis requires measuring the fitness of genotypes carrying known numbers of mutations. Otherwise, accelerating fitness loss could be explained by increased genetic mutation rates. Here we segregated mutations accumulated over 4800 generations in haploid and diploid MA lines of the yeast Saccharomyces cerevisiae. We found no correspondence between an accelerated fitness decline and synergistic epistasis among deleterious mutations in haploid lines. Pairs of mutations showed no overall epistasis. Furthermore, several lines of evidence indicate that genetic mutation rates did not increase in the MA lines. Crucially, segregant fitness analyses revealed that MA accelerated in both haploid and diploid lines, even though the fitness of diploid lines was nearly constant during the MA experiment. This suggests that the accelerated fitness decline in haploids was caused by cryptic environmental factors that increased mutation rates in all lines during the last third of the lines’ transfers. In addition, we provide new estimates of deleterious mutation rates, including lethal mutations, and highlight that nearly all the mutational load we observed was due to one or two mutations having a large effect on fitness. PMID:26596348

  15. Accelerating Mutational Load Is Not Due to Synergistic Epistasis or Mutator Alleles in Mutation Accumulation Lines of Yeast.

    PubMed

    Jasmin, Jean-Nicolas; Lenormand, Thomas

    2016-02-01

    Much of our knowledge about the fitness effects of new mutations has been gained from mutation accumulation (MA) experiments. Yet the fitness effect of single mutations is rarely measured in MA experiments. This raises several issues, notably for inferring epistasis for fitness. The acceleration of fitness decline in MA lines has been taken as evidence for synergistic epistasis, but establishing the role of epistasis requires measuring the fitness of genotypes carrying known numbers of mutations. Otherwise, accelerating fitness loss could be explained by increased genetic mutation rates. Here we segregated mutations accumulated over 4800 generations in haploid and diploid MA lines of the yeast Saccharomyces cerevisiae. We found no correspondence between an accelerated fitness decline and synergistic epistasis among deleterious mutations in haploid lines. Pairs of mutations showed no overall epistasis. Furthermore, several lines of evidence indicate that genetic mutation rates did not increase in the MA lines. Crucially, segregant fitness analyses revealed that MA accelerated in both haploid and diploid lines, even though the fitness of diploid lines was nearly constant during the MA experiment. This suggests that the accelerated fitness decline in haploids was caused by cryptic environmental factors that increased mutation rates in all lines during the last third of the lines' transfers. In addition, we provide new estimates of deleterious mutation rates, including lethal mutations, and highlight that nearly all the mutational load we observed was due to one or two mutations having a large effect on fitness. Copyright © 2016 by the Genetics Society of America.

  16. 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

  17. Epistasis in monkeyflowers.

    PubMed

    Kelly, John K

    2005-12-01

    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.

  18. Functional regression method for whole genome eQTL epistasis analysis with sequencing data.

    PubMed

    Xu, Kelin; Jin, Li; Xiong, Momiao

    2017-05-18

    Epistasis plays an essential rule in understanding the regulation mechanisms and is an essential component of the genetic architecture of the gene expressions. However, interaction analysis of gene expressions remains fundamentally unexplored due to great computational challenges and data availability. Due to variation in splicing, transcription start sites, polyadenylation sites, post-transcriptional RNA editing across the entire gene, and transcription rates of the cells, RNA-seq measurements generate large expression variability and collectively create the observed position level read count curves. A single number for measuring gene expression which is widely used for microarray measured gene expression analysis is highly unlikely to sufficiently account for large expression variation across the gene. Simultaneously analyzing epistatic architecture using the RNA-seq and whole genome sequencing (WGS) data poses enormous challenges. We develop a nonlinear functional regression model (FRGM) with functional responses where the position-level read counts within a gene are taken as a function of genomic position, and functional predictors where genotype profiles are viewed as a function of genomic position, for epistasis analysis with RNA-seq data. Instead of testing the interaction of all possible pair-wises SNPs, the FRGM takes a gene as a basic unit for epistasis analysis, which tests for the interaction of all possible pairs of genes and use all the information that can be accessed to collectively test interaction between all possible pairs of SNPs within two genome regions. By large-scale simulations, we demonstrate that the proposed FRGM for epistasis analysis can achieve the correct type 1 error and has higher power to detect the interactions between genes than the existing methods. The proposed methods are applied to the RNA-seq and WGS data from the 1000 Genome Project. The numbers of pairs of significantly interacting genes after Bonferroni correction

  19. 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].

  20. 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

  1. Effect of varying epistasis on the evolution of recombination.

    PubMed

    Kouyos, Roger D; Otto, Sarah P; Bonhoeffer, Sebastian

    2006-06-01

    Whether recombination decelerates or accelerates a population's response to selection depends, at least in part, on how fitness-determining loci interact. Realistically, all genomes likely contain fitness interactions both with positive and with negative epistasis. Therefore, it is crucial to determine the conditions under which the potential beneficial effects of recombination with negative epistasis prevail over the detrimental effects of recombination with positive epistasis. Here, we examine the simultaneous effects of diverse epistatic interactions with different strengths and signs in a simplified model system with independent pairs of interacting loci and selection acting only on the haploid phase. We find that the average form of epistasis does not predict the average amount of linkage disequilibrium generated or the impact on a recombination modifier when compared to results using the entire distribution of epistatic effects and associated single-mutant effects. Moreover, we show that epistatic interactions of a given strength can produce very different effects, having the greatest impact when selection is weak. In summary, we observe that the evolution of recombination at mutation-selection balance might be driven by a small number of interactions with weak selection rather than by the average epistasis of all interactions. We illustrate this effect with an analysis of published data of Saccharomyces cerevisiae. Thus to draw conclusions on the evolution of recombination from experimental data, it is necessary to consider the distribution of epistatic interactions together with the associated selection coefficients.

  2. Dissection of complex gene expression using the combined analysis of pleiotropy and epistasis.

    PubMed

    Philip, Vivek M; Tyler, Anna L; Carter, Gregory W

    2014-01-01

    Global transcript expression experiments are commonly used to investigate the biological processes that underlie complex traits. These studies can exhibit complex patterns of pleiotropy when trans-acting genetic factors influence overlapping sets of multiple transcripts. Dissecting these patterns into biological modules with distinct genetic etiology can provide models of how genetic variants affect specific processes that contribute to a trait. Here we identify transcript modules associated with pleiotropic genetic factors and apply genetic interaction analysis to disentangle the regulatory architecture in a mouse intercross study of kidney function. The method, called the combined analysis of pleiotropy and epistasis (CAPE), has been previously used to model genetic networks for multiple physiological traits. It simultaneously models multiple phenotypes to identify direct genetic influences as well as influences mediated through genetic interactions. We first identify candidate trans expression quantitative trait loci (eQTL) and the transcripts potentially affected. We then clustered the transcripts into modules of co-expressed genes, from which we compute summary module phenotypes. Finally, we applied CAPE to map the network of interacting module QTL (modQTL) affecting the gene modules. The resulting network mapped how multiple modQTL both directly and indirectly affect modules associated with metabolic functions and biosynthetic processes. This work demonstrates how the integration of pleiotropic signals in gene expression data can be used to infer a complex hypothesis of how multiple loci interact to co-regulate transcription programs, thereby providing additional constraints to prioritize validation experiments.

  3. Dynamic QTL and epistasis analysis on seedling root traits in upland cotton.

    PubMed

    Liang, Qingzhi; Li, Pengbo; Hu, Cheng; Hua, Hua; Li, Zhaohu; Rong, Yihua; Wang, Kunbo; Hua, Jinping

    2014-04-01

    Roots are involved in acquisition of water and nutrients, as well as in providing structural support to plant. The root system provides a dynamic model for developmental analysis. Here, we investigated quantitative trait loci (QTL), dynamic conditional QTL and epistatic interactions for seedling root traits using an upland cotton F2 population and a constructed genetic map. Totally, 37 QTLs for root traits, 35 dynamic conditional QTLs based on the net increased amount of root traits (root tips, forks, length, surface area and volume) (i) after transplanting 10 days compared to 5 days, and (ii) after transplanting 15 days to 10 days were detected. Obvious dynamic characteristic of QTL and dynamic conditional QTL existed at different developmental stages of root because QTL and dynamic conditional QTL had not been detected simultaneously. We further confirmed that additive and dominance effects of QTL qRSA-chr1-1 in interval time 5 to 10 DAT (days after transplant) offset the effects in 10 to 15 DAT. Lots of two-locus interactions for root traits were identified unconditionally or dynamically, and a few epistatic interactions were only detected simultaneously in interval time of 5-10 DAT and 10-15 DAT, suggesting different interactive genetic mechanisms on root development at different stages. Dynamic conditional QTL and epistasis effects provide new attempts to understand the dynamics of roots and provide clues for root architecture selection in upland cotton.

  4. Optimizing Dietary Restriction for Genetic Epistasis Analysis and Gene Discovery in C. elegans

    PubMed Central

    Mair, William; Panowski, Siler H.; Shaw, Reuben J.; Dillin, Andrew

    2009-01-01

    Dietary restriction (DR) increases mammalian lifespan and decreases susceptibility to many age-related diseases. Lifespan extension due to DR is conserved across a wide range of species. Recent research has focused upon genetically tractable model organisms such as C. elegans to uncover the genetic mechanisms that regulate the response to DR, in the hope that this information will provide insight into the mammalian response and yield potential therapeutic targets. However, no consensus exists as to the best protocol to apply DR to C. elegans and potential key regulators of DR are protocol-specific. Here we define a DR method that better fulfills criteria required for an invertebrate DR protocol to mirror mammalian studies. The food intake that maximizes longevity varies for different genotypes and informative epistasis analysis with another intervention is only achievable at this ‘optimal DR’ level. Importantly therefore, the degree of restriction imposed using our method can easily be adjusted to determine the genotype-specific optimum DR level. We used this protocol to test two previously identified master regulators of DR in the worm. In contrast to previous reports, we find that DR can robustly extend the lifespan of worms lacking the AMP-activated protein kinase catalytic subunit AAK2 or the histone deacetylase SIR-2.1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity. PMID:19229346

  5. Genotype Correlation Analysis Reveals Pathway-Based Functional Disequilibrium and Potential Epistasis in the Human Interactome

    PubMed Central

    Bush, William S.; Haines, Jonathan L.

    2016-01-01

    Epistasis is thought to be a pervasive part of complex phenotypes due to the dynamics and complexity of biological systems, and a further understanding of epistasis in the context of biological pathways may provide insight into the etiology of complex disease. In this study, we use genotype data from the International HapMap Project to characterize the functional dependencies between alleles in the human interactome as defined by KEGG pathways. We performed chi-square tests to identify non-independence between functionally-related SNP pairs within parental Caucasian and Yoruba samples. We further refine this list by testing for skewed transmission of pseudo-haplotypes to offspring using a haplotype-based TDT test. From these analyses, we identify pathways enriched for functional disequilibrium, and a set of 863 SNP pairs (representing 453 gene pairs) showing consistent non-independence and transmission distortion. These results represent gene pairs with strong evidence of epistasis within the context of a biological function.

  6. Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis

    PubMed Central

    Pesonen, Maiju; Musser, James M.; Bentley, Stephen D.; Aurell, Erik; Corander, Jukka

    2017-01-01

    enhances the future potential of epistasis analysis for systems biology, and can complement genome-wide association studies as a means of formulating hypotheses for targeted experimental work. PMID:28207813

  7. Interacting networks of resistance, virulence and core machinery genes identified by genome-wide epistasis analysis.

    PubMed

    Skwark, Marcin J; Croucher, Nicholas J; Puranen, Santeri; Chewapreecha, Claire; Pesonen, Maiju; Xu, Ying Ying; Turner, Paul; Harris, Simon R; Beres, Stephen B; Musser, James M; Parkhill, Julian; Bentley, Stephen D; Aurell, Erik; Corander, Jukka

    2017-02-01

    enhances the future potential of epistasis analysis for systems biology, and can complement genome-wide association studies as a means of formulating hypotheses for targeted experimental work.

  8. Analysis of heterogeneity and epistasis in physiological mixed populations by combined structural equation modelling and latent class analysis

    PubMed Central

    Fenger, Mogens; Linneberg, Allan; Werge, Thomas; Jørgensen, Torben

    2008-01-01

    homogenous subpopulations and on inclusion of epistasis in the analysis, whereas epistasis (i.e. genetic networks) is ubiquitous and should be the basis in modelling any biological process. PMID:18611252

  9. The causes of epistasis.

    PubMed

    de Visser, J Arjan G M; Cooper, Tim F; Elena, Santiago F

    2011-12-22

    Since Bateson's discovery that genes can suppress the phenotypic effects of other genes, gene interactions-called epistasis-have been the topic of a vast research effort. Systems and developmental biologists study epistasis to understand the genotype-phenotype map, whereas evolutionary biologists recognize the fundamental importance of epistasis for evolution. Depending on its form, epistasis may lead to divergence and speciation, provide evolutionary benefits to sex and affect the robustness and evolvability of organisms. That epistasis can itself be shaped by evolution has only recently been realized. Here, we review the empirical pattern of epistasis, and some of the factors that may affect the form and extent of epistasis. Based on their divergent consequences, we distinguish between interactions with or without mean effect, and those affecting the magnitude of fitness effects or their sign. Empirical work has begun to quantify epistasis in multiple dimensions in the context of metabolic and fitness landscape models. We discuss possible proximate causes (such as protein function and metabolic networks) and ultimate factors (including mutation, recombination, and the importance of natural selection and genetic drift). We conclude that, in general, pleiotropy is an important prerequisite for epistasis, and that epistasis may evolve as an adaptive or intrinsic consequence of changes in genetic robustness and evolvability.

  10. Genetic analysis of an allergic rhinitis cohort reveals an intercellular epistasis between FAM134B and CD39

    PubMed Central

    2014-01-01

    Background Extracellular ATP is a pro-inflammatory molecule released by damaged cells. Regulatory T cells (Treg) can suppress inflammation by hydrolysing this molecule via ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1), also termed as CD39. Multiple studies have reported differences in CD39+ Treg percentages in diseases such as multiple sclerosis, Hepatitis B and HIV-1. In addition, CD39 polymorphisms have been implicated in immune-phenotypes such as susceptibility to inflammatory bowel disease and AIDS progression. However none of the studies published so far has linked disease-associated variants with differences in CD39 Treg surface expression. This study aims at identifying variants affecting CD39 expression on Treg and at evaluating their association with allergic rhinitis, a disease characterized by a strong Treg involvement. Methods Cohorts consisting of individuals of different ethnicities were employed to identify any association of CD39 variants to surface expression. Significant variant(s) were tested for disease association in a published GWAS cohort by one-locus and two-locus genetic analyses based on logistic models. Further functional characterization was performed using existing microarray data and quantitative RT-PCR on sorted cells. Results Our study shows that rs7071836, a promoter SNP in the CD39 gene region, affects the cell surface expression on Treg cells but not on other CD39+ leukocyte subsets. Epistasis analysis revealed that, in conjunction with a SNP upstream of the FAM134B gene (rs257174), it increased the risk of allergic rhinitis (P = 1.98 × 10-6). As a promoter SNP, rs257174 controlled the expression of the gene in monocytes but, notably, not in Treg cells. Whole blood transcriptome data of three large cohorts indicated an inverse relation in the expression of the two proteins. While this observation was in line with the epistasis data, it also implied that a functional link must exist. Exposure of monocytes to

  11. Bayesian analysis of additive epistasis arising from new mutations in mice.

    PubMed

    Casellas, Joaquim; Gianola, Daniel; Medrano, Juan F

    2014-08-13

    The continuous uploading of polygenic additive mutational variability has been reported in several studies in laboratory species with an inbred genetic background. These studies have focused on the direct contribution of new mutations without considering the possibility of epistatic effects derived from the interaction of new mutations with pre-existing polymorphisms. In this work we focused on this main topic and analysed the statistical and biological relevance of the epistatic variance for 9 week body weight in two populations of inbred mice. We developed a new linear mixed model parameterization where founder-related additive genetic variability, additive mutational variability and the interaction terms between both sources of variation were accounted for under a Bayesian design and without requiring the inversion of a matrix of epistatic genetic covariances. The analyses focused on a six-generations data set from C57BL/6J mice (n = 3736) and a five-generations data set from C57BL/6J(hg/hg) mice (n = 2843). The deviance information criterion (DIC) clearly favoured the model accounting for epistatic variability with reductions larger than 50 DIC units in both populations. Modal estimates for founder related, mutational and epistatic heritabilities were 0·068, 0·011 and 0·095 in C57BL/6J and 0·060, 0·010 and 0·113 in C57BL/6J(hg/hg), ruling out any doubt about the biological relevance of epistasis originating from new mutations in mice. These results contribute new insights on the relevance of epistasis in the genetic architecture of mammals and serve as an important component of an additional source of genetic heterogeneity for inbred strains of laboratory mice.

  12. 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.

  13. Estimating directional epistasis

    PubMed Central

    Le Rouzic, Arnaud

    2014-01-01

    Epistasis, i.e., the fact that gene effects depend on the genetic background, is a direct consequence of the complexity of genetic architectures. Despite this, most of the models used in evolutionary and quantitative genetics pay scant attention to genetic interactions. For instance, the traditional decomposition of genetic effects models epistasis as noise around the evolutionarily-relevant additive effects. Such an approach is only valid if it is assumed that there is no general pattern among interactions—a highly speculative scenario. Systematic interactions generate directional epistasis, which has major evolutionary consequences. In spite of its importance, directional epistasis is rarely measured or reported by quantitative geneticists, not only because its relevance is generally ignored, but also due to the lack of simple, operational, and accessible methods for its estimation. This paper describes conceptual and statistical tools that can be used to estimate directional epistasis from various kinds of data, including QTL mapping results, phenotype measurements in mutants, and artificial selection responses. As an illustration, I measured directional epistasis from a real-life example. I then discuss the interpretation of the estimates, showing how they can be used to draw meaningful biological inferences. PMID:25071828

  14. Biological knowledge-driven analysis of epistasis in human GWAS with application to lipid traits.

    PubMed

    Ma, Li; Keinan, Alon; Clark, Andrew G

    2015-01-01

    While the importance of epistasis is well established, specific gene-gene interactions have rarely been identified in human genome-wide association studies (GWAS), mainly due to low power associated with such interaction tests. In this chapter, we integrate biological knowledge and human GWAS data to reveal epistatic interactions underlying quantitative lipid traits, which are major risk factors for coronary artery disease. To increase power to detect interactions, we only tested pairs of SNPs filtered by prior biological knowledge, including GWAS results, protein-protein interactions (PPIs), and pathway information. Using published GWAS and 9,713 European Americans (EA) from the Atherosclerosis Risk in Communities (ARIC) study, we identified an interaction between HMGCR and LIPC affecting high-density lipoprotein cholesterol (HDL-C) levels. We then validated this interaction in additional multiethnic cohorts from ARIC, the Framingham Heart Study, and the Multi-Ethnic Study of Atherosclerosis. Both HMGCR and LIPC are involved in the metabolism of lipids and lipoproteins, and LIPC itself has been marginally associated with HDL-C. Furthermore, no significant interaction was detected using PPI and pathway information, mainly due to the stringent significance level required after correcting for the large number of tests conducted. These results suggest the potential of biological knowledge-driven approaches to detect epistatic interactions in human GWAS, which may hold the key to exploring the role gene-gene interactions play in connecting genotypes and complex phenotypes in future GWAS.

  15. Epistasis in protein evolution

    PubMed Central

    Starr, Tyler N.

    2016-01-01

    Abstract 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

  16. Epistasis correlates to genomic complexity

    PubMed Central

    Sanjuán, Rafael; Elena, Santiago F.

    2006-01-01

    Whether systematic genetic interactions (epistasis) occur at the genomic scale remains a challenging topic in evolutionary biology. Epistasis should make a significant contribution to variation in complex traits and influence the evolution of genetic systems as sex, diploidy, dominance, or the contamination of genomes with deleterious mutations. We have collected data from widely different organisms and quantified epistasis in a common, per-generation scale. Simpler genomes, such as those of RNA viruses, display antagonistic epistasis (mutations have smaller effects together than expected); bacterial microorganisms do not apparently deviate from independent effects, whereas in multicellular eukaryotes, a transition toward synergistic epistasis occurs (mutations have larger effects together than expected). We propose that antagonistic epistasis might be a property of compact genomes with few nonpleiotropic biological functions, whereas in complex genomes, synergism might emerge from mutational robustness. PMID:16983079

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

    PubMed Central

    Vaysse, Amaury; Wei, Qingyi; Chen, Wei V.; Mohamdi, Hamida; Maubec, Eve; Lavielle, Nolwenn; Galan, Pilar; Lathrop, Mark; Avril, Marie-Françoise; Lee, Jeffrey E.

    2015-01-01

    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 (FDR≤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

  18. Consequences of Epistasis on Growth in an Erhualian × White Duroc Pig Cross

    PubMed Central

    Guo, Yuanmei

    2017-01-01

    Epistasis describes an interaction between the effects of loci. We included epistasis in quantitative trait locus (QTL) mapping of growth at a series of ages in a cross of a Chinese pig breed, Erhualian, with a commercial line, White Duroc. Erhualian pigs have much lower growth rates than White Duroc. We improved a method for genomewide testing of epistasis and present a clear analysis workflow. We also suggest a new approach for interpreting epistasis results where significant additive and dominance effects of a locus in specific backgrounds are determined. In total, seventeen QTL were found and eleven showed epistasis. Loci on chromosomes 2, 3, 4 and 7 were highlighted as affecting growth at more than one age or forming an interaction network. Epistasis resulted in both the QTL on chromosomes 3 and 7 having effects in opposite directions. We believe it is the first time for the chromosome 7 locus that an allele from a Chinese breed has been found to decrease growth. The consequences of epistasis were diverse. Results were impacted by using growth rather than body weight as the phenotype and by correcting for an effect of mother. Epistasis made a considerable contribution to growth in this population and modelling epistasis was important for accurately determining QTL effects. PMID:28060815

  19. 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.

  20. Parallel emergence of negative epistasis across experimental lineages.

    PubMed

    Zee, Peter C; Velicer, Gregory J

    2017-01-27

    Epistatic interactions can greatly impact evolutionary phenomena, particularly the process of adaptation. Here, we leverage four parallel experimentally evolved lineages to study the emergence and trajectories of epistatic interactions in the social bacterium Myxococcus xanthus. A social gene (pilA) necessary for effective group swarming on soft agar had been deleted from the common ancestor of these lineages. During selection for competitiveness at the leading edge of growing colonies, two lineages evolved qualitatively novel mechanisms for greatly increased swarming on soft agar, whereas the other two lineages evolved relatively small increases in swarming. By reintroducing pilA into different genetic backgrounds along the four lineages, we tested whether parallel lineages showed similar patterns of epistasis. In particular, we tested whether a pattern of negative epistasis between accumulating mutations and pilA previously found in the fastest lineage would be found only in the two evolved lineages with the fastest and most striking swarming phenotypes, or rather was due to common epistatic structure across all lineages arising from the generic fixation of adaptive mutations. Our analysis reveals the emergence of negative epistasis across all four independent lineages. Further, we present results showing that the observed negative epistasis is not due exclusively to evolving populations approaching a maximum phenotypic value that inherently limits positive effects of pilA reintroduction, but rather involves direct antagonistic interactions between accumulating mutations and the reintroduced social gene.

  1. The causes of epistasis in genetic networks.

    PubMed

    Macía, Javier; Solé, Ricard V; Elena, Santiago F

    2012-02-01

    Epistasis refers to the nonadditive interactions between genes in determining phenotypes. Considerable efforts have shown that, even for a given organism, epistasis may vary both in intensity and sign. Recent comparative studies supported that the overall sign of epistasis switches from positive to negative as the complexity of an organism increases, and it has been hypothesized that this change shall be a consequence of the underlying gene network properties. Why should this be the case? What characteristics of genetic networks determine the sign of epistasis? Here we show, by evolving genetic networks that differ in their complexity and robustness against perturbations but that perform the same tasks, that robustness increased with complexity and that epistasis was positive for small nonrobust networks but negative for large robust ones. Our results indicate that robustness and negative epistasis emerge as a consequence of the existence of redundant elements in regulatory structures of genetic networks and that the correlation between complexity and epistasis is a byproduct of such redundancy, allowing for the decoupling of epistasis from the underlying network complexity. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  2. Epistasis and the Evolution of Antimicrobial Resistance

    PubMed Central

    Wong, Alex

    2017-01-01

    The fitness effects of a mutation can depend, sometimes dramatically, on genetic background; this phenomenon is often referred to as “epistasis.” Epistasis can have important practical consequences in the context of antimicrobial resistance (AMR). For example, genetic background plays an important role in determining the costs of resistance, and hence in whether resistance will persist in the absence of antibiotic pressure. Furthermore, interactions between resistance mutations can have important implications for the evolution of multi-drug resistance. I argue that there is a need to better characterize the extent and nature of epistasis for mutations and horizontally transferred elements conferring AMR, particularly in clinical contexts. Furthermore, I suggest that epistasis should be an important consideration in attempts to slow or limit the evolution of AMR. PMID:28261193

  3. Epistasis and the Evolution of Antimicrobial Resistance.

    PubMed

    Wong, Alex

    2017-01-01

    The fitness effects of a mutation can depend, sometimes dramatically, on genetic background; this phenomenon is often referred to as "epistasis." Epistasis can have important practical consequences in the context of antimicrobial resistance (AMR). For example, genetic background plays an important role in determining the costs of resistance, and hence in whether resistance will persist in the absence of antibiotic pressure. Furthermore, interactions between resistance mutations can have important implications for the evolution of multi-drug resistance. I argue that there is a need to better characterize the extent and nature of epistasis for mutations and horizontally transferred elements conferring AMR, particularly in clinical contexts. Furthermore, I suggest that epistasis should be an important consideration in attempts to slow or limit the evolution of AMR.

  4. Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome.

    PubMed

    Wang, Heming; Choi, Yoonha; Tayo, Bamidele; Wang, Xuefeng; Morris, Nathan; Zhang, Xiang; Broeckel, Uli; Hanis, Craig; Kardia, Sharon; Redline, Susan; Cooper, Richard S; Tang, Hua; Zhu, Xiaofeng

    2017-02-01

    The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years and the existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting nonindependence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two-locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints. In this study, we developed a novel method to detect fitness epistasis by testing the correlation between local ancestries on different chromosomes in an admixed population. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes 4 and 6 that show significant local ancestry correlation (P-value = 4.01 × 10(-8) ) that can be potentially attributed to fitness epistasis. However, we also observed substantial local ancestry correlation that cannot be explained by systemic ancestry inference bias. To our knowledge, this study is the first to systematically examine evidence of fitness epistasis across the human genome. © 2016 WILEY PERIODICALS, INC.

  5. Pervasive Cryptic Epistasis in Molecular Evolution

    PubMed Central

    Lunzer, Mark; Golding, G. Brian; Dean, Antony M.

    2010-01-01

    The functional effects of most amino acid replacements accumulated during molecular evolution are unknown, because most are not observed naturally and the possible combinations are too numerous. We created 168 single mutations in wild-type Escherichia coli isopropymalate dehydrogenase (IMDH) that match the differences found in wild-type Pseudomonas aeruginosa IMDH. 104 mutant enzymes performed similarly to E. coli wild-type IMDH, one was functionally enhanced, and 63 were functionally compromised. The transition from E. coli IMDH, or an ancestral form, to the functional wild-type P. aeruginosa IMDH requires extensive epistasis to ameliorate the combined effects of the deleterious mutations. This result stands in marked contrast with a basic assumption of molecular phylogenetics, that sites in sequences evolve independently of each other. Residues that affect function are scattered haphazardly throughout the IMDH structure. We screened for compensatory mutations at three sites, all of which lie near the active site and all of which are among the least active mutants. No compensatory mutations were found at two sites indicating that a single site may engage in compound epistatic interactions. One complete and three partial compensatory mutations of the third site are remote and lie in a different domain. This demonstrates that epistatic interactions can occur between distant (>20Å) sites. Phylogenetic analysis shows that incompatible mutations were fixed in different lineages. PMID:20975933

  6. Interactive analysis environment of unified accelerator libraries

    NASA Astrophysics Data System (ADS)

    Fine, V.; Malitsky, N.; Talman, R.

    2006-04-01

    Unified Accelerator Libraries (UAL, http://www.ual.bnl.gov) software is an open accelerator simulation environment addressing a broad spectrum of accelerator tasks ranging from efficient online-oriented modeling to full-scale realistic beam dynamics studies. The paper introduces a new package integrating UAL simulation algorithms with the QT-based Graphical User Interface and the ROOT data analysis and visualization framework ( http://root.cern.ch). The primary user application is implemented as an interactive and configurable Accelerator Physics Player. Its interface to visualization components is based on the QT layer ( http://root.bnl.gov) supported by the STAR experiment.

  7. Enabling personal genomics with an explicit test of epistasis.

    PubMed

    Greene, Casey S; Himmelstein, Daniel S; Nelson, Heather H; Kelsey, Karl T; Williams, Scott M; Andrew, Angeline S; Karagas, Margaret R; Moore, Jason H

    2010-01-01

    One goal of personal genomics is to use information about genomic variation to predict who is at risk for various common diseases. Technological advances in genotyping have spawned several personal genetic testing services that market genotyping services directly to the consumer. An important goal of consumer genetic testing is to provide health information along with the genotyping results. This has the potential to integrate detailed personal genetic and genomic information into healthcare decision making. Despite the potential importance of these advances, there are some important limitations. One concern is that much of the literature that is used to formulate personal genetics reports is based on genetic association studies that consider each genetic variant independently of the others. It is our working hypothesis that the true value of personal genomics will only be realized when the complexity of the genotype-to-phenotype mapping relationship is embraced, rather than ignored. We focus here on complexity in genetic architecture due to epistasis or nonlinear gene-gene interaction. We have previously developed a multifactor dimensionality reduction (MDR) algorithm and software package for detecting nonlinear interactions in genetic association studies. In most prior MDR analyses, the permutation testing strategy used to assess statistical significance was unable to differentiate MDR models that captured only interaction effects from those that also detected independent main effects. Statistical interpretation of MDR models required post-hoc analysis using entropy-based measures of interaction information. We introduce here a novel permutation test that allows the effects of nonlinear interactions between multiple genetic variants to be specifically tested in a manner that is not confounded by linear additive effects. We show using simulated nonlinear interactions that the power using the explicit test of epistasis is no different than a standard permutation

  8. Two-Stage Genome-Wide Search for Epistasis with Implementation to Recombinant Inbred Lines (RIL) Populations

    PubMed Central

    Goldstein, Pavel; Korol, Abraham B.; Reiner-Benaim, Anat

    2014-01-01

    Objective and Methods This paper proposes an inegrative two-stage genome-wide search for pairwise epistasis on expression quantitative trait loci (eQTL). The traits are clustered into multi-trait complexes that account for correlations between them that may result from common epistasis effects. The search is done by first screening for epistatic regions and then using dense markers within the identified regions, resulting in substantial reduction in the number of tests for epistasis. The FDR is controlled using a hierarchical procedure that accounts for the search structure. Each combination of trait and marker-pair is tested using a model that accounts for both statistical and functional interpretations of epistasis and considers orthogonal effects, such that their contributions to heritability can be estimated individually. We examine the impact of using multi-trait complexes rather than single traits, and of using a hierarchical search for epistasis rather than skipping the initial screen for epistatic regions. We apply the proposed algorithm on Arabidopsis transcription data. Principal Findings Both epistasis detection power and heritability contributed by epistasis increased when using multi-trait complexes rather than single traits. Epistatic effects common to the eQTLs included in the complexes have higher chance of being identified by analysis of multi-trait complexes, particularly when epistatic effects on individual traits are small. Compared to direct testing for all potential epistatic effects, the hierarchical search was substantially more powerful in detecting epistasis, while controlling the FDR at the desired level. Association in functional roles within genomic regions was observed, supporting an initial screen for epistatic QTLs. PMID:25536193

  9. 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.

  10. 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).

  11. 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

  12. Systematic epistasis analysis of the contributions of protein kinase A- and mitogen-activated protein kinase-dependent signaling to nutrient limitation-evoked responses in the yeast Saccharomyces cerevisiae.

    PubMed

    Chen, Raymond E; Thorner, Jeremy

    2010-07-01

    Cellular responses to environmental stimuli require conserved signal transduction pathways. In budding yeast (Saccharomyces cerevisiae), nutrient limitation induces morphological changes that depend on the protein kinase A (PKA) pathway and the Kss1 mitogen-activated protein kinase (MAPK) pathway. It was unclear to what extent and at what level there is synergy between these two distinct signaling modalities. We took a systematic genetic approach to clarify the relationship between these inputs. We performed comprehensive epistasis analysis of mutants lacking different combinations of all relevant pathway components. We found that these two pathways contribute additively to nutrient limitation-induced haploid invasive growth. Moreover, full derepression of either pathway rendered it individually sufficient for invasive growth and thus, normally, both are required only because neither is maximally active. Furthermore, in haploids, the MAPK pathway contributes more strongly than the PKA pathway to cell elongation and adhesion, whereas nutrient limitation-induced unipolar budding is independent of both pathways. In contrast, in diploids, upon nutrient limitation the MAPK pathway regulates cell elongation, the PKA pathway regulates unipolar budding, and both regulate cell adhesion. Thus, although there are similarities between haploids and diploids, cell type-specific differences clearly alter the balance of the signaling inputs required to elicit the various nutrient limitation-evoked cellular behaviors.

  13. Personal computer accelerates dam analysis

    SciTech Connect

    Slopek, R.J. )

    1991-12-01

    Analyzing the stability of a dam can require several months of calculations - depending upon the number of dam cross sections and the variety of loadings that are studied. Monenco Consultants Limited, an engineering firm with its head office in Calgary, Alberta, has evaluated the safety of existing dams at more than 40 water resource developments in the last 20 years. Realizing the complexity of these evaluations, Monenco engineers were interested in developing techniques that would reduce the hours of professional time required for stability calculations, and therefore the cost to the dams owners. The firm eventually developed a microcomputer program for its engineers to use in the stability analysis of concrete gravity dams and two spread-sheets to use with the program for analyzing uplift and internal stresses. Using the computer programs cuts man-hours spent in analysis by about 75 percent and reduces the possibility of error in multiple calculations. Ultimately, the programs allow the engineer to spend more time in detailed analysis of a structure during a safety evaluation and less time performing tedious calculations.

  14. Epistasis and Its Implications for Personal Genetics

    PubMed Central

    Moore, Jason H.; Williams, Scott M.

    2009-01-01

    The widespread availability of high-throughput genotyping technology has opened the door to the era of personal genetics, which brings to consumers the promise of using genetic variations to predict individual susceptibility to common diseases. Despite easy access to commercial personal genetics services, our knowledge of the genetic architecture of common diseases is still very limited and has not yet fulfilled the promise of accurately predicting most people at risk. This is partly because of the complexity of the mapping relationship between genotype and phenotype that is a consequence of epistasis (gene-gene interaction) and other phenomena such as gene-environment interaction and locus heterogeneity. Unfortunately, these aspects of genetic architecture have not been addressed in most of the genetic association studies that provide the knowledge base for interpreting large-scale genetic association results. We provide here an introductory review of how epistasis can affect human health and disease and how it can be detected in population-based studies. We provide some thoughts on the implications of epistasis for personal genetics and some recommendations for improving personal genetics in light of this complexity. PMID:19733727

  15. Analysis techniques for residual acceleration data

    NASA Technical Reports Server (NTRS)

    Rogers, Melissa J. B.; Alexander, J. Iwan D.; Snyder, Robert S.

    1990-01-01

    Various aspects of residual acceleration data are of interest to low-gravity experimenters. Maximum and mean values and various other statistics can be obtained from data as collected in the time domain. Additional information may be obtained through manipulation of the data. Fourier analysis is discussed as a means of obtaining information about dominant frequency components of a given data window. Transformation of data into different coordinate axes is useful in the analysis of experiments with different orientations and can be achieved by the use of a transformation matrix. Application of such analysis techniques to residual acceleration data provides additional information than what is provided in a time history and increases the effectiveness of post-flight analysis of low-gravity experiments.

  16. Likelihood analysis of the Local Group acceleration

    NASA Astrophysics Data System (ADS)

    Schmoldt, I.; Branchini, E.; Teodoro, L.; Efstathiou, G.; Frenk, C. S.; Keeble, O.; McMahon, R.; Maddox, S.; Oliver, S.; Rowan-Robinson, M.; Saunders, W.; Sutherland, W.; Tadros, H.; White, S. D. M.

    1999-04-01

    We compute the acceleration of the Local Group using 11 206 IRAS galaxies from the recently completed all-sky PSCz redshift survey. Measuring the acceleration vector in redshift space generates systematic uncertainties caused by the redshift-space distortions in the density field. We therefore assign galaxies to their real-space positions by adopting a non-parametric model for the velocity field that relies solely on the linear gravitational instability (GI) and linear biasing hypotheses. Remaining systematic contributions to the measured acceleration vector are corrected for by using PSCz mock catalogues from N-body experiments. The resulting acceleration vector points ~15 away from the CMB dipole apex, with a remarkable alignment between small- and large-scale contributions. A considerable fraction (~65 per cent) of the measured acceleration is generated within 40 h^-1 Mpc, with a non-negligible contribution from scales between 90 and 140 h^-1 Mpc, after which the acceleration amplitude seems to have converged. The local group acceleration from PSCz appears to be consistent with the one determined from the IRAS 1.2-Jy galaxy catalogue once the different contributions from shot noise have been taken into account. The results are consistent with the gravitational instability hypothesis and do not indicate any strong deviations from the linear biasing relation on large scales. A maximum-likelihood analysis of the cumulative PSCz dipole is performed within a radius of 150 h^-1 Mpc, in which we account for non-linear effects, shot noise and finite sample size. The aim is to constrain the beta=Omega^0.6/b parameter and the power spectrum of density fluctuations. We obtain beta=0.70^+0.35_-0.2 at 1sigma confidence level. The likelihood analysis is not very sensitive to the shape of the power spectrum, because of the rise in the amplitude of the dipole beyond 40 h^-1 Mpc and the increase in shot noise on large scales. There is, however, a weak indication that within the

  17. EpiGPU: exhaustive pairwise epistasis scans parallelized on consumer level graphics cards.

    PubMed

    Hemani, Gibran; Theocharidis, Athanasios; Wei, Wenhua; Haley, Chris

    2011-06-01

    Hundreds of genome-wide association studies have been performed over the last decade, but as single nucleotide polymorphism (SNP) chip density has increased so has the computational burden to search for epistasis [for n SNPs the computational time resource is O(n(n-1)/2)]. While the theoretical contribution of epistasis toward phenotypes of medical and economic importance is widely discussed, empirical evidence is conspicuously absent because its analysis is often computationally prohibitive. To facilitate resolution in this field, tools must be made available that can render the search for epistasis universally viable in terms of hardware availability, cost and computational time. By partitioning the 2D search grid across the multicore architecture of a modern consumer graphics processing unit (GPU), we report a 92× increase in the speed of an exhaustive pairwise epistasis scan for a quantitative phenotype, and we expect the speed to increase as graphics cards continue to improve. To achieve a comparable computational improvement without a graphics card would require a large compute-cluster, an option that is often financially non-viable. The implementation presented uses OpenCL--an open-source library designed to run on any commercially available GPU and on any operating system. The software is free, open-source, platformindependent and GPU-vendor independent. It can be downloaded from http://sourceforge.net/projects/epigpu/.

  18. Analysis of acceleration signals using wavelet transform.

    PubMed

    Sekine, M; Tamura, T; Akay, M; Togawa, T; Fukui, Y

    2000-06-01

    In this study, we attempted to discriminate the acceleration signal for horizontal level and stairway walking using wavelet-based fractal analysis method. The acceleration signal was measured close to the center of gravity of the body, while the subjects walked continuously in the corridor and up and down the stairs. We used the wavelet-based fractal analysis method to discriminate walking pattern. The parameter H which is related directly to the fractal dimension was estimated by the wavelet coefficient and was changed into low value during walking upstairs. By manually setting the threshold level for individual, it was possible to discriminate walking upstairs from the other walking type. However, the common feature among subjects was not shown between level walking and walking downstairs.

  19. Detecting epistasis with the marginal epistasis test in genetic mapping studies of quantitative traits

    PubMed Central

    Zeng, Ping; Mukherjee, Sayan; Zhou, Xiang

    2017-01-01

    Epistasis, commonly defined as the interaction between multiple genes, is an important genetic component underlying phenotypic variation. Many statistical methods have been developed to model and identify epistatic interactions between genetic variants. However, because of the large combinatorial search space of interactions, most epistasis mapping methods face enormous computational challenges and often suffer from low statistical power due to multiple test correction. Here, we present a novel, alternative strategy for mapping epistasis: instead of directly identifying individual pairwise or higher-order interactions, we focus on mapping variants that have non-zero marginal epistatic effects—the combined pairwise interaction effects between a given variant and all other variants. By testing marginal epistatic effects, we can identify candidate variants that are involved in epistasis without the need to identify the exact partners with which the variants interact, thus potentially alleviating much of the statistical and computational burden associated with standard epistatic mapping procedures. Our method is based on a variance component model, and relies on a recently developed variance component estimation method for efficient parameter inference and p-value computation. We refer to our method as the “MArginal ePIstasis Test”, or MAPIT. With simulations, we show how MAPIT can be used to estimate and test marginal epistatic effects, produce calibrated test statistics under the null, and facilitate the detection of pairwise epistatic interactions. We further illustrate the benefits of MAPIT in a QTL mapping study by analyzing the gene expression data of over 400 individuals from the GEUVADIS consortium. PMID:28746338

  20. Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding

    PubMed Central

    Wilke, Claus O; Lenski, Richard E; Adami, Christoph

    2003-01-01

    Background The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed. Results We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances. Conclusions Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes. PMID:12590655

  1. Compensatory mutations cause excess of antagonistic epistasis in RNA secondary structure folding.

    PubMed

    Wilke, Claus O; Lenski, Richard E; Adami, Christoph

    2003-02-05

    The rate at which fitness declines as an organism's genome accumulates random mutations is an important variable in several evolutionary theories. At an intuitive level, it might seem natural that random mutations should tend to interact synergistically, such that the rate of mean fitness decline accelerates as the number of random mutations is increased. However, in a number of recent studies, a prevalence of antagonistic epistasis (the tendency of multiple mutations to have a mitigating rather than reinforcing effect) has been observed. We studied in silico the net amount and form of epistatic interactions in RNA secondary structure folding by measuring the fraction of neutral mutants as a function of mutational distance d. We found a clear prevalence of antagonistic epistasis in RNA secondary structure folding. By relating the fraction of neutral mutants at distance d to the average neutrality at distance d, we showed that this prevalence derives from the existence of many compensatory mutations at larger mutational distances. Our findings imply that the average direction of epistasis in simple fitness landscapes is directly related to the density with which fitness peaks are distributed in these landscapes.

  2. 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.

  3. 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

  4. Code comparison for accelerator design and analysis

    SciTech Connect

    Parsa, Z.

    1988-01-01

    We present a comparison between results obtained from standard accelerator physics codes used for the design and analysis of synchrotrons and storage rings, with programs SYNCH, MAD, HARMON, PATRICIA, PATPET, BETA, DIMAD, MARYLIE and RACE-TRACK. In our analysis we have considered 5 (various size) lattices with large and small angles including AGS Booster (10/degree/ bend), RHIC (2.24/degree/), SXLS, XLS (XUV ring with 45/degree/ bend) and X-RAY rings. The differences in the integration methods used and the treatment of the fringe fields in these codes could lead to different results. The inclusion of nonlinear (e.g., dipole) terms may be necessary in these calculations specially for a small ring. 12 refs., 6 figs., 10 tabs.

  5. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1.

    PubMed

    Kirino, Yohei; Bertsias, George; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Ozyazgan, Yilmaz; Sacli, F Sevgi; Erer, Burak; Inoko, Hidetoshi; Emrence, Zeliha; Cakar, Atilla; Abaci, Neslihan; Ustek, Duran; Satorius, Colleen; Ueda, Atsuhisa; Takeno, Mitsuhiro; Kim, Yoonhee; Wood, Geryl M; Ombrello, Michael J; Meguro, Akira; Gül, Ahmet; Remmers, Elaine F; Kastner, Daniel L

    2013-02-01

    Individuals with Behçet's disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behçet's disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behçet's disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 × 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 × 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçet's disease.

  6. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1

    PubMed Central

    Kirino, Yohei; Bertsias, George; Ishigatsubo, Yoshiaki; Mizuki, Nobuhisa; Tugal-Tutkun, Ilknur; Seyahi, Emire; Ozyazgan, Yilmaz; Sacli, F. Sevgi; Erer, Burak; Inoko, Hidetoshi; Emrence, Zeliha; Cakar, Atilla; Abaci, Neslihan; Ustek, Duran; Satorius, Colleen; Ueda, Atsuhisa; Takeno, Mitsuhiro; Kim, Yoonhee; Wood, Geryl M.; Ombrello, Michael J.; Meguro, Akira; Gül, Ahmet; Remmers, Elaine F.; Kastner, Daniel L.

    2013-01-01

    Patients with Behçet's disease (BD) suffer from episodic inflammation often affecting the orogenital mucosa, skin, and eyes. To discover new BD-susceptibility loci, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish BD patients and 1,278 controls. We identified novel associations at CCR1, STAT4, and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln, recessively conferred disease risk. These findings replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis p < 2 × 10−9). We also found evidence for interaction between HLA-B*51 and ERAP1 (p = 9 × 10−4). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (MHC-I, ERAP1, and IL23R, and the MHC-I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and BD. PMID:23291587

  7. Analysis of a triple testcross design with recombinant inbred lines reveals a significant role of epistasis in heterosis for biomass-related traits in Arabidopsis.

    PubMed

    Kusterer, Barbara; Muminovic, Jasmina; Utz, H Friedrich; Piepho, Hans-Peter; Barth, Susanne; Heckenberger, Martin; Meyer, Rhonda C; Altmann, Thomas; Melchinger, Albrecht E

    2007-04-01

    Primary causes of heterosis are still unknown. Our goal was to investigate the extent and underlying genetic causes of heterosis for five biomass-related traits in Arabidopsis thaliana. We (i) investigated the relative contribution of dominance and epistatic effects to heterosis in the hybrid C24 x Col-0 by generation means analysis and estimates of variance components based on a triple testcross (TTC) design with recombinant inbred lines (RILs), (ii) estimated the average degree of dominance, and (iii) examined the importance of reciprocal and maternal effects in this cross. In total, 234 RILs were crossed to parental lines and their F1's. Midparent heterosis (MPH) was high for rosette diameter at 22 days after sowing (DAS) and 29 DAS, growth rate (GR), and biomass yield (BY). Using the F2-metric, directional dominance prevailed for the majority of traits studied but reciprocal and maternal effects were not significant. Additive and dominance variances were significant for all traits. Additive x additive and dominance x dominance variances were significant for all traits but GR. We conclude that dominance as well as digenic and possibly higher-order epistatic effects play an important role in heterosis for biomass-related traits. Our results encourage the use of Arabidopsis hybrid C24 x Col-0 for identification and description of quantitative trait loci (QTL) for heterosis for biomass-related traits and further genomic studies.

  8. Coevolution of robustness, epistasis, and recombination favors asexual reproduction.

    PubMed

    MacCarthy, Thomas; Bergman, Aviv

    2007-07-31

    The prevalence of sexual reproduction remains one of the most perplexing phenomena in evolutionary biology. The deterministic mutation hypothesis postulates that sexual reproduction will be advantageous under synergistic epistasis, a condition in which mutations cause a greater reduction in fitness when combined than would be expected from their individual effects. The inverse condition, antagonistic epistasis, correspondingly is predicted to favor asexual reproduction. To assess this hypothesis, we introduce a finite population evolutionary process that combines a recombination modifier formalism with a gene-regulatory network model. We demonstrate that when reproductive mode and epistasis are allowed to coevolve, asexual reproduction outcompetes sexual reproduction. In addition, no correlation is found between the level of synergistic epistasis and the fixation time of the asexual mode. However, a significant correlation is found between the level of antagonistic epistasis and asexual mode fixation time. This asymmetry can be explained by the greater reduction in fitness imposed by sexual reproduction as compared with asexual reproduction. Our findings present evidence and suggest plausible explanations that challenge both the deterministic mutation hypothesis and recent arguments asserting the importance of emergent synergistic epistasis in the maintenance of sexual reproduction.

  9. Unraveling epistasis with triple testcross progenies of near-isogenic lines.

    PubMed

    Reif, Jochen C; Kusterer, Barbara; Piepho, Hans-Peter; Meyer, Rhonda C; Altmann, Thomas; Schön, Chris C; Melchinger, Albrecht E

    2009-01-01

    Libraries of near-isogenic lines (NILs) are a powerful plant genetic resource to map quantitative trait loci (QTL). Nevertheless, QTL mapping with NILs is mostly restricted to genetic main effects. Here we propose a two-step procedure to map additive-by-additive digenic epistasis with NILs. In the first step, a generation means analysis of parents, their F(1) hybrid, and one-segment NILs and their triple testcross (TTC) progenies is used to identify in a one-dimensional scan loci exhibiting QTL-by-background interactions. In a second step, one-segment NILs with significant additive-by-additive background interactions are used to produce particular two-segment NILs to test for digenic epistatic interactions between these segments. We evaluated our approach by analyzing a random subset of a genomewide Arabidopsis thaliana NIL library for growth-related traits. The results of our experimental study illustrated the potential of the presented two-step procedure to map additive-by-additive digenic epistasis with NILs. Furthermore, our findings suggested that additive main effects as well as additive-by-additive digenic epistasis strongly influence the genetic architecture underlying growth-related traits of A. thaliana.

  10. 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

  11. 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.

  12. Walking analysis using an acceleration sensor.

    PubMed

    Tsuruoka, Yuriko; Shibasaki, Ryosuke

    2007-01-01

    It is important to evaluate walking stability to improve people's health. There are many cases of unstable walking even if people think they are in good health. A small, light acceleration sensor was attached to subjects' center of gravity to measure the acceleration displacement while the subjects were walking. By using the seasonal adjustment model it was possible to predict the periodic fluctuations observed, decomposing the original data into factors representing stability and instability. We suggest the walking stability of each subject using the ratio of the variance of instability to the variance of stability. This study provides useful information for understanding walking systems in preventive medicine and rehabilitative medicine.

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

    PubMed

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

    2009-02-09

    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.

  14. Genomic Prediction of Genotypic Effects with Epistasis and Environment Interactions for Yield-Related Traits of Rapeseed (Brassica napus L.)

    PubMed Central

    Luo, Xiang; Ding, Yi; Zhang, Linzhong; Yue, Yao; Snyder, John H.; Ma, Chaozhi; Zhu, Jun

    2017-01-01

    Oilseed rape (Brassica napus) is an economically important oil crop, yet the genetic architecture of its complex traits remain largely unknown. Here, genome-wide association study was conducted for eight yield-related traits to dissect the genetic architecture of additive, dominance, epistasis, and their environment interaction. Additionally, the optimal genotype combination and the breeding value of superior line, superior hybrid and existing best line in mapping population were predicted for each trait in two environments based on the predicted genotypic effects. As a result, 17 quantitative trait SNPs (QTSs) were identified significantly for target traits with total heritability varied from 58.47 to 87.98%, most of which were contributed by dominance, epistasis, and environment-specific effects. The results indicated that non-additive effects were large contributions to heritability and epistasis, and also noted that environment interactions were important variants for oilseed breeding. Our study facilitates the understanding of genetic basis of rapeseed yield trait, helps to accelerate rapeseed breading, and also offers a roadmap for precision plant breeding via marker-assisted selection. PMID:28270831

  15. On the evolution of epistasis III: the haploid case with mutation.

    PubMed

    Liberman, Uri; Feldman, Marcus

    2008-03-01

    Whether interaction between genes is better represented by synergistic or antagonistic epistasis has been a focus of experimental research in bacterial population genetics. Our previous research on evolution of modifiers of epistasis in diploid systems has indicated that the strength of positive or negative epistasis should increase provided linkage disequilibrium is maintained. Here we study a modifier of epistasis in fitness between two loci in a haploid system. Epistasis is modified in the neighborhood of a mutation-selection balance. We show that when linkage in the three-locus system is tight, an increase in the frequency of a modifier allele that induces either more negative or more positive epistasis is possible. Epistasis here can be measured on either an additive or multiplicative scale.

  16. RAMI analysis and modeling for the LANSCE accelerator systems

    SciTech Connect

    Macek, R.J.; Wilkinson, C.A.

    1995-10-01

    Reliability, availability, maintainability, and inspectability (RAMI) have become important issues for the high-power machines being planned for applications such as accelerator transmutation of nuclear waste (ATW), accelerator production of tritium (APT) and the next generation spallation neutron source. Beam reliability and beam availability are vitally important specifications to the present users of accelerator-driven spallation neutron sources, synchrotron light sources and medical accelerators. At Los Alamos, improved beam availability is a key goal in the planned LANSCE improvement program. Clearly, the capability to adequately model and predict the reliability and availability of complex accelerator systems will be of great value in assessing and optimizing RAMI measures in accelerator design and improvement programs. To date, no major accelerator project has developed comprehensive reliability models although the Advance Photon Source at ANL has started work on reliability analysis for selected subsystems. In this paper the authors discuss their experience in developing RAMI analysis and modeling for the LANSCE Accelerator Systems. Progress has been made in developing suitable measures and functions to characterize user risk, in logging of needed data on failure rates and repair/down times, and in developing a first-pass RAMI model for selected subsystems. Plans have been made for a more complete RAMI model. In addition, the authors discuss their experience in the use of probabilistic risk assessment (PRA) methodology for estimation of the reliability of active, instrumentation-based, radiation safety systems at LANSCE.

  17. Computational analysis of a pulsed inductive plasma accelerator

    NASA Astrophysics Data System (ADS)

    Corpening, Jeremy H.

    The pulsed inductive plasma accelerator allows for ionization of a cold gas propellant to plasma and acceleration of plasma with the same current pulse and without plasma contact with any part. This is beneficial since erosion is never a problem and lifetimes are limited only by the amount of carried propellant. To date, work involving the pulsed inductive plasma accelerator concept has been largely experimental with minimal computational analysis. The goal of the present research was to develop a computational tool using Maxwell's equations coupled with the Navier-Stokes fluid equations to fully analyze a pulsed inductive plasma accelerator. A plasma model was developed using the Saha equation and partition functions to calculate all required thermodynamic properties. The solution to Maxwell's equations was verified accurate and then coupled computations with propellant plasma were conducted. These coupled computations showed good order of magnitude accuracy with a simple onedimensional model however failed when the plasma began to accelerate due to the Lorentz force. The electric field, magnetic field, current density, and Lorentz force were all aligned in the proper vector directions. The computational failure occurred due to rapid, fictitious increases in the induced electric field in the vacuum created between the accelerating plasma and drive coil. Possible solutions to this problem are to decrease the time step and refine the grid density. Although complete acceleration of propellant plasma has yet to be computationally computed, this study has shown successful coupled computations with Maxwell and Navier-Stokes equations for a pulsed inductive plasma accelerator.

  18. Accelerator mass spectrometry (AMS) in plutonium analysis.

    PubMed

    Strumińska-Parulska, Dagmara I

    The paper summarizes the results of the (240)Pu/(239)Pu atomic ratio studies in atmospheric fallout samples collected in 1986 over Gdynia (Poland) as well as three Baltic fish species collected in 1997 using the accelerator mass spectrometry. A new generation of AMS has been developed during last years and this method is an efficient and good technique to measure long-lived radioisotopes in the environment and provides the most accurate determination of the atomic ratios between (240)Pu and (239)Pu. The nuclide compositions of plutonium in filter samples correspond to their means of production. AMS measurements of atmospheric fallout collected in April showed sufficient increase of the (240)Pu/(239)Pu atomic ratio from 0.28 from March to 0.47. Also such high increase of (240)Pu/(239)Pu atomic ratio, close to reactor core (240)Pu/(239)Pu atomic ratio, was observed in September and equaled 0.47.

  19. 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.

  20. A balanced accuracy function for epistasis modeling in imbalanced datasets using multifactor dimensionality reduction.

    PubMed

    Velez, Digna R; White, Bill C; Motsinger, Alison A; Bush, William S; Ritchie, Marylyn D; Williams, Scott M; Moore, Jason H

    2007-05-01

    Multifactor dimensionality reduction (MDR) was developed as a method for detecting statistical patterns of epistasis. The overall goal of MDR is to change the representation space of the data to make interactions easier to detect. It is well known that machine learning methods may not provide robust models when the class variable (e.g. case-control status) is imbalanced and accuracy is used as the fitness measure. This is because most methods learn patterns that are relevant for the larger of the two classes. The goal of this study was to evaluate three different strategies for improving the power of MDR to detect epistasis in imbalanced datasets. The methods evaluated were: (1) over-sampling that resamples with replacement the smaller class until the data are balanced, (2) under-sampling that randomly removes subjects from the larger class until the data are balanced, and (3) balanced accuracy [(sensitivity+specificity)/2] as the fitness function with and without an adjusted threshold. These three methods were compared using simulated data with two-locus epistatic interactions of varying heritability (0.01, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4) and minor allele frequency (0.2, 0.4) that were embedded in 100 replicate datasets of varying sample sizes (400, 800, 1600). Each dataset was generated with different ratios of cases to controls (1 : 1, 1 : 2, 1 : 4). We found that the balanced accuracy function with an adjusted threshold significantly outperformed both over-sampling and under-sampling and fully recovered the power. These results suggest that balanced accuracy should be used instead of accuracy for the MDR analysis of epistasis in imbalanced datasets.

  1. 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.

  2. The evolution of sex and recombination in response to abiotic or coevolutionary fluctuations in epistasis.

    PubMed

    Gandon, Sylvain; Otto, Sarah P

    2007-04-01

    Evolutionary biologists have identified several factors that could explain the widespread phenomena of sex and recombination. One hypothesis is that host-parasite interactions favor sex and recombination because they favor the production of rare genotypes. A problem with many of the early models of this so-called Red Queen hypothesis is that several factors are acting together: directional selection, fluctuating epistasis, and drift. It is thus difficult to identify what exactly is selecting for sex in these models. Is one factor more important than the others or is it the synergistic action of these different factors that really matters? Here we focus on the analysis of a simple model with a single mechanism that might select for sex: fluctuating epistasis. We first analyze the evolution of sex and recombination when the temporal fluctuations are driven by the abiotic environment. We then analyze the evolution of sex and recombination in a two-species coevolutionary model, where directional selection is absent (allele frequencies remain fixed) and temporal variation in epistasis is induced by coevolution with the antagonist species. In both cases we contrast situations with weak and strong selection and derive the evolutionarily stable (ES) recombination rate. The ES recombination rate is most sensitive to the period of the cycles, which in turn depends on the strength of epistasis. In particular, more virulent parasites cause more rapid cycles and consequently increase the ES recombination rate of the host. Although the ES strategy is maximized at an intermediate period, some recombination is favored even when fluctuations are very slow. By contrast, the amplitude of the cycles has no effect on the ES level of sex and recombination, unless sex and recombination are costly, in which case higher-amplitude cycles allow the evolution of higher rates of sex and recombination. In the coevolutionary model, the amount of recombination in the interacting species also has

  3. Analysis of flame acceleration in open or vented obstructed pipes

    NASA Astrophysics Data System (ADS)

    Bychkov, Vitaly; Sadek, Jad; Akkerman, V'yacheslav

    2017-01-01

    While flame propagation through obstacles is often associated with turbulence and/or shocks, Bychkov et al. [V. Bychkov et al., Phys. Rev. Lett. 101, 164501 (2008), 10.1103/PhysRevLett.101.164501] have revealed a shockless, conceptually laminar mechanism of extremely fast flame acceleration in semiopen obstructed pipes (one end of a pipe is closed; a flame is ignited at the closed end and propagates towards the open one). The acceleration is devoted to a powerful jet flow produced by delayed combustion in the spaces between the obstacles, with turbulence playing only a supplementary role in this process. In the present work, this formulation is extended to pipes with both ends open in order to describe the recent experiments and modeling by Yanez et al. [J. Yanez et al., arXiv:1208.6453] as well as the simulations by Middha and Hansen [P. Middha and O. R. Hansen, Process Safety Prog. 27, 192 (2008) 10.1002/prs.10242]. It is demonstrated that flames accelerate strongly in open or vented obstructed pipes and the acceleration mechanism is similar to that in semiopen ones (shockless and laminar), although acceleration is weaker in open pipes. Starting with an inviscid approximation, we subsequently incorporate hydraulic resistance (viscous forces) into the analysis for the sake of comparing its role to that of a jet flow driving acceleration. It is shown that hydraulic resistance is actually not required to drive flame acceleration. In contrast, this is a supplementary effect, which moderates acceleration. On the other hand, viscous forces are nevertheless an important effect because they are responsible for the initial delay occurring before the flame acceleration onset, which is observed in the experiments and simulations. Accounting for this effect provides good agreement between the experiments, modeling, and the present theory.

  4. Analysis of flame acceleration in open or vented obstructed pipes.

    PubMed

    Bychkov, Vitaly; Sadek, Jad; Akkerman, V'yacheslav

    2017-01-01

    While flame propagation through obstacles is often associated with turbulence and/or shocks, Bychkov et al. [V. Bychkov et al., Phys. Rev. Lett. 101, 164501 (2008)10.1103/PhysRevLett.101.164501] have revealed a shockless, conceptually laminar mechanism of extremely fast flame acceleration in semiopen obstructed pipes (one end of a pipe is closed; a flame is ignited at the closed end and propagates towards the open one). The acceleration is devoted to a powerful jet flow produced by delayed combustion in the spaces between the obstacles, with turbulence playing only a supplementary role in this process. In the present work, this formulation is extended to pipes with both ends open in order to describe the recent experiments and modeling by Yanez et al. [J. Yanez et al., arXiv:1208.6453] as well as the simulations by Middha and Hansen [P. Middha and O. R. Hansen, Process Safety Prog. 27, 192 (2008)10.1002/prs.10242]. It is demonstrated that flames accelerate strongly in open or vented obstructed pipes and the acceleration mechanism is similar to that in semiopen ones (shockless and laminar), although acceleration is weaker in open pipes. Starting with an inviscid approximation, we subsequently incorporate hydraulic resistance (viscous forces) into the analysis for the sake of comparing its role to that of a jet flow driving acceleration. It is shown that hydraulic resistance is actually not required to drive flame acceleration. In contrast, this is a supplementary effect, which moderates acceleration. On the other hand, viscous forces are nevertheless an important effect because they are responsible for the initial delay occurring before the flame acceleration onset, which is observed in the experiments and simulations. Accounting for this effect provides good agreement between the experiments, modeling, and the present theory.

  5. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

    PubMed Central

    Traglia, Michela; Tsang, Kathryn; Bearden, Carrie E.; Rauen, Katherine A.

    2017-01-01

    Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway. PMID:28076348

  6. 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.

  7. Analysis of Accelerants in Fire Debris - Data Interpretation.

    PubMed

    Bertsch, W

    1997-06-01

    Analysis of accelerants in fire debris involves the isolation of residual volatiles from the matrix and the analysis of these volatiles, usually by gas chromatography (GC). The resulting chromatograms are interpreted by comparing to a library of accelerant chromatograms obtained under similar conditions. This review first mentions ASTM's system in classifying fire accelerants into light petroleum distillates, gasoline, medium petroleum distillates, kerosene, heavy petroleum distillates, and unclassified compounds. Chromatograms with well-resolved n-alkane homolog patterns are most recognizable. Chromatograms that are inadequately resolved can be improved by columns having higher efficiency or selectivity, while those with too much interference can be improved by physical removal or reduction of these interfering compounds or selective detection. Using a mass spectrometer (MS) as the detector in GC/MS applications allows the display of common ions shared by compounds with similar structural features, thus greatly facilitating pattern recognition practices. Computer algorithms are now available for automated recognition of patterns possessed by various categories of accelerants. The state-of-the-art in forensic laboratories' analysis of accelerants in fire debris is presented as an appendix to this review. Data generated in annual proficiency tests over an 8-year period (1987-1995) revealed increased use of GC/MS instrumentation and some persisting problems, which include false positives and difficulties associated with component discrimination in the sample preparation process and recognition of partially evaporated distillates.

  8. 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.

  9. Relationship between epistasis and aggressiveness in resistance of pepper (Capsicum annuum L.) to Phytophthora nicotianae.

    PubMed

    Bnejdi, Fethi; Saadoun, Morad; Allagui, Mohamed Bechir; Hanbury, Colin; Gazzah, Mohamed El

    2010-04-01

    This study evaluated the types of gene action governing the inheritance of resistance to Phytophthora nicotianae necrosis in populations derived from two crosses involving two susceptible (Beldi and Nabeul II) and one resistant (CM334) cultivars of pepper (Capsicum annuum L.). Populations, composed of Pr, Ps, F(1) , F (2) , BC (1) Pr, and BC (1) Ps generations, were inoculated with six P. nicotianae isolates. Generation means analysis indicated that an additive-dominance model was appropriate for P. nicotianae isolates Pn (Ko1) , Pn (Ko2) and Pn (Kr1) , which showed low aggressiveness in the two crosses. For the more aggressive isolates Pn (Bz1) , Pn (Bz2) and Pn (Kr2) , epistasis was an integral component of resistance in the two crosses. The presence of epistasis in the resistance of pepper to P. nicotianae was dependent on the level of aggressiveness of the isolates. Selection in pepper with less aggressive isolates was efficient, but not with more aggressive isolates; on the other hand, selection with more aggressive isolates was more stable. The minimum number of genes controlling resistance was estimated at up to 2.71. In the majority of cases, the additive variance was significant and greater than the environmental and dominance variance.

  10. Detecting High-Order Epistasis in Nonlinear Genotype-Phenotype Maps.

    PubMed

    Sailer, Zachary R; Harms, Michael J

    2017-03-01

    High-order epistasis has been observed in many genotype-phenotype maps. These multi-way interactions between mutations may be useful for dissecting complex traits and could have profound implications for evolution. Alternatively, they could be a statistical artifact. High-order epistasis models assume the effects of mutations should add, when they could in fact multiply or combine in some other nonlinear way. A mismatch in the "scale" of the epistasis model and the scale of the underlying map would lead to spurious epistasis. In this article, we develop an approach to estimate the nonlinear scales of arbitrary genotype-phenotype maps. We can then linearize these maps and extract high-order epistasis. We investigated seven experimental genotype-phenotype maps for which high-order epistasis had been reported previously. We find that five of the seven maps exhibited nonlinear scales. Interestingly, even after accounting for nonlinearity, we found statistically significant high-order epistasis in all seven maps. The contributions of high-order epistasis to the total variation ranged from 2.2 to 31.0%, with an average across maps of 12.7%. Our results provide strong evidence for extensive high-order epistasis, even after nonlinear scale is taken into account. Further, we describe a simple method to estimate and account for nonlinearity in genotype-phenotype maps.

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

    PubMed

    Lalić, Jasna; Elena, Santiago F

    2013-02-23

    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.

  12. 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

  13. Detecting High-Order Epistasis in Nonlinear Genotype-Phenotype Maps

    PubMed Central

    Sailer, Zachary R.; Harms, Michael J.

    2017-01-01

    High-order epistasis has been observed in many genotype-phenotype maps. These multi-way interactions between mutations may be useful for dissecting complex traits and could have profound implications for evolution. Alternatively, they could be a statistical artifact. High-order epistasis models assume the effects of mutations should add, when they could in fact multiply or combine in some other nonlinear way. A mismatch in the “scale” of the epistasis model and the scale of the underlying map would lead to spurious epistasis. In this article, we develop an approach to estimate the nonlinear scales of arbitrary genotype-phenotype maps. We can then linearize these maps and extract high-order epistasis. We investigated seven experimental genotype-phenotype maps for which high-order epistasis had been reported previously. We find that five of the seven maps exhibited nonlinear scales. Interestingly, even after accounting for nonlinearity, we found statistically significant high-order epistasis in all seven maps. The contributions of high-order epistasis to the total variation ranged from 2.2 to 31.0%, with an average across maps of 12.7%. Our results provide strong evidence for extensive high-order epistasis, even after nonlinear scale is taken into account. Further, we describe a simple method to estimate and account for nonlinearity in genotype-phenotype maps. PMID:28100592

  14. Effect of inter- and intragenic epistasis on the heritability of oil content in rapeseed (Brassica napus L.).

    PubMed

    Würschum, Tobias; Maurer, Hans Peter; Dreyer, Felix; Reif, Jochen C

    2013-02-01

    The loci detected by association mapping which are involved in the expression of important agronomic traits in crops often explain only a small proportion of the total genotypic variance. Here, 17 SNPs derived from 9 candidate genes from the triacylglycerol biosynthetic pathway were studied in an association analysis in a population of 685 diverse elite rapeseed inbred lines. The 685 lines were evaluated for oil content, as well as for glucosinolates, yield, and thousand-kernel weight in field trials at 4 locations. We detected main effects for most of the studied genes illustrating that genetic diversity for oil content can be exploited by the selection of favorable alleles. In addition to main effects, both intergenic and intragenic epistasis was detected that contributes to a considerable amount to the genotypic variance observed for oil content. The proportion of explained genotypic variance was doubled when in addition to main effects epistasis was considered. Therefore, a knowledge-based improvement of oil content in rapeseed should also take such favorable epistatic interactions into account. Our results suggest, that the observed high contribution of epistasis may to some extent explain the missing heritability in genome-wide association studies.

  15. Signature energetic analysis of accelerate electron beam after first acceleration station by accelerating stand of Joint Institute for Nuclear Research

    NASA Astrophysics Data System (ADS)

    Sledneva, A. S.; Kobets, V. V.

    2017-06-01

    The linear electron accelerator based on the LINAC - 800 accelerator imported from the Netherland is created at Joint Institute for Nuclear Research in the framework of the project on creation of the Testbed with an electron beam of a linear accelerator with an energy up to 250 MV. Currently two accelerator stations with a 60 MV energy of a beam are put in operation and the work is to put the beam through accelerating section of the third accelerator station. The electron beam with an energy of 23 MeV is used for testing the crystals (BaF2, CsI (native), and LYSO) in order to explore the opportunity to use them in particle detectors in experiments: Muon g-2, Mu2e, Comet, whose preparation requires a detailed study of the detectors properties such as their irradiation by the accelerator beams.

  16. E/M launcher vibration and acceleration data analysis

    SciTech Connect

    Grzesik, R.G.; Mitchell, D.E.; Sebastian, J.H. ); Chin, I.W. )

    1991-01-01

    This paper reports on acquired acceleration curves for projectiles electromagnetically launched out of the non-stiff, (epoxy fiber wrapped copper rails) 50 mm Benet barrel which were very noisy and difficult to interpret. The cause for the noise was assumed to be the induced vibration from the barrel and projectile. Standard numerical smoothing techniques were not deemed plausible candidates for mathematical analysis because using them alone would have resulted in curves which would have been superficially smoothed over, concealing possibly interesting transient responses and/or distorting valuable acceleration data. The barrel low frequency vibrations were too interwoven with the acceleration signal and could not be extracted non-intrusively, and the high frequency barrel vibrations were not apparent. The projectile vibrations turned out to be negligible being on the order of magnitude of the accelerometer's background noise.

  17. Model-Based Multifactor Dimensionality Reduction to detect epistasis for quantitative traits in the presence of error-free and noisy data.

    PubMed

    Mahachie John, Jestinah M; Van Lishout, François; Van Steen, Kristel

    2011-06-01

    Detecting gene-gene interactions or epistasis in studies of human complex diseases is a big challenge in the area of epidemiology. To address this problem, several methods have been developed, mainly in the context of data dimensionality reduction. One of these methods, Model-Based Multifactor Dimensionality Reduction, has so far mainly been applied to case-control studies. In this study, we evaluate the power of Model-Based Multifactor Dimensionality Reduction for quantitative traits to detect gene-gene interactions (epistasis) in the presence of error-free and noisy data. Considered sources of error are genotyping errors, missing genotypes, phenotypic mixtures and genetic heterogeneity. Our simulation study encompasses a variety of settings with varying minor allele frequencies and genetic variance for different epistasis models. On each simulated data, we have performed Model-Based Multifactor Dimensionality Reduction in two ways: with and without adjustment for main effects of (known) functional SNPs. In line with binary trait counterparts, our simulations show that the power is lowest in the presence of phenotypic mixtures or genetic heterogeneity compared to scenarios with missing genotypes or genotyping errors. In addition, empirical power estimates reduce even further with main effects corrections, but at the same time, false-positive percentages are reduced as well. In conclusion, phenotypic mixtures and genetic heterogeneity remain challenging for epistasis detection, and careful thought must be given to the way important lower-order effects are accounted for in the analysis.

  18. 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.

  19. 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.

  20. 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.

  1. Analysis of Male Pheromones That Accelerate Female Reproductive Organ Development

    PubMed Central

    Flanagan, Kelly A.; Webb, William; Stowers, Lisa

    2011-01-01

    Male odors can influence a female's reproductive physiology. In the mouse, the odor of male urine results in an early onset of female puberty. Several volatile and protein pheromones have previously been reported to each account for this bioactivity. Here we bioassay inbred BALB/cJ females to study pheromone-accelerated uterine growth, a developmental hallmark of puberty. We evaluate the response of wild-type and mutant mice lacking a specialized sensory transduction channel, TrpC2, and find TrpC2 function to be necessary for pheromone-mediated uterine growth. We analyze the relative effectiveness of pheromones previously identified to accelerate puberty through direct bioassay and find none to significantly accelerate uterine growth in BALB/cJ females. Complementary to this analysis, we have devised a strategy of partial purification of the uterine growth bioactivity from male urine and applied it to purify bioactivity from three different laboratory strains. The biochemical characteristics of the active fraction of all three strains are inconsistent with that of previously known pheromones. When directly analyzed, we are unable to detect previously known pheromones in urine fractions that generate uterine growth. Our analysis indicates that pheromones emitted by males to advance female puberty remain to be identified. PMID:21347429

  2. Analysis of male pheromones that accelerate female reproductive organ development.

    PubMed

    Flanagan, Kelly A; Webb, William; Stowers, Lisa

    2011-02-08

    Male odors can influence a female's reproductive physiology. In the mouse, the odor of male urine results in an early onset of female puberty. Several volatile and protein pheromones have previously been reported to each account for this bioactivity. Here we bioassay inbred BALB/cJ females to study pheromone-accelerated uterine growth, a developmental hallmark of puberty. We evaluate the response of wild-type and mutant mice lacking a specialized sensory transduction channel, TrpC2, and find TrpC2 function to be necessary for pheromone-mediated uterine growth. We analyze the relative effectiveness of pheromones previously identified to accelerate puberty through direct bioassay and find none to significantly accelerate uterine growth in BALB/cJ females. Complementary to this analysis, we have devised a strategy of partial purification of the uterine growth bioactivity from male urine and applied it to purify bioactivity from three different laboratory strains. The biochemical characteristics of the active fraction of all three strains are inconsistent with that of previously known pheromones. When directly analyzed, we are unable to detect previously known pheromones in urine fractions that generate uterine growth. Our analysis indicates that pheromones emitted by males to advance female puberty remain to be identified.

  3. 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.

  4. 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.

  5. Predicting epistasis: an experimental test of metabolic control theory with bacterial transcription and translation.

    PubMed

    MacLean, R C

    2010-03-01

    Epistatic interactions between mutations are thought to play a crucial role in a number of evolutionary processes, including adaptation and sex. Evidence for epistasis is abundant, but tests of general theoretical models that can predict epistasis are lacking. In this study, I test the ability of metabolic control theory to predict epistasis using a novel experimental approach that combines phenotypic and genetic perturbations of enzymes involved in gene expression and protein synthesis in the bacterium Pseudomonas aeruginosa. These experiments provide experimental support for two key predictions of metabolic control theory: (i) epistasis between genes involved in the same pathway is antagonistic; (ii) epistasis becomes increasingly antagonistic as mutational severity increases. Metabolic control theory is a general theory that applies to any set of genes that are involved in the same linear processing chain, not just metabolic pathways, and I argue that this theory is likely to have important implications for predicting epistasis between functionally coupled genes, such as those involved in antibiotic resistance. Finally, this study highlights the fact that phenotypic manipulations of gene activity provide a powerful method for studying epistasis that complements existing genetic methods.

  6. Dissection of the PHO pathway in Schizosaccharomyces pombe using epistasis and the alternate repressor adenine.

    PubMed

    Estill, Molly; Kerwin-Iosue, Christine L; Wykoff, Dennis D

    2015-05-01

    In Saccharomyces cerevisiae, intracellular phosphate levels are maintained by the PHO pathway, activation of which is assayed by increased phosphatase activity. The PHO pathway of Schizosaccharomyces pombe upregulates phosphatase activity (encoded by pho1 (+)) during low extracellular phosphate levels, but the underlying mechanism is poorly understood. We utilized an alternate repressor of pho1 (+) expression (adenine supplementation) along with epistasis analysis to develop a model of how S. pombe PHO pathway components interact. Analyzing Pho1 activity in S. pombe PHO pathway deletion mutants during adenine starvation, we observed most mutants with a phosphatase defect in phosphate starvation also had a defect in adenine starvation. Pho7, a transcription factor in the PHO pathway, is necessary for an adenine starvation-mediated increase in Pho1 activity. Comparing adenine starvation to phosphate starvation, there are differences in the degree to which individual mutants regulate the two responses. Through epistasis studies, we identified two positive regulatory arms and one repressive arm of the PHO pathway. PKA activation is a positive regulator of Pho1 activity under both environmental conditions and is critical for transducing adenine concentrations in the cell. The synthesis of IP7 also appears critical for the induction of Pho1 activity during adenine starvation, but IP7 is not critical during phosphate starvation, which differs from S. cerevisiae. Finally, Csk1 is critical for repression of pho1 (+) expression during phosphate starvation. We believe all of these regulatory arms converge to increase transcription of pho1 (+) and some of the regulation acts through pho7 (+).

  7. Acceleration of dynamic fluorescence molecular tomography with principal component analysis

    PubMed Central

    Zhang, Guanglei; He, Wei; Pu, Huangsheng; Liu, Fei; Chen, Maomao; Bai, Jing; Luo, Jianwen

    2015-01-01

    Dynamic fluorescence molecular tomography (FMT) is an attractive imaging technique for three-dimensionally resolving the metabolic process of fluorescent biomarkers in small animal. When combined with compartmental modeling, dynamic FMT can be used to obtain parametric images which can provide quantitative pharmacokinetic information for drug development and metabolic research. However, the computational burden of dynamic FMT is extremely huge due to its large data sets arising from the long measurement process and the densely sampling device. In this work, we propose to accelerate the reconstruction process of dynamic FMT based on principal component analysis (PCA). Taking advantage of the compression property of PCA, the dimension of the sub weight matrix used for solving the inverse problem is reduced by retaining only a few principal components which can retain most of the effective information of the sub weight matrix. Therefore, the reconstruction process of dynamic FMT can be accelerated by solving the smaller scale inverse problem. Numerical simulation and mouse experiment are performed to validate the performance of the proposed method. Results show that the proposed method can greatly accelerate the reconstruction of parametric images in dynamic FMT almost without degradation in image quality. PMID:26114027

  8. Acceleration of dynamic fluorescence molecular tomography with principal component analysis.

    PubMed

    Zhang, Guanglei; He, Wei; Pu, Huangsheng; Liu, Fei; Chen, Maomao; Bai, Jing; Luo, Jianwen

    2015-06-01

    Dynamic fluorescence molecular tomography (FMT) is an attractive imaging technique for three-dimensionally resolving the metabolic process of fluorescent biomarkers in small animal. When combined with compartmental modeling, dynamic FMT can be used to obtain parametric images which can provide quantitative pharmacokinetic information for drug development and metabolic research. However, the computational burden of dynamic FMT is extremely huge due to its large data sets arising from the long measurement process and the densely sampling device. In this work, we propose to accelerate the reconstruction process of dynamic FMT based on principal component analysis (PCA). Taking advantage of the compression property of PCA, the dimension of the sub weight matrix used for solving the inverse problem is reduced by retaining only a few principal components which can retain most of the effective information of the sub weight matrix. Therefore, the reconstruction process of dynamic FMT can be accelerated by solving the smaller scale inverse problem. Numerical simulation and mouse experiment are performed to validate the performance of the proposed method. Results show that the proposed method can greatly accelerate the reconstruction of parametric images in dynamic FMT almost without degradation in image quality.

  9. 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.

  10. 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.

  11. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. 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…

  13. [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.

  14. Robustness and epistasis in mutation-selection models

    NASA Astrophysics Data System (ADS)

    Wolff, Andrea; Krug, Joachim

    2009-09-01

    We investigate the fitness advantage associated with the robustness of a phenotype against deleterious mutations using deterministic mutation-selection models of a quasispecies type equipped with a mesa-shaped fitness landscape. We obtain analytic results for the robustness effect which become exact in the limit of infinite sequence length. Thereby, we are able to clarify a seeming contradiction between recent rigorous work and an earlier heuristic treatment based on mapping to a Schrödinger equation. We exploit the quantum mechanical analogy to calculate a correction term for finite sequence lengths and verify our analytic results by numerical studies. In addition, we investigate the occurrence of an error threshold for a general class of epistatic landscapes and show that diminishing epistasis is a necessary but not sufficient condition for error threshold behaviour.

  15. Epistasis-Induced Evolutionary Plateaus in Selection Responses.

    PubMed

    Le Rouzic, Arnaud; Álvarez-Castro, José M

    2016-12-01

    Understanding and predicting evolution is a central challenge in both population and quantitative genetics. The amount of genetic variance for quantitative traits available in a population conditions the particular way in which this population will (or will not) evolve under natural or artificial selection. Here, we explore the potential of gene-gene interactions (epistasis) to induce evolutionary plateaus at which evolutionary change virtually collapses for a number of generations, followed by the release of previously cryptic genetic variation. First, we demonstrate theoretically that a wide range of epistatic interactions has the potential to generate temporary decelerations in the course of response to selection. Second, we perform simulations to show that such microevolutionary plateaus may occur in selection responses under empirically based assumptions. Finally, we show that such events can be traced in artificial selection experiments, thus providing further empirical evidence for this phenomenon.

  16. Influence of epistasis on response to genomic selection using complete sequence data.

    PubMed

    Forneris, Natalia S; Vitezica, Zulma G; Legarra, Andres; Pérez-Enciso, Miguel

    2017-08-25

    The effect of epistasis on response to selection is a highly debated topic. Here, we investigated the impact of epistasis on response to sequence-based selection via genomic best linear prediction (GBLUP) in a regime of strong non-symmetrical epistasis under divergent selection, using real Drosophila sequence data. We also explored the possible advantage of including epistasis in the evaluation model and/or of knowing the causal mutations. Response to selection was almost exclusively due to changes in allele frequency at a few loci with a large effect. Response was highly asymmetric (about four phenotypic standard deviations higher for upward than downward selection) due to the highly skewed site frequency spectrum. Epistasis accentuated this asymmetry and affected response to selection by modulating the additive genetic variance, which was sustained for longer under upward selection whereas it eroded rapidly under downward selection. Response to selection was quite insensitive to the evaluation model, especially under an additive scenario. Nevertheless, including epistasis in the model when there was none eventually led to lower accuracies as selection proceeded. Accounting for epistasis in the model, if it existed, was beneficial but only in the medium term. There was not much gain in response if causal mutations were known, compared to using sequence data, which is likely due to strong linkage disequilibrium, high heritability and availability of phenotypes on candidates. Epistatic interactions affect the response to genomic selection by modulating the additive genetic variance used for selection. Epistasis releases additive variance that may increase response to selection compared to a pure additive genetic action. Furthermore, genomic evaluation models and, in particular, GBLUP are robust, i.e. adding complexity to the model did not modify substantially the response (for a given architecture).

  17. 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.

  18. 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.

  19. Epistasis and its relationship to canalization in the RNA virus phi 6.

    PubMed Central

    Burch, Christina L; Chao, Lin

    2004-01-01

    Although deleterious mutations are believed to play a critical role in evolution, assessing their realized effect has been difficult. A key parameter governing the effect of deleterious mutations is the nature of epistasis, the interaction between the mutations. RNA viruses should provide one of the best systems for investigating the nature of epistasis because the high mutation rate allows a thorough investigation of mutational effects and interactions. Nonetheless, previous investigations of RNA viruses by S. Crotty and co-workers and by S. F. Elena have been unable to detect a significant effect of epistasis. Here we provide evidence that positive epistasis is characteristic of deleterious mutations in the RNA bacteriophage phi 6. We estimated the effects of deleterious mutations by performing mutation-accumulation experiments on five viral genotypes of decreasing fitness. We inferred positive epistasis because viral genotypes with low fitness were found to be less sensitive to deleterious mutations. We further examined environmental sensitivity in these genotypes and found that low-fitness genotypes were also less sensitive to environmental perturbations. Our results suggest that even random mutations impact the degree of canalization, the buffering of a phenotype against genetic and environmental perturbations. In addition, our results suggest that genetic and environmental canalization have the same developmental basis and finally that an understanding of the nature of epistasis may first require an understanding of the nature of canalization. PMID:15238511

  20. 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

  1. Epistasis together with partial dominance, over-dominance and QTL by environment interactions contribute to yield heterosis in upland cotton.

    PubMed

    Shang, Lianguang; Liang, Qingzhi; Wang, Yumei; Zhao, Yanpeng; Wang, Kunbo; Hua, Jinping

    2016-07-01

    QTL mapping based on backcross and RIL populations suggests that epistasis together with partial dominance, over-dominance and their environmental interactions of QTLs play an important role in yield heterosis in upland cotton. A backcross population (BC) was constructed to explore the genetic basis of heterosis in upland cotton (Gossypium hirsutum L.). For yield and yield components, recombinant inbred line (RIL) and BC populations were evaluated simultaneously at three different locations. A total of 35 and 30 quantitative trait loci (QTLs) were detected based on the RILs and BC data, respectively. Six (16.7 %) additive QTLs, 19 (52.8 %) partial dominant QTLs and 11 (30.6 %) over-dominant QTLs were detected by single-locus analysis using composite interval mapping in BC population. QTLs detected for mid-parent heterosis (MPH) were mostly related to those detected in the BC population. No significant correlation was found between marker heterozygosity and performance. It indicated that heterozygosity was not always favorable for performance. Two-locus analysis revealed 46, 25 and 12 QTLs with main effects (M-QTLs), and 55, 63 and 33 QTLs involved in digenic interactions (E-QTLs) were detected for yield and yield components in RIL, BC and MPH, respectively. A large number of M-QTLs and E-QTLs showed QTL by environment interactions (QEs) in three environments. These results suggest that epistasis together with partial dominance, over-dominance and QEs all contribute to yield heterosis in upland cotton.

  2. 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.

  3. 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).

  4. Bayesian accelerated failure time analysis with application to veterinary epidemiology.

    PubMed

    Bedrick, E J; Christensen, R; Johnson, W O

    2000-01-30

    Standard methods for analysing survival data with covariates rely on asymptotic inferences. Bayesian methods can be performed using simple computations and are applicable for any sample size. We propose a practical method for making prior specifications and discuss a complete Bayesian analysis for parametric accelerated failure time regression models. We emphasize inferences for the survival curve rather than regression coefficients. A key feature of the Bayesian framework is that model comparisons for various choices of baseline distribution are easily handled by the calculation of Bayes factors. Such comparisons between non-nested models are difficult in the frequentist setting. We illustrate diagnostic tools and examine the sensitivity of the Bayesian methods. Copyright 2000 John Wiley & Sons, Ltd.

  5. Model Independent Analysis of Beam Centroid Dynamics in Accelerators

    SciTech Connect

    Wang, Chun-xi

    2003-04-21

    Fundamental issues in Beam-Position-Monitor (BPM)-based beam dynamics observations are studied in this dissertation. The major topic is the Model-Independent Analysis (MIA) of beam centroid dynamics. Conventional beam dynamics analysis requires a certain machine model, which itself of ten needs to be refined by beam measurements. Instead of using any particular machine model, MIA relies on a statistical analysis of the vast amount of BPM data that often can be collected non-invasively during normal machine operation. There are two major parts in MIA. One is noise reduction and degrees-of-freedom analysis using a singular value decomposition of a BPM-data matrix, which constitutes a principal component analysis of BPM data. The other is a physical base decomposition of the BPM-data matrix based on the time structure of pulse-by-pulse beam and/or machine parameters. The combination of these two methods allows one to break the resolution limit set by individual BPMs and observe beam dynamics at more accurate levels. A physical base decomposition is particularly useful for understanding various beam dynamics issues. MIA improves observation and analysis of beam dynamics and thus leads to better understanding and control of beams in both linacs and rings. The statistical nature of MIA makes it potentially useful in other fields. Another important topic discussed in this dissertation is the measurement of a nonlinear Poincare section (one-turn) map in circular accelerators. The beam dynamics in a ring is intrinsically nonlinear. In fact, nonlinearities are a major factor that limits stability and influences the dynamics of halos. The Poincare section map plays a basic role in characterizing and analyzing such a periodic nonlinear system. Although many kinds of nonlinear beam dynamics experiments have been conducted, no direct measurement of a nonlinear map has been reported for a ring in normal operation mode. This dissertation analyzes various issues concerning map

  6. Learning genetic epistasis using Bayesian network scoring criteria

    PubMed Central

    2011-01-01

    Background Gene-gene epistatic interactions likely play an important role in the genetic basis of many common diseases. Recently, machine-learning and data mining methods have been developed for learning epistatic relationships from data. A well-known combinatorial method that has been successfully applied for detecting epistasis is Multifactor Dimensionality Reduction (MDR). Jiang et al. created a combinatorial epistasis learning method called BNMBL to learn Bayesian network (BN) epistatic models. They compared BNMBL to MDR using simulated data sets. Each of these data sets was generated from a model that associates two SNPs with a disease and includes 18 unrelated SNPs. For each data set, BNMBL and MDR were used to score all 2-SNP models, and BNMBL learned significantly more correct models. In real data sets, we ordinarily do not know the number of SNPs that influence phenotype. BNMBL may not perform as well if we also scored models containing more than two SNPs. Furthermore, a number of other BN scoring criteria have been developed. They may detect epistatic interactions even better than BNMBL. Although BNs are a promising tool for learning epistatic relationships from data, we cannot confidently use them in this domain until we determine which scoring criteria work best or even well when we try learning the correct model without knowledge of the number of SNPs in that model. Results We evaluated the performance of 22 BN scoring criteria using 28,000 simulated data sets and a real Alzheimer's GWAS data set. Our results were surprising in that the Bayesian scoring criterion with large values of a hyperparameter called α performed best. This score performed better than other BN scoring criteria and MDR at recall using simulated data sets, at detecting the hardest-to-detect models using simulated data sets, and at substantiating previous results using the real Alzheimer's data set. Conclusions We conclude that representing epistatic interactions using BN models

  7. CAFE: aCcelerated Alignment-FrEe sequence analysis.

    PubMed

    Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A; Waterman, Michael S; Sun, Fengzhu

    2017-05-03

    Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, $d_2^*$ and $d_2^S$ are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. CDC7/DBF4 functions in the translesion synthesis branch of the RAD6 epistasis group in Saccharomyces cerevisiae.

    PubMed Central

    Pessoa-Brandão, Luis; Sclafani, Robert A

    2004-01-01

    CDC7 and DBF4 encode the essential Cdc7-Dbf4 protein kinase required for DNA replication in eukaryotes from yeast to human. Cdc7-Dbf4 is also required for DNA damage-induced mutagenesis, one of several postreplicational DNA damage tolerance mechanisms mediated by the RAD6 epistasis group. Several genes have been determined to function in separate branches within this group, including RAD5, REV3/REV7 (Pol zeta), RAD30 (Pol eta), and POL30 (PCNA). An extensive genetic analysis of the interactions between CDC7 and REV3, RAD30, RAD5, or POL30 in response to DNA damage was done to determine its role in the RAD6 pathway. CDC7, RAD5, POL30, and RAD30 were found to constitute four separate branches of the RAD6 epistasis group in response to UV and MMS exposure. CDC7 is also shown to function separately from REV3 in response to MMS. However, they belong in the same pathway in response to UV. We propose that the Cdc7-Dbf4 kinase associates with components of the translesion synthesis pathway and that this interaction is dependent upon the type of DNA damage. Finally, activation of the DNA damage checkpoint and the resulting cell cycle delay is intact in cdc7Delta mcm5-bob1 cells, suggesting a direct role for CDC7 in DNA repair/damage tolerance. PMID:15342501

  9. Hybrid breakdown caused by epistasis-based recessive incompatibility in a cross of rice (Oryza sativa L.).

    PubMed

    Matsubara, Kazuki; Yamamoto, Eiji; Mizobuchi, Ritsuko; Yonemaru, Jun-ichi; Yamamoto, Toshio; Kato, Hiroshi; Yano, Masahiro

    2015-01-01

    Viability and fertility in organisms depend on epistatic interactions between loci maintained in lineages. Here, we describe reduced fitness of segregants (hybrid breakdown, HB) that emerged in an F2 population derived from a cross between 2 rice (Oryza sativa L.) cultivars, "Tachisugata" (TS) and "Hokuriku 193" (H193), despite both parents and F1s showing normal fitness. Quantitative trait locus (QTL) analyses detected 13 QTLs for 4 morphological traits associated with the HB and 6 associated with principal component scores calculated from values of the morphological traits in the F2 population. Two-way analysis of variance of the putative QTLs identified 4 QTL pairs showing significant epistasis; among them, a pair on chromosomes 1 and 12 made the greatest contribution to HB. The finding was supported by genetic experiments using F3 progeny. HB emerged only when a plant was homozygous for the TS allele at the QTL on chromosome 1 and homozygous for the H193 allele at the QTL on chromosome 12, indicating that each allele behaves as recessive to the other. Our results support the idea that epistasis is an essential part of hybrid fitness.

  10. 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

  11. 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

  12. Two rules for the detection and quantification of epistasis and other interaction effects.

    PubMed

    Wagner, Günter P

    2015-01-01

    Traditionally statistical interactions and epistasis are defined with respect to the ANOVA model of additive effects; that is, epistasis is defined as a deviation from the additive mode of combining main effects of gene substitutions. Furthermore, the definition is relative to a particular scale and epistasis can potentially be eliminated by a non-linear transformation of the underlying phenotype variables. The latter fact raises questions of the scientific validity of the concept if interaction, given its presumed arbitrariness. Here I am arguing that the arbitrariness in the definition and detection of epistasis, and any other interaction, can be eliminated if we observe measurement theoretical constraints on the treatment of quantitative data. I propose two principles for determining the appropriate reference model for the detection of epistasis. The first is the principle of effect propagation stating that the scale type of the effect measure determines the reference model for defining epistasis. For instance, if effects are measured as differences, then the reference model has to be additive. If the reference effects are fold differences, then the reference model has to be multiplicative. A mathematical justification for this rule is provided. The second principle is called irrelevant effects and derives from the principle of meaningfulness in measurement theory. In short, the rule says that the reference model is determined by the allowable scale transformations of the variables measured. The justification for this rule is that any mathematical model in which these variables figure have to be invariant to allowable scale transformations. These two rules can effectively eliminate the arbitrariness in the definition, detection, and quantification of epistasis or any other interaction effect.

  13. 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

  14. Multiple drug resistance genes in malaria -- from epistasis to epidemiology.

    PubMed

    Duraisingh, Manoj T; Refour, Philippe

    2005-08-01

    A decline in our ability to successfully treat patients with malaria infections of the parasitic protozoan Plasmodium falciparum with cheap quinoline drugs has led to a huge escalation in morbidity and mortality in recent years. Many approaches have been taken, including classical genetics, reverse genetics and molecular epidemiology, to identify the molecular determinants underlying this resistance. The contribution of the P. falciparum multidrug resistance gene, pfmdr1, to antimalarial resistance has been a source of controversy for over a decade since it was first identified. In the current issue of Molecular Microbiology, Sidhu and colleagues use powerful reverse genetics to demonstrate the importance of commonly occurring alleles of pfmdr1 in conferring resistance to the second-line drugs quinine and sensitivity to the new alternatives mefloquine and artemisinin. They also elegantly highlight the importance of genetic background and epistasis between pfmdr1 and other potential modulators of drug resistance. Such molecular knowledge will facilitate surveillance/monitoring and aid the development of strategies for the reversal of resistance.

  15. Multidimensional Epistasis and the Transitory Advantage of Sex

    PubMed Central

    Nowak, Stefan; Neidhart, Johannes; Szendro, Ivan G.; Krug, Joachim

    2014-01-01

    Identifying and quantifying the benefits of sex and recombination is a long-standing problem in evolutionary theory. In particular, contradictory claims have been made about the existence of a benefit of recombination on high dimensional fitness landscapes in the presence of sign epistasis. Here we present a comparative numerical study of sexual and asexual evolutionary dynamics of haploids on tunably rugged model landscapes under strong selection, paying special attention to the temporal development of the evolutionary advantage of recombination and the link between population diversity and the rate of adaptation. We show that the adaptive advantage of recombination on static rugged landscapes is strictly transitory. At early times, an advantage of recombination arises through the possibility to combine individually occurring beneficial mutations, but this effect is reversed at longer times by the much more efficient trapping of recombining populations at local fitness peaks. These findings are explained by means of well-established results for a setup with only two loci. In accordance with the Red Queen hypothesis the transitory advantage can be prolonged indefinitely in fluctuating environments, and it is maximal when the environment fluctuates on the same time scale on which trapping at local optima typically occurs. PMID:25232825

  16. 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

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

    PubMed

    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 the

  18. 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

  19. 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.

  20. 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

    2016-05-07

    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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Long-Range Epistasis Mediated by Structural Change in a Model of Ligand Binding Proteins.

    PubMed

    Nelson, Erik D; Grishin, Nick V

    2016-01-01

    Recent analyses of amino acid mutations in proteins reveal that mutations at many pairs of sites are epistatic-i.e., their effects on fitness are non-additive-the combined effect of two mutations being significantly larger or smaller than the sum of their effects considered independently. Interestingly, epistatic sites are not necessarily near each other in the folded structure of a protein, and may even be located on opposite sides of a molecule. However, the mechanistic reasons for long-range epistasis remain obscure. Here, we study long-range epistasis in proteins using a previously developed model in which off-lattice polymers are evolved under ligand binding constraints. Epistatic effects in the model are qualitatively similar to those recently reported for small proteins, and many are long-range. We find that a major reason for long-range epistasis is conformational change-a recurrent theme in both positive and negative epistasis being the transfer, or exchange of material between the ordered nucleus, which supports the binding site, and the liquid-like surface of a folded molecule. These local transitions in phase and folded structure are largely responsible for long-range epistasis in our model.

  2. Long-Range Epistasis Mediated by Structural Change in a Model of Ligand Binding Proteins

    PubMed Central

    Grishin, Nick V.

    2016-01-01

    Recent analyses of amino acid mutations in proteins reveal that mutations at many pairs of sites are epistatic—i.e., their effects on fitness are non—additive—the combined effect of two mutations being significantly larger or smaller than the sum of their effects considered independently. Interestingly, epistatic sites are not necessarily near each other in the folded structure of a protein, and may even be located on opposite sides of a molecule. However, the mechanistic reasons for long–range epistasis remain obscure. Here, we study long–range epistasis in proteins using a previously developed model in which off–lattice polymers are evolved under ligand binding constraints. Epistatic effects in the model are qualitatively similar to those recently reported for small proteins, and many are long–range. We find that a major reason for long–range epistasis is conformational change—a recurrent theme in both positive and negative epistasis being the transfer, or exchange of material between the ordered nucleus, which supports the binding site, and the liquid–like surface of a folded molecule. These local transitions in phase and folded structure are largely responsible for long–range epistasis in our model. PMID:27870911

  3. High-performance computing in accelerating structure design and analysis

    NASA Astrophysics Data System (ADS)

    Li, Zenghai; Folwell, Nathan; Ge, Lixin; Guetz, Adam; Ivanov, Valentin; Kowalski, Marc; Lee, Lie-Quan; Ng, Cho-Kuen; Schussman, Greg; Stingelin, Lukas; Uplenchwar, Ravindra; Wolf, Michael; Xiao, Liling; Ko, Kwok

    2006-03-01

    Future high-energy accelerators such as the Next Linear Collider (NLC) will accelerate multi-bunch beams of high current and low emittance to obtain high luminosity, which put stringent requirements on the accelerating structures for efficiency and beam stability. While numerical modeling has been quite standard in accelerator R&D, designing the NLC accelerating structure required a new simulation capability because of the geometric complexity and level of accuracy involved. Under the US DOE Advanced Computing initiatives (first the Grand Challenge and now SciDAC), SLAC has developed a suite of electromagnetic codes based on unstructured grids and utilizing high-performance computing to provide an advanced tool for modeling structures at accuracies and scales previously not possible. This paper will discuss the code development and computational science research (e.g. domain decomposition, scalable eigensolvers, adaptive mesh refinement) that have enabled the large-scale simulations needed for meeting the computational challenges posed by the NLC as well as projects such as the PEP-II and RIA. Numerical results will be presented to show how high-performance computing has made a qualitative improvement in accelerator structure modeling for these accelerators, either at the component level (single cell optimization), or on the scale of an entire structure (beam heating and long-range wakefields).

  4. High-Performance Computing in Accelerating Structure Design And Analysis

    SciTech Connect

    Li, Z.H.; Folwell, N.; Ge, Li-Xin; Guetz, A.; Ivanov, V.; Kowalski, M.; Lee, L.Q.; Ng, C.K.; Schussman, G.; Stingelin, L.; Uplenchwar, R.; Wolf, M.; Xiao, L.L.; Ko, K.; /SLAC /PSI, Villigen /Illinois U., Urbana

    2006-06-27

    Future high-energy accelerators such as the Next Linear Collider (NLC) will accelerate multi-bunch beams of high current and low emittance to obtain high luminosity, which put stringent requirements on the accelerating structures for efficiency and beam stability. While numerical modeling has been quite standard in accelerator R&D, designing the NLC accelerating structure required a new simulation capability because of the geometric complexity and level of accuracy involved. Under the US DOE Advanced Computing initiatives (first the Grand Challenge and now SciDAC), SLAC has developed a suite of electromagnetic codes based on unstructured grids and utilizing high performance computing to provide an advanced tool for modeling structures at accuracies and scales previously not possible. This paper will discuss the code development and computational science research (e.g. domain decomposition, scalable eigensolvers, adaptive mesh refinement) that have enabled the large-scale simulations needed for meeting the computational challenges posed by the NLC as well as projects such as the PEP-II and RIA. Numerical results will be presented to show how high performance computing has made a qualitative improvement in accelerator structure modeling for these accelerators, either at the component level (single cell optimization), or on the scale of an entire structure (beam heating and long range wakefields).

  5. Analysis of dynamic EMG and acceleration measurements in Parkinson's disease.

    PubMed

    Rissanen, Saara M; Kankaanpaa, Markku; Tarvainen, Mika P; Meigal, Alexander; Nuutinen, Juho; Tarkka, Ina M; Airaksinen, Olavi; Karjalainen, Pasi A

    2008-01-01

    In this paper, we bring out modern methods that are potential in analysing differences in the dynamic surface electromyographic (EMG) and acceleration measurements between patients with Parkinson's disease (PD) and healthy persons. These methods are the correlation dimension of EMG, the recurrence rate of EMG, the power of acceleration and the sample entropy of acceleration. In this study, these methods were used to extract features from surface EMG and acceleration recordings measured during elbow flexion and extension movements. The extracted features were used to form high-dimensional feature vectors and the dimensionality of these vectors was then reduced by using the principal component approach. Finally, the feature vectors were discriminated between subjects by using the principal components. The discrimination power of the presented approach was tested with EMG and acceleration data measured from 46 patients with PD (on-medication) and 59 healthy controls. Discrimination results showed that the present method was able to discriminate dynamic EMG and acceleration recordings between patients with PD and healthy controls. Therefore, dynamic surface EMG and acceleration measurements may have potential in the objective and quantitative assessment and diagnosis of PD.

  6. Accelerating next generation sequencing data analysis with system level optimizations.

    PubMed

    Kathiresan, Nagarajan; Temanni, Ramzi; Almabrazi, Hakeem; Syed, Najeeb; Jithesh, Puthen V; Al-Ali, Rashid

    2017-08-22

    Next generation sequencing (NGS) data analysis is highly compute intensive. In-memory computing, vectorization, bulk data transfer, CPU frequency scaling are some of the hardware features in the modern computing architectures. To get the best execution time and utilize these hardware features, it is necessary to tune the system level parameters before running the application. We studied the GATK-HaplotypeCaller which is part of common NGS workflows, that consume more than 43% of the total execution time. Multiple GATK 3.x versions were benchmarked and the execution time of HaplotypeCaller was optimized by various system level parameters which included: (i) tuning the parallel garbage collection and kernel shared memory to simulate in-memory computing, (ii) architecture-specific tuning in the PairHMM library for vectorization, (iii) including Java 1.8 features through GATK source code compilation and building a runtime environment for parallel sorting and bulk data transfer (iv) the default 'on-demand' mode of CPU frequency is over-clocked by using 'performance-mode' to accelerate the Java multi-threads. As a result, the HaplotypeCaller execution time was reduced by 82.66% in GATK 3.3 and 42.61% in GATK 3.7. Overall, the execution time of NGS pipeline was reduced to 70.60% and 34.14% for GATK 3.3 and GATK 3.7 respectively.

  7. Preliminary analysis of accelerated space flight ionizing radiation testing

    NASA Technical Reports Server (NTRS)

    Wilson, J. W.; Stock, L. V.; Carter, D. J.; Chang, C. K.

    1982-01-01

    A preliminary analysis shows that radiation dose equivalent to 30 years in the geosynchronous environment can be accumulated in a typical composite material exposed to space for 2 years or less onboard a spacecraft orbiting from perigee of 300 km out to the peak of the inner electron belt (approximately 2750 km). Future work to determine spacecraft orbits better tailored to materials accelerated testing is indicated. It is predicted that a range of 10 to the 9th power to 10 to the 10th power rads would be accumulated in 3-6 mil thick epoxy/graphite exposed by a test spacecraft orbiting in the inner electron belt. This dose is equivalent to the accumulated dose that this material would be expected to have after 30 years in a geosynchronous orbit. It is anticipated that material specimens would be brought back to Earth after 2 years in the radiation environment so that space radiation effects on materials could be analyzed by laboratory methods.

  8. Photon Activation Analysis at the Idaho Accelerator Center

    SciTech Connect

    Wells, Douglas P.; Cole, Philip L.; Segebade, Christian R.

    2010-08-04

    Activation methods require minimal sample preparation and provide sufficiently high sensitivity for detecting the vast majority of the elements throughout the periodic table. In this paper we shall discuss photon activation analysis (PAA) at the Idaho Accelerator Center. The process of PAA begins with exposing a sample with photons in the energy range of 10 to 30 MeV. Many nuclides in the sample will become activated and, in turn, these radionuclides will decay by emitting characteristic radiation. These characteristic radiation decays are the telltale signatures for identifying elements which can then be measured with spectrometers such as a high-purity Germanium detector. PAA is not an 'absolute' method, as the samples under investigation must be irradiated along with a reference or calibrating material having a well-known elemental composition. The quantitative evaluation is performed through comparing the two resulting element spectra from the unknown sample and reference material. Besides the obvious advantage of being non-destructive, PAA has minimal contamination issues. Moreover, materials that are difficult to treat chemically, such as certain refractory metals, dusts, ashes, etc., offer no hindrance to the technique of PAA. A further advantage is that PAA is very well suited for investigated minute samples (sub-milligram dust particles) to very large ones (in the multi-kg range). PAA is a robust technique as there are no real limitations concerning the nature of material to be studied.

  9. Analysis of electron acceleration in a vacuum beat wave

    NASA Astrophysics Data System (ADS)

    Salamin, Yousef I.; Keitel, Christoph H.

    2000-11-01

    We present an exact analytic investigation of the electron dynamics in the field of two linearly polarized interfering copropagating laser beams of different frequencies, arbitrary intensities, and arbitrary relative polarizations. In one part of the paper, the laser fields are modelled by plane waves and in another part the fields are allowed to have one-dimensional sin2 pulse shapes which model focusing in the propagation direction. The general situation in which the electron is injected at an angle with the common direction of wave propagation is considered throughout. A cycle-by-cycle analysis of the electron motion, and its momentum and energy exchange with the laser fields is conducted. It is found that an electron may be accelerated, even from rest, to GeV energies over short distances using present-day laser field intensities. This leads, in principle, to energy gradients in the TeV m-1 range. The trajectory calculations also show clearly that the electron gets scattered away from its initial direction of motion during interaction with the laser fields. The transverse as well as longitudinal motions may be followed exactly using our equations, and predictions could thus be made concerning where the electron should, in principle, be ejected in order for it to emerge with a particular energy gain.

  10. [Failure analysis of medical linear accelerator with reliability analyses].

    PubMed

    Zakimi, Ken; Watanabe, Hiroyuki; Ishida, Hideki; Take, Toshio; Kato, Mitsuyoshi; Iwai, Tsugunori; Nitta, Masaru; Kato, Kyouichi; Nakazawa, Yasuo

    2014-12-01

    We analyzed a number of cases about the Linac troubles in our hospital and have examined the effect of preventive maintenance with Weibull analysis and exponential distribution from April 2001 to March 2012. The total failure by irradiation disabled was 1, 192. (1) Medical linear accelerator (MLC) system was 24.0%, (2) radiation dosimetry system 13.1%, and the (3) cooling-water system was 26.5%. It accounts for 63.6% of the total number of failures. Each parameter value m, which means the shape parameter, and the failure period expectancy of parts μ were (1) 1.21, 1.46/3.9, 3.8 years. 3.7, 3.6 years. (2) 2.84, 1.59/6.6, 4.3 years. 6.7, 5.9 years. (3) 5.12, 4.16/6.1, 8.5 years. 6.1, 8.5 years. Each shape parameter was m>1. It is believed that they are in the worn-out failure period. To prevent failure, MLC performance should be overhauled once every 3 years and a cooling unit should be overhauled once every 7 years. Preventive maintenance is useful in assessing the failure of radiation therapy equipment. In a radiation dosimetry part, you can make a preemptive move before the failure by changing the monitor's dosimeter board with a new part from the repairs stockpiled every 6 months for maintenance.

  11. 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

  12. Field analysis of a dielectric-loaded rectangular waveguide accelerating structure

    NASA Astrophysics Data System (ADS)

    Xiao, Liling; Gai, Wei; Sun, Xiang

    2002-01-01

    Recently, there has been some interest in planar or rectangular dielectric accelerating structures for future high-gradient linear accelerators. In this paper, we present a detailed analysis of the modes of a dielectric-loaded rectangular waveguide accelerating structure based on a circuit model approximation and mode matching method. In general, the acceleration field in a synchronous acceleration mode is nonuniform in the two transverse dimensions. We show, however, that by using a series of rectangular structures successively rotated by 90°, the net accelerating force can be made almost uniform. Characteristic parameters such as R/Q, group velocity, and attenuation constant for X- and W-band accelerators are calculated. The longitudinal wakefields experienced by a relativistic charged particle beam in these structures are also presented. These analytical results are also compared with numerical calculations using the MAFIA code suite demonstrating the validity of our analytic approach.

  13. Field analysis of a dielectric-loaded rectangular waveguide accelerating structure.

    PubMed

    Xiao, Liling; Gai, Wei; Sun, Xiang

    2002-01-01

    Recently, there has been some interest in planar or rectangular dielectric accelerating structures for future high-gradient linear accelerators. In this paper, we present a detailed analysis of the modes of a dielectric-loaded rectangular waveguide accelerating structure based on a circuit model approximation and mode matching method. In general, the acceleration field in a synchronous acceleration mode is nonuniform in the two transverse dimensions. We show, however, that by using a series of rectangular structures successively rotated by 90 degrees, the net accelerating force can be made almost uniform. Characteristic parameters such as R/Q, group velocity, and attenuation constant for X- and W-band accelerators are calculated. The longitudinal wakefields experienced by a relativistic charged particle beam in these structures are also presented. These analytical results are also compared with numerical calculations using the MAFIA code suite demonstrating the validity of our analytic approach.

  14. Epistasis × environment interactions among Arabidopsis thaliana glucosinolate genes impact complex traits and fitness in the field.

    PubMed

    Kerwin, Rachel E; Feusier, Julie; Muok, Alise; Lin, Catherine; Larson, Brandon; Copeland, Daniel; Corwin, Jason A; Rubin, Matthew J; Francisco, Marta; Li, Baohua; Joseph, Bindu; Weinig, Cynthia; Kliebenstein, Daniel J

    2017-08-01

    Despite the growing number of studies showing that genotype × environment and epistatic interactions control fitness, the influences of epistasis × environment interactions on adaptive trait evolution remain largely uncharacterized. Across three field trials, we quantified aliphatic glucosinolate (GSL) defense chemistry, leaf damage, and relative fitness using mutant lines of Arabidopsis thaliana varying at pairs of causal aliphatic GSL defense genes to test the impact of epistatic and epistasis × environment interactions on adaptive trait variation. We found that aliphatic GSL accumulation was primarily influenced by additive and epistatic genetic variation, leaf damage was primarily influenced by environmental variation and relative fitness was primarily influenced by epistasis and epistasis × environment interactions. Epistasis × environment interactions accounted for up to 48% of the relative fitness variation in the field. At a single field site, the impact of epistasis on relative fitness varied significantly over 2 yr, showing that epistasis × environment interactions within a location can be temporally dynamic. These results suggest that the environmental dependency of epistasis can profoundly influence the response to selection, shaping the adaptive trajectories of natural populations in complex ways, and deserves further consideration in future evolutionary studies. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  15. 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.

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

    PubMed

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

    2013-08-02

    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.

  17. 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.

  18. Feature-Based Analysis of Plasma-Based Particle Acceleration Data

    SciTech Connect

    Rubel, 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.

  19. Capacitating epistasis--detection and role in the genetic architecture of complex traits.

    PubMed

    Pettersson, Mats E; Carlborg, Orjan

    2015-01-01

    Here, we discuss the potential role of capacitating epistasis in the genetic architecture of complex traits. Two alternative methods for identifying such gene-gene interactions in genetic association studies-mapping of variance controlling loci and the variance plane ratio (VPR) method-are introduced. An overview of the theoretical foundation of the methods is presented together with a discussion on their implementation and available software for performing these analyses. We conclude by highlighting a few examples of capacitating epistasis described in the literature and its potential impacts on the genetics of complex traits.

  20. Population Genetics of Marine Pelecypods. III. Epistasis between Functionally Related Isoenzymes of MYTILUS EDULIS

    PubMed Central

    Mitton, Jeffry B.; Koehn, Richard K.

    1973-01-01

    The distribution of interlocus genotypic combinations was examined in Mytilus edulis for interdependence between two loci synthesizing functionally related isoenzymes. There is significant dependence between the Leucine Aminopeptidase and Aminopeptidase loci, which we attribute to epistasis, since the magnitude of dependency varies with age. Furthermore, dependency varies in magnitude with position in the intertidal zone from which samples were taken, suggesting that epistasis is a function of the combination of certain non-homologous alleles as well as of the environmental circumstance in which the combinations occur. PMID:4700061

  1. Selective genotyping with epistasis can be utilized for a major quantitative trait locus mapping in hypertension in rats.

    PubMed Central

    Ohno, Y; Tanase, H; Nabika, T; Otsuka, K; Sasaki, T; Suzawa, T; Morii, T; Yamori, Y; Saruta, T

    2000-01-01

    Epistasis used to be considered an obstacle in mapping quantitative trait loci (QTL) despite its significance. Numerous epistases have proved to be involved in quantitative genetics. We established a backcross model that demonstrates a major QTL for hypertension (Ht). Seventy-eight backcrossed rats (BC), derived from spontaneously hypertensive rats (SHR) and normotensive Fischer 344 rats, showed bimodal distribution of systolic blood pressure (BP) values and a phenotypic segregation ratio consistent with 1:1. In this backcross analysis, sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (Serca) II heterozygotes showed widespread bimodality in frequency distribution of BP values and obviously demonstrated Ht. First, in genome-wide screening, Mapmaker/QTL analysis mapped Ht at a locus between D1Mgh8 and D1Mit4 near Sa in all 78 BC. The peak logarithm of the odds (LOD) score reached 5.3. Second, Serca II heterozygous and homozygous BC were analyzed separately using Mapmaker/QTL. In the 35 Serca II heterozygous BC, the peak LOD score was 3.8 at the same locus whereas it did not reach statistical significance in the 43 Serca II homozygotes. Third, to map Ht efficiently, we selected 18 Serca II heterozygous BC with 9 highest and 9 lowest BP values. In these 18 BC, the peak LOD score reached 8.1. In 17 of the 18, D1Mgh8 genotypes (homo or hetero) qualitatively cosegregated with BP phenotypes (high or low) (P < 0.0001, by chi-square analysis). In conclusion, selective genotyping with epistasis can be utilized for a major QTL mapping near Sa on chromosome 1 in SHR. PMID:10835399

  2. Analysis of powerful local acceleration of solar wind particles

    NASA Astrophysics Data System (ADS)

    Molotkov, I. A.; Ryabova, N. A.

    2017-07-01

    Collisionless plasma of the solar wind is considered. A number of physical processes in this plasma lead to the formation of magnetic islands that are potential traps for charged particles. The merging and contractions of magnetic islands cause a powerful acceleration of these particles to energies over 1 MeV. This work continues the study in recent years on modeling of the acceleration of charged particles of the solar wind. Our analytical solution of the transport equations allowed us to find the exact number of particles with energies exceeding given level.

  3. Improving power output of inertial energy harvesters by employing principal component analysis of input acceleration

    NASA Astrophysics Data System (ADS)

    Smilek, Jan; Hadas, Zdenek

    2017-02-01

    In this paper we propose the use of principal component analysis to process the measured acceleration data in order to determine the direction of acceleration with the highest variance on given frequency of interest. This method can be used for improving the power generated by inertial energy harvesters. Their power output is highly dependent on the excitation acceleration magnitude and frequency, but the axes of acceleration measurements might not always be perfectly aligned with the directions of movement, and therefore the generated power output might be severely underestimated in simulations, possibly leading to false conclusions about the feasibility of using the inertial energy harvester for the examined application.

  4. 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)

  5. eQTL epistasis: detecting epistatic effects and inferring hierarchical relationships of genes in biological pathways.

    PubMed

    Kang, Mingon; Zhang, Chunling; Chun, Hyung-Wook; Ding, Chris; Liu, Chunyu; Gao, Jean

    2015-03-01

    Epistasis is the interactions among multiple genetic variants. It has emerged to explain the 'missing heritability' that a marginal genetic effect does not account for by genome-wide association studies, and also to understand the hierarchical relationships between genes in the genetic pathways. The Fisher's geometric model is common in detecting the epistatic effects. However, despite the substantial successes of many studies with the model, it often fails to discover the functional dependence between genes in an epistasis study, which is an important role in inferring hierarchical relationships of genes in the biological pathway. We justify the imperfectness of Fisher's model in the simulation study and its application to the biological data. Then, we propose a novel generic epistasis model that provides a flexible solution for various biological putative epistatic models in practice. The proposed method enables one to efficiently characterize the functional dependence between genes. Moreover, we suggest a statistical strategy for determining a recessive or dominant link among epistatic expression quantitative trait locus to enable the ability to infer the hierarchical relationships. The proposed method is assessed by simulation experiments of various settings and is applied to human brain data regarding schizophrenia. The MATLAB source codes are publicly available at: http://biomecis.uta.edu/epistasis. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. 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.

  7. Combining growth-promoting genes leads to positive epistasis in Arabidopsis thaliana

    PubMed Central

    Vanhaeren, Hannes; Gonzalez, Nathalie; Coppens, Frederik; De Milde, Liesbeth; Van Daele, Twiggy; Vermeersch, Mattias; Eloy, Nubia B; Storme, Veronique; Inzé, Dirk

    2014-01-01

    Several genes positively influence final leaf size in Arabidopsis when mutated or overexpressed. The connections between these growth regulators are still poorly understood although such knowledge would further contribute to understand the processes driving leaf growth. In this study, we performed a combinatorial screen with 13 transgenic Arabidopsis lines with an increased leaf size. We found that from 61 analyzed combinations, 39% showed an additional increase in leaf size and most resulted from a positive epistasis on growth. Similar to what is found in other organisms in which such an epistasis assay was performed, only few genes were highly connected in synergistic combinations as we observed a positive epistasis in the majority of the combinations with samba, BRI1OE or SAUR19OE. Furthermore, positive epistasis was found with combinations of genes with a similar mode of action, but also with genes which affect distinct processes, such as cell proliferation and cell expansion. DOI: http://dx.doi.org/10.7554/eLife.02252.001 PMID:24843021

  8. 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

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

    PubMed Central

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

    2016-01-01

    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

  10. Case–Cohort Analysis with Accelerated Failure Time Model

    PubMed Central

    Kong, Lan; Cai, Jianwen

    2010-01-01

    Summary In a case–cohort design, covariates are assembled only for a subcohort that is randomly selected from the entire cohort and any additional cases outside the subcohort. This design is appealing for large cohort studies of rare disease, especially when the exposures of interest are expensive to ascertain for all the subjects. We propose statistical methods for analyzing the case–cohort data with a semiparametric accelerated failure time model that interprets the covariates effects as to accelerate or decelerate the time to failure. Asymptotic properties of the proposed estimators are developed. The finite sample properties of case–cohort estimator and its relative efficiency to full cohort estimator are assessed via simulation studies. A real example from a study of cardiovascular disease is provided to illustrate the estimating procedure. PMID:18537948

  11. Analysis of complex cardiovascular flow with three-component acceleration-encoded MRI.

    PubMed

    Barker, Alex J; Staehle, Felix; Bock, Jelena; Jung, Bernd A; Markl, Michael

    2012-01-01

    Functional information regarding cardiac performance, pressure gradients, and local flow derangement are available from blood acceleration fields. Thus, this study examines a 2D and 3D phase contrast sequence optimized to efficiently encode three-directional, time-resolved acceleration in vitro and in vivo. Stenosis phantom acceleration measurements were compared to acceleration derived from standard velocity encoded phase contrast-magnetic resonance imaging (i.e., "velocity-derived acceleration"). For in vivo analysis, three-directional 2D acceleration maps were compared to velocity-derived acceleration using regions proximal and distal to the aortic valve in six healthy volunteers at 1.5 and 3.0 T (voxel size = 1.4 × 2.1 × 8 mm, temporal resolution = 16-20 ms). In addition, a 4D acceleration sequence was evaluated for feasibility in a healthy volunteer and postrepair biscuspid aortic valve patient with an ascending aortic aneurysm. The phantom magnetic resonance acceleration measurements were more accurate (nonturbulent root mean square error = 2.2 vs. 5.1 m/s(2) for phase contrast-magnetic resonance imaging) and 10 times less noisy (nonturbulent σ = 0.9 vs. 13.6 m/s(2) for phase contrast-magnetic resonance imaging) than velocity-derived acceleration. Acceleration mapping of the left ventricular outflow tract and aortic arch exhibited signal voids colocated with complex flow events such as vortex formation and high order motion. 4D acceleration data, visualized in combination with the velocity data, may provide new insight into complex flow phenomena.

  12. 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

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

    PubMed

    Bürger, Reinhard

    2010-09-01

    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

  14. On accelerated flow of MHD powell–eyring fluid via homotopy analysis method

    NASA Astrophysics Data System (ADS)

    Salah, Faisal; Viswanathan, K. K.; Aziz, Zainal Abdul

    2017-09-01

    The aim of this article is to obtain the approximate analytical solution for incompressible magnetohydrodynamic (MHD) flow for Powell–Eyring fluid induced by an accelerated plate. Both constant and variable accelerated cases are investigated. Approximate analytical solution in each case is obtained by using the Homotopy Analysis Method (HAM). The resulting nonlinear analysis is carried out to generate the series solution. Finally, Graphical outcomes of different values of the material constants parameters on the velocity flow field are discussed and analyzed.

  15. Intra-rater and inter-rater reliabilities of real-time acceleration gait analysis system.

    PubMed

    Osaka, Hiroshi; Shinkoda, Koichi; Watanabe, Susumu; Fujita, Daisuke; Kobara, Kenichi; Yoshimura, Yosuke; Ito, Tomotaka

    2016-01-01

    The purposes of this study were to construct a real-time acceleration gait analysis system equipped with software to analyse real-time trunk acceleration during walking and to examine the intra-rater and inter-rater reliabilities of the this system. This system has been comprised of an accelerometer, an acceleration amplifier, a transmitter, two foot switches, a receiver and a personal computer installed with the real-time acceleration analysis software. The acceleration signals received were analysed using the real-time acceleration analysis software, and gait parameters were calculated. The subjects were 20 healthy individuals and two raters. The intra-rater and inter-rater reliabilities of the measurement results obtained from this system were examined by performing intraclass correlation coefficients (ICC) and Bland-Altman analysis. The intra-rater and inter-rater ICCs ranged from 0.61 to 0.92 in any gait parameters. In the Bland-Altman analysis, neither fixed nor proportional bias was found in any of the gait parameters. From the ICC and Bland-Altman analysis results, the gait measurement using this system clearly demonstrates that the intra-rater and inter-rater measurements had good reproducibility. Owing to this system, we can improve the clinical efficiency of gait analysis and gait training for physiotherapy. Implication for Rehabilitation This study focused on the advantage of a gait analysis method using an accelerometer and constructed a gait analysis system that calculates real-time gait parameters from trunk acceleration measurements during walking. The gait analysis using this system has good intra-rater and inter-rater reliabilities, and using this system can improve the clinical efficiency of gait analysis and gait training.

  16. 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.

  17. Beam Position Monitor and Energy Analysis at the Fermilab Accelerator Science and Technology Facility

    SciTech Connect

    Lopez, David Juarez

    2015-08-01

    Fermilab Accelerator Science and Technology Facility has produced its first beam with an energy of 20 MeV. This energy is obtained by the acceleration at the Electron Gun and the Capture Cavity 2 (CC2). When fully completed, the accelerator will consist of a photoinjector, one International Liner Collider (ILC)-type cryomodule, multiple accelerator R&D beamlines, and a downstream beamline to inject 300 MeV electrons into the Integrable Optics Test Accelerator (IOTA). We calculated the total energy of the beam and the corresponding energy to the Electron Gun and CC2. Subsequently, a Beam Position Monitors (BPM) error analysis was done, to calculate the device actual resolution.

  18. 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

  19. 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

  20. A universal postprocessing toolkit for accelerator simulation and data analysis.

    SciTech Connect

    Borland, M.

    1998-12-16

    The Self-Describing Data Sets (SDDS) toolkit comprises about 70 generally-applicable programs sharing a common data protocol. At the Advanced Photon Source (APS), SDDS performs the vast majority of operational data collection and processing, most data display functions, and many control functions. In addition, a number of accelerator simulation codes use SDDS for all post-processing and data display. This has three principle advantages: first, simulation codes need not provide customized post-processing tools, thus simplifying development and maintenance. Second, users can enhance code capabilities without changing the code itself, by adding SDDS-based pre- and post-processing. Third, multiple codes can be used together more easily, by employing SDDS for data transfer and adaptation. Given its broad applicability, the SDDS file protocol is surprisingly simple, making it quite easy for simulations to generate SDDS-compliant data. This paper discusses the philosophy behind SDDS, contrasting it with some recent trends, and outlines the capabilities of the toolkit. The paper also gives examples of using SDDS for accelerator simulation.

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

    DOE PAGES

    Li, W.; Thorne, R. M.; Bortnik, J.; ...

    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

  2. Coupled microvibration analysis of a reaction wheel assembly including gyroscopic effects in its accelerance

    NASA Astrophysics Data System (ADS)

    Zhang, Zhe; Aglietti, Guglielmo S.; Ren, Weijia

    2013-10-01

    This article discusses the coupled microvibration analysis of a cantilever configured Reaction Wheel Assembly with soft-suspension system. A RWA-seismic mass coupled microvibration measurement system is presented and its model validated against test results. The importance of the RWA driving point accelerances in coupled microvibration analysis is thoroughly discussed. A RWA accelerance measurement system has been designed to measure the driving point accelerances in both static (flywheel not spinning) and dynamic (flywheel spinning) conditions. Analytically, RWA static accelerance is obtained by frequency response analysis of a finite element model. The traditionally ignored gyroscopic effects in the accelerances are included in the model and their effects with respect to traditional models are shown both theoretically and experimentally. Although at high angular speed, when nonlinearities in the microvibrations prevent an accurate simulation, it is shown that the predicted microvibrations match more closely with the test results when considering gyroscopic effects in RWA accelerances than those predicted using the traditional method. The presented coupled microvibration analysis method is also very efficient in practice and is applicable in an industrial environment.

  3. CONTROL SYSTEM ANALYSIS FOR THE PERTURBED LINEAR ACCELERATOR RF SYSTEM

    SciTech Connect

    SUNG-IL KWON; AMY H. REGAN

    2002-04-10

    This paper addresses the modeling problem of the linear accelerator RF system in SNS. Klystrons are modeled as linear parameter varying systems. The effect of the high voltage power supply ripple on the klystron output voltage and the output phase is modeled as an additive disturbance. The cavity is modeled as a linear system and the beam current is modeled as the exogenous disturbance. The output uncertainty of the low level RF system which results from the uncertainties in the RF components and cabling is modeled as multiplicative uncertainty. Also, the feedback loop uncertainty and digital signal processing signal conditioning subsystem uncertainties are lumped together and are modeled as multiplicative uncertainty. Finally, the time delays in the loop are modeled as a lumped time delay. For the perturbed open loop system, the closed loop system performance, and stability are analyzed with the PI feedback controller.

  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. Accelerated rare event sampling: Refinement and Ising model analysis

    NASA Astrophysics Data System (ADS)

    Yevick, David; Lee, Yong Hwan

    In this paper, a recently introduced accelerated sampling technique [D. Yevick, Int. J. Mod. Phys. C 27, 1650041 (2016)] for constructing transition matrices is further developed and applied to a two-dimensional 32×32 Ising spin system. By permitting backward displacements up to a certain limit for each forward step while evolving the system to first higher and then lower energies within a restricted interval that is steadily displaced toward zero temperature as the computation proceeds, accuracy can be greatly enhanced. Simultaneously, the elements obtained from numerous independent calculations are collected in a single transition matrix. The relative accuracy of this novel method is established through a comparison to a transition matrix procedure based on the Metropolis algorithm in which the temperature is appropriately varied during the calculation and the results interpreted in terms of the distribution of realizations over both energy and magnetization.

  6. EPR analysis of the effects of accelerated carbon ion and fast neutron irradiations on table sugar.

    PubMed

    Mikou, M; Benzina, S; Bischoff, P; Denis, J M; Gueulette, J

    2009-09-01

    Table sugar samples were irradiated with accelerated carbon ions and fast neutrons. Electron paramagnetic resonance (EPR) analysis performed after the irradiation revealed a complex spectrum similar to that observed after gamma-ray irradiations. The total concentration of the paramagnetic centers induced by accelerated carbon ions and neutrons was proportional to the absorbed dose. Good stability of the produced free radicals was observed for a typical period of sugar storage. Sugar was more sensitive to accelerated carbon ions than to neutrons. The results show that table sugar can be a useful material for dosimetry in the case of a radiation accident.

  7. Epistasis and the temporal change in the additive variance-covariance matrix induced by drift.

    PubMed

    López-Fanjul, Carlos; Fernández, Almudena; Toro, Miguel A

    2004-08-01

    The effect of population bottlenecks on the components of the genetic covariance generated by two neutral independent epistatic loci has been studied theoretically (additive, covA; dominance, covD; additive-by-additive, covAA; additive-by-dominance, covAD; and dominance-by-dominance, covDD). The additive-by-additive model and a more general model covering all possible types of marginal gene action at the single-locus level (additive/dominance epistatic model) were considered. The covariance components in an infinitely large panmictic population (ancestral components) were compared with their expected values at equilibrium over replicates randomly derived from the base population, after t consecutive bottlenecks of equal size N (derived components). Formulae were obtained in terms of the allele frequencies and effects at each locus, the corresponding epistatic effects and the inbreeding coefficient Ft. These expressions show that the contribution of nonadditive loci to the derived additive covariance (covAt) does not linearly decrease with inbreeding, as in the pure additive case, and may initially increase or even change sign in specific situations. Numerical examples were also analyzed, restricted for simplicity to the case of all covariance components being positive. For additive-by-additive epistasis, the condition covAt > covA only holds for high frequencies of the allele decreasing the metric traits at each locus (negative allele) if epistasis is weak, or for intermediate allele frequencies if it is strong. For the additive/dominance epistatic model, however, covAt > covA applies for low frequencies of the negative alleles at one or both loci and mild epistasis, but this result can be progressively extended to intermediate frequencies as epistasis becomes stronger. Without epistasis the same qualitative results were found, indicating that marginal dominance induced by epistasis can be considered as the primary cause of an increase of the additive covariance

  8. 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.

  9. REVIEW: Epistasis and dominance in the emergence of catalytic function as exemplified by the evolution of plant terpene synthases.

    PubMed

    Cheema, Jitender; Faraldos, Juan A; O'Maille, Paul E

    2017-02-01

    Epistasis, the interaction between mutations and the genetic background, is a pervasive force in evolution that is difficult to predict yet derives from a simple principle - biological systems are interconnected. Therefore, one effect may be intimately linked to another, hence interdependent. Untangling epistatic interactions between and within genes is a vibrant area of research. Deriving a mechanistic understanding of epistasis is a major challenge. Particularly, elucidating how epistasis can attenuate the effects of otherwise dominant mutations that control phenotypes. Using the emergence of terpene cyclization in specialized metabolism as an excellent example, this review describes the process of discovery and interpretation of dominance and epistasis in relation to current efforts. Specifically, we outline experimental approaches to isolating epistatic networks of mutations in protein structure, formally quantifying epistatic interactions, then building biochemical models with chemical mechanisms in efforts to achieve an understanding of the physical basis for epistasis. From these models we describe informed conjectures about past evolutionary events that underlie the emergence, divergence and specialization of terpene synthases to illustrate key principles of the constraining forces of epistasis in enzyme function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family

    PubMed Central

    2017-01-01

    Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. PMID:28053111

  11. Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family.

    PubMed

    Redondo, Rodrigo A F; de Vladar, Harold P; Włodarski, Tomasz; Bollback, Jonathan P

    2017-01-01

    Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the ϕX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. © 2017 The Authors.

  12. 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

  13. 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

  14. 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.

  15. Phase space analysis of the accelerating multifluid Universe

    NASA Astrophysics Data System (ADS)

    Odintsov, S. D.; Oikonomou, V. K.; Tretyakov, Petr V.

    2017-08-01

    We study in detail the phase space of a Friedmann-Robertson-Walker universe filled with various cosmological fluids that may or may not interact. We use various expressions for the equation of state, and we analyze the physical significance of the resulting fixed points. In addition, we discuss the effects of the stability or an instability of some fixed points. Moreover, we study an interesting phenomenological scenario for which there is an oscillating interaction between the dark energy and dark matter fluid. As we demonstrate, in the context of the model we use, at early times the interaction is negligible, and it starts to grow as the cosmic time approaches the late-time era. Also the cosmological dynamical system is split into two distinct dynamical systems that have two distinct de Sitter fixed points, with the early-time de Sitter point being unstable. This framework gives an explicit example of the unification of the early-time with late-time acceleration. Finally, we discuss in some detail the physical interpretation of the various models we present in this work.

  16. 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.

  17. Hamiltonian analysis for linearly acceleration-dependent Lagrangians

    SciTech Connect

    Cruz, Miguel E-mail: roussjgc@gmail.com E-mail: efrojas@uv.mx; Gómez-Cortés, Rosario E-mail: roussjgc@gmail.com E-mail: efrojas@uv.mx; Rojas, Efraín E-mail: roussjgc@gmail.com E-mail: efrojas@uv.mx; Molgado, Alberto E-mail: roussjgc@gmail.com E-mail: efrojas@uv.mx

    2016-06-15

    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.

  18. NWSC nickel cadmium spacecraft cell accelerated life test program data analysis

    NASA Technical Reports Server (NTRS)

    Lander, J.

    1980-01-01

    An analysis of the data leading to a proposed accelerated life test scheme to test a nickel cadmium cell under spacecraft usage conditions is described. The amount and concentration of electrolyte and the amount of precharge in the cell are discussed in relation to the design of the cell and the accelerated test design. A failure analysis of the cell is summarized. The analysis included such environmental test variables as the depth of discharge, the temperature, the amount of recharge and the charge and discharge rate.

  19. Epistasis and natural selection shape the mutational architecture of complex traits.

    PubMed

    Jones, Adam G; Bürger, Reinhard; Arnold, Stevan J

    2014-05-14

    The evolutionary trajectories of complex traits are constrained by levels of genetic variation as well as genetic correlations among traits. As the ultimate source of all genetic variation is mutation, the distribution of mutations entering populations profoundly affects standing variation and genetic correlations. Here we use an individual-based simulation model to investigate how natural selection and gene interactions (that is, epistasis) shape the evolution of mutational processes affecting complex traits. We find that the presence of epistasis allows natural selection to mould the distribution of mutations, such that mutational effects align with the selection surface. Consequently, novel mutations tend to be more compatible with the current forces of selection acting on the population. These results suggest that in many cases mutational effects should be seen as an outcome of natural selection rather than as an unbiased source of genetic variation that is independent of other evolutionary processes.

  20. Thermal analysis of SC quadrupoles in accelerator interaction regions

    SciTech Connect

    Novitski, Igor; Zlobin, Alexander V.; /Fermilab

    2006-09-01

    This paper presents results of a thermal analysis and operation margin calculation performed for NbTi and Nb{sub 3}Sn low-beta quadrupoles in collider interaction regions. Results of the thermal analysis for NbTi quadrupoles are compared with the relevant experimental data. An approach to quench limit measurements for Nb{sub 3}Sn quadrupoles is discussed.

  1. Effect of acceleration forces during transport through a pneumatic tube system on ROTEM® analysis.

    PubMed

    Amann, Gerhard; Zehntner, Christine; Marti, Florian; Colucci, Giuseppe

    2012-03-09

    ROTEM® is considered a helpful point-of-care device to monitor blood coagulation in emergency situations. Centrally performed analysis is desirable but rapid transport of blood samples is an important prerequisite. The effect of acceleration forces on sample transport through a pneumatic tube system on ROTEM® should be tested at each institution to exclude a pre-analytical influence. The aims of the present work were: (i) to investigate the effect of pneumatic tube transport on ROTEM® parameters; (ii) to compare blood sample transport via pneumatic tube vs. manual transportation; and (iii) to determine the effect of acceleration forces on ROTEM® parameters. This is a single centre study with 20 healthy volunteers. Five whole blood samples were transferred to the central haematology laboratory by either normal transport or pneumatic delivery with different speed and acceleration forces. EXTEM, INTEM, FIBTEM and APTEM were analysed in parallel with two ROTEM® devices and compared. Acceleration forces were measured during transport with two different instruments. Increment of transport time, speed and distance resulted in an augmentation of acceleration forces and peaks. All results of the ROTEM® analysis after manual transport or pneumatic delivery were within normal range. However, increase in acceleration forces resulted in minimally but statistically significant changes in multiple ROTEM® parameters. The higher the acceleration forces, the more ROTEM® parameters are influenced. Acceleration forces during transport through a pneumatic tube system have an influence on ROTEM® parameters. Prior to transfer blood samples via pneumatic tube system these influences should be tested to exclude clinically relevant blood coagulation activation in vitro.

  2. Pervasive Sign Epistasis between Conjugative Plasmids and Drug-Resistance Chromosomal Mutations

    PubMed Central

    Carvalho, Luís M.; Reis, Ana M.; Gordo, Isabel; Trindade, Sandra; Dionisio, Francisco

    2011-01-01

    Multidrug-resistant bacteria arise mostly by the accumulation of plasmids and chromosomal mutations. Typically, these resistant determinants are costly to the bacterial cell. Yet, recently, it has been found that, in Escherichia coli bacterial cells, a mutation conferring resistance to an antibiotic can be advantageous to the bacterial cell if another antibiotic-resistance mutation is already present, a phenomenon called sign epistasis. Here we study the interaction between antibiotic-resistance chromosomal mutations and conjugative (i.e., self-transmissible) plasmids and find many cases of sign epistasis (40%)—including one of reciprocal sign epistasis where the strain carrying both resistance determinants is fitter than the two strains carrying only one of the determinants. This implies that the acquisition of an additional resistance plasmid or of a resistance mutation often increases the fitness of a bacterial strain already resistant to antibiotics. We further show that there is an overall antagonistic interaction between mutations and plasmids (52%). These results further complicate expectations of resistance reversal by interdiction of antibiotic use. PMID:21829372

  3. Pervasive sign epistasis between conjugative plasmids and drug-resistance chromosomal mutations.

    PubMed

    Silva, Rui F; Mendonça, Sílvia C M; Carvalho, Luís M; Reis, Ana M; Gordo, Isabel; Trindade, Sandra; Dionisio, Francisco

    2011-07-01

    Multidrug-resistant bacteria arise mostly by the accumulation of plasmids and chromosomal mutations. Typically, these resistant determinants are costly to the bacterial cell. Yet, recently, it has been found that, in Escherichia coli bacterial cells, a mutation conferring resistance to an antibiotic can be advantageous to the bacterial cell if another antibiotic-resistance mutation is already present, a phenomenon called sign epistasis. Here we study the interaction between antibiotic-resistance chromosomal mutations and conjugative (i.e., self-transmissible) plasmids and find many cases of sign epistasis (40%)--including one of reciprocal sign epistasis where the strain carrying both resistance determinants is fitter than the two strains carrying only one of the determinants. This implies that the acquisition of an additional resistance plasmid or of a resistance mutation often increases the fitness of a bacterial strain already resistant to antibiotics. We further show that there is an overall antagonistic interaction between mutations and plasmids (52%). These results further complicate expectations of resistance reversal by interdiction of antibiotic use.

  4. What’s Downstream? A Set of Classroom Exercises to Help Students Understand Recessive Epistasis

    PubMed Central

    Knight, Jennifer K.; Wood, William B.; Smith, Michelle K.

    2013-01-01

    Undergraduate students in genetics and developmental biology courses often struggle with the concept of epistasis because they are unaware that the logic of gene interactions differs between enzymatic pathways and signaling pathways. If students try to develop and memorize a single simple rule for predicting epistatic relationships without taking into account the nature of the pathway under consideration, they can become confused by cases where the rule does not apply. To remedy this problem, we developed a short pre-/post-test, an in-class activity for small groups, and a series of clicker questions about recessive epistasis in the context of a signaling pathway that intersects with an enzymatic pathway. We also developed a series of homework problems that provide deliberate practice in applying concepts in epistasis to different pathways and experimental situations. Students show significant improvement from pretest to posttest, and perform well on homework and exam questions following this activity. Here we describe these materials, as well as the formative and summative assessment results from one group of students to show how the activities impact student learning. PMID:24358383

  5. 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

  6. Genomic prediction with epistasis models: on the marker-coding-dependent performance of the extended GBLUP and properties of the categorical epistasis model (CE).

    PubMed

    Martini, Johannes W R; Gao, Ning; Cardoso, Diercles F; Wimmer, Valentin; Erbe, Malena; Cantet, Rodolfo J C; Simianer, Henner

    2017-01-03

    Epistasis marker effect models incorporating products of marker values as predictor variables in a linear regression approach (extended GBLUP, EGBLUP) have been assessed as potentially beneficial for genomic prediction, but their performance depends on marker coding. Although this fact has been recognized in literature, the nature of the problem has not been thoroughly investigated so far. We illustrate how the choice of marker coding implicitly specifies the model of how effects of certain allele combinations at different loci contribute to the phenotype, and investigate coding-dependent properties of EGBLUP. Moreover, we discuss an alternative categorical epistasis model (CE) eliminating undesired properties of EGBLUP and show that the CE model can improve predictive ability. Finally, we demonstrate that the coding-dependent performance of EGBLUP offers the possibility to incorporate prior experimental information into the prediction method by adapting the coding to already available phenotypic records on other traits. Based on our results, for EGBLUP, a symmetric coding {-1,1} or {-1,0,1} should be preferred, whereas a standardization using allele frequencies should be avoided. Moreover, CE can be a valuable alternative since it does not possess the undesired theoretical properties of EGBLUP. However, which model performs best will depend on characteristics of the data and available prior information. Data from previous experiments can for instance be incorporated into the marker coding of EGBLUP.

  7. Single-image molecular analysis for accelerated fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Wang, Yan Mei

    2011-03-01

    We have developed a new single-molecule fluorescence imaging analysis method, SIMA, to improve the temporal resolution of single-molecule localization and tracking studies to millisecond timescales without compromising the nanometer range spatial resolution [1,2]. In this method, the width of the fluorescence intensity profile of a static or mobile molecule, imaged using submillisecond to milliseconds exposure time, is used for localization and dynamics analysis. We apply this method to three single-molecule studies: (1) subdiffraction molecular separation measurements, (2) axial localization precision measurements, and (3) protein diffusion coefficient measurements in free solution. Applications of SIMA in flagella IFT particle analysis, localizations of UgtP (a cell division regulator protein) in live cells, and diffusion coefficient measurement of LacI in vitro and in vivo will be discussed.

  8. 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.

  9. 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.

  10. Vibration isolation analysis of clutches based on trouble shooting of vehicle accelerating noise

    NASA Astrophysics Data System (ADS)

    Liu, Xue-Lai; Shangguan, Wen-Bin; Jing, Xingjian; Ahmed, Waizuddin

    2016-11-01

    Vehicle accelerating noise is a troublesome issue commonly existing in automobiles, leading to negative passenger experience. Considering real experimental results and practical issues, a nonlinear 3-degree of freedom (DOF) torsional model of the clutch system is developed for reducing abnormal noise during vehicle accelerating. In this model, the nonlinear characteristics of the multi-staged clutch damper and the gear backlash are carefully studied. This greatly facilitates the analysis of the vibration transmission characteristics of the clutch and helps understanding of the influence of each critical physical parameter on noise generation. To reduce the accelerating noise, an optimization method for the clutch dynamics is proposed, based on the parameter analysis results, and the effectiveness is validated both in simulations and experiments.

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

    PubMed

    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.

  12. Accelerator-based chemical and elemental analysis of atmospheric aerosols

    NASA Astrophysics Data System (ADS)

    Mentes, Besim

    Aerosol particles have always been present in the atmosphere, arising from natural sources. But it was not until recently when emissions from anthropogenic (man made) sources began to dominate, that atmospheric aerosols came into focus and the aerosol science in the environmental perspective started to grow. These sources emit or produce particles with different elemental and chemical compositions, as well as different sizes of the individual aerosols. The effects of increased pollution of the atmosphere are many, and have different time scales. One of the effects known today is acid rain, which causes problems for vegetation. Pollution is also a direct human health risk, in many cities where traffic driven by combustion engines is forbidden at certain times when the meteorological conditions are unfavourable. Aerosols play an important role in the climate, and may have both direct and indirect effect which cause cooling of the planet surface, in contrast to the so-called greenhouse gases. During this work a technique for chemical and elemental analysis of atmospheric aerosols and an elemental analysis methodology for upper tropospheric aerosols have been developed. The elemental analysis is performed by the ion beam analysis (IBA) techniques, PIXE (elements heavier than Al). PESA (C, N and O), cPESA (H) and pNRA (Mg and Na). The chemical speciation of atmospheric aerosols is obtained by ion beam thermography (IBT). During thermography the sample temperature is stepwise increased and the IBA techniques are used to continuously monitor the elemental concentration. A thermogram is obtained for each element. The vaporisation of the compounds in the sample appears as a concentration decrease in the thermograms at characteristic vaporisation temperatures (CVTs). Different aspects of IBT have been examined in Paper I to IV. The features of IBT are: almost total elemental speciation of the aerosol mass, chemical speciation of the inorganic compounds, carbon content

  13. EMG and acceleration signal analysis for quantifying the effects of medication in Parkinson's disease.

    PubMed

    Rissanen, Saara M; Kankaanpaa, Markku; Tarvainen, Mika P; Nuutinen, Juho; Airaksinen, Olavi; Karjalainen, Pasi A

    2011-01-01

    Parkinson's disease (PD) is characterized by motor disabilities that can be alleviated reasonably with appropriate medication. However, there is a lack of objective methods for quantifying the efficacy of treatment in PD. We applied here an objective method for quantifying the effects of medication in PD using EMG and acceleration measurements and analysis. In the method, four signal features were calculated from the EMG and acceleration recordings of both sides of the body: the kurtosis and recurrence rate of EMG, and the amplitude and sample entropy of acceleration. Principal component approach was used for reducing the number of variables. EMG and acceleration data measured from nine PD patients were used for analysis. The patients were measured in four different medication conditions: with medication off, and two and three and four hours after taking the medication. The results showed that in eight patients the EMG recordings changed into less spiky and the acceleration recordings into more complex after taking the medication. A reverse phenomenon in the signal characteristics was observed in seven patients 3-4 hours after taking the medication. The results indicate that the presented method is potentially useful for quantifying objectively the effects of medication on the neuromuscular function in PD.

  14. 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.

  15. Neutronics analysis for an accelerator-based nuclear waste transmuter

    SciTech Connect

    Sailor, W.C.; Beard, C.A.

    1993-07-01

    The neutronic analysis for a target/blanket design that is capable of supporting the high level waste stream from 2.5 LWR`s is described. The target consists of a set of solid tungsten and lead plates, cooled by heavy water and surrounded by a lead annulus. The annular blanket, which surrounds the target, consists of a set of AcO{sub 2} slurry bearing tubes, each 3 meters long, surrounded by heavy water moderator. Heat removal from the slurry tubes is by passing the rapidly moving slurry through an external heat exchanger. There are separate regions for long-lived fission product burning. Using the Monte Carlo codes LAHET and MCNP we have optimized the design for a minimum beam current of 62.5 mA of 1.6 GeV protons.

  16. WarpIV: In situ visualization and analysis of ion accelerator simulations

    DOE PAGES

    Rubel, Oliver; Loring, Burlen; Vay, Jean -Luc; ...

    2016-05-09

    The generation of short pulses of ion beams through the interaction of an intense laser with a plasma sheath offers the possibility of compact and cheaper ion sources for many applications--from fast ignition and radiography of dense targets to hadron therapy and injection into conventional accelerators. To enable the efficient analysis of large-scale, high-fidelity particle accelerator simulations using the Warp simulation suite, the authors introduce the Warp In situ Visualization Toolkit (WarpIV). WarpIV integrates state-of-the-art in situ visualization and analysis using VisIt with Warp, supports management and control of complex in situ visualization and analysis workflows, and implements integrated analyticsmore » to facilitate query- and feature-based data analytics and efficient large-scale data analysis. WarpIV enables for the first time distributed parallel, in situ visualization of the full simulation data using high-performance compute resources as the data is being generated by Warp. The authors describe the application of WarpIV to study and compare large 2D and 3D ion accelerator simulations, demonstrating significant differences in the acceleration process in 2D and 3D simulations. WarpIV is available to the public via https://bitbucket.org/berkeleylab/warpiv. The Warp In situ Visualization Toolkit (WarpIV) supports large-scale, parallel, in situ visualization and analysis and facilitates query- and feature-based analytics, enabling for the first time high-performance analysis of large-scale, high-fidelity particle accelerator simulations while the data is being generated by the Warp simulation suite. Furthermore, this supplemental material https://extras.computer.org/extra/mcg2016030022s1.pdf provides more details regarding the memory profiling and optimization and the Yee grid recentering optimization results discussed in the main article.« less

  17. WarpIV: In situ visualization and analysis of ion accelerator simulations

    SciTech Connect

    Rubel, Oliver; Loring, Burlen; Vay, Jean -Luc; Grote, David P.; Lehe, Remi; Bulanov, Stepan; Vincenti, Henri; Bethel, E. Wes

    2016-05-09

    The generation of short pulses of ion beams through the interaction of an intense laser with a plasma sheath offers the possibility of compact and cheaper ion sources for many applications--from fast ignition and radiography of dense targets to hadron therapy and injection into conventional accelerators. To enable the efficient analysis of large-scale, high-fidelity particle accelerator simulations using the Warp simulation suite, the authors introduce the Warp In situ Visualization Toolkit (WarpIV). WarpIV integrates state-of-the-art in situ visualization and analysis using VisIt with Warp, supports management and control of complex in situ visualization and analysis workflows, and implements integrated analytics to facilitate query- and feature-based data analytics and efficient large-scale data analysis. WarpIV enables for the first time distributed parallel, in situ visualization of the full simulation data using high-performance compute resources as the data is being generated by Warp. The authors describe the application of WarpIV to study and compare large 2D and 3D ion accelerator simulations, demonstrating significant differences in the acceleration process in 2D and 3D simulations. WarpIV is available to the public via https://bitbucket.org/berkeleylab/warpiv. The Warp In situ Visualization Toolkit (WarpIV) supports large-scale, parallel, in situ visualization and analysis and facilitates query- and feature-based analytics, enabling for the first time high-performance analysis of large-scale, high-fidelity particle accelerator simulations while the data is being generated by the Warp simulation suite. Furthermore, this supplemental material https://extras.computer.org/extra/mcg2016030022s1.pdf provides more details regarding the memory profiling and optimization and the Yee grid recentering optimization results discussed in the main article.

  18. WarpIV: In Situ Visualization and Analysis of Ion Accelerator Simulations.

    PubMed

    Rubel, Oliver; Loring, Burlen; Vay, Jean-Luc; Grote, David P; Lehe, Remi; Bulanov, Stepan; Vincenti, Henri; Bethel, E Wes

    2016-01-01

    The generation of short pulses of ion beams through the interaction of an intense laser with a plasma sheath offers the possibility of compact and cheaper ion sources for many applications--from fast ignition and radiography of dense targets to hadron therapy and injection into conventional accelerators. To enable the efficient analysis of large-scale, high-fidelity particle accelerator simulations using the Warp simulation suite, the authors introduce the Warp In situ Visualization Toolkit (WarpIV). WarpIV integrates state-of-the-art in situ visualization and analysis using VisIt with Warp, supports management and control of complex in situ visualization and analysis workflows, and implements integrated analytics to facilitate query- and feature-based data analytics and efficient large-scale data analysis. WarpIV enables for the first time distributed parallel, in situ visualization of the full simulation data using high-performance compute resources as the data is being generated by Warp. The authors describe the application of WarpIV to study and compare large 2D and 3D ion accelerator simulations, demonstrating significant differences in the acceleration process in 2D and 3D simulations. WarpIV is available to the public via https://bitbucket.org/berkeleylab/warpiv. The Warp In situ Visualization Toolkit (WarpIV) supports large-scale, parallel, in situ visualization and analysis and facilitates query- and feature-based analytics, enabling for the first time high-performance analysis of large-scale, high-fidelity particle accelerator simulations while the data is being generated by the Warp simulation suite. This supplemental material https://extras.computer.org/extra/mcg2016030022s1.pdf provides more details regarding the memory profiling and optimization and the Yee grid recentering optimization results discussed in the main article.

  19. WarpIV: In situ visualization and analysis of ion accelerator simulations

    SciTech Connect

    Rubel, Oliver; Loring, Burlen; Vay, Jean -Luc; Grote, David P.; Lehe, Remi; Bulanov, Stepan; Vincenti, Henri; Bethel, E. Wes

    2016-05-09

    The generation of short pulses of ion beams through the interaction of an intense laser with a plasma sheath offers the possibility of compact and cheaper ion sources for many applications--from fast ignition and radiography of dense targets to hadron therapy and injection into conventional accelerators. To enable the efficient analysis of large-scale, high-fidelity particle accelerator simulations using the Warp simulation suite, the authors introduce the Warp In situ Visualization Toolkit (WarpIV). WarpIV integrates state-of-the-art in situ visualization and analysis using VisIt with Warp, supports management and control of complex in situ visualization and analysis workflows, and implements integrated analytics to facilitate query- and feature-based data analytics and efficient large-scale data analysis. WarpIV enables for the first time distributed parallel, in situ visualization of the full simulation data using high-performance compute resources as the data is being generated by Warp. The authors describe the application of WarpIV to study and compare large 2D and 3D ion accelerator simulations, demonstrating significant differences in the acceleration process in 2D and 3D simulations. WarpIV is available to the public via https://bitbucket.org/berkeleylab/warpiv. The Warp In situ Visualization Toolkit (WarpIV) supports large-scale, parallel, in situ visualization and analysis and facilitates query- and feature-based analytics, enabling for the first time high-performance analysis of large-scale, high-fidelity particle accelerator simulations while the data is being generated by the Warp simulation suite. Furthermore, this supplemental material https://extras.computer.org/extra/mcg2016030022s1.pdf provides more details regarding the memory profiling and optimization and the Yee grid recentering optimization results discussed in the main article.

  20. Status of MAPA (Modular Accelerator Physics Analysis) and the Tech-X Object-Oriented Accelerator Library

    NASA Astrophysics Data System (ADS)

    Cary, J. R.; Shasharina, S.; Bruhwiler, D. L.

    1998-04-01

    The MAPA code is a fully interactive accelerator modeling and design tool consisting of a GUI and two object-oriented C++ libraries: a general library suitable for treatment of any dynamical system, and an accelerator library including many element types plus an accelerator class. The accelerator library inherits directly from the system library, which uses hash tables to store any relevant parameters or strings. The GUI can access these hash tables in a general way, allowing the user to invoke a window displaying all relevant parameters for a particular element type or for the accelerator class, with the option to change those parameters. The system library can advance an arbitrary number of dynamical variables through an arbitrary mapping. The accelerator class inherits this capability and overloads the relevant functions to advance the phase space variables of a charged particle through a string of elements. Among other things, the GUI makes phase space plots and finds fixed points of the map. We discuss the object hierarchy of the two libraries and use of the code.

  1. Role of epistasis on the fixation probability of a non-mutator in an adapted asexual population.

    PubMed

    James, Ananthu

    2016-10-21

    The mutation rate of a well adapted population is prone to reduction so as to have a lower mutational load. We aim to understand the role of epistatic interactions between the fitness affecting mutations in this process. Using a multitype branching process, the fixation probability of a single non-mutator emerging in a large asexual mutator population is analytically calculated here. The mutator population undergoes deleterious mutations at constant, but at a much higher rate than that of the non-mutator. We find that antagonistic epistasis lowers the chances of mutation rate reduction, while synergistic epistasis enhances it. Below a critical value of epistasis, the fixation probability behaves non-monotonically with variation in the mutation rate of the background population. Moreover, the variation of this critical value of the epistasis parameter with the strength of the mutator is discussed in the appendix. For synergistic epistasis, when selection is varied, the fixation probability reduces overall, with damped oscillations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. 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.

  3. Analysis of output trends from Varian 2100C/D and 600C/D accelerators.

    PubMed

    Grattan, M W D; Hounsell, A R

    2011-01-07

    Analysis of Varian linear accelerator output trends is reported. Two groups, consisting of four matched Varian 2100C/D and four matched Varian 600C/D accelerators, with different designs of monitor chamber, have been investigated and the data acquired from regular calibrated ion chamber/electrometer measurements of the output performance of the eight accelerators analysed. The trend of machine output with time, having removed the effect of adjusting the monitor chamber response, was compared on a monthly and annual basis for monitor chambers with ages ranging between 1 year and 7 years. The results indicate that the response is generally consistent within each set of accelerators with different monitor chamber designs. Those used in a Varian 600C/D machine result in a reduction in measured output over time, with an average monthly reduction of 0.35 ± 0.09% over the course of the first 4 years of use. The chambers used in a 2100C/D accelerator result in an increase in measured output over time, with an average monthly increase of 0.26 ± 0.09% over the course of the first 4 years of use. The output increase then reduces towards the end of this period of time, with the average monthly change falling to -0.03 ± 0.02% for the following 3 years. The output response trend was similar for all clinical energies used on the 2100C/D accelerators--6, 15 MV x-ray beams, and 4, 6, 9, 12, 16 and 20 MeV electron beams. By tracking these changes it has been possible to predict the response over time to allow appropriate adjustments in monitor chamber response to maintain a measured accelerator output within tolerance and give confidence in performance. It has also provided data to indicate the need for planned preventative intervention and indicate if the monitor chamber response is behaving as expected.

  4. Field analysis of a dielectric-loaded rectangular waveguide accelerating structure.

    SciTech Connect

    Xiao, L.; Gai, W.; Sun, X.

    2001-07-16

    In this paper, we present a detailed analysis of the modes of a dielectric-loaded rectangular waveguide accelerating structure. In general, the acceleration field in a synchronous acceleration mode is non-uniform in the two transverse dimensions. However, we could use an array of these structures rotated alternatively by 90 degrees to get a focusing-defocusing force continuously as a simple FODO lattice, while maintaining uniform energy gain. The expressions of characteristic parameters such as R/Q, group velocity and attenuation constant are given. The longitudinal wake field experienced by a relativistic charged particle beam in the structure is also presented. These analytical results are also compared with numerical calculations using the MAFIA code suite demonstrating the validity of our analytic approach.

  5. 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.

  6. 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.

  7. Synergistic interaction between ankle and knee during hopping revealed through induced acceleration analysis.

    PubMed

    João, Filipa; Veloso, António; Cabral, Sílvia; Moniz-Pereira, Vera; Kepple, Thomas

    2014-02-01

    The forces produced by the muscles can deliver energy to a target segment they are not attached to, by transferring this energy throughout the other segments in the chain. This is a synergistic way of functioning, which allows muscles to accelerate or decelerate segments in order to reach the target one. The purpose of this study was to characterize the contribution of each lower extremity joint to the vertical acceleration of the body's center of mass during a hopping exercise. To accomplish this, an induced acceleration analysis was performed using a model with eight segments. The results indicate that the strategies produced during a hopping exercise rely on the synergy between the knee and ankle joints, with most of the vertical acceleration being produced by the knee extensors, while the ankle plantar flexors act as stabilizers of the foot. This synergy between the ankle and the knee is perhaps a mechanism that allows the transfer of power from the knee muscles to the ground, and we believe that in this particular task the net action of the foot and ankle moments is to produce a stable foot with little overall acceleration.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. A Developmental Systems Perspective on Epistasis: Computational Exploration of Mutational Interactions in Model Developmental Regulatory Networks

    PubMed Central

    Gutiérrez, Jayson

    2009-01-01

    The way in which the information contained in genotypes is translated into complex phenotypic traits (i.e. embryonic expression patterns) depends on its decoding by a multilayered hierarchy of biomolecular systems (regulatory networks). Each layer of this hierarchy displays its own regulatory schemes (i.e. operational rules such as +/− feedback) and associated control parameters, resulting in characteristic variational constraints. This process can be conceptualized as a mapping issue, and in the context of highly-dimensional genotype-phenotype mappings (GPMs) epistatic events have been shown to be ubiquitous, manifested in non-linear correspondences between changes in the genotype and their phenotypic effects. In this study I concentrate on epistatic phenomena pervading levels of biological organization above the genetic material, more specifically the realm of molecular networks. At this level, systems approaches to studying GPMs are specially suitable to shed light on the mechanistic basis of epistatic phenomena. To this aim, I constructed and analyzed ensembles of highly-modular (fully interconnected) networks with distinctive topologies, each displaying dynamic behaviors that were categorized as either arbitrary or functional according to early patterning processes in the Drosophila embryo. Spatio-temporal expression trajectories in virtual syncytial embryos were simulated via reaction-diffusion models. My in silico mutational experiments show that: 1) the average fitness decay tendency to successively accumulated mutations in ensembles of functional networks indicates the prevalence of positive epistasis, whereas in ensembles of arbitrary networks negative epistasis is the dominant tendency; and 2) the evaluation of epistatic coefficients of diverse interaction orders indicates that, both positive and negative epistasis are more prevalent in functional networks than in arbitrary ones. Overall, I conclude that the phenotypic and fitness effects of multiple

  11. Epistasis between SPINK5 and TSLP Genes Contributes to Childhood Asthma

    PubMed Central

    Biagini Myers, Jocelyn M.; Martin, Lisa J.; Butsch Kovacic, Melinda; Mersha, Tesfaye B.; He, Hua; Pilipenko, Valentina; Lindsey, Mark A.; Ericksen, Mark B.; Bernstein, David I; LeMasters, Grace K.; Lockey, James E.; Khurana Hershey, Gurjit K.

    2014-01-01

    Background Epithelial genes have previously been associated with asthma, but only explain a small fraction of heritability. In part, this may be due to epistasis that is often not considered. Objective To determine independent and epistatic associations between FLG, SPINK5 and TSLP gene variants and childhood asthma. Methods Using a candidate gene approach, we genotyped 29 variants in FLG, SPINK5 and TSLP in asthmatic, allergic, and non-allergic-non-asthmatic white and black children participating in the well-phenotyped Greater Cincinnati Pediatric Clinic Repository (GCPCR). Associations with asthma were also assessed in six replication populations. Results We observed independent associations of variants in SPINK5 (p=0.003) and TSLP (p=0.006) with childhood asthma; a SPINK5 SNP was replicated. In subjects with one or more SPINK5 risk alleles, the absence of the TSLP protective minor alleles was associated with a significant increase in asthma (67% vs. 53%, p=0.0017). In contrast, the presence or absence of TSLP minor alleles did not affect asthma risk in subjects without the SPINK5 risk alleles. The SPINK5 and TSLP epistasis was replicated in a black population (p=0.036) that did not display independent association with variants in these genes. Conclusions Our results support epistasis between SPINK5 and TSLP which contributes to childhood asthma. These findings emphasize the importance of utilizing biology to inform analyses to identify genetic susceptibility to complex diseases. The results from our study have clinical relevance and support that the therapeutic effects of anti-TSLP therapy in asthmatics may be dependent on SPINK5 genotype. PMID:24831437

  12. 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.

  13. 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.

  14. 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.

  15. Association mapping for epistasis and environmental interaction of yield traits in 323 cotton cultivars under 9 different environments.

    PubMed

    Jia, Yinhua; Sun, Xiwei; Sun, Junling; 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.

  16. 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

  17. 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.

  18. Radiation shielding analysis of a special linear accelerator for electron beam and X-ray.

    PubMed

    Kang, W G; Pyo, S H; Alkhuraiji, T S; Han, B S; Kang, C M

    2017-01-31

    The King AbdulAziz City for Science & Technology in the Kingdom of Saudi Arabia plans to build a 10 MeV, 15 kW linear accelerator (LINAC) for electron beam and X-ray. The accelerator will be supplied by EB Tech, Republic of Korea, and the design and construction of the accelerator building will be conducted in the cooperation with EB Tech. This report presents the shielding analysis of the accelerator building using the Monte Carlo N-Particle Transport Code (MCNP). In order to improve the accuracy in estimating deep radiation penetration and to reduce computation time, various variance reduction techniques, including the weight window (WW) method, the deterministic transport (DXTRAN) spheres were considered. Radiation levels were estimated at selected locations in the shielding facility running MCNP6 for particle histories up to 1.0×10+8. The final results indicated that the calculated doses at all selected detector locations met the dose requirement of 50 mSv/yr, which is the United State Nuclear Regulatory Commission (U.S. NRC) requirement.

  19. Proton and Helium Injection Into First Order Fermi Acceleration at Shocks: Hybrid Simulation and Analysis

    NASA Astrophysics Data System (ADS)

    Dudnikova, Galina; Malkov, Mikhail; Sagdeev, Roald; Liseykina, Tatjana; Hanusch, Adrian

    2016-10-01

    Elemental composition of galactic cosmic rays (CR) probably holds the key to their origin. Most likely, they are accelerated at collisionless shocks in supernova remnants, but the acceleration mechanism is not entirely understood. One complicated problem is ``injection'', a process whereby the shock selects a tiny fraction of particles to keep on crossing its front and gain more energy. Comparing the injection rates of particles with different mass to charge ratio is a powerful tool for studying this process. Recent advances in measurements of CR He/p ratio have provided particularly important new clues. We performed a series of hybrid simulations and analyzed a joint injection of protons and Helium, in conjunction with upstream waves they generate. The emphasis of this work is on the bootstrap aspects of injection manifested in particle confinement to the shock and, therefore, their continuing acceleration by the self-driven waves. The waves are initially generated by He and protons in separate spectral regions, and their interaction plays a crucial role in particle acceleration. The work is ongoing and new results will be reported along with their analysis and comparison with the latest data from the AMS-02 space-based spectrometer. Work supported Grant RFBR 16-01-00209, NASA ATP-program under Award NNX14AH36G, and by the US Department of Energy under Award No. DE-FG02-04ER54738.

  20. UV-accelerated test based on analysis of field-exposed PV modules

    NASA Astrophysics Data System (ADS)

    Shioda, T.

    2011-09-01

    We proposed an UV accelerated test condition for an EVA encapsulant, based on analysis of long term field exposed PV modules. We found that strong UV irradiation into EVA encapsulant test sample led to the fast decomposition of UV absorber formulated in EVA encapsulant, which has never seen in the field exposed PV modules. Thus, the integrating UV intensity of 60 W/m2 and black panel temperature of 110°C using a xenon weather-o-meter were suitable as an UV accelerated test condition. With this proposed test condition, which shows that 1 week exposure by xenon light corresponds to 1 year field exposure, we can predict discoloration rate of EVA encapsulant. In addition, we evaluated change in peel strength to glass for Mitsui's and the other commercially available EVA encapsulants during UV accelerated test with the proposed condition. There was no large change in peel strength for our EVA encapsulant during the UV accelerated test. On the other hand, we observed that the competitor's EVA encapsulant showed the large decrease of peel strength to glass at early stage, even no change in yellowness index (YI). This result indicates not only YI change but also peel strength change should be evaluated for design of reliable PV module and encapsulant.

  1. Focal spot motion of linear accelerators and its effect on portal image analysis.

    PubMed

    Sonke, Jan-Jakob; Brand, Bob; van Herk, Marcel

    2003-06-01

    The focal spot of a linear accelerator is often considered to have a fully stable position. In practice, however, the beam control loop of a linear accelerator needs to stabilize after the beam is turned on. As a result, some motion of the focal spot might occur during the start-up phase of irradiation. When acquiring portal images, this motion will affect the projected position of anatomy and field edges, especially when low exposures are used. In this paper, the motion of the focal spot and the effect of this motion on portal image analysis are quantified. A slightly tilted narrow slit phantom was placed at the isocenter of several linear accelerators and images were acquired (3.5 frames per second) by means of an amorphous silicon flat panel imager positioned approximately 0.7 m below the isocenter. The motion of the focal spot was determined by converting the tilted slit images to subpixel accurate line spread functions. The error in portal image analysis due to focal spot motionwas estimated by a subtraction of the relative displacement of the projected slit from the relative displacement of the field edges. It was found that the motion of the focal spot depends on the control system and design of the accelerator. The shift of the focal spot at the start of irradiation ranges between 0.05-0.7 mm in the gun-target (GT) direction. In the left-right (AB) direction the shift is generally smaller. The resulting error in portal image analysis due to focal spotmotion ranges between 0.05-1.1 mm for a dose corresponding to two monitor units (MUs). For 20 MUs, the effect of the focal spot motion reduces to 0.01-0.3 mm. The error in portal image analysis due to focal spot motion can be reduced by reducing the applied dose rate.

  2. Numerical analysis of the sensitivity of crystal growth experiments to spacecraft residual acceleration

    NASA Technical Reports Server (NTRS)

    Alexander, J. I. D.; Amiroudine, Sakir; Ouazzani, Jalil; Rosenberger, Franz

    1992-01-01

    An analysis is conducted of the sensitivity of the Bridgman-Stockbarger crystal growth method, using an idealized model for a range of operating and boundary conditions over a variety of accelerations. Attention is given to the dopant nonuniformity at the melt-crystal interface. The largest compositional nonuniformities are found to occur for disturbances whose amplitudes are greater than 10 exp 6 g, and frequencies below 0.1 Hz.

  3. 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.

  4. Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila.

    PubMed

    Vijendravarma, R K; Kawecki, T J

    2013-12-01

    Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.

  5. 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.

  6. 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

    2016-07-08

    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.

  7. Epistasis in tomato color mutations involves regulation of phytoene synthase 1 expression by cis-carotenoids.

    PubMed

    Kachanovsky, David E; Filler, Shdema; Isaacson, Tal; Hirschberg, Joseph

    2012-11-13

    Tomato (Solanum lycopersicum) fruit accumulate the red carotenoid pigment lycopene. The recessive mutation yellow-flesh (locus r) in tomato eliminates fruit carotenoids by disrupting the activity of the fruit-specific phytoene synthase (PSY1), the first committed step in the carotenoid biosynthesis pathway. Fruits of the recessive mutation tangerine (t) appear orange due to accumulation of 7,9,7',9'-tetra-cis-lycopene (prolycopene) as a result of a mutation in the carotenoid cis-trans isomerase. It was established 60 y ago that tangerine is epistatic to yellow-flesh. This uncharacteristic epistasis interaction defies a paradigm in biochemical genetics arguing that mutations that disrupt enzymes acting early in a biosynthetic pathway are epistatic to other mutations that block downstream steps in the same pathway. To explain this conundrum, we have investigated the interaction between tangerine and yellow-flesh at the molecular level. Results presented here indicate that allele r(2997) of yellow-flesh eliminates transcription of PSY1 in fruits. In a genetic background of tangerine, transcription of PSY1 is partially restored to a level sufficient for producing phytoene and downstream carotenoids. Our results revealed the molecular mechanism underlying the epistasis of t over r and suggest the involvement of cis-carotenoid metabolites in a feedback regulation of PSY1 gene expression.

  8. Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus.

    PubMed

    Monnahan, Patrick J; Kelly, John K

    2015-05-01

    The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population's ability to respond to selection.

  9. Epistasis Is a Major Determinant of the Additive Genetic Variance in Mimulus guttatus

    PubMed Central

    Monnahan, Patrick J.; Kelly, John K.

    2015-01-01

    The influence of genetic interactions (epistasis) on the genetic variance of quantitative traits is a major unresolved problem relevant to medical, agricultural, and evolutionary genetics. The additive genetic component is typically a high proportion of the total genetic variance in quantitative traits, despite that underlying genes must interact to determine phenotype. This study estimates direct and interaction effects for 11 pairs of Quantitative Trait Loci (QTLs) affecting floral traits within a single population of Mimulus guttatus. With estimates of all 9 genotypes for each QTL pair, we are able to map from QTL effects to variance components as a function of population allele frequencies, and thus predict changes in variance components as allele frequencies change. This mapping requires an analytical framework that properly accounts for bias introduced by estimation errors. We find that even with abundant interactions between QTLs, most of the genetic variance is likely to be additive. However, the strong dependency of allelic average effects on genetic background implies that epistasis is a major determinant of the additive genetic variance, and thus, the population’s ability to respond to selection. PMID:25946702

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Design and analysis of solder connections using accelerated approximate procedure with disturbed state concept

    NASA Astrophysics Data System (ADS)

    Whitenack, Russell

    The accelerated approximate procedure developed and used herein for analysis, design and parametric optimization in electronic packaging is based on the disturbed state concept (DSC) and the hierarchical single surface (HISS) constitutive models. Over the past many years the benefits of the DSC/HISS model, compared to those of available plasticity models, have been demonstrated and validated for a wide range of materials and solder connections. When the DSC/HISS model is implemented in a two-dimensional finite element code, it is well suited for failure analyses of lead/tin solder connections under cyclic thermal and mechanical loading that are typically occur in electronic packages. Unfortunately, an analysis of a single solder connection, for approximately 4000 or more cycles, can require much effort and computer time, which may be too long to be of practical use. The accelerated approximate procedure significantly reduces the effort and the analysis time to approximately 10 to 15 minutes on a Pentium 4, 3.2 GHz personal computer. The main emphasis of this dissertation is the use of the unified DSC model with the finite element procedure to predict the behavior of chip-substrate solder connections. The DSC code is used to validate the performance of a number of packages (144 BPGA, 313 PBGA) tested in the laboratory under thermomechanical loading. Using the accelerated approximate procedure, the effect of the variable thickness solder connection in a plane stress idealization is compared with that of the constant thickness assumption, and a three-dimensional analysis. It shows that the analysis with variable thickness (in plane stress idealization) yields improved results. The accelerated approximate procedure is then used to perform parametric design analyses of a solder connection by varying a number of important factors such as connection size, shape and misalignment. The effects of varying the DSC/HISS parameters on cycle life are also analyzed. The results of

  15. 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.

  16. Reciprocal sign epistasis and truncation selection: When is recombination favorable in a pre-breeding program with a selfing species?

    PubMed

    Vagne, Constance; David, Jacques; Tavaud, Muriel; Fontez, Bénédicte

    2015-12-07

    Since the dawn of agriculture, humans have applied artificial selection on traits of interest, regardless of their genetic architecture. Yet, still today, most models used to study and streamline this process overlook genetic interactions. In this study, we determined the conditions in which a target genotype can be fixed when truncation selection is applied on an epistatic trait. Previous studies have shown that reciprocal sign epistasis with two fitness peaks of unequal height involves multiple equilibrium states, i.e. below one critical parameter value, such as a critical recombination rate, one genotype may be fixed, and above it, another one may be fixed. Using a haploid bi-locus model, we identified which genotype would be fixed, and how quickly, in an infinite population selected for a phenotypic trait subject to reciprocal sign epistasis with unequal peak heights, depending on two criteria: the recombination rate and percentage of selected individuals. The critical parameter values at which bistability sets in, were also calculated. These results were complemented by stochastic simulations in finite populations. Our results confirmed that, in the case of fitness under reciprocal sign epistasis, high recombination rates induce blockage at the local optimum or attainment of an equilibrium state between the two peaks. However, if linkage disequilibrium is negative in the initial population, recombination is necessary to create the most favorable genotype. Therefore, in this case, reciprocal sign epistasis favors non-null recombination rates, particularly if selection is intense. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Multiphysics Analysis of Frequency Detuning in Superconducting RF Cavities for Proton Particle Accelerators

    SciTech Connect

    Awida, M. H.; Gonin, I.; Passarelli, D.; Sukanov, A.; Khabiboulline, T.; Yakovlev, V.

    2016-01-22

    Multiphysics analyses for superconducting cavities are essential in the course of cavity design to meet stringent requirements on cavity frequency detuning. Superconducting RF cavities are the core accelerating elements in modern particle accelerators whether it is proton or electron machine, as they offer extremely high quality factors thus reducing the RF losses per cavity. However, the superior quality factor comes with the challenge of controlling the resonance frequency of the cavity within few tens of hertz bandwidth. In this paper, we investigate how the multiphysics analysis plays a major role in proactively minimizing sources of frequency detuning, specifically; microphonics and Lorentz Force Detuning (LFD) in the stage of RF design of the cavity and mechanical design of the niobium shell and the helium vessel.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Utilization of Integrated Process Control, Data Capture, and Data Analysis in Construction of Accelerator Systems

    SciTech Connect

    Bonnie Madre; Charles Reece; Joseph Ozelis; Valerie Bookwalter

    2003-05-12

    Jefferson Lab has developed a web-based system that integrates commercial database, data analysis, document archiving and retrieval, and user interface software, into a coherent knowledge management product (Pansophy). This product provides important tools for the successful pursuit of major projects such as accelerator system development and construction, by offering elements of process and procedure control, data capture and review, and data mining and analysis. After a period of initial development, Pansophy is now being used in Jefferson Lab's SNS superconducting linac construction effort, as a means for structuring and implementing the QA program, for process control and tracking, and for cryomodule test data capture and presentation/analysis. Development of Pansophy is continuing, in particular data queries and analysis functions that are the cornerstone of its utility.

  3. 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.

  4. 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.

  5. Conservation and Rewiring of Functional Modules Revealed by an Epistasis Map in Fission Yeast

    PubMed Central

    Roguev, Assen; Bandyopadhyay, Sourav; Zofall, Martin; Zhang, Ke; Fischer, Tamas; Collins, Sean R.; Qu, Hongjing; Shales, Michael; Park, Han-Oh; Hayles, Jacqueline; Hoe, Kwang-Lae; Kim, Dong-Uk; Ideker, Trey; Grewal, Shiv I.; Weissman, Jonathan S.; Krogan, Nevan J.

    2009-01-01

    An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a previously unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that, whereas negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially. PMID:18818364

  6. A shift from magnitude to sign epistasis during adaptive evolution of a bacterial social trait.

    PubMed

    Zee, Peter C; Mendes-Soares, Helena; Yu, Yuen-Tsu N; Kraemer, Susanne A; Keller, Heike; Ossowski, Stephan; Schneeberger, Korbinian; Velicer, Gregory J

    2014-09-01

    Although the importance of epistasis in evolution has long been recognized, remarkably little is known about the processes by which epistatic interactions evolve in real time in specific biological systems. Here, we have characterized how the epistatic fitness relationship between a social gene and an adapting genome changes radically over a short evolutionary time frame in the social bacterium Myxococcus xanthus. We show that a highly beneficial effect of this social gene in the ancestral genome is gradually reduced--and ultimately reversed into a deleterious effect--over the course of an experimental adaptive trajectory in which a primitive form of novel cooperation evolved. This reduction and reversal of a positive social allelic effect is driven solely by changes in the genetic context in which the gene is expressed as new mutations are sequentially fixed during adaptive evolution, and explicitly demonstrates a significant evolutionary change in the genetic architecture of an ecologically important social trait.

  7. OncoSimulR: genetic simulation with arbitrary epistasis and mutator genes in asexual populations.

    PubMed

    Diaz-Uriarte, Ramon

    2017-06-15

    OncoSimulR implements forward-time genetic simulations of biallelic loci in asexual populations with special focus on cancer progression. Fitness can be defined as an arbitrary function of genetic interactions between multiple genes or modules of genes, including epistasis, restrictions in the order of accumulation of mutations, and order effects. Mutation rates can differ among genes, and can be affected by (anti)mutator genes. Also available are sampling from simulations (including single-cell sampling), plotting the genealogical relationships of clones and generating and plotting fitness landscapes. Implemented in R and C ++, freely available from BioConductor for Linux, Mac and Windows under the GNU GPL license. Version 2.5.9 or higher available from: http://www.bioconductor.org/packages/devel/bioc/html/OncoSimulR.html . GitHub repository at: https://github.com/rdiaz02/OncoSimul. ramon.diaz@iib.uam.es. Supplementary data are available at Bioinformatics online.

  8. Conservation and rewiring of functional modules revealed by an epistasis map in fission yeast.

    PubMed

    Roguev, Assen; Bandyopadhyay, Sourav; Zofall, Martin; Zhang, Ke; Fischer, Tamas; Collins, Sean R; Qu, Hongjing; Shales, Michael; Park, Han-Oh; Hayles, Jacqueline; Hoe, Kwang-Lae; Kim, Dong-Uk; Ideker, Trey; Grewal, Shiv I; Weissman, Jonathan S; Krogan, Nevan J

    2008-10-17

    An epistasis map (E-MAP) was constructed in the fission yeast, Schizosaccharomyces pombe, by systematically measuring the phenotypes associated with pairs of mutations. This high-density, quantitative genetic interaction map focused on various aspects of chromosome function, including transcription regulation and DNA repair/replication. The E-MAP uncovered a previously unidentified component of the RNA interference (RNAi) machinery (rsh1) and linked the RNAi pathway to several other biological processes. Comparison of the S. pombe E-MAP to an analogous genetic map from the budding yeast revealed that, whereas negative interactions were conserved between genes involved in similar biological processes, positive interactions and overall genetic profiles between pairs of genes coding for physically associated proteins were even more conserved. Hence, conservation occurs at the level of the functional module (protein complex), but the genetic cross talk between modules can differ substantially.

  9. Analysis of longitudinal bunching in an FEL driven two-beam accelerator

    SciTech Connect

    Lidia, S.; Gardelle, J.; Lefevre, T.; Donohue, J.T.; Gouard, P.; Rullier, J.L.; Vermare, C.

    2000-08-01

    Recent experiments have explored the use of a free-electron laser (FEL) as a buncher for a microwave two-beam accelerator, and the subsequent driving of a standing-wave rf output cavity. Here the authors present a deeper analysis of the longitudinal dynamics of the electron bunches as they are transported from the end of the FEL and through the output cavity. In particular, the authors examine the effect of the transport region and cavity aperture to filter the bunched portion of the beam.

  10. 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.

  11. Ferrographic analysis of wear debris generated in accelerated rolling element fatigue tests

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.; Parker, R. J.

    1977-01-01

    Ferrographic analysis was used to determine the types and quantities of wear particles generated during accelerated rolling contact fatigue tests. The NASA five-ball rolling contact fatigue tester was used. Ball specimens were made of AMS 5749, a corrosion-resistant high-temperature bearing steel. The lubricant was a super-refined naphthenic mineral oil. Conditions included a maximum Hertz stress of 5.52 billion Pa and a shaft speed of 10,000 rpm. Four types of wear particles were observed: normal rubbing wear particles, fatigue spall particles, spheres, and friction polymer.

  12. 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.

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

    DOE PAGES

    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

  14. Characterizing gene-gene interactions in a statistical epistasis network of twelve candidate genes for obesity.

    PubMed

    De, Rishika; Hu, Ting; Moore, Jason H; Gilbert-Diamond, Diane

    2015-01-01

    Recent findings have reemphasized the importance of epistasis, or gene-gene interactions, as a contributing factor to the unexplained heritability of obesity. Network-based methods such as statistical epistasis networks (SEN), present an intuitive framework to address the computational challenge of studying pairwise interactions between thousands of genetic variants. In this study, we aimed to analyze pairwise interactions that are associated with Body Mass Index (BMI) between SNPs from twelve genes robustly associated with obesity (BDNF, ETV5, FAIM2, FTO, GNPDA2, KCTD15, MC4R, MTCH2, NEGR1, SEC16B, SH2B1, and TMEM18). We used information gain measures to identify all SNP-SNP interactions among and between these genes that were related to obesity (BMI > 30 kg/m(2)) within the Framingham Heart Study Cohort; interactions exceeding a certain threshold were used to build an SEN. We also quantified whether interactions tend to occur more between SNPs from the same gene (dyadicity) or between SNPs from different genes (heterophilicity). We identified a highly connected SEN of 709 SNPs and 1241 SNP-SNP interactions. Combining the SEN framework with dyadicity and heterophilicity analyses, we found 1 dyadic gene (TMEM18, P-value = 0.047) and 3 heterophilic genes (KCTD15, P-value = 0.045; SH2B1, P-value = 0.003; and TMEM18, P-value = 0.001). We also identified a lncRNA SNP (rs4358154) as a key node within the SEN using multiple network measures. This study presents an analytical framework to characterize the global landscape of genetic interactions from genome-wide arrays and also to discover nodes of potential biological significance within the identified network.

  15. 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.

  16. LeuT conformational sampling utilizing accelerated molecular dynamics and principal component analysis.

    PubMed

    Thomas, James R; Gedeon, Patrick C; Grant, Barry J; Madura, Jeffry D

    2012-07-03

    Monoamine transporters (MATs) function by coupling ion gradients to the transport of dopamine, norepinephrine, or serotonin. Despite their importance in regulating neurotransmission, the exact conformational mechanism by which MATs function remains elusive. To this end, we have performed seven 250 ns accelerated molecular dynamics simulations of the leucine transporter, a model for neurotransmitter MATs. By varying the presence of binding-pocket leucine substrate and sodium ions, we have sampled plausible conformational states representative of the substrate transport cycle. The resulting trajectories were analyzed using principal component analysis of transmembrane helices 1b and 6a. This analysis revealed seven unique structures: two of the obtained conformations are similar to the currently published crystallographic structures, one conformation is similar to a proposed open inward structure, and four conformations represent novel structures of potential importance to the transport cycle. Further analysis reveals that the presence of binding-pocket sodium ions is necessary to stabilize the locked-occluded and open-inward conformations.

  17. Useful technique for analysis and control of the acceleration beam phase in the azimuthally varying field cyclotron

    NASA Astrophysics Data System (ADS)

    Kurashima, Satoshi; Yuyama, Takahiro; Miyawaki, Nobumasa; Kashiwagi, Hirotsugu; Okumura, Susumu; Fukuda, Mitsuhiro

    2010-03-01

    We have developed a new technique for analysis and control of the acceleration beam phase in the cyclotron. In this technique, the beam current pattern at a fixed radius r is measured by slightly scanning the acceleration frequency in the cyclotron. The acceleration beam phase is obtained by analyzing symmetry of the current pattern. Simple procedure to control the acceleration beam phase by changing coil currents of a few trim coils was established. The beam phase width is also obtained by analyzing gradient of the decreasing part of the current pattern. We verified reliability of this technique with 260 MeV N20e7+ beams which were accelerated on different tuning condition of the cyclotron. When the acceleration beam phase was around 0°, top of the energy gain of cosine wave, and the beam phase width was about 6° in full width at half maximum, a clear turn pattern of the beam was observed with a differential beam probe in the extraction region. Beam phase widths of ion beams at acceleration harmonics of h =1 and h =2 were estimated without beam cutting by phase-defining slits. We also calculated the beam phase widths roughly from the beam current ratio between the injected beam and the accelerated beam in the cyclotron without operating the beam buncher. Both beam phase widths were almost the same for h =1, while phase compressions by a factor of about 3 were confirmed for h =2.

  18. Useful technique for analysis and control of the acceleration beam phase in the azimuthally varying field cyclotron

    SciTech Connect

    Kurashima, Satoshi; Yuyama, Takahiro; Miyawaki, Nobumasa; Kashiwagi, Hirotsugu; Okumura, Susumu; Fukuda, Mitsuhiro

    2010-03-15

    We have developed a new technique for analysis and control of the acceleration beam phase in the cyclotron. In this technique, the beam current pattern at a fixed radius r is measured by slightly scanning the acceleration frequency in the cyclotron. The acceleration beam phase is obtained by analyzing symmetry of the current pattern. Simple procedure to control the acceleration beam phase by changing coil currents of a few trim coils was established. The beam phase width is also obtained by analyzing gradient of the decreasing part of the current pattern. We verified reliability of this technique with 260 MeV {sup 20}Ne{sup 7+} beams which were accelerated on different tuning condition of the cyclotron. When the acceleration beam phase was around 0 deg., top of the energy gain of cosine wave, and the beam phase width was about 6 deg. in full width at half maximum, a clear turn pattern of the beam was observed with a differential beam probe in the extraction region. Beam phase widths of ion beams at acceleration harmonics of h=1 and h=2 were estimated without beam cutting by phase-defining slits. We also calculated the beam phase widths roughly from the beam current ratio between the injected beam and the accelerated beam in the cyclotron without operating the beam buncher. Both beam phase widths were almost the same for h=1, while phase compressions by a factor of about 3 were confirmed for h=2.

  19. 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

  20. Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis

    PubMed Central

    Hill, Andrew; Loh, Po-Ru; Bharadwaj, Ragu B.; Pons, Pascal; Shang, Jingbo; Guinan, Eva; Lakhani, Karim; Kilty, Iain

    2017-01-01

    Abstract Background: The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Results: Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in <6 months by providing rapid access to highly skilled programmers with specialized, difficult-to-find skill sets. Through a crowd-based contest a combination of computational, numeric, and algorithmic approaches was identified that accelerated the logistic regression in PLINK 1.07 by 18- to 45-fold. Combining contest-derived logistic regression code with coarse-grained parallelization, multithreading, and associated changes to data initialization code further developed through distributed innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this

  1. Stepwise Distributed Open Innovation Contests for Software Development: Acceleration of Genome-Wide Association Analysis.

    PubMed

    Hill, Andrew; Loh, Po-Ru; Bharadwaj, Ragu B; Pons, Pascal; Shang, Jingbo; Guinan, Eva; Lakhani, Karim; Kilty, Iain; Jelinsky, Scott A

    2017-05-01

    The association of differing genotypes with disease-related phenotypic traits offers great potential to both help identify new therapeutic targets and support stratification of patients who would gain the greatest benefit from specific drug classes. Development of low-cost genotyping and sequencing has made collecting large-scale genotyping data routine in population and therapeutic intervention studies. In addition, a range of new technologies is being used to capture numerous new and complex phenotypic descriptors. As a result, genotype and phenotype datasets have grown exponentially. Genome-wide association studies associate genotypes and phenotypes using methods such as logistic regression. As existing tools for association analysis limit the efficiency by which value can be extracted from increasing volumes of data, there is a pressing need for new software tools that can accelerate association analyses on large genotype-phenotype datasets. Using open innovation (OI) and contest-based crowdsourcing, the logistic regression analysis in a leading, community-standard genetics software package (PLINK 1.07) was substantially accelerated. OI allowed us to do this in <6 months by providing rapid access to highly skilled programmers with specialized, difficult-to-find skill sets. Through a crowd-based contest a combination of computational, numeric, and algorithmic approaches was identified that accelerated the logistic regression in PLINK 1.07 by 18- to 45-fold. Combining contest-derived logistic regression code with coarse-grained parallelization, multithreading, and associated changes to data initialization code further developed through distributed innovation, we achieved an end-to-end speedup of 591-fold for a data set size of 6678 subjects by 645 863 variants, compared to PLINK 1.07's logistic regression. This represents a reduction in run time from 4.8 hours to 29 seconds. Accelerated logistic regression code developed in this project has been incorporated

  2. 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

  3. GPU-accelerated analysis and visualization of large structures solved by molecular dynamics flexible fitting.

    PubMed

    Stone, John E; McGreevy, Ryan; Isralewitz, Barry; Schulten, Klaus

    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-à-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.

  4. Analysis of a fractional-order couple model with acceleration in feelings.

    PubMed

    Koca, Ilknur; Ozalp, Nuri

    2013-01-01

    A fractional-order nonlinear dynamical model of couple has been introduced. Upper bounds are obtained for a fractional-order nonlinear dynamical model. Also different from other models, a model with the order 2 α is discussed. We are expecting an acceleration in feelings; that is why we increase the order of the derivative between 1 < 2α ≤ 2. Stability analysis of the fractional-order nonlinear dynamical model of involving two persons is studied using the fractional Routh-Hurwitz criteria. By using stability analysis on fractional-order system, we obtain sufficient condition on the parameters for the locally asymptotic stability of equilibrium points. Finally, numerical simulations are presented to verify the obtained results.

  5. 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

  6. Analysis of the Chirplet Transform-Based Algorithm for Radar Detection of Accelerated Targets

    NASA Astrophysics Data System (ADS)

    Galushko, V. G.; Vavriv, D. M.

    2017-06-01

    Purpose: Efficiency analysis of an optimal algorithm of chirp signal processing based on the chirplet transform as applied to detection of radar targets in uniformly accelerated motion. Design/methodology/approach: Standard methods of the optimal filtration theory are used to investigate the ambiguity function of chirp signals. Findings: An analytical expression has been derived for the ambiguity function of chirp signals that is analyzed with respect to detection of radar targets moving at a constant acceleration. Sidelobe level and characteristic width of the ambiguity function with respect to the coordinates frequency and rate of its change have been estimated. The gain in the signal-to-noise ratio has been assessed that is provided by the algorithm under consideration as compared with application of the standard Fourier transform to detection of chirp signals against a “white” noise background. It is shown that already with a comparatively small (<20) number of processing channels (elementary filters with respect to the frequency change rate) the gain in the signal-tonoise ratio exceeds 10 dB. A block diagram of implementation of the algorithm under consideration is suggested on the basis of a multichannel weighted Fourier transform. Recommendations as for selection of the detection algorithm parameters have been developed. Conclusions: The obtained results testify to efficiency of application of the algorithm under consideration to detection of radar targets moving at a constant acceleration. Nevertheless, it seems expedient to perform computer simulations of its operability with account for the noise impact along with trial measurements in real conditions.

  7. 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.

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

    NASA Astrophysics Data System (ADS)

    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.

  9. 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.

  10. 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.}

  11. Improvement of trace element analysis system using RIKEN electron cyclotron resonance ion source and linear accelerator

    SciTech Connect

    Kidera, M.; Nakagawa, T.; Takahashi, K.; Enomoto, S.; Igarashi, K.; Fujimaki, M.; Ikezawa, E.; Kamigaito, O.; Kase, M.; Goto, A.; Yano, Y.

    2006-03-15

    We have developed a new analytical system that consists of an electron cyclotron resonance ion source (RIKEN 18 GHz ECRIS) and a RIKEN heavy ion linear accelerator (RILAC). This system is called trace element analysis using electron cyclotron resonance ion source and RILAC (ECRIS-RILAC-TEA). ECRIS-RILAC-TEA has several advantages as described in the work of Kidera et al. [AIP Conf. Proc. 749, 85 (2005)]. However, many experimental results during the last several years revealed a few problems: (1) large background contamination in the ECRIS, particularly at the surface of the plasma chamber wall, (2) high counting of the ionization chamber and the data taking system that is monitored by the direct beam from the accelerator, and (3) difficulty in the selection of the pilot sample and pilot beam production from the ECRIS for the purpose of normalization. In order to overcome these problems, we conducted several test experiments over the past year. In this article, we report the experimental results in detail and future plans for improving this system.

  12. First Results from a Principal Component Analysis of Tycho's SNR: Evidence for Cosmic Ray Ion Acceleration

    NASA Astrophysics Data System (ADS)

    Warren, J. S.; Hughes, J. P.; Badenes, C.

    2005-12-01

    We present results from a Principal Component Analysis (PCA) of Tycho's supernova remnant (SNR). PCA is a statistical technique we implemented to characterize X-ray spectra extracted from distinct spatial regions across the entire image of the remnant. We used the PCA to determine the location of the contact discontinuity (CD) in Tycho, which marks the boundary between shocked ejecta and shocked interstellar material, and found an azimuthal-angle-averaged radius of 241". For the average radius of the outer blast wave (BW) we found 251". Taking account of projection effects, the ratio of BW:CD is 1:0.93, which is inconsistent with adiabatic hydrodynamic models of SNR evolution. The BW:CD ratio can be explained if cosmic ray acceleration of ions is occurring at the forward shock. Such a scenario is further supported by evidence from the morphology and spectral nature of the BW emission for the acceleration of cosmic ray electrons. We also present PCA results regarding the ranges in Si and Fe composition in Tycho, and a newly uncovered spectral variation in the form of a low energy excess that has not been previously noted.

  13. FADTTSter: accelerating hypothesis testing with functional analysis of diffusion tensor tract statistics

    NASA Astrophysics Data System (ADS)

    Noel, Jean; Prieto, Juan C.; Styner, Martin

    2017-03-01

    Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) is a toolbox for analysis of white matter (WM) fiber tracts. It allows associating diffusion properties along major WM bundles with a set of covariates of interest, such as age, diagnostic status and gender, and the structure of the variability of these WM tract properties. However, to use this toolbox, a user must have an intermediate knowledge in scripting languages (MATLAB). FADTTSter was created to overcome this issue and make the statistical analysis accessible to any non-technical researcher. FADTTSter is actively being used by researchers at the University of North Carolina. FADTTSter guides non-technical users through a series of steps including quality control of subjects and fibers in order to setup the necessary parameters to run FADTTS. Additionally, FADTTSter implements interactive charts for FADTTS' outputs. This interactive chart enhances the researcher experience and facilitates the analysis of the results. FADTTSter's motivation is to improve usability and provide a new analysis tool to the community that complements FADTTS. Ultimately, by enabling FADTTS to a broader audience, FADTTSter seeks to accelerate hypothesis testing in neuroimaging studies involving heterogeneous clinical data and diffusion tensor imaging. This work is submitted to the Biomedical Applications in Molecular, Structural, and Functional Imaging conference. The source code of this application is available in NITRC.

  14. 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

  15. A Theoretical Analysis of Anderson Acceleration and Its Application in Multiphysics Simulation for Light-Water Reactors

    NASA Astrophysics Data System (ADS)

    Toth, Alexander Raymond

    In this work, we are concerned with both contributing to the theoretical foundation for Anderson acceleration, a method for accelerating the convergence rate of Picard iteration, and evaluating its performance in the context of coupled multiphysics problems in nuclear reactor simulation. Anderson acceleration proceeds by maintaining a depth of previous iterate information in order to compute a new iterate as a linear combination of previous evaluations of the fixed-point map, where the linear combination coefficients are obtained by solving a linear leastsquares problem. Prior to this work, theory for this method was fairly sparse, dealing mainly with showing its relation to quasi-Newton multisecant updating and, when applied to linear problems, GMRES iteration. The analysis presented in this work significantly expands upon the theory for this method. As this method is intended as an acceleration method for Picard iteration, our analysis concerns problems for which Picard iteration is convergent, namely when the fixed-point mapping is contractive. We present analysis which represent the first convergence results for limited-memory variations of Anderson acceleration and for nonlinear problems. Additionally, we present analysis for several variations on the standard Anderson acceleration method. In particular, we consider a variation which adjusts the memory utilization in order to maintain good conditioning of the least-squares problem, and we present local improvement results for the case in which the fixed-point map can only be evaluated approximately. With respect to coupled multiphysics problems, we examine Anderson acceleration as an alternative to Picard iteration in the context of black-box code coupling in nuclear reactor simulation. Picard iteration comes with several drawbacks in this context, namely relatively slow convergence and poor robustness. To test the potential for Anderson acceleration to improve upon the weaknesses of Picard iteration, we first

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Analysis Of Acceleration Of Chasing Flight Of The Male Housefly With The Aid Of HSP

    NASA Astrophysics Data System (ADS)

    Shaowu, Zhang; Xiang, Wang; Shaoxiang, Zhou

    1989-06-01

    The housefly is equipped with an excellent visual guidance, flight control system which enables it to track small, fast moving objects in its visual field[1,2]. These mechanisms of visual orientation and guidance were investigated by means of an analysis of chasing flight induced by visual objects [3-8]. The acceleration of the chasing fly was investigated by analyzing the trajectories of its chasing flight in free flight conditions in a cage. In order to record the three-dimensional trajectories of the flies in the cage, a mirror was mounted beneath the bottom of the cage at 45 degree angle. A high speed cine camera was used and run at 200 frames per second.

  1. 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.

  2. Fast Electromagnetic Analysis of MRI Transmit RF Coils Based on Accelerated Integral Equation Methods.

    PubMed

    Villena, Jorge Fernandez; Polimeridis, Athanasios G; Eryaman, Yigitcan; Adalsteinsson, Elfar; Wald, Lawrence L; White, Jacob K; Daniel, Luca

    2016-11-01

    A fast frequency domain full-wave electromagnetic simulation method is introduced for the analysis of MRI coils loaded with the realistic human body models. The approach is based on integral equation methods decomposed into two domains: 1) the RF coil array and shield, and 2) the human body region where the load is placed. The analysis of multiple coil designs is accelerated by introducing the precomputed magnetic resonance Green functions (MRGFs), which describe how the particular body model used responds to the incident fields from external sources. These MRGFs, which are precomputed once for a given body model, can be combined with any integral equation solver and reused for the analysis of many coil designs. This approach provides a fast, yet comprehensive, analysis of coil designs, including the port S-parameters and the electromagnetic field distribution within the inhomogeneous body. The method solves the full-wave electromagnetic problem for a head array in few minutes, achieving a speed up of over 150 folds with root mean square errors in the electromagnetic field maps smaller than 0.4% when compared to the unaccelerated integral equation-based solver. This enables the characterization of a large number of RF coil designs in a reasonable time, which is a first step toward an automatic optimization of multiple parameters in the design of transmit arrays, as illustrated in this paper, but also receive arrays.

  3. Accelerated design and quality control of impact modifiers for plastics through atomic force microscopy (AFM) analysis

    NASA Astrophysics Data System (ADS)

    Moeller, Gunter

    2011-03-01

    Standard polymer resins are often too brittle or do not meet other mechanical property requirements for typical polymer applications. To achieve desired properties it is common to disperse so called ``impact modifiers'', which are spherical latex particles with diameters of much less than one micrometer, into the pure resin. Understanding and control of the entire process from latex particle formation to subsequent dispersion into polymer resins are necessary to accelerate the development of new materials that meet specific application requirements. In this work AFM imaging and nanoindentation techniques in combination with AFM-based spectroscopic techniques were applied to assess latex formation and dispersion. The size and size distribution of the latex particles can be measured based on AFM amplitude modulation images. AFM phase images provide information about the chemical homogeneity of individual particles. Nanoindentation may be used to estimate their elastic and viscoelastic properties. Proprietary creep and nanoscale Dynamic Mechanical Analysis (DMA) tests that we have developed were used to measure these mechanical properties. The small size of dispersed latex inclusions requires local mechanical and spectroscopic analysis techniques with high lateral and spatial resolution. We applied the CRAVE AFM method, developed at NIST, to perform mechanical analysis of individual latex inclusions and compared results with those obtained using nanoscale DMA. NanoIR, developed by Anasys Inc., and principal component confocal Raman were used for spectroscopic analysis and results from both techniques compared.

  4. 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

  5. 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.

  6. 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.

  7. Common analysis of the relativistic klystron and the standing-wave free-electron laser two-beam accelerator

    SciTech Connect

    Wurtele, J.S.; Whittum, D.H.; Sessler, A.M.

    1992-07-01

    This paper summarizes a new formalism which makes the analysis and understanding of both the relativistic klystron (RK) and the standing-wave free-electron laser (SWFEL) two-beam accelerator (TBA) available to a wide audience of accelerator physicists. A ``coupling impedance`` for both the RK and SWFEL is introduced, which can include realistic cavity features, such as beam and vacuum ports, in a simple manner. The RK and SWFEL macroparticle equations, which govern the energy and phase evolution of successive bunches in the beam, are of identical form, differing only by multiplicative factors. The analysis allows, for the first time, a relative comparison of the RF and SWFEL TBAs.

  8. The L(1/2) regularization approach for survival analysis in the accelerated failure time model.

    PubMed

    Chai, Hua; Liang, Yong; Liu, Xiao-Ying

    2015-09-01

    The analysis of high-dimensional and low-sample size microarray data for survival analysis of cancer patients is an important problem. It is a huge challenge to select the significantly relevant bio-marks from microarray gene expression datasets, in which the number of genes is far more than the size of samples. In this article, we develop a robust prediction approach for survival time of patient by a L(1/2) regularization estimator with the accelerated failure time (AFT) model. The L(1/2) regularization could be seen as a typical delegate of L(q)(0analysis by the L(1/2) regularized AFT model compared with other L1 type regularization methods. The proposed procedures are applied to five real DNA microarray datasets to efficiently predict the survival time of patient based on a set of clinical prognostic factors and gene signatures. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. 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.

  10. 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.

  11. Genetic architecture of metabolic rate: environment specific epistasis between mitochondrial and nuclear genes in an insect.

    PubMed

    Arnqvist, Göran; Dowling, Damian K; Eady, Paul; Gay, Laurene; Tregenza, Tom; Tuda, Midori; Hosken, David J

    2010-12-01

    The extent to which mitochondrial DNA (mtDNA) variation is involved in adaptive evolutionary change is currently being reevaluated. In particular, emerging evidence suggests that mtDNA genes coevolve with the nuclear genes with which they interact to form the energy producing enzyme complexes in the mitochondria. This suggests that intergenomic epistasis between mitochondrial and nuclear genes may affect whole-organism metabolic phenotypes. Here, we use crossed combinations of mitochondrial and nuclear lineages of the seed beetle Callosobruchus maculatus and assay metabolic rate under two different temperature regimes. Metabolic rate was affected by an interaction between the mitochondrial and nuclear lineages and the temperature regime. Sequence data suggests that mitochondrial genetic variation has a role in determining the outcome of this interaction. Our genetic dissection of metabolic rate reveals a high level of complexity, encompassing genetic interactions over two genomes, and genotype × genotype × environment interactions. The evolutionary implications of these results are twofold. First, because metabolic rate is at the root of life histories, our results provide insights into the complexity of life-history evolution in general, and thermal adaptation in particular. Second, our results suggest a mechanism that could contribute to the maintenance of nonneutral mtDNA polymorphism. © 2010 The Author(s). Evolution© 2010 The Society for the Study of Evolution.

  12. Ethnic variation in genetic disease: possible roles of hitchhiking and epistasis.

    PubMed

    Wagener, D K; Cavalli-Sforza, L L

    1975-05-01

    The high incidence of some genetic diseases in certain ethnic groups is important in planning of medical genetic programs. Simple interaction models predict that at least some lethal recessive alleles will have "hitchhiked" to increased frequencies because of linkage to genes whose alleles have been favored by selection for other reasons in certain populations. In the absence of linkage or epistasis with a gene favored by selection, heterozygote advantage for a recessive lethal may produce the same phenomenon. In the hitchhiking model (linkage), the increase in the gene frequency is temporary, but the length of time that the increased gene frequency is at least double the base frequency may be quite long. Changes in gene frequency for the unlinked epistatic model result in a new equilibrium with a possibly higher gene frequency. The most likely chromosomal regions in which hitchhiked lethal recessives would be found are in the vicinity of genes whose allelic frequencies vary substantially among human racial groups (e.g., Gm, Rh, Duffy, lactose tolerance, or HL-A). There will be a hitchhiking effect if recombination distance is less than the selective advantage. The closer the linkage of two loci, the easier hitchhiking effects will be to detect. Hitchhiking is suggested by nonrandom association of the recessive disease and one of the selected markers, as in the case of Gm and cystic fibrosis. However, there is so far insufficient evidence of linkage between them. More pedigree information is necessary than is now available.

  13. Isolation, characterization and epistasis of fluoride-resistant mutants of Caenorhabditis elegans.

    PubMed

    Katsura, I; Kondo, K; Amano, T; Ishihara, T; Kawakami, M

    1994-01-01

    We have isolated 13 fluoride-resistant mutants of the nematode Caenorhabditis elegans. All the mutations are recessive and mapped to five genes. Mutants in three of the genes (class 1 genes: flr-1 X, flr-3 IV, and flr-4 X) are resistant to 400 micrograms/ml NaF. Furthermore, they grow twice as slowly as and have smaller brood size than wild-type worms even in the absence of fluoride ion. In contrast, mutants in the other two genes (class 2 genes: flr-2 V and flr-5 V) are only partially resistant to 400 micrograms/ml NaF, and they have almost normal growth rates and brood sizes in the absence of fluoride ion. Studies on the phenotypes of double mutants showed that class 2 mutations are epistatic to class 1 mutations concerning growth rate and brood size but hypostatic with respect to fluoride resistance. We propose two models that can explain the epistasis. Since fluoride ion depletes calcium ion, inhibits some protein phosphatases and activates trimeric G-proteins, studies on these mutants may lead to discovery of a new signal transduction system that controls the growth of C. elegans.

  14. Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models.

    PubMed

    Hu, Ting; Andrew, Angeline S; Karagas, Margaret R; Moore, Jason H

    2013-01-01

    The rapid development of sequencing technologies makes thousands to millions of genetic attributes available for testing associations with various biological traits. Searching this enormous high-dimensional data space imposes a great computational challenge in genome-wide association studies. We introduce a network-based approach to supervise the search for three-locus models of disease susceptibility. Such statistical epistasis networks (SEN) are built using strong pairwise epistatic interactions and provide a global interaction map to search for higher-order interactions by prioritizing genetic attributes clustered together in the networks. Applying this approach to a population-based bladder cancer dataset, we found a high susceptibility three-way model of genetic variations in DNA repair and immune regulation pathways, which holds great potential for studying the etiology of bladder cancer with further biological validations. We demonstrate that our SEN-supervised search is able to find a small subset of three-locus models with significantly high associations at a substantially reduced computational cost.

  15. Quantification of various APP-mRNA isoforms and epistasis in Lesch-Nyhan disease.

    PubMed

    Nguyen, Khue Vu; Nyhan, William L

    2017-03-16

    The present work is the development of a simple and specific kinetic method based on RT-PCR technique coupled with direct sequencing for quantification of various amyloid precursor protein-mRNA isoforms (APP-mRNA isoforms) in biological samples, especially for identifying the most abundant one that may decisive for the normal status or disease risk. Application of this kinetic method to the Lesch-Nyhan disease (LND) was performed and results indicated an epistasis between mutated hypoxanthine phosphoribosyltransferase1 (HPRT1) and APP genes. APP-mRNA isoform of 624bp, with a deletion starting after 49bp of the 5' end of exon 3 followed by a complete deletion of exons 4-15, mutations in exon 1: c.22C>T, p.L18F, and exon 3: c.269A>G, p.Q90R encoding APP207 isoform, was the most abundant one in most of the LND patients and would be responsible for the neurobehavioral syndrome in these patients. The method is useful for identifying the defective APP-mRNA isoform in LND patients, and in neurodevelopmental and neurodegenerative disorders in which the APP gene is involved in the pathogenesis of diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, and Alzheimer's disease, and may pave the way for new strategies applicable to rational antisense drugs design. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. COMT x DRD4 epistasis impacts prefrontal cortex function underlying response control.

    PubMed

    Heinzel, Sebastian; Dresler, Thomas; Baehne, Christina G; Heine, Monika; Boreatti-Hümmer, Andrea; Jacob, Christian P; Renner, Tobias J; Reif, Andreas; Lesch, Klaus-Peter; Fallgatter, Andreas J; Ehlis, Ann-Christine

    2013-06-01

    The prefrontal cortex plays a major role in cognitive control, but it is unclear how single genes and gene-gene interactions (genetic epistasis) impact neural and behavioral phenotypes. Both dopamine (DA) availability ("inverted U-model") and excitatory versus inhibitory DA receptor stimulation ("dual-state theory") have been linked to important principles of prefrontal processing. Catechol-O-methyltransferase (COMT; Val158Met) and DA D4-receptor (DRD4; 48 bp VNTR) genotypes were analyzed for effects on behavioral and neural correlates of prefrontal response control (NoGo-anteriorization, NGA) using a Go-NoGo task and electroencephalography (114 controls and 181 patients with attention-deficit/hyperactivity disorder).  DRD4 and COMT epistatically interacted on the NGA, whereas single genes and diagnosis showed no significant impact. Subjects with presumably relatively increased D4-receptor function (DRD4: no 7R-alleles) displayed an inverted U-relationship between the NGA and increasing COMT-dependent DA levels, whereas subjects with decreased D4-sensitivity (7R) showed a U-relationship. This interaction was supported by 7R-allele dose effects and mirrored by reaction time variability (non-significant after multiple testing correction). Combining previous theories of prefrontal DA functioning, neural stability at intermediate DA levels may be accompanied by the risk of overly decreased neural flexibility if inhibitory DA receptor function is additionally decreased. Our findings might help to disentangle the genetic basis of dopaminergic mechanisms underlying prefrontal (dys)function.

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

    PubMed Central

    Shliaha, Pavel; Schwarz, Roland; Capuano, Floriana; Vowinckel, Jakob; Radmanesfahar, Elahe; Krüger, Antje; Calvani, Enrica; Michel, Steve; Börno, Stefan; Christen, Stefan; Patil, Kiran Raosaheb; Timmermann, Bernd; Lilley, Kathryn S; Ralser, Markus

    2016-01-01

    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 a likely determinant of gene expression. Here, we addressed the importance of the metabolic-genetic background by monitoring transcriptome, proteome, and metabolome in a repertoire of sixteen 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 showed, on average, 83% overlap between unrelated auxotrophs, and 35% with previously published transcriptomes generated for non-metabolic gene knock-outs. Background-dependent gene expression correlated with metabolic flux and acted, predominantly through masking or suppression, on 88% of transcriptional interactions epistatically. As 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 for 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

  18. Congenic mice reveal genetic epistasis and overlapping disease loci for autoimmune diabetes and listeriosis.

    PubMed

    Wang, Nancy; Elso, Colleen M; Mackin, Leanne; Mannering, Stuart I; Strugnell, Richard A; Wijburg, Odilia L; Brodnicki, Thomas C

    2014-08-01

    The nonobese diabetic (NOD) mouse strain serves as a genomic standard for assessing how allelic variation for insulin-dependent diabetes (Idd) loci affects the development of autoimmune diabetes. We previously demonstrated that C57BL/6 (B6) mice harbor a more diabetogenic allele than NOD mice for the Idd14 locus when introduced onto the NOD genetic background. New congenic NOD mouse strains, harboring smaller B6-derived intervals on chromosome 13, now localize Idd14 to an ~18-Mb interval and reveal a new locus, Idd31. Notably, the B6 allele for Idd31 confers protection against diabetes, but only in the absence of the diabetogenic B6 allele for Idd14, indicating genetic epistasis between these two loci. Moreover, congenic mice that are more susceptible to diabetes are more resistant to Listeria monocytogenes infection. This result co-localizes Idd14 and Listr2, a resistance locus for listeriosis, to the same genomic interval and indicates that congenic NOD mice may also be useful for localizing resistance loci for infectious disease.

  19. On epigenetics and epistasis: hybrids and their non-additive interactions

    PubMed Central

    Smith, Lisa M; Weigel, Detlef

    2012-01-01

    EMBO J 31 2, 257–266 (2012); published online 12162011 Hybrid seeds have been a key component of greatly increasing the yield of many important crops, foremost of maize. If the parents are properly chosen, non-additive interactions between diverged genomes can lead to strongly superior performance of the F1 progeny, known as heterosis. While many different explanations have been advanced, a consensus for the causes of genome-wide positive epistasis in hybrids has not emerged. In this issue of The EMBO Journal, Shivaprasad and colleagues describe a new mechanism that can account for heterosis often being a genome-wide phenomenon. These authors show that small RNA (sRNA) loci of tomato can exhibit transgressive activity, which can in turn lead to epigenetic and gene expression changes within hybrid progeny. This is particularly exciting because many sRNAs are produced from non-coding regions or transposable elements (TEs), which diverge more quickly than protein-coding genes and thus provide more opportunity for unexpected genetic interactions. PMID:22193717

  20. 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.

  1. DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility.

    PubMed

    Ambatipudi, Srikant; Horvath, Steve; Perrier, Flavie; Cuenin, Cyrille; Hernandez-Vargas, Hector; Le Calvez-Kelm, Florence; Durand, Geoffroy; Byrnes, Graham; Ferrari, Pietro; Bouaoun, Liacine; Sklias, Athena; Chajes, Véronique; Overvad, Kim; Severi, Gianluca; Baglietto, Laura; Clavel-Chapelon, Françoise; Kaaks, Rudolf; Barrdahl, Myrto; Boeing, Heiner; Trichopoulou, Antonia; Lagiou, Pagona; Naska, Androniki; Masala, Giovanna; Agnoli, Claudia; Polidoro, Silvia; Tumino, Rosario; Panico, Salvatore; Dollé, Martijn; Peeters, Petra H M; Onland-Moret, N Charlotte; Sandanger, Torkjel M; Nøst, Therese H; Weiderpass, Elisabete; Quirós, J Ramón; Agudo, Antonio; Rodriguez-Barranco, Miguel; Huerta Castaño, José María; Barricarte, Aurelio; Fernández, Ander Matheu; Travis, Ruth C; Vineis, Paolo; Muller, David C; Riboli, Elio; Gunter, Marc; Romieu, Isabelle; Herceg, Zdenko

    2017-04-01

    A vast majority of human malignancies are associated with ageing, and age is a strong predictor of cancer risk. Recently, DNA methylation-based marker of ageing, known as 'epigenetic clock', has been linked with cancer risk factors. This study aimed to evaluate whether the epigenetic clock is associated with breast cancer risk susceptibility and to identify potential epigenetics-based biomarkers for risk stratification. Here, we profiled DNA methylation changes in a nested case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (n = 960) using the Illumina HumanMethylation 450K BeadChip arrays and used the Horvath age estimation method to calculate epigenetic age for these samples. Intrinsic epigenetic age acceleration (IEAA) was estimated as the residuals by regressing epigenetic age on chronological age. We observed an association between IEAA and breast cancer risk (OR, 1.04; 95% CI, 1.007-1.076, P = 0.016). One unit increase in IEAA was associated with a 4% increased odds of developing breast cancer (OR, 1.04; 95% CI, 1.007-1.076). Stratified analysis based on menopausal status revealed that IEAA was associated with development of postmenopausal breast cancers (OR, 1.07; 95% CI, 1.020-1.11, P = 0.003). In addition, methylome-wide analyses revealed that a higher mean DNA methylation at cytosine-phosphate-guanine (CpG) islands was associated with increased risk of breast cancer development (OR per 1 SD = 1.20; 95 %CI: 1.03-1.40, P = 0.02) whereas mean methylation levels at non-island CpGs were indistinguishable between cancer cases and controls. Epigenetic age acceleration and CpG island methylation have a weak, but statistically significant, association with breast cancer susceptibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Age- and gender-specific epistasis between ADA and TNF-α influences human life-expectancy.

    PubMed

    Napolioni, Valerio; Carpi, Francesco M; Giannì, Paola; Sacco, Roberto; Di Blasio, Luca; Mignini, Fiorenzo; Lucarini, Nazzareno; Persico, Antonio M

    2011-11-01

    Aging is a complex phenotype with multiple determinants but a strong genetic component significantly impacts on survival to extreme ages. The dysregulation of immune responses occurring with increasing age is believed to contribute to human morbidity and mortality. Conversely, some genetic determinants of successful aging might reside in those polymorphisms for the immune system genes regulating immune responses. Here we examined the main effects of single loci and multi-locus interactions to test the hypothesis that the adenosine deaminase (ADA) and tumor necrosis factor alpha (TNF-α) genes may influence human life-expectancy. ADA (22G>A, rs73598374) and TNF-α (-308G>A, rs1800629; -238G>A, rs361525) functional SNPs have been determined for 1071 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals<66 years old (<73 years old), the second class of individuals 66-88 years old (73-91 years old), and the third class of individuals>88 years old (>91 years old). Single-locus analysis showed that only ADA 22G>A is significantly associated with human life-expectancy in males (comparison 1 (age class 2 vs. age class 1), O.R. 1.943, P=0.036; comparison 2 (age class 3 vs. age class 2), O.R. 0.320, P=0.0056). Age- and gender-specific patterns of epistasis between ADA and TNF-α were found using Generalized Multifactor Dimensionality Reduction (GMDR). In comparison 1, a significant two-loci interaction occurs in females between ADA 22G>A and TNF-α -238G>A (Sign Test P=0.011). In comparison 2, both two-loci and three-loci interaction are significant associated with increased life-expectancy over 88 years in males. In conclusion, we report that a combination of functional SNPs within ADA and TNF-α genes can influence life-expectancy in a gender

  3. Role of sugammadex in accelerating postoperative discharge: A meta-analysis.

    PubMed

    Carron, Michele; Zarantonello, Francesco; Lazzarotto, Nadia; Tellaroli, Paola; Ori, Carlo

    2017-06-01

    Sugammadex has been introduced for reversal of neuromuscular blockade (NMB) induced by rocuronium (or vecuronium). Although its efficacy and safety have been established, data are conflicting as to whether it accelerates discharge to the surgical ward compared with neostigmine, which is traditionally used for reversing NMB. The object of this systematic review and meta-analysis was to review the research comparing sugammadex and neostigmine in the context of patient discharge after general anesthesia. Systematic review and meta-analysis. University medical hospital. Five-hundred eighteen patients from six studies were included. A comprehensive search was conducted using PubMed, Web of Science, Google Scholar, and Cochrane Library electronic databases to identify randomized controlled trials written in English. Two reviewers independently selected the studies, extracted data regarding postoperative discharge, and assessed the trials' methodological quality and evidence level. Postoperative discharge time was determined from the operating room (OR) to the postanesthesia care unit (PACU) and from the PACU to the surgical ward. This study was conducted using PRISMA methodology. Time to discharge after NMB reversal with sugammadex or neostigmine. Compared with neostigmine, sugammadex was associated with a significantly faster discharge from the OR to the PACU (mean difference [MD]=22.14min, 95% CI (14.62, 29.67), P<0.0001, I(2)=0%) and from the PACU to the surgical ward (MD=16.95min, 95% CI (0.23, 33.67), P=0.0469, I(2)=98.4%). Similarly, discharge-readiness was shorter for sugammadex than for neostigmine from the OR to the PACU (MD=5.58min, 95% CI (3.03, 8.14), P≤0.0001, I(2)=0%). However, discharge-readiness was similar in both groups for patients moving from the PACU to the surgical ward (MD=-1.10min, 95% CI (-5.69, 3.50), P=0.6394, I(2)=25.3%). Results from this meta-analysis suggest that sugammadex accelerates postoperative discharge of patients after general

  4. Accelerated test design

    NASA Technical Reports Server (NTRS)

    Mcdermott, P. P.

    1980-01-01

    The design of an accelerated life test program for electric batteries is discussed. A number of observations and suggestions on the procedures and objectives for conducting an accelerated life test program are presented. Equations based on nonlinear regression analysis for predicting the accelerated life test parameters are discussed.

  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.

  6. A hardware acceleration based on high-level synthesis approach for glucose-insulin analysis

    NASA Astrophysics Data System (ADS)

    Daud, Nur Atikah Mohd; Mahmud, Farhanahani; Jabbar, Muhamad Hairol

    2017-01-01

    In this paper, the research is focusing on Type 1 Diabetes Mellitus (T1DM). Since this disease requires a full attention on the blood glucose concentration with the help of insulin injection, it is important to have a tool that able to predict that level when consume a certain amount of carbohydrate during meal time. Therefore, to make it realizable, a Hovorka model which is aiming towards T1DM is chosen in this research. A high-level language is chosen that is C++ to construct the mathematical model of the Hovorka model. Later, this constructed code is converted into intellectual property (IP) which is also known as a hardware accelerator by using of high-level synthesis (HLS) approach which able to improve in terms of design and performance for glucose-insulin analysis tool later as will be explained further in this paper. This is the first step in this research before implementing the design into system-on-chip (SoC) to achieve a high-performance system for the glucose-insulin analysis tool.

  7. 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.

  8. Enhanced analysis of steroids by gas chromatography/mass spectrometry using microwave-accelerated derivatization.

    PubMed

    Bowden, John A; Colosi, Dominic M; Stutts, Whitney L; Mora-Montero, Diana C; Garrett, Timothy J; Yost, Richard A

    2009-08-15

    Derivatization of steroids is typically required before analysis by gas chromatography/mass spectrometry (GC/MS); nevertheless, the derivatization process can often be time-consuming and irreproducible. Although several strategies have been employed to enhance this process, few have the potential of microwave-accelerated derivatization (MAD) to be more efficient than traditional thermal derivatization methods. MAD using a synthesis microwave system was evaluated and compared to traditional thermal derivatization methods in terms of yield, reproducibility, and overall analysis time. Parameters affecting MAD, including reaction temperature, time, and power, were systematically optimized for several silyl reagents (BSTFA with TMCS, MSTFA, and BSA) and other derivatization procedures (MOX reagent and MTBSTFA). MSTFA was found to derivatize best with the microwave, as demonstrated by the enhanced relative response factors (RRFs). BSTFA with TMCS, on the other hand, did not couple as well, but RRF values improved significantly upon addition of polar solvents. The rapid (1 min) derivatization reactions associated with MAD had comparable RRFs for all reagents with those obtained with thermal heating (>30 min). This study highlights the best methods for analyzing a comprehensive variety of steroids and also provides ideal strategies for MAD of steroids on an individual or class level.

  9. Application of failure mode and effects analysis to intracranial stereotactic radiation surgery by linear accelerator.

    PubMed

    Masini, Laura; Donis, Laura; Loi, Gianfranco; Mones, Eleonora; Molina, Elisa; Bolchini, Cesare; Krengli, Marco

    2014-01-01

    The aim of this study was to analyze the application of the failure modes and effects analysis (FMEA) to intracranial stereotactic radiation surgery (SRS) by linear accelerator in order to identify the potential failure modes in the process tree and adopt appropriate safety measures to prevent adverse events (AEs) and near-misses, thus improving the process quality. A working group was set up to perform FMEA for intracranial SRS in the framework of a quality assurance program. FMEA was performed in 4 consecutive tasks: (1) creation of a visual map of the process; (2) identification of possible failure modes; (3) assignment of a risk probability number (RPN) to each failure mode based on tabulated scores of severity, frequency of occurrence and detectability; and (4) identification of preventive measures to minimize the risk of occurrence. The whole SRS procedure was subdivided into 73 single steps; 116 total possible failure modes were identified and a score of severity, occurrence, and detectability was assigned to each. Based on these scores, RPN was calculated for each failure mode thus obtaining values from 1 to 180. In our analysis, 112/116 (96.6%) RPN values were <60, 2 (1.7%) between 60 and 125 (63, 70), and 2 (1.7%) >125 (135, 180). The 2 highest RPN scores were assigned to the risk of using the wrong collimator's size and incorrect coordinates on the laser target localizer frame. Failure modes and effects analysis is a simple and practical proactive tool for systematic analysis of risks in radiation therapy. In our experience of SRS, FMEA led to the adoption of major changes in various steps of the SRS procedure.

  10. Can Accelerators Accelerate Learning?

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-01

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ) [1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  11. Can Accelerators Accelerate Learning?

    SciTech Connect

    Santos, A. C. F.; Fonseca, P.; Coelho, L. F. S.

    2009-03-10

    The 'Young Talented' education program developed by the Brazilian State Funding Agency (FAPERJ)[1] makes it possible for high-schools students from public high schools to perform activities in scientific laboratories. In the Atomic and Molecular Physics Laboratory at Federal University of Rio de Janeiro (UFRJ), the students are confronted with modern research tools like the 1.7 MV ion accelerator. Being a user-friendly machine, the accelerator is easily manageable by the students, who can perform simple hands-on activities, stimulating interest in physics, and getting the students close to modern laboratory techniques.

  12. Accelerated roadbuilding on the north umpqua—an economic analysis.

    Treesearch

    Brian R. Payne

    1972-01-01

    This study evaluates the economic desirability of accelerated roadbuilding for access to old-growth timber on a unit of the Umpqua National Forest in Oregon. As of 1966, four accelerated roadbuilding alternatives were found economically inferior to the then current rate of construction. Only in the case of substantial, continuing inflation were projected rates of...

  13. PARTICLE ACCELERATOR

    DOEpatents

    Teng, L.C.

    1960-01-19

    ABS>A combination of two accelerators, a cyclotron and a ring-shaped accelerator which has a portion disposed tangentially to the cyclotron, is described. Means are provided to transfer particles from the cyclotron to the ring accelerator including a magnetic deflector within the cyclotron, a magnetic shield between the ring accelerator and the cyclotron, and a magnetic inflector within the ring accelerator.

  14. 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

  15. 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)

  16. Linear to non linear analysis for positron acceleration in plasma hollow channel wakefields

    NASA Astrophysics Data System (ADS)

    Amorim, Ligia Diana; An, Weiming; Mori, Warren B.; Vieira, Jorge

    2016-10-01

    Plasma wakefield accelerators are promising candidates for future generation compact accelerators. The standard regime of operation, non-linear or blowout regime, is reached when a particle bunch space charge or laser pulse ponderomotive force radially expels plasma electrons forming a bucket of ions that defocus positron bunches, thus preventing their acceleration. To avoid defocusing, hollow plasma channels have been considered. The corresponding wakefields have been examined in the linear and non-linear excitation regimes for electrons. It is therefore important to extend the theory for positron acceleration, particularly in the nonlinear regime where the wakefields strongly differ. In this work we explore the wakefield structure, examine the differences between the electron and positron beam cases, and explore positron acceleration in nonlinear regimes. We support our findings with multi-dimensional particle-in-cell simulations performed with OSIRIS and quasi-3D and QuickPIC.

  17. 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).

  18. Analysis of Monte Carlo accelerated iterative methods for sparse linear systems: Analysis of Monte Carlo accelerated iterative methods for sparse linear systems

    DOE PAGES

    Benzi, Michele; Evans, Thomas M.; Hamilton, Steven P.; ...

    2017-03-05

    Here, we consider hybrid deterministic-stochastic iterative algorithms for the solution of large, sparse linear systems. Starting from a convergent splitting of the coefficient matrix, we analyze various types of Monte Carlo acceleration schemes applied to the original preconditioned Richardson (stationary) iteration. We expect that these methods will have considerable potential for resiliency to faults when implemented on massively parallel machines. We also establish sufficient conditions for the convergence of the hybrid schemes, and we investigate different types of preconditioners including sparse approximate inverses. Numerical experiments on linear systems arising from the discretization of partial differential equations are presented.

  19. Seismic Hazard Analysis based on Earthquake Vulnerability and Peak Ground Acceleration using Microseismic Method at Universitas Negeri Semarang

    NASA Astrophysics Data System (ADS)

    Sulistiawan, H.; Supriyadi; Yulianti, I.

    2017-02-01

    Microseismic is a harmonic vibration of land that occurs continuously at a low frequency. The characteristics of microseismic represents the characteristics of the soil layer based on the value of its natural frequency. This paper presents the analysis of seismic hazard at Universitas Negeri Semarang using microseismic method. The data acquisition was done at 20 points with distance between points 300 m by using three component’s seismometer. The data was processed using Horizontal to Vertical Spectral Ratio (HVSR) method to obtain the natural frequency and amplification value. The value of the natural frequency and amplification used to determine the value of the earthquake vulnerability and peak ground acceleration (PGA). The result shows then the earthquake vulnerability value range from 0.2 to 7.5, while the value of the average peak ground acceleration (PGA) is in the range 10-24 gal. Therefore, the average peak ground acceleration equal to earthquake intensity IV MMI scale.

  20. Comparative Analysis of Peak Ground Acceleration Before and After Padang Earthquake 2009 Using Mc. Guirre Method

    NASA Astrophysics Data System (ADS)

    Ayu Rahmalia, Diah; Nilamprasasti, Hesti

    2017-04-01

    We have analyzed the earthquakes data in West Sumatra province to determine peak ground acceleration value. The peak ground acceleration is a parameter that describes the strength of the tremor that ever happened. This paper aims to compare the value of the peak ground acceleration by considering the b-value before and after the Padang earthquake 2009. This research was carried out in stages, starting by taking the earthquake data in West Sumatra province with boundary coordinates 0.923° LU - 2.811° LS and 97.075° - 102.261° BT, before and after the 2009 Padang earthquake with a magnitude ≥ 3 and depth of ≤ 300 km, calculation of the b-value, and ended by creating peak ground acceleration map based on Mc. Guirre empirical formula with Excel and Surfer software. Based on earthquake data from 2002 until before Padang earthquake 2009, the b-value is 0.874 while the b-value after the Padang earthquake in 2009 to 2016 is 0.891. Considering b value, it can be known that peak ground acceleration before and after the 2009 Padang earthquake might be different. Based on the seismic data before 2009, the peak ground acceleration value of West Sumatra province is ranged from 7,002 to 308.875 gal. This value will be compared by the value of the peak ground acceleration after the Padang earthquake in 2009 which ranged from 7,946 to 372,736 gal.

  1. Beam dynamics analysis of femtosecond microbunches produced by the staged electron laser acceleration experiment

    NASA Astrophysics Data System (ADS)

    Zhou, F.; Cline, D. B.; Kimura, W. D.

    2003-05-01

    Preservation of the femtosecond (fs) microbunches, created during laser acceleration, is a crucial step to enable staging of the laser acceleration process. This paper focuses on the optimization of the beam dynamics of fs microbunches transported through the staged electron laser acceleration (STELLA-II) experiment being carried out at the Brookhaven National Laboratory Accelerator Test Facility. STELLA-II consists of an inverse free electron laser (IFEL) untapered undulator, which acts as an electron beam energy modulator; a magnetic chicane, which acts as a buncher; a second IFEL tapered undulator, which acts as an accelerator; and a dipole, which serves as an energy spectrometer. When the energy-modulated macrobunch traverses through the chicane and a short drift space, microbunches of order fs in duration (i.e., ˜3 fs FWHM) are formed. The 3-fs microbunches are accelerated by interacting with a high-power CO2 laser beam in the following tapered undulator. These extremely short microbunches may experience significant space charge and coherent synchrotron radiation effects when traversing the STELLA-II transport line. These effects are analyzed and the safe operating conditions are determined. With less than 0.5-pC microbunch charge, both microbunch debunching and emittance growth are negligible, and the energy-spread increase is less than 5%. These results are also useful for the laser electron acceleration project at SLAC and in possible future programs where the fs microbunches are employed for other purposes.

  2. 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.

  3. 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.

  4. Accelerating All-Atom Normal Mode Analysis with Graphics Processing Unit.

    PubMed

    Liu, Li; Liu, Xiaofeng; Gong, Jiayu; Jiang, Hualiang; Li, Honglin

    2011-06-14

    All-atom normal mode analysis (NMA) is an efficient way to predict the collective motions in a given macromolecule, which is essential for the understanding of protein biological function and drug design. However, the calculations are limited in time scale mainly because the required diagonalization of the Hessian matrix by Householder-QR transformation is a computationally exhausting task. In this paper, we demonstrate the parallel computing power of the graphics processing unit (GPU) in NMA by mapping Householder-QR transformation onto GPU using Compute Unified Device Architecture (CUDA). The results revealed that the GPU-accelerated all-atom NMA could reduce the runtime of diagonalization significantly and achieved over 20× speedup over CPU-based NMA. In addition, we analyzed the influence of precision on both the performance and the accuracy of GPU. Although the performance of GPU with double precision is weaker than that with single precision in theory, more accurate results and an acceptable speedup of double precision were obtained in our approach by reducing the data transfer time to a minimum. Finally, the inherent drawbacks of GPU and the corresponding solution to deal with the limitation in computational scale are also discussed in this study.

  5. Analysis of transmitted optical spectrum enabling accelerated testing of CPV designs

    NASA Astrophysics Data System (ADS)

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

    2009-08-01

    Concentrated photovoltaics (CPV) has recently gained interest based on its scalability and expected low levelized cost of electricity. The reliability of materials used in CPV systems, however, is not well established. The current qualification test for photodegradation of CPV modules includes only real-time ultraviolet (UV) exposure, i.e. methods for accelerated UV testing have not been developed. Therefore, the UV and infrared (IR) spectra transmitted through representative optical systems is evaluated in this paper. The measurements of concentrating optics are used to assess expected optical performance as well as to understand how to quantify damaging optical exposure. Optical properties (transmittance, refractive index, reflectance, and absorptance) of candidate materials are identified. The dose and flux analysis here identifies the increased significance of IR (as opposed to UV) exposure for CPV systems, particularly for the most concentrating systems. For these, the UV dose may not greatly exceed the unconcentrated global solar condition, but the thermal load scales nearly directly with the geometric concentration.

  6. Analysis and environmental application of 129I at the Xi’an Accelerator Mass Spectrometry Center

    NASA Astrophysics Data System (ADS)

    Zhou, Weijian; Chen, Ning; Hou, Xiaolin; Zhang, Luyuan; Liu, Qi; He, Chaohui; Fan, Yukun; Luo, Maoyi; Zhao, Yaolin; Wang, Zhiwen

    2013-01-01

    The newly established 3 MV Accelerator Mass Spectrometry (AMS) facility in Xi’an, with an instrument background of 2 × 10-14 for 129I/127I ratio, provides efficient analytical capability to carry out 129I environmental tracing studies. Chemical separation methods of iodine from different types of samples have been established at the Xi’an AMS Center, including solvent extraction and combustion followed by extraction or coprecipitation depending on sample types. A carrier free method for iodine separation and AMS measurement of ultra low level 129I in samples with low total iodine concentration has been established, which can be used for analysis of geological samples for 129I dating. Some environmental samples collected in China have been analyzed using the developed methods. The analytical results show 129I/127I ratios of (0.9-1.1) × 10-10 for seawater collected adjacent to a nuclear power plant, and (3.02-5.43) × 10-10 for soil samples collected in a less than 10 km area surrounding the NPP. These values are not significantly different from those measured in remote areas, reflecting a safe nuclear environment in terms of 129I level.

  7. CFD Analysis and Design of Detailed Target Configurations for an Accelerator-Driven Subcritical System

    SciTech Connect

    Kraus, Adam; Merzari, Elia; Sofu, Tanju; Zhong, Zhaopeng; Gohar, Yousry

    2016-08-01

    High-fidelity analysis has been utilized in the design of beam target options for an accelerator driven subcritical system. Designs featuring stacks of plates with square cross section have been investigated for both tungsten and uranium target materials. The presented work includes the first thermal-hydraulic simulations of the full, detailed target geometry. The innovative target cooling manifold design features many regions with complex flow features, including 90 bends and merging jets, which necessitate three-dimensional fluid simulations. These were performed using the commercial computational fluid dynamics code STAR-CCM+. Conjugate heat transfer was modeled between the plates, cladding, manifold structure, and fluid. Steady-state simulations were performed but lacked good residual convergence. Unsteady simulations were then performed, which converged well and demonstrated that flow instability existed in the lower portion of the manifold. It was established that the flow instability had little effect on the peak plate temperatures, which were well below the melting point. The estimated plate surface temperatures and target region pressure were shown to provide sufficient margin to subcooled boiling for standard operating conditions. This demonstrated the safety of both potential target configurations during normal operation.

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

    PubMed

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

    2015-01-15

    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. 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. 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 22× 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. To our best knowledge, this is the first demonstration of GPU application in neural circuit mapping and electrophysiology-based data processing. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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

  10. 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.

  11. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    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.

  13. 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

  14. Replication by the Epistasis Project of the interaction between the genes for IL-6 and IL-10 in the risk of Alzheimer's disease

    PubMed Central

    Combarros, Onofre; van Duijn, Cornelia M; Hammond, Naomi; Belbin, Olivia; Arias-Vásquez, Alejandro; Cortina-Borja, Mario; Lehmann, Michael G; Aulchenko, Yurii S; Schuur, Maaike; Kölsch, Heike; Heun, Reinhard; Wilcock, Gordon K; Brown, Kristelle; Kehoe, Patrick G; Harrison, Rachel; Coto, Eliecer; Alvarez, Victoria; Deloukas, Panos; Mateo, Ignacio; Gwilliam, Rhian; Morgan, Kevin; Warden, Donald R; Smith, A David; Lehmann, Donald J

    2009-01-01

    Background Chronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10). Methods We examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls. Results We replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded. Conclusion We suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. PMID:19698145

  15. 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

  16. Cellular effects and epistasis among three determinants of adaptation in experimental populations of Saccharomyces cerevisiae.

    PubMed

    Parreiras, Lucas S; Kohn, Linda M; Anderson, James B

    2011-10-01

    Epistatic interactions in which the phenotypic effect of an allele is conditional on its genetic background have been shown to play a central part in various evolutionary processes. In a previous study (J. B. Anderson et al., Curr. Biol. 20:1383-1388, 2010; J. R. Dettman, C. Sirjusingh, L. M. Kohn, and J. B. Anderson, Nature 447:585-588, 2007), beginning with a common ancestor, we identified three determinants of fitness as mutant alleles (each designated with the letter "e") that arose in replicate Saccharomyces cerevisiae populations propagated in two different environments, a low-glucose and a high-salt environment. In a low-glucose environment, MDS3e and MKT1e interacted positively to confer a fitness advantage. Also, PMA1e from a high-salt environment interacted negatively with MKT1e in a low-glucose environment, an example of a Dobzhansky-Muller incompatibility that confers reproductive isolation. Here we showed that the negative interaction between PMA1e and MKT1e is mediated by alterations in intracellular pH, while the positive interaction between MDS3e and MKT1e is mediated by changes in gene expression affecting glucose transporter genes. We specifically addressed the evolutionary significance of the positive interaction by showing that the presence of the MDS3 mutation is a necessary condition for the spread and fixation of the new mutations at the identical site in MKT1. The expected mutations in MKT1 rose to high frequencies in two of three experimental populations carrying MDS3e but not in any of three populations carrying the ancestral allele. These data show how positive and negative epistasis can contribute to adaptation and reproductive isolation.

  17. 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. Copyright © 2016 by the Genetics Society of America.

  18. 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.

  19. Dominance and epistasis are the main contributors to heterosis for plant height in rice.

    PubMed

    Shen, Guojing; Zhan, Wei; Chen, Huaxia; Xing, Yongzhong

    2014-02-01

    The genetic basis of heterosis has been debated for over 100 years regarding whether dominance or overdominance plays a more important role and the answer is still unclear. The major limitation to assess the contribution of a single locus has been the genetic background noise due to genome-wide segregation of multiple loci. To dissect the genetic basis of heterosis at a single locus for plant height, we developed a set of 202 chromosome segment substitution lines (CSSLs) of an elite hybrid, Shanyou 63, the best hybrid rice in China in the 1990s. Fifteen CSSLs had varied plant heights within lines. A total of 15 partial dominance QTLs for plant height were detected in these 15 CSSL-F2 populations. All hybrids between the 15 CSSLs and the recurrent parent, Zhenshan 97, were shorter than the corresponding CSSLs, but taller than Zhenshan 97. These indicated that these 15 QTLs were also heterosis loci (HLs) contributed to heterosis acted in dominance. Each HL contributed from -7.4 to 14.4% of midparent heterosis. Additive by additive (AA) and additive by dominance (AD) interactions were detected in the Tetra-F2 population segregating at the four major QTLs with the largest effects on plant height. Substantial negative AA effects were detected between two major QTLs QPH7.2 and QPH7.3, which increased heterosis in the study. Thus we concluded that dominance and epistasis are the major genetic basis of plant height heterosis, which could explain the better parent heterosis in Shanyou 63.

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

    DOE PAGES

    Melero, Cristina; Ollikainen, Noah; Harwood, Ian; ...

    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

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

    PubMed Central

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

    2014-01-01

    Reengineering 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. Although 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. PMID:25313039

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

    PubMed

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

    2014-10-28

    Reengineering 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. Although 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.

  3. Cost-effective GPU-grid for genome-wide epistasis calculations.

    PubMed

    Pütz, B; Kam-Thong, T; Karbalai, N; Altmann, A; Müller-Myhsok, B

    2013-01-01

    Until recently, genotype studies were limited to the investigation of single SNP effects due to the computational burden incurred when studying pairwise interactions of SNPs. However, some genetic effects as simple as coloring (in plants and animals) cannot be ascribed to a single locus but only understood when epistasis is taken into account [1]. It is expected that such effects are also found in complex diseases where many genes contribute to the clinical outcome of affected individuals. Only recently have such problems become feasible computationally. The inherently parallel structure of the problem makes it a perfect candidate for massive parallelization on either grid or cloud architectures. Since we are also dealing with confidential patient data, we were not able to consider a cloud-based solution but had to find a way to process the data in-house and aimed to build a local GPU-based grid structure. Sequential epistatsis calculations were ported to GPU using CUDA at various levels. Parallelization on the CPU was compared to corresponding GPU counterparts with regards to performance and cost. A cost-effective solution was created by combining custom-built nodes equipped with relatively inexpensive consumer-level graphics cards with highly parallel GPUs in a local grid. The GPU method outperforms current cluster-based systems on a price/performance criterion, as a single GPU shows speed performance comparable up to 200 CPU cores. The outlined approach will work for problems that easily lend themselves to massive parallelization. Code for various tasks has been made available and ongoing development of tools will further ease the transition from sequential to parallel algorithms.

  4. 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

  5. FAM-MDR: a flexible family-based multifactor dimensionality reduction technique to detect epistasis using related individuals.

    PubMed

    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

    2010-04-22

    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.

  6. Both Epistasis and Diversifying Selection Drive the Structural Evolution of the Ebola Virus Glycoprotein Mucin-Like Domain

    PubMed Central

    Ibeh, Neke; Nshogozabahizi, Jean Claude

    2016-01-01

    ABSTRACT Throughout the last 3 decades, Ebola virus (EBOV) outbreaks have been confined to isolated areas within Central Africa; however, the 2014 variant reached unprecedented transmission and mortality rates. While the outbreak was still under way, it was reported that the variant leading up to this outbreak evolved faster than previous EBOV variants, but evidence for diversifying selection was undetermined. Here, we test this selection hypothesis and show that while previous EBOV outbreaks were preceded by bursts of diversification, evidence for site-specific diversifying selection during the emergence of the 2014 EBOV clade is weak. However, we show strong evidence supporting an interplay between selection and correlated evolution (epistasis), particularly in the mucin-like domain (MLD) of the EBOV glycoprotein. By reconstructing ancestral structures of the MLD, we further propose a structural mechanism explaining how the substitutions that accumulated between 1918 and 1969 distorted the MLD, while more recent epistatic substitutions restored part of the structure, with the most recent substitution being adaptive. We suggest that it is this complex interplay between weak selection, epistasis, and structural constraints that has shaped the evolution of the 2014 EBOV variant. IMPORTANCE The role that selection plays in the emergence of viral epidemics remains debated, particularly in the context of the 2014 EBOV outbreak. Most critically, should such evidence exist, it is generally unclear how this relates to function and increased virulence. Here, we show that the viral lineage leading up to the 2014 outbreak underwent a complex interplay between selection and correlated evolution (epistasis) in a protein region that is critical for immune evasion. We then reconstructed the three-dimensional structure of this domain and showed that the initial mutations in this lineage deformed the structure, while subsequent mutations restored part of the structure. Along this

  7. 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.

  8. 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.

  9. The use of vapour phase ultra-violet spectroscopy for the analysis of arson accelerants in fire scene debris.

    PubMed

    McCurdy, R J; Atwell, T; Cole, M D

    2001-12-01

    A method has been developed for the analysis of arson accelerants in fire scene debris by vapour phase ultra-violet (UV) spectroscopy. The method is rapid, inexpensive, simple to use and is sufficiently sensitive and discriminating to be of use for the analysis of crime scene samples. Application to casework samples is described. On occasion, the method offers additional information to that which can be obtained by gas chromatography-flame ionisation detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) and represents a useful adjunct to these techniques. In addition, the method offers advantages where the use of GC-MS analysis of arson accelerants in fire scene debris is not a practical proposition.

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

    PubMed

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

    2012-03-08

    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.

  11. Application of Failure Mode and Effects Analysis to Intraoperative Radiation Therapy Using Mobile Electron Linear Accelerators

    SciTech Connect

    Ciocca, Mario; Cantone, Marie-Claire; Veronese, Ivan; Cattani, Federica; Pedroli, Guido; Molinelli, Silvia; Vitolo, Viviana; Orecchia, Roberto

    2012-02-01

    Purpose: Failure mode and effects analysis (FMEA) represents a prospective approach for risk assessment. A multidisciplinary working group of the Italian Association for Medical Physics applied FMEA to electron beam intraoperative radiation therapy (IORT) delivered using mobile linear accelerators, aiming at preventing accidental exposures to the patient. Methods and Materials: FMEA was applied to the IORT process, for the stages of the treatment delivery and verification, and consisted of three steps: 1) identification of the involved subprocesses; 2) identification and ranking of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system, based on the product of three parameters (severity, frequency of occurrence and detectability, each ranging from 1 to 10); 3) identification of additional safety measures to be proposed for process quality and safety improvement. RPN upper threshold for little concern of risk was set at 125. Results: Twenty-four subprocesses were identified. Ten potential failure modes were found and scored, in terms of RPN, in the range of 42-216. The most critical failure modes consisted of internal shield misalignment, wrong Monitor Unit calculation and incorrect data entry at treatment console. Potential causes of failure included shield displacement, human errors, such as underestimation of CTV extension, mainly because of lack of adequate training and time pressures, failure in the communication between operators, and machine malfunctioning. The main effects of failure were represented by CTV underdose, wrong dose distribution and/or delivery, unintended normal tissue irradiation. As additional safety measures, the utilization of a dedicated staff for IORT, double-checking of MU calculation and data entry and finally implementation of in vivo dosimetry were suggested. Conclusions: FMEA appeared as a useful tool for prospective evaluation of patient safety in radiotherapy. The

  12. Comprehensive transcriptome analysis reveals accelerated genic evolution in a Tibet fish, Gymnodiptychus pachycheilus.

    PubMed

    Yang, Liandong; Wang, Ying; Zhang, Zhaolei; He, Shunping

    2014-12-26

    Elucidating the genetic mechanisms of organismal adaptation to the Tibetan Plateau at a genomic scale can provide insights into the process of adaptive evolution. Many highland species have been investigated and various candidate genes that may be responsible for highland adaptation have been identified. However, we know little about the genomic basis of adaptation to Tibet in fishes. Here, we performed transcriptome sequencing of a schizothoracine fish (Gymnodiptychus pachycheilus) and used it to identify potential genetic mechanisms of highland adaptation. We obtained totally 66,105 assembled unigenes, of which 7,232 were assigned as putative one-to-one orthologs in zebrafish. Comparative gene annotations from several species indicated that at least 350 genes lost and 41 gained since the divergence between G. pachycheilus and zebrafish. An analysis of 6,324 orthologs among zebrafish, fugu, medaka, and spotted gar identified consistent evidence for genome-wide accelerated evolution in G. pachycheilus and only the terminal branch of G. pachycheilus had an elevated Ka/Ks ratio than the ancestral branch. Many functional categories related to hypoxia and energy metabolism exhibited rapid evolution in G. pachycheilus relative to zebrafish. Genes showing signature of rapid evolution and positive selection in the G. pachycheilus lineage were also enriched in functions associated with energy metabolism and hypoxia. The first genomic resources for fish in the Tibetan Plateau and evolutionary analyses provided some novel insights into highland adaptation in fishes and served as a foundation for future studies aiming to identify candidate genes underlying the genetic bases of adaptation to Tibet in fishes.

  13. Automated combustion accelerator mass spectrometry for the analysis of biomedical samples in the low attomole range.

    PubMed

    van Duijn, Esther; Sandman, Hugo; Grossouw, Dimitri; Mocking, Johannes A J; Coulier, Leon; Vaes, Wouter H J

    2014-08-05

    The increasing role of accelerator mass spectrometry (AMS) in biomedical research necessitates modernization of the traditional sample handling process. AMS was originally developed and used for carbon dating, therefore focusing on a very high precision but with a comparably low sample throughput. Here, we describe the combination of automated sample combustion with an elemental analyzer (EA) online coupled to an AMS via a dedicated interface. This setup allows direct radiocarbon measurements for over 70 samples daily by AMS. No sample processing is required apart from the pipetting of the sample into a tin foil cup, which is placed in the carousel of the EA. In our system, up to 200 AMS analyses are performed automatically without the need for manual interventions. We present results on the direct total (14)C count measurements in <2 μL human plasma samples. The method shows linearity over a range of 0.65-821 mBq/mL, with a lower limit of quantification of 0.65 mBq/mL (corresponding to 0.67 amol for acetaminophen). At these extremely low levels of activity, it becomes important to quantify plasma specific carbon percentages. This carbon percentage is automatically generated upon combustion of a sample on the EA. Apparent advantages of the present approach include complete omission of sample preparation (reduced hands-on time) and fully automated sample analysis. These improvements clearly stimulate the standard incorporation of microtracer research in the drug development process. In combination with the particularly low sample volumes required and extreme sensitivity, AMS strongly improves its position as a bioanalysis method.

  14. Comprehensive Transcriptome Analysis Reveals Accelerated Genic Evolution in a Tibet Fish, Gymnodiptychus pachycheilus

    PubMed Central

    Yang, Liandong; Wang, Ying; Zhang, Zhaolei; He, Shunping

    2015-01-01

    Elucidating the genetic mechanisms of organismal adaptation to the Tibetan Plateau at a genomic scale can provide insights into the process of adaptive evolution. Many highland species have been investigated and various candidate genes that may be responsible for highland adaptation have been identified. However, we know little about the genomic basis of adaptation to Tibet in fishes. Here, we performed transcriptome sequencing of a schizothoracine fish (Gymnodiptychus pachycheilus) and used it to identify potential genetic mechanisms of highland adaptation. We obtained totally 66,105 assembled unigenes, of which 7,232 were assigned as putative one-to-one orthologs in zebrafish. Comparative gene annotations from several species indicated that at least 350 genes lost and 41 gained since the divergence between G. pachycheilus and zebrafish. An analysis of 6,324 orthologs among zebrafish, fugu, medaka, and spotted gar identified consistent evidence for genome-wide accelerated evolution in G. pachycheilus and only the terminal branch of G. pachycheilus had an elevated Ka/Ks ratio than the ancestral branch. Many functional categories related to hypoxia and energy metabolism exhibited rapid evolution in G. pachycheilus relative to zebrafish. Genes showing signature of rapid evolution and positive selection in the G. pachycheilus lineage were also enriched in functions associated with energy metabolism and hypoxia. The first genomic resources for fish in the Tibetan Plateau and evolutionary analyses provided some novel insights into highland adaptation in fishes and served as a foundation for future studies aiming to identify candidate genes underlying the genetic bases of adaptation to Tibet in fishes. PMID:25543049

  15. Impedance-based analysis and study of phase sensitivity in slow-wave two-beam accelerators

    SciTech Connect

    Wurtele, J.S.; Whittum, D.H.; Sessler, A.M.

    1992-06-01

    This paper presents a new formalism which makes the analysis and understanding of both the relativistic klystron (RK) and the standing-wave free-electron laser (SWFEL) two-beam accelerator (TBA) available to a wide audience of accelerator physicists. A ``coupling impedance`` for both the RK and SWFEWL is introduced, which can include realistic cavity features, such as beam and vacuum ports, in a simple manner. The RK and SWFEL macroparticle equations, which govern the energy and phase evolution of successive bunches in the beam, are of identical form, differing only by multiplicative factors. Expressions are derived for the phase and amplitude sensitivities of the TBA schemes to errors (shot-to-shot jitter) in current and energy. The analysis allows, for the first time, relative comparisons of the RK and the SWFEL TBAs.

  16. Impedance-based analysis and study of phase sensitivity in slow-wave two-beam accelerators

    SciTech Connect

    Wurtele, J.S. ); Whittum, D.H. , Tsukuba, Oho, Ibaraki, 305 ); Sessler, A.M. )

    1992-07-01

    This paper presents a new formalism which makes the analysis and understanding of both the relativistic klystron (RK) and the standing-wave free-electron laser (SWFEL) two-beam accelerator (TBA) available to a wide audience of accelerator physicists. A coupling impedance'' for both the RK and SWFEWL is introduced, which can include realistic cavity features, such as beam and vacuum ports, in a simple manner. The RK and SWFEL macroparticle equations, which govern the energy and phase evolution of successive bunches in the beam, are of identical form, differing only by multiplicative factors. Expressions are derived for the phase and amplitude sensitivities of the TBA schemes to errors (shot-to-shot jitter) in current and energy. The analysis allows, for the first time, relative comparisons of the RK and the SWFEL TBAs.

  17. Field-Analysis of Vacuum Free-Space LaserAcceleration from Rough-Surface and Absorbing Thin Boundaries

    SciTech Connect

    Plettner, Thomas; /Stanford U., Ginzton Lab.

    2008-06-02

    This script presents a field-based analysis of laser acceleration of relativistic electrons in a free space that is bounded by a thin scattering or by a thin absorbing surface. The laser acceleration process is analyzed in terms of the inverse-radiation formalism and compared to the more familiar field path-integral analysis method. When the scattering boundary is modeled as a linear-index medium the predictions for laser-electron interactions from both field methods are found to agree. For the absorbing boundary both interaction pictures are also found to agree provided that the inverse radiation method is generalized to include absorption of energy from the boundary that is modeled as a linear ohmic-loss object.

  18. 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

    2015-12-29

    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. Copyright © 2016 Shang et al.

  19. 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

  20. Problems and pit-falls in testing for G × E and epistasis in candidate gene studies of human behavior.

    PubMed

    Eaves, Lindon; Verhulst, Brad

    2014-11-01

    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.

  1. 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

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

    PubMed Central

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

    2015-01-01

    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

  3. Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to fixed incompatibilities between species of Drosophila

    PubMed Central

    Montooth, Kristi L.; Meiklejohn, Colin D.; Abt, Dawn N.; Rand, David M.

    2010-01-01

    Efficient mitochondrial function requires physical interactions between the proteins encoded by the mitochondrial and nuclear genomes. Co-evolution between these genomes may result in the accumulation of incompatibilities between divergent lineages. We test whether mitochondrial-nuclear incompatibilities have accumulated within the Drosophila melanogaster species subgroup by combining divergent mitochondrial and nuclear lineages and quantifying the effects on relative fitness. Precise placement of nine mtDNAs from D. melanogaster, D. simulans and D. mauritiana into two D. melanogaster nuclear genetic backgrounds reveals significant mitochondrial-nuclear epistasis affecting fitness in females. Combining the mitochondrial genomes with three different D. melanogaster X chromosomes reveals significant epistasis for male fitness between X-linked and mitochondrial variation. However, we find no evidence that the more than 500 fixed differences between the mitochondrial genomes of D. melanogaster and the D. simulans species complex are incompatible with the D. melanogaster nuclear genome. Rather, the interactions of largest effect occur between mitochondrial and nuclear polymorphisms that segregate within species of the D. melanogaster species subgroup. We propose that a low mitochondrial substitution rate, resulting from a low mutation rate and/or efficient purifying selection, precludes the accumulation of mitochondrial-nuclear incompatibilities among these Drosophila species. PMID:20624176

  4. Analysis of the Acceleration Process of SEPs by an Interplanetary Shock for Bastille Day Event

    NASA Astrophysics Data System (ADS)

    Le, G. M.; Han, Y. B.

    Based on the solar energetic particle (SEP) data from ACE and GOES satellites, the acceleration of SEP by CME-driven shock in interplanetary space was investigated. The results showed that the acceleration process of SEP by the Bastille CME-driven shock ran through the whole space from the sun to the magnetosphere. The highest energy of SEP accelerated by the shock was greater than 100MeV. A magnetic bottle associated with the CME captured a lot of high energy particles with some of them having energy greater than 100MeV. Based on magnetic field data of solar wind observed by ACE data, we found that the the magnetic bottle associated with the Bastille CME was the sheath caused by the CME in fact.

  5. Simulation analysis for effects of bone loss on acceleration tolerance of human lumbar vertebra

    NASA Astrophysics Data System (ADS)

    Ma, Honglei; Zhang, Feng; Zhu, Yu; Xiao, Yanhua; Wazir, Abrar

    2014-02-01

    The purpose of the present study was to analyze and predict the changes in acceleration tolerance of human vertebra as a result of bone loss caused by long-term space flight. A human L3-L4 vertebra FEM model was constructed, in which the cancellous bone was separated, and surrounding ligaments were also taken into account. The simulation results demonstrated that bone loss has more of an effect on the acceleration tolerance in x-direction. The results serve to aid in the creation of new acceleration tolerance standards, ensuring astronauts return home safely after long-term space flight. This study shows that more attention should be focused on the bone degradation of crew members and to create new protective designs for space capsules in the future.

  6. Analysis of possible improvement of acceleration of a high-velocity air-breathing flying vehicle

    NASA Astrophysics Data System (ADS)

    Goonko, Yu. P.; Mazhul, I. I.

    2008-09-01

    Results of parametric calculations of the total aeropropulsive characteristics and characteristics of acceleration of a small-scale high-velocity flying vehicle with an air-breathing engine are presented. Integral parameters of acceleration from the flight Mach number M∞ = 4 to M∞ = 7 are determined, namely, the time required fuel stock, and range. A schematic configuration of the vehicle is considered, which allows studying the basic parameters, such as the forebody shape, the angles of surfaces of compression of the stream captured by the inlet, angles of external aerodynamic surfaces of the airframe, relative planform area of the wing panels, and relative area of the nozzle cross section. A comparative estimate of the effect of these parameters shows that it is possible to improve the characteristics of acceleration of vehicles of the type considered.

  7. Calcium isolation from large-volume human urine samples for 41Ca analysis by accelerator mass spectrometry.

    PubMed

    Miller, James J; Hui, Susanta K; Jackson, George S; Clark, Sara P; Einstein, Jane; Weaver, Connie M; Bhattacharyya, Maryka H

    2013-08-01

    Calcium oxalate precipitation is the first step in preparation of biological samples for (41)Ca analysis by accelerator mass spectrometry. A simplified protocol for large-volume human urine samples was characterized, with statistically significant increases in ion current and decreases in interference. This large-volume assay minimizes cost and effort and maximizes time after (41)Ca administration during which human samples, collected over a lifetime, provide (41)Ca:Ca ratios that are significantly above background.

  8. Analysis of flow acceleration during erythrocyte filtration: dependence of hematocrit and cell rigidity.

    PubMed

    Lindmark, K; Engström, K G

    1996-01-01

    At flow onset the blood filtration rate accelerates to a steady state, this may affect the interpretation of red blood cell (RBC) filterability. We studied the acceleration of flow while the pressure is built up across the filter to analyse effects of various hematocrits and RBC rigidity by glutaraldehyde (GA) hardening. This was analysed by a new filtration system with high time resolution and unlimited filtration volume. The system uses a digital balance that samples the accumulated weight (e.g., filtration rate through 5 microns Nucleopore membranes) with on-line computer communication. The filtration is computer controlled via a pneumatic valve. White blood cells (WBC) were removed prior to filtration by a WBC-eliminating filter to avoid clogging artifacts. When flow is initiated a steady state is reached at 0.3-0.4 s. This timing was also tested and confirmed by a video monitoring technique of filtration flow into a horizontal pipette. The digital balance has a mathematical function to reduce the effects of vibration noise; when this function was activated the apparent acceleration was retarded to 1.2 s. With any of these techniques the steady state timing did not vary with the hematocrit, however, the volume of filtered suspension during acceleration varied with both the hematocrit and the GA hardening (p < 0.001). Extrapolation to yield the initial filtration rate from the relative flow curve (RBC suspension divided by buffer flow) varied depending on if the acceleration phase was included or not. In the most unfavourable situation, with GA-hardened RBC, this difference was 340% (p < 0.01). The slope to calculate clogging rate was affected in a similar way. Moreover, with the most GA-hardened RBC a delay in flow onset was observed with this technique. The acceleration phenomenon may cause artifacts in systems employing volume-derived filtration kinetics because of fixed volumes of filtrated medium.

  9. Negative Epistasis between Sickle and Foetal Haemoglobin Suggests a Reduction in Protection against Malaria

    PubMed Central

    Mmbando, Bruno P.; Mgaya, Josephine; Cox, Sharon E.; Mtatiro, Siana N.; Soka, Deogratias; Rwezaula, Stella; Meda, Elineema; Msaki, Evarist; Snow, Robert W.; Jeffries, Neal; Geller, Nancy L.; Makani, Julie

    2015-01-01

    Background Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection. Methods The study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tanzania. SCD status was categorized into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was diagnosed using rapid diagnostic test and/or blood film. Logistic regression and generalized estimating equations models were used to evaluate associations between SCD status, HbF and malaria. Findings 2,049 individuals with age range 0-70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed. At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared to HbAS 1.24% and HbSS 1.34% (p<0.001). Mean HbF was lower in those with malaria compared to those without malaria in HbAA (0.43% vs 0.82%) but was the reverse in HbSS (8.10% vs 5.59%). An increase in HbF was associated with a decrease in risk of malaria OR=0.50 (95%CI: 0.28, 0.90; p=0.021) in HbAA, whereas for HbSS the risk of malaria increased OR=2.94 (1.44, 5.98; p=0.003). A similar pattern was seen during multiple visits; HbAA OR=0.52 (0.34, 0.80; p=0.003) vs HbSS OR=2.01 (1.27, 3.23; p=0.003). Conclusion Higher prevalence of malaria in HbAA compared to HbAS and HbSS confirmed the protective effect of HbS. Lower prevalence of malaria in HbAA with high HbF supports a protective effect of HbF. However, in HbSS, the higher prevalence of malaria with high levels of HbF suggests loss of malaria protection. This is the first epidemiological study to suggest a negative epistasis between HbF and HbS on malaria. PMID:25965586

  10. Theoretical analysis of acceleration measurements in a model of an operating wind turbine

    NASA Astrophysics Data System (ADS)

    White, Jonathan R.; Adams, Douglas E.; Rumsey, Mark A.

    2010-04-01

    Wind loading from turbulence and gusts can cause damage in horizontal axis wind turbines. These unsteady loads and the resulting damage initiation and propagation are difficult to predict. Unsteady loads enter at the rotor and are transmitted to the drivetrain. The current generation of wind turbine has drivetrain-mounted vibration and bearing temperature sensors, a nacelle-mounted inertial measurement unit, and a nacelle-mounted anemometer and wind vane. Some advanced wind turbines are also equipped with strain measurements at the root of the rotor. This paper analyzes additional measurements in a rotor blade to investigate the complexity of these unsteady loads. By identifying the spatial distribution, amplitude, and frequency bandwidth of these loads, design improvements could be facilitated to reduce uncertainties in reliability predictions. In addition, dynamic load estimates could be used in the future to control high-bandwidth aerodynamic actuators distributed along the rotor blade to reduce the saturation of slower pitch actuators currently used for wind turbine blades. Local acceleration measurements are made along a rotor blade to infer operational rotor states including deflection and dynamic modal contributions. Previous work has demonstrated that acceleration measurements can be experimentally acquired on an operating wind turbine. Simulations on simplified rotor blades have also been used to demonstrate that mean blade loading can be estimated based on deflection estimates. To successfully apply accelerometers in wind turbine applications for load identification, the spectral and spatial characteristics of each excitation source must be understood so that the total acceleration measurement can be decomposed into contributions from each source. To demonstrate the decomposition of acceleration measurements in conjunction with load estimation methods, a flexible body model has been created with MSC.ADAMSThe benefit of using a simulation model as opposed

  11. Theoretical analysis of acceleration measurements in a model of an operating wind turbine.

    SciTech Connect

    Adams, Douglas E.; Rumsey, Mark Allen; White, Jonathan Randall

    2010-04-01

    Wind loading from turbulence and gusts can cause damage in horizontal axis wind turbines. These unsteady loads and the resulting damage initiation and propagation are difficult to predict. Unsteady loads enter at the rotor and are transmitted to the drivetrain. The current generation of wind turbine has drivetrain-mounted vibration and bearing temperature sensors, a nacelle-mounted inertial measurement unit, and a nacelle-mounted anemometer and wind vane. Some advanced wind turbines are also equipped with strain measurements at the root of the rotor. This paper analyzes additional measurements in a rotor blade to investigate the complexity of these unsteady loads. By identifying the spatial distribution, amplitude, and frequency bandwidth of these loads, design improvements could be facilitated to reduce uncertainties in reliability predictions. In addition, dynamic load estimates could be used in the future to control high-bandwidth aerodynamic actuators distributed along the rotor blade to reduce the saturation of slower pitch actuators currently used for wind turbine blades. Local acceleration measurements are made along a rotor blade to infer operational rotor states including deflection and dynamic modal contributions. Previous work has demonstrated that acceleration measurements can be experimentally acquired on an operating wind turbine. Simulations on simplified rotor blades have also been used to demonstrate that mean blade loading can be estimated based on deflection estimates. To successfully apply accelerometers in wind turbine applications for load identification, the spectral and spatial characteristics of each excitation source must be understood so that the total acceleration measurement can be decomposed into contributions from each source. To demonstrate the decomposition of acceleration measurements in conjunction with load estimation methods, a flexible body model has been created with MSC.ADAMS{copyright} The benefit of using a simulation model

  12. Off-normal and failure condition analysis of the MITICA negative-ion accelerator

    SciTech Connect

    Chitarin, Giuseppe Aprile, Daniele; Agostinetti, Piero; Marconato, Nicolò; Marcuzzi, Diego; Serianni, Gianluigi; Veltri, Pierluigi; Zaccaria, Pierluigi

    2016-02-15

    The negative-ion accelerator for the MITICA neutral beam injector has been designed and optimized in order to reduce the thermo-mechanical stresses in all components below limits compatible with the required fatigue life. However, deviation from the expected beam performances can be caused by “off-normal” operating conditions of the accelerator. The purpose of the present work is to identify and analyse all the “off-normal” operating conditions, which could possibly become critical in terms of thermo-mechanical stresses or of degradation of the optical performances of the beam.

  13. Off-normal and failure condition analysis of the MITICA negative-ion accelerator

    NASA Astrophysics Data System (ADS)

    Chitarin, Giuseppe; Agostinetti, Piero; Aprile, Daniele; Marconato, Nicolò; Marcuzzi, Diego; Serianni, Gianluigi; Veltri, Pierluigi; Zaccaria, Pierluigi

    2016-02-01

    The negative-ion accelerator for the MITICA neutral beam injector has been designed and optimized in order to reduce the thermo-mechanical stresses in all components below limits compatible with the required fatigue life. However, deviation from the expected beam performances can be caused by "off-normal" operating conditions of the accelerator. The purpose of the present work is to identify and analyse all the "off-normal" operating conditions, which could possibly become critical in terms of thermo-mechanical stresses or of degradation of the optical performances of the beam.

  14. Off-normal and failure condition analysis of the MITICA negative-ion accelerator.

    PubMed

    Chitarin, Giuseppe; Agostinetti, Piero; Aprile, Daniele; Marconato, Nicolò; Marcuzzi, Diego; Serianni, Gianluigi; Veltri, Pierluigi; Zaccaria, Pierluigi

    2016-02-01

    The negative-ion accelerator for the MITICA neutral beam injector has been designed and optimized in order to reduce the thermo-mechanical stresses in all components below limits compatible with the required fatigue life. However, deviation from the expected beam performances can be caused by "off-normal" operating conditions of the accelerator. The purpose of the present work is to identify and analyse all the "off-normal" operating conditions, which could possibly become critical in terms of thermo-mechanical stresses or of degradation of the optical performances of the beam.

  15. Predicting punching acceleration from selected strength and power variables in elite karate athletes: a multiple regression analysis.

    PubMed

    Loturco, Irineu; Artioli, Guilherme Giannini; Kobal, Ronaldo; Gil, Saulo; Franchini, Emerson

    2014-07-01

    This study investigated the relationship between punching acceleration and selected strength and power variables in 19 professional karate athletes from the Brazilian National Team (9 men and 10 women; age, 23 ± 3 years; height, 1.71 ± 0.09 m; and body mass [BM], 67.34 ± 13.44 kg). Punching acceleration was assessed under 4 different conditions in a randomized order: (a) fixed distance aiming to attain maximum speed (FS), (b) fixed distance aiming to attain maximum impact (FI), (c) self-selected distance aiming to attain maximum speed, and (d) self-selected distance aiming to attain maximum impact. The selected strength and power variables were as follows: maximal dynamic strength in bench press and squat-machine, squat and countermovement jump height, mean propulsive power in bench throw and jump squat, and mean propulsive velocity in jump squat with 40% of BM. Upper- and lower-body power and maximal dynamic strength variables were positively correlated to punch acceleration in all conditions. Multiple regression analysis also revealed predictive variables: relative mean propulsive power in squat jump (W·kg-1), and maximal dynamic strength 1 repetition maximum in both bench press and squat-machine exercises. An impact-oriented instruction and a self-selected distance to start the movement seem to be crucial to reach the highest acceleration during punching execution. This investigation, while demonstrating strong correlations between punching acceleration and strength-power variables, also provides important information for coaches, especially for designing better training strategies to improve punching speed.

  16. Pedestrian movement analysis in transfer station corridor: Velocity-based and acceleration-based

    NASA Astrophysics Data System (ADS)

    Ji, Xiangfeng; Zhang, Jian; Hu, Yongkai; Ran, Bin

    2016-05-01

    In this paper, pedestrians are classified into aggressive and conservative ones by their temper. Aggressive pedestrians' walking through crowd in transfer station corridor is analyzed. Treating pedestrians as particles, this paper uses the modified social force model (MSFM) as the building block, where forces involve self-driving force, repulsive force and friction force. The proposed model in this paper is a discrete model combining the MSFM and cellular automata (CA) model, where the updating rules of the CA are redefined with MSFM. Due to the continuity of values generated by the MSFM, we use the fuzzy logic to discretize the continuous values into cells pedestrians can move in one step. With the observation that stimulus around pedestrians influences their acceleration directly, an acceleration-based movement model is presented, compared to the generally reviewed velocity-based movement model. In the acceleration-based model, a discretized version of kinematic equation is presented based on the acceleration discretized with fuzzy logic. In real life, some pedestrians would rather keep their desired speed and this is also mimicked in this paper, which is called inertia. Compared to the simple triangular membership function, a trapezoidal membership function and a piecewise linear membership function are used to capture pedestrians' inertia. With the trapezoidal and the piecewise linear membership function, many overlapping scenarios should be carefully handled and Dubois and Prade's four-index method is used to completely describe the relative relationship of fuzzy quantities. Finally, a simulation is constructed to demonstrate the effect of our model.

  17. Finite element analysis of head-neck kinematics under simulated rear impact at different accelerations.

    PubMed

    Zhang, Qing Hang; Tan, Soon Huat; Teo, Ee Chon

    2008-07-01

    The information on the variation of ligament strains over time after rear impact has been seldom investigated. In the current study, a detailed three-dimensional C0-C7 finite element model of the whole head-neck complex developed previously was modified to include T1 vertebra. Rear impact of half sine-pulses with peak values of 3.5g, 5g, 6.5g and 8g respectively were applied to the inferior surface of the T1 vertebral body to validate the simulated variations of the intervertebral segmental rotations and to investigate the ligament tensions of the cervical spine under different levels of accelerations. The simulated kinematics of the head-neck complex showed relatively good agreement with the experimental data with most of the predicted peak values falling within one standard deviation of the experimental data. Under rear impact, the whole C0-T1 structure formed an S-shaped curvature with flexion at the upper levels and extension at the lower levels at early stage after impact, during which the lower cervical levels might experience hyperextensions. The predicted high resultant strain of the capsular ligaments, even at low impact acceleration compared with other ligament groups, suggests their susceptibility to injury. The peak impact acceleration has a significant effect on the potential injury of ligaments. Under higher accelerations, most ligaments will reach failure strain in a much shorter time immediately after impact.

  18. Quantitative analysis of flare accelerated electrons through their hard X-ray and microwave radiation

    NASA Technical Reports Server (NTRS)

    Klein, K. L.; Trottet, G.

    1985-01-01

    Hard X-ray and microwave modelling that takes into account the temporal evolution of the electron spectrum as well as the inhomogeneity of the magnetic field and the ambient medium in the radio source is presented. This method is illustrated for the June 29 1980 10:41 UT event. The implication on the process of acceleration/injection is discussed.

  19. Predictors of Local Recurrence Following Accelerated Partial Breast Irradiation: A Pooled Analysis

    SciTech Connect

    Shah, Chirag; Wilkinson, John Ben; Lyden, Maureen; Beitsch, Peter; Vicini, Frank A.

    2012-04-01

    Purpose: To analyze a pooled set of nearly 2,000 patients treated on the American Society of Breast Surgeons (ASBS) Mammosite Registry Trial and at William Beaumont Hospital (WBH) to identify factors associated with local recurrence following accelerated partial breast irradiation (APBI). Methods and Materials: A total of 1,961 women underwent partial breast irradiation between April 1993 and November 2010 as part of the ASBS Registry Trial or at WBH. Rates of ipsilateral breast tumor recurrence (IBTR), regional recurrence (RR), distant metastases (DM), disease-free survival (DFS), cause-specific survival (CSS), and overall survival (OS) were analyzed for each group and for the pooled cohort. Clinical, pathologic, and treatment-related variables were analyzed including age, tumor stage/size, estrogen receptor status, surgical margins, and lymph node status to determine their association with IBTR. Results: The two groups weres similar, but WBH patients were more frequently node positive, had positive margins, and were less likely to be within the American Society for Radiation Oncology-unsuitable group. At 5 years, the rates of IBTR, RR, DM, DFS, CSS, and OS for the pooled group of patients were 2.9%, 0.5%, 2.4%, 89.1%, 98.5%, and 91.8%, respectively. The 5-year rate of true recurrence/marginal miss was 0.8%. Univariate analysis of IBTR found that negative estrogen receptor status (odds ratio [OR], 2.83, 95% confidence interval 1.55-5.13, p = 0.0007) was the only factor significantly associated with IBTR, while a trend was seen for age less than 50 (OR 1.80, 95% confidence interval 0.90-3.58, p = 0.10). Conclusions: Excellent 5-year outcomes were seen following APBI in over 1,900 patients. Estrogen receptor negativity was the only factor associated with IBTR, while a trend for age less than 50 was noted. Significant differences in factors associated with IBTR were noted between cohorts, suggesting that factors driving IBTR may be predicated based on the risk

  20. Analysis of EMG and acceleration signals for quantifying the effects of deep brain stimulation in Parkinson's disease.

    PubMed

    Rissanen, Saara M; Kankaanpää, Markku; Tarvainen, Mika P; Novak, Vera; Novak, Peter; Hu, Kun; Manor, Brad; Airaksinen, Olavi; Karjalainen, Pasi A

    2011-09-01

    Deep brain stimulation (DBS) is effective in reducing motor symptoms in Parkinson's disease (PD). However, objective methods for quantifying its efficacy are lacking. We present a principal component (PC)-based tracking method for quantifying the effects of DBS in PD by using electromyography (EMG) and acceleration measurements. Ten parameters capturing PD characteristic signal features were initially extracted from isometric EMG and acceleration recordings. Using a PC approach, the original parameters were transformed into a smaller number of PCs. Finally, the effects of DBS were quantified by examining the PCs in a low-dimensional feature space. The EMG and acceleration data from 13 PD patients with DBS ON and OFF, and 13 healthy age-matched controls were used for analysis. Clinical evaluation of patients showed that their motor symptoms were effectively reduced with DBS. The analysis results showed that the signal characteristics of 12 patients were more similar to those of the healthy controls with DBS ON than with DBS OFF. These observations indicate that the PC-based tracking method can be used to objectively quantify the effects of DBS on the neuromuscular function of PD patients. Further studies are suggested to estimate the clinical sensitivity of the method to different types of PD.

  1. Analysis of EMG and Acceleration Signals for Quantifying the Effects of Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Kankaanpää, Markku; Tarvainen, Mika P.; Novak, Vera; Novak, Peter; Hu, Kun; Manor, Brad; Airaksinen, Olavi; Karjalainen, Pasi A.

    2013-01-01

    Deep brain stimulation (DBS) is effective in reducing motor symptoms in Parkinson’s disease (PD). However, objective methods for quantifying its efficacy are lacking. We present a principal component (PC) -based tracking method for quantifying the effects of DBS in PD by using EMG and acceleration measurements. Ten parameters capturing PD characteristic signal features were initially extracted from isometric EMG and acceleration recordings. Using a PC approach, the original parameters were transformed into a smaller number of PCs. Finally, the effects of DBS were quantified by examining the PCs in a low-dimensional feature space. The EMG and acceleration data from 13 PD patients with DBS on and off, and 13 healthy age-matched controls were used for analysis. Clinical evaluation of patients showed that their motor symptoms were effectively reduced with DBS. The analysis results showed that the signal characteristics of 12 patients were more similar to those of the healthy controls with DBS on than with DBS off. These observations indicate that the PC-based tracking method can be used to objectively quantify the effects of DBS on the neuromuscular function of PD patients. Further studies are suggested to estimate the clinical sensitivity of the method to different types of PD. PMID:21672674

  2. Ultra-trace analysis of (41)Ca in urine by accelerator mass spectrometry: an inter-laboratory comparison.

    PubMed

    Jackson, George S; Hillegonds, Darren J; Muzikar, Paul; Goehring, Brent

    2013-10-15

    A (41)Ca interlaboratory comparison between Lawrence Livermore National Laboratory (LLNL) and the Purdue Rare Isotope Laboratory (PRIME Lab) has been completed. Analysis of the ratios assayed by accelerator mass spectrometry (AMS) shows that there is no statistically significant difference in the ratios. Further, Bayesian analysis shows that the uncertainties reported by both facilities are correct with the possibility of a slight under-estimation by one laboratory. Finally, the chemistry procedures used by the two facilities to produce CaF2 for the cesium sputter ion source are robust and don't yield any significant differences in the final result.

  3. Ultra-trace analysis of 41Ca in urine by accelerator mass spectrometry: an inter-laboratory comparison

    PubMed Central

    Jackson, George S.; Hillegonds, Darren J.; Muzikar, Paul; Goehring, Brent

    2013-01-01

    A 41Ca interlaboratory comparison between Lawrence Livermore National Laboratory (LLNL) and the Purdue Rare Isotope Laboratory (PRIME Lab) has been completed. Analysis of the ratios assayed by accelerator mass spectrometry (AMS) shows that there is no statistically significant difference in the ratios. Further, Bayesian analysis shows that the uncertainties reported by both facilities are correct with the possibility of a slight under-estimation by one laboratory. Finally, the chemistry procedures used by the two facilities to produce CaF2 for the cesium sputter ion source are robust and don't yield any significant differences in the final result. PMID:24179312

  4. Future accelerators (?)

    SciTech Connect

    John Womersley

    2003-08-21

    I describe the future accelerator facilities that are currently foreseen for electroweak scale physics, neutrino physics, and nuclear structure. I will explore the physics justification for these machines, and suggest how the case for future accelerators can be made.

  5. Functional Data Analysis of Spaceflight-Induced Changes in Coordination and Phase in Head Pitch Acceleration During Treadmill Walking

    NASA Technical Reports Server (NTRS)

    Miller, Christopher; Peters, Brian; Feiveson, Alan; Bloomberg, Jacob

    2011-01-01

    Astronauts returning from spaceflight experience neurovestibular disturbances during head movements and attempt to mitigate them by limiting head motion. Analyses to date of the head movements made during walking have concentrated on amplitude and variability measures extracted from ensemble averages of individual gait cycles. Phase shifts within each gait cycle can be determined by functional data analysis through the computation of time-warping functions. Large, localized variations in the timing of peaks in head kinematics may indicate changes in coordination. The purpose of this study was to determine timing changes in head pitch acceleration of astronauts during treadmill walking before and after flight. Six astronauts (5M/1F; age = 43.5+/-6.4yr) participated in the study. Subjects walked at 1.8 m/sec (4 mph) on a motorized treadmill while reading optotypes displayed on a computer screen 4 m in front of their eyes. Three-dimensional motion of the subject s head was recorded with an Inertial Measurement Unit (IMU) device. Data were recorded twice before flight and four times after landing. The head pitch acceleration was calculated by taking the time derivative of the pitch velocity data from the IMU. Data for each session with each subject were time-normalized into gait cycles, then registered to align significant features and create a mean curve. The mean curves of each postflight session for each subject were re-registered based on their preflight mean curve to create time-warping functions. The root mean squares (RMS) of these warping functions were calculated to assess the deviation of head pitch acceleration mean curves in each postflight session from the preflight mean curve. After landing, most crewmembers exhibited localized shifts within their head pitch acceleration regimes, with the greatest deviations in RMS occurring on landing day or 1 day after landing. These results show that the alteration of head pitch coordination due to spaceflight may be

  6. 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

  7. Application of High-performance Visual Analysis Methods to Laser Wakefield Particle Acceleration Data

    SciTech Connect

    Rubel, Oliver; Prabhat, Mr.; Wu, Kesheng; Childs, Hank; Meredith, Jeremy; Geddes, Cameron G.R.; Cormier-Michel, Estelle; Ahern, Sean; Weber, Gunther H.; Messmer, Peter; Hagen, Hans; Hamann, Bernd; Bethel, E. Wes

    2008-08-28

    Our work combines and extends techniques from high-performance scientific data management and visualization to enable scientific researchers to gain insight from extremely large, complex, time-varying laser wakefield particle accelerator simulation data. We extend histogram-based parallel coordinates for use in visual information display as well as an interface for guiding and performing data mining operations, which are based upon multi-dimensional and temporal thresholding and data subsetting operations. To achieve very high performance on parallel computing platforms, we leverage FastBit, a state-of-the-art index/query technology, to accelerate data mining and multi-dimensional histogram computation. We show how these techniques are used in practice by scientific researchers to identify, visualize and analyze a particle beam in a large, time-varying dataset.

  8. Simulation and analysis of TE wave propagation for measurement of electron cloud densities in particle accelerators

    NASA Astrophysics Data System (ADS)

    Sonnad, Kiran G.; Hammond, Kenneth C.; Schwartz, Robert M.; Veitzer, Seth A.

    2014-08-01

    The use of transverse electric (TE) waves has proved to be a powerful, noninvasive method for estimating the densities of electron clouds formed in particle accelerators. Results from the plasma simulation program VSim have served as a useful guide for experimental studies related to this method, which have been performed at various accelerator facilities. This paper provides results of the simulation and modeling work done in conjunction with experimental efforts carried out at the Cornell electron storage ring “Test Accelerator” (CESRTA). This paper begins with a discussion of the phase shift induced by electron clouds in the transmission of RF waves, followed by the effect of reflections along the beam pipe, simulation of the resonant standing wave frequency shifts and finally the effects of external magnetic fields, namely dipoles and wigglers. A derivation of the dispersion relationship of wave propagation for arbitrary geometries in field free regions with a cold, uniform cloud density is also provided.

  9. Quantitative elemental analysis of an industrial mineral talc, using accelerator-based analytical technique

    NASA Astrophysics Data System (ADS)

    Olabanji, S. O.; Ige, A. O.; Mazzoli, C.; Ceccato, D.; Ajayi, E. O. B.; De Poli, M.; Moschini, G.

    2005-10-01

    Accelerator-based technique of PIXE was employed for the determination of the elemental concentration of an industrial mineral, talc. Talc is a very versatile mineral in industries with several applications. Due to this, there is a need to know its constituents to ensure that the workers are not exposed to health risks. Besides, microscopic tests on some talc samples in Nigeria confirm that they fall within the BP British Pharmacopoeia standard for tablet formation. However, for these samples to become a local source of raw material for pharmaceutical grade talc, the precise elemental compositions should be established which is the focus of this work. Proton beam produced by the 2.5 MV AN 2000 Van de Graaff accelerator at INFN, LNL, Legnaro, Padova, Italy was used for the PIXE measurements. The results which show the concentration of different elements in the talc samples, their health implications and metabolic roles are presented and discussed.

  10. Bayesian Analysis of Step-Stress Accelerated Life Test with Exponential Distribution

    SciTech Connect

    Lee, J.; Pan, R.

    2012-04-01

    In this article, we propose a general Bayesian inference approach to the step-stress accelerated life test with type II censoring. We assume that the failure times at each stress level are exponentially distributed and the test units are tested in an increasing order of stress levels. We formulate the prior distribution of the parameters of life-stress function and integrate the engineering knowledge of product failure rate and acceleration factor into the prior. The posterior distribution and the point estimates for the parameters of interest are provided. Through the Markov chain Monte Carlo technique, we demonstrate a nonconjugate prior case using an industrial example. It is shown that with the Bayesian approach, the statistical precision of parameter estimation is improved and, consequently, the required number of failures could be reduced.

  11. Analysis of requirements for accelerating the development of geothermal energy resources in California

    NASA Technical Reports Server (NTRS)

    Fredrickson, C. D.

    1978-01-01

    Various resource data are presented showing that geothermal energy has the potential of satisfying a singificant part of California's increasing energy needs. General factors slowing the development of geothermal energy in California are discussed and required actions to accelerate its progress are presented. Finally, scenarios for developing the most promising prospects in the state directed at timely on-line power are given. Specific actions required to realize each of these individual scenarios are identified.

  12. Contaminant Analysis of Polycrystalline and Single Crystal Niobium Used in Accelerator Cavities

    SciTech Connect

    F. A. Stevie; Z. Zhu; D. P. Griffis; G. R. Myneni; P. Kneisel

    2005-07-10

    Secondary Ion Mass Spectrometry (SIMS) can characterize the surface and near surface of Nb used in accelerator cavities. Results show Nb oxide in the 2-3 nm range, a depleted H concentration in the oxide compared with the bulk, and N, C, O lower in an annealed single crystal sample than several polycrystalline samples. Other metallic contaminants are primarily at the surface, but tantalum is distributed uniformly through the material.

  13. Verification analysis of the toroidal accelerator rotor platform wind energy conversion system: Summary report

    SciTech Connect

    Duffy, R.E.

    1988-09-01

    This report describes research undertaken at Rensselaer Polytechnic Institute for the purpose of evaluating the performance, defining the structure and system configurations, and assessing the economic merit of the Toroidal Accelerator Rotor Platform (TARP) wind energy conversion system. The TARP wind energy system is a highly versatile system-design having broad-based application potential ranging from small-kilowatt capacity units to large-megawatt utility-scale power plants. 4 refs., 27 figs., 19 tabs.

  14. Impact Acceleration Response of the Selspot Motion Analysis System and an Endevco Angular Accelerometer

    DTIC Science & Technology

    1990-02-01

    consists of caliper brakes which grip the track rails when activated by onboard compressed nitrogen gas. The track rails are one inch thick and the total...coasting or by brake application. Various acceleration profiles may be obtained by changing the differential pressures, the travel length of the...thrust assembly and the metering structure on the thrust piston. The sled glides along the track rails on 21 twelve glide pads. The sled braking system

  15. Doppler Broadening Analysis of Steel Specimens Using Accelerator Based In Situ Pair Production

    NASA Astrophysics Data System (ADS)

    Makarashvili, V.; Wells, D. P.; Roy, A. K.

    2009-03-01

    Positron Annihilation Spectroscopy (PAS) techniques can be utilized as a sensitive probe of defects in materials. Studying these microscopic defects is very important for a number of industries in order to predict material failure or structural integrity. We have been developing gamma-induced pair-production techniques to produce positrons in thick samples (˜4-40 g/cm2, or ˜0.5-5 cm in steel). These techniques are called 'Accelerator-based Gamma-induced Positron Annihilation Spectroscopy' (AG-PAS). We have begun testing the capabilities of this technique for imaging of defect densities in thick structural materials. As a first step, a linear accelerator (LINAC) was employed to produce photon beams by stopping 15 MeV electrons in a 1 mm thick tungsten converter. The accelerator is capable of operating with 30-60 ns pulse width, up to 200 mA peak current at 1 kHz repetition rate. The highly collimated bremsstrahlung beam impinged upon our steel tensile specimens, after traveling through a 1.2 m thick concrete wall. Annihilation radiation was detected by a well-shielded and collimated high-purity germanium detector (HPGe). Conventional Doppler broadening spectrometry (DBS) was performed to determine S, W and T parameters for our samples.

  16. Continuous wavelet transform analysis of acceleration signals measured from a wave buoy.

    PubMed

    Chuang, Laurence Zsu-Hsin; Wu, Li-Chung; Wang, Jong-Hao

    2013-08-19

    Accelerometers, which can be installed inside a floating platform on the sea, are among the most commonly used sensors for operational ocean wave measurements. To examine the non-stationary features of ocean waves, this study was conducted to derive a wavelet spectrum of ocean waves and to synthesize sea surface elevations from vertical acceleration signals of a wave buoy through the continuous wavelet transform theory. The short-time wave features can be revealed by simultaneously examining the wavelet spectrum and the synthetic sea surface elevations. The in situ wave signals were applied to verify the practicality of the wavelet-based algorithm. We confirm that the spectral leakage and the noise at very-low-frequency bins influenced the accuracies of the estimated wavelet spectrum and the synthetic sea surface elevations. The appropriate thresholds of these two factors were explored. To study the short-time wave features from the wave records, the acceleration signals recorded from an accelerometer inside a discus wave buoy are analysed. The results from the wavelet spectrum show the evidence of short-time nonlinear wave events. Our study also reveals that more surface profiles with higher vertical asymmetry can be found from short-time nonlinear wave with stronger harmonic spectral peak. Finally, we conclude that the algorithms of continuous wavelet transform are practical for revealing the short-time wave features of the buoy acceleration signals.

  17. Continuous Wavelet Transform Analysis of Acceleration Signals Measured from a Wave Buoy

    PubMed Central

    Chuang, Laurence Zsu-Hsin; Wu, Li-Chung; Wang, Jong-Hao

    2013-01-01

    Accelerometers, which can be installed inside a floating platform on the sea, are among the most commonly used sensors for operational ocean wave measurements. To examine the non-stationary features of ocean waves, this study was conducted to derive a wavelet spectrum of ocean waves and to synthesize sea surface elevations from vertical acceleration signals of a wave buoy through the continuous wavelet transform theory. The short-time wave features can be revealed by simultaneously examining the wavelet spectrum and the synthetic sea surface elevations. The in situ wave signals were applied to verify the practicality of the wavelet-based algorithm. We confirm that the spectral leakage and the noise at very-low-frequency bins influenced the accuracies of the estimated wavelet spectrum and the synthetic sea surface elevations. The appropriate thresholds of these two factors were explored. To study the short-time wave features from the wave records, the acceleration signals recorded from an accelerometer inside a discus wave buoy are analysed. The results from the wavelet spectrum show the evidence of short-time nonlinear wave events. Our study also reveals that more surface profiles with higher vertical asymmetry can be found from short-time nonlinear wave with stronger harmonic spectral peak. Finally, we conclude that the algorithms of continuous wavelet transform are practical for revealing the short-time wave features of the buoy acceleration signals. PMID:23966188

  18. Neutronics analysis of three beam-filter assemblies for an accelerator-based BNCT facility

    SciTech Connect

    Bleuel, D.L.; Costes, S.V.; Donahue, R.J.; Ludewigt, B.A.

    1997-08-01

    Three moderator materials, AlF{sub 3}/Al, D{sub 2}O and LiF, have been analyzed for clinical usefulness using the reaction {sup 7}Li(p,n) as an accelerator driven neutron source. Proton energies between 2.1 MeV and 2.6 MeV have been investigated. Radiation transport in the reflector/moderator assembly is simulated using the MCNP program. Depth-dose distributions in a head phanton are calculated with the BNCT-RTPE patient treatment planning program from INEEL using the MCNP generated neutron and photon spectra as the subsequent source. Clinical efficacy is compared using the current BMRR protocol for all designs. Depth-dose distributions are compared for a fixed normal tissue tolerance dose of 12.5 Gy-Eq. Radiation analyses also include a complete anthropomorphic phantom. Results of organ and whole body dose components are presented for several designs. Results indicate that high quality accelerator beams may produce clinically favorable treatments to deep-seated tumors when compared to the BMRR beam. Also discussed are problems identified in comparing accelerator and reactor based designs using in-air figures of merit as well as some results of spectrum-averaged RBE`s.

  19. Development and analysis of a metal-fueled accelerator-driven burner

    SciTech Connect

    Lypsch, F.; Hill, R.N.

    1994-08-01

    The purpose of this paper is to compare the safety characteristics of an accelerator driven metal fueled fast system to a critical core on a consistent basis to determine how these characteristics are affected solely by subcritically of the system. To accomplish this an accelerator proton beam/tungsten neutron source model is surrounded by a subcritical blanket using metallic fuel and sodium as coolant. The consequences of typical accident transients, namely unprotected transient overpower (TOP), loss of heat sink (LOHS), and loss of flow (LOP) were calculated for the hybrid system and compared to corresponding results for a metal-fueled fast reactor. Results indicate that the subcritical system exhibits superior performance for TOP (reactivity-induced) transits; however, only in the critical system are reactivity feedbacks able to cause passive shutdown in the LOHS ad LOP events. Therefore, for a full spectrum of accident initiators considered, the overall safety behavior of accelerator-driven metal-fueled systems can neither be concluded to be worse nor to be better than advanced reactor designs which rely on passive safety features.

  20. Measuring Model Rocket Acceleration.

    ERIC Educational Resources Information Center

    Jenkins, Randy A.

    1993-01-01

    Presents an experiment that measures the acceleration and velocity of a model rocket. Lift-off information is transmitted to a computer that creates a graph of the velocity. Discusses the analysis of the computer-generated data and differences between calculated and experimental velocity and acceleration of several rocket types. (MDH)

  1. Measuring Model Rocket Acceleration.

    ERIC Educational Resources Information Center

    Jenkins, Randy A.

    1993-01-01

    Presents an experiment that measures the acceleration and velocity of a model rocket. Lift-off information is transmitted to a computer that creates a graph of the velocity. Discusses the analysis of the computer-generated data and differences between calculated and experimental velocity and acceleration of several rocket types. (MDH)

  2. Switched Matrix Accelerator

    SciTech Connect

    Whittum, David H

    2000-10-04

    We describe a new concept for a microwave circuit functioning as a charged-particle accelerator at mm-wavelengths, permitting an accelerating gradient higher than conventional passive circuits can withstand consistent with cyclic fatigue. The device provides acceleration for multiple bunches in parallel channels, and permits a short exposure time for the conducting surface of the accelerating cavities. Our analysis includes scalings based on a smooth transmission line model and a complementary treatment with a coupled-cavity simulation. We provide also an electromagnetic design for the accelerating structure, arriving at rough dimensions for a seven-cell accelerator matched to standard waveguide and suitable for bench tests at low power in air at 91.392. GHz. A critical element in the concept is a fast mm-wave switch suitable for operation at high-power, and we present the considerations for implementation in an H-plane tee. We discuss the use of diamond as the photoconductor switch medium.

  3. Development and Use of Life-Cycle Analysis Capabilites To Evaluate, Select, and Implement Plans to Accelerate Hanford Site Cleanup

    SciTech Connect

    Shay, Michael R.; Johnson, Wayne L.; Frey, Jeffrey A.

    2004-02-28

    Over the past year the U.S. Department of Energy (DOE) has made significant progress in developing and executing plans to transform and accelerate cleanup of the Hanford Site. Notable progress has been in the cleanup of the River Corridor, including the relocation of spent nuclear fuel to the Central Plateau, and the stabilization of plutonium materials. However, difficult work still remains. DOE has already accelerated the completion of the Environmental Management (EM) cleanup mission from 2070 to 2035 and believes its completion can be achieved even sooner by reducing excess conservatism, substantively changing technical strategy and management approach, and making new front-end investments. Work is well under way in the detailed planning, analyses and decision making required to implement and support the execution of the accelerated cleanup program at Hanford. Various cleanup, contract, and regulatory approaches are being explored. DOE has instituted a process that allows DOE to efficiently explore and test alternative cleanup approaches using a life-cycle model. This paper provides a means to share the planning approach and the life-cycle modeling and analysis tools used with other sites and interested parties. This paper will be of particular interest to analysts performing similar planning and evaluations at other sites as well as provide insight into the current status of Hanford’s cleanup program and DOE’s plans for the future.

  4. A new convergence analysis and perturbation resilience of some accelerated proximal forward–backward algorithms with errors

    NASA Astrophysics Data System (ADS)

    Reem, Daniel; De Pierro, Alvaro

    2017-04-01

    Many problems in science and engineering involve, as part of their solution process, the consideration of a separable function which is the sum of two convex functions, one of them possibly non-smooth. Recently a few works have discussed inexact versions of several accelerated proximal methods aiming at solving this minimization problem. This paper shows that inexact versions of a method of Beck and Teboulle (fast iterative shrinkable tresholding algorithm) preserve, in a Hilbert space setting, the same (non-asymptotic) rate of convergence under some assumptions on the decay rate of the error terms The notion of inexactness discussed here seems to be rather simple, but, interestingly, when comparing to related works, closely related decay rates of the errors terms yield closely related convergence rates. The derivation sheds some light on the somewhat mysterious origin of some parameters which appear in various accelerated methods. A consequence of the analysis is that the accelerated method is perturbation resilient, making it suitable, in principle, for the superiorization methodology. By taking this into account, we re-examine the superiorization methodology and significantly extend its scope. This work was supported by FAPESP 2013/19504-9. The second author was supported also by CNPq grant 306030/2014-4.

  5. Mechanical Design and Analysis of a 200 MHz, Bolt-together RFQ forthe Accelerator Driven Neutron Source

    SciTech Connect

    Virostek, Steve; Hoff, Matt; Li, Derun; Staples, John; Wells,Russell

    2007-06-20

    A high-yield neutron source to screen sea-land cargocontainers for shielded Special Nuclear Materials (SNM) has been designedat LBNL [1,2]. The Accelerator-Driven Neutron Source (ADNS) uses theD(d,n)3He reaction to create a forward directed neutron beam. Keycomponents are a high-current radio-frequency quadrupole (RFQ)accelerator and a high-power target capable of producing a neutron fluxof>107 n/(cm2 cdot s) at a distance of 2.5 m. The mechanical designand analysis of the four-module, bolt-together RFQ will be presentedhere. Operating at 200 MHz, the 5.1 m long RFQ will accelerate a 40 mAdeuteron beam to 6 MeV. At a 5 percent duty factor, the time-average d+beam current on target is 1.5 mA. Each of the 1.27 m long RFQ moduleswill consist of four solid OFHC copper vanes. A specially designed 3-DO-ring will provide vacuum sealing between both the vanes and themodules. RF connections are made with canted coil spring contacts. Aseries of 60 water-cooled pi-mode rods provides quadrupole modestabilization. A set of 80 evenly spaced fixed slug tuners is used forfinal frequency adjustment and local field perturbationcorrection.

  6. The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project

    PubMed Central

    2010-01-01

    Background The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine β-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls. Methods We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD. Results We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain. Conclusions Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here. PMID:21070631

  7. 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.

  8. 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.

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

    PubMed

    Liang, Qingzhi; Shang, Lianguang; 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.

  10. 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

  11. Distribution of mutational fitness effects and of epistasis in the 5' untranslated region of a plant RNA virus.

    PubMed

    Bernet, Guillermo P; Elena, Santiago F

    2015-12-07

    Understanding the causes and consequences of phenotypic variability is a central topic of evolutionary biology. Mutations within non-coding cis-regulatory regions are thought to be of major effect since they affect the expression of downstream genes. To address the evolutionary potential of mutations affecting such regions in RNA viruses, we explored the fitness properties of mutations affecting the 5'-untranslated region (UTR) of a prototypical member of the picorna-like superfamily, Tobacco etch virus (TEV). This 5' UTR acts as an internal ribosomal entry site (IRES) and is essential for expression of all viral genes. We determined in vitro the folding of 5' UTR using the selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) technique. Then, we created a collection of single-nucleotide substitutions on this region and evaluated the statistical properties of their fitness effects in vivo. We found that, compared to random mutations affecting coding sequences, mutations at the 5' UTR were of weaker effect. We also created double mutants by combining pairs of these single mutations and found variation in the magnitude and sign of epistatic interactions, with an enrichment of cases of positive epistasis. A correlation exists between the magnitude of fitness effects and the size of the perturbation made in the RNA folding structure, suggesting that the larger the departure from the predicted fold, the more negative impact in viral fitness. Evidence that mutational fitness effects on the short 5' UTR regulatory sequence of TEV are weaker than those affecting its coding sequences have been found. Epistasis among pairs of mutations on the 5' UTR ranged between the extreme cases of synthetic lethal and compensatory. A plausible hypothesis to explain all these observations is that the interaction between the 5' UTR and the host translational machinery was shaped by natural selection to be robust to mutations, thus ensuring the homeostatic expression of viral

  12. What Factors Are Associated with Grade Acceleration? An Analysis and Comparison of Two U.S. Databases

    ERIC Educational Resources Information Center

    Wells, Ryan; Lohman, David; Marron, Maureen

    2009-01-01

    The benefits of whole-grade acceleration for the highest achieving students in K-12 education are widely acknowledged. However, much less is known about which personal, family, and school factors are correlated with student acceleration. Which children are grade accelerated in K-7 education? Have factors associated with grade acceleration changed…

  13. Improving the design and analysis of superconducting magnets for particle accelerators

    SciTech Connect

    Gupta, Ramesh Chandra

    1996-11-01

    High energy particle accelerators are now the primary means of discovering the basic building blocks of matter and understanding the forces between them. In order to minimize the cost of building these machines, superconducting magnets are used in essentially all present day high energy proton and heavy ion colliders. The cost of superconducting magnets is typically in the range of 20--30% of the total cost of building such machines. The circulating particle beam goes through these magnets a large number of times (over hundreds of millions). The luminosity performance and life time of the beam in these machines depends significantly on the field quality in these magnets. Therefore, even a small error in the magnetic field shape may create a large cumulative effect in the beam trajectory to throw the particles of the magnet aperture. The superconducting accelerator magnets must, therefore, be designed and constructed so that these errors are small. In this thesis the research and development work will be described 3which has resulted in significant improvements in the field quality of the superconducting magnets for the Relativistic Heavy Ion Collider (RHIC). The design and the field quality improvements in the prototype of the main collider dipole magnet for the Superconducting Super Collider (SSC) will also be presented. RHIC will accelerate and collide two counter rotating beams of heavy ions up to 100 GeV/u and protons up to 250 GeV. It is expected that RHIC will create a hot, dense quark-gluon plasma and the conditions which, according to the Big Bang theory, existed in the early universe.

  14. SU-C-BRD-03: Analysis of Accelerator Generated Text Logs for Preemptive Maintenance

    SciTech Connect

    Able, CM; Baydush, AH; Nguyen, C; Munley, MT; Gersh, J; Ndlovu, A; Rebo, I; Booth, J; Perez, M; Sintay, B

    2014-06-15

    Purpose: To develop a model to analyze medical accelerator generated parameter and performance data that will provide an early warning of performance degradation and impending component failure. Methods: A robust 6 MV VMAT quality assurance treatment delivery was used to test the constancy of accelerator performance. The generated text log files were decoded and analyzed using statistical process control (SPC) methodology. The text file data is a single snapshot of energy specific and overall systems parameters. A total of 36 system parameters were monitored which include RF generation, electron gun control, energy control, beam uniformity control, DC voltage generation, and cooling systems. The parameters were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and the parameter/system specification. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: the value of 1 standard deviation from the mean operating parameter of 483 TB systems, a small fraction (≤ 5%) of the operating range, or a fraction of the minor fault deviation. Results: There were 34 parameters in which synthetic errors were introduced. There were 2 parameters (radial position steering coil, and positive 24V DC) in which the errors did not exceed the limit of the I/MR chart. The I chart limit was exceeded for all of the remaining parameters (94.2%). The MR chart limit was exceeded in 29 of the 32 parameters (85.3%) in which the I chart limit was exceeded. Conclusion: Statistical process control I/MR evaluation of text log file parameters may be effective in providing an early warning of performance degradation or component failure for digital medical accelerator systems. Research is Supported by Varian Medical Systems, Inc.

  15. An Analysis of the Airspeeds and Normal Accelerations of sikorsky S-42A Airplanes in Commercial Transport Operation

    DTIC Science & Technology

    1948-10-01

    t1111 ~ e:a:ee lgbt mUes. Tbe lo&ds of tbe Slkorsl<y S -42A oere leu conservative than tbe loads of tbe...n~ (’) :::c ~.-----~--------------------------------------~ r ~ o= s ~ ~~~ NATIONAL ADVISORY COMMITTEE FOR AERONAUTICS TECHNICAL NOTE No...1733 .& !!!"’!!!"’!!! :u ~~< 1:-’ s tn="TT ~tD z 3 AN ANALYSIS OF THE AIRSPEEDS AND NORMAL ACCELERATIONS OF SIKORSKY S -42A AIRPLANES 1N

  16. Application of accelerated solvent extraction in the analysis of organic contaminants, bioactive and nutritional compounds in food and feed.

    PubMed

    Sun, Hanwen; Ge, Xusheng; Lv, Yunkai; Wang, Anbang

    2012-05-11

    Accelerated solvent extraction (ASE) has become a popular green extraction technology for different classes of organic contaminants present in numerous kinds of food and feed for food safety. The parameters affecting ASE efficiency and application advancement of ASE in the analysis of organic contaminants, natural toxins compounds as well as bioactive and nutritional compounds in animal origin food, plant origin food and animal feed are reviewed in detail. ASE is a fully automated and reliable extraction technique with many advantages over traditional extraction techniques, so it could be especially useful for routine analyses of pollutants in food and feed.

  17. Surface Analysis of OFE-Copper X-Band Accelerating Structures and Possible Correlation to RF Breakdown Events

    SciTech Connect

    Harvey, S

    2003-10-08

    X-band accelerator structures meeting the Next Linear Collider (NLC) design requirements have been found to suffer vacuum surface damage caused by radio frequency (RF) breakdown, when processed to high electric-field gradients. Improved understanding of these breakdown events is desirable for the development of structure designs, fabrication procedures, and processing techniques that minimize structure damage. RF reflected wave analysis and acoustic sensor pickup have provided breakdowns localization in RF structures. Particle contaminations found following clean autopsy of four RF-processed travelling wave structures, have been catalogued and analyzed. Their influence on RF breakdown, as well as that of several other material-based properties, will be discussed.

  18. ACCELERATORS: Preliminary application of turn-by-turn data analysis to the SSRF storage ring

    NASA Astrophysics Data System (ADS)

    Chen, Jian-Hui; Zhao, Zhen-Tang

    2009-07-01

    There is growing interest in utilizing the beam position monitor turn-by-turn (TBT) data to debug accelerators. TBT data can be used to determine the linear optics, coupled optics and nonlinear behaviors of the storage ring lattice. This is not only a useful complement to other methods of determining the linear optics such as LOCO, but also provides a possibility to uncover more hidden phenomena. In this paper, a preliminary application of a β function measurement to the SSRF storage ring is presented.

  19. Analysis of accelerator based neutron spectra for BNCT using proton recoil spectroscopy

    SciTech Connect

    Wielopolski, L.; Ludewig, H.; Powell, J.R.; Raparia, D.; Alessi, J.G.; Lowenstein, D.I.

    1999-03-01

    Boron Neutron Capture Therapy (BNCT) is a promising binary treatment modality for high-grade primary brain tumors (glioblastoma multiforme, GM) and other cancers. BNCT employs a boron-10 containing compound that preferentially accumulates in the cancer cells in the brain. Upon neutron capture by {sup 10}B energetic alpha particles and triton released at the absorption site kill the cancer cell. In order to gain penetration depth in the brain Fairchild proposed, for this purpose, the use of energetic epithermal neutrons at about 10 keV. Phase 1/2 clinical trials of BNCT for GM are underway at the Brookhaven Medical Research Reactor (BMRR) and at the MIT Reactor, using these nuclear reactors as the source for epithermal neutrons. In light of the limitations of new reactor installations, e.g. cost, safety and licensing, and limited capability for modulating the reactor based neutron beam energy spectra, alternative neutron sources are being contemplated for wider implementation of this modality in a hospital environment. For example, accelerator based neutron sources offer the possibility of tailoring the neutron beams, in terms of improved depth-dose distributions, to the individual and offer, with relative ease, the capability of modifying the neutron beam energy and port size. In previous work new concepts for compact accelerator/target configuration were published. In this work, using the Van de Graaff accelerator the authors have explored different materials for filtering and reflecting neutron beams produced by irradiating a thick Li target with 1.8 to 2.5 MeV proton beams. However, since the yield and the maximum neutron energy emerging from the Li-7(p,n)Be-7 reaction increase with increase in the proton beam energy, there is a need for optimization of the proton energy versus filter and shielding requirements to obtain the desired epithermal neutron beam. The MCNP-4A computer code was used for the initial design studies that were verified with benchmark

  20. A pilot in the loop analysis of helicopter acceleration/deceleration maneuvers

    NASA Technical Reports Server (NTRS)

    Heffley, R. K.

    1982-01-01

    Helicopter flight acceleration/deceleration maneuvers are quantified and put to use in the fields of handling qualities, flight training and evaluation of simulator fidelity. The three specific cases include the normal speed change maneuver, the nap-of-the-Earth dash/quickstop, and the decelerating approach to hover. All of these maneuvers share common generic features in terms of pilot adaptation and mathematical description; yet each differs in terms of the essential feedback loop structure, implications for handling qualities requirements, and simulator fidelity criteria.

  1. Ferrographic analysis of wear debris generated in accelerated rolling element fatigue tests

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.; Parker, R. J.

    1977-01-01

    The types and quantities of wear particles generated during accelerated ball rolling contact fatigue tests were determined. Ball specimens were made of AMS 5749, a corrosion resistant, high-temperature bearing steel. The lubricant was a super-refined naphthenic mineral oil. Conditions included a maximum Hertz stress of 5.215 times 10 to the 9th power Pa and a shaft speed of 10,000 rpm. Four types of wear particles were observed; normal rubbing wear particles, fatigue spall particles, spheres, and friction polymer.

  2. Photoneutron Flux Measurement via Neutron Activation Analysis in a Radiotherapy Bunker with an 18 MV Linear Accelerator

    NASA Astrophysics Data System (ADS)

    Çeçen, Yiğit; Gülümser, Tuğçe; Yazgan, Çağrı; Dapo, Haris; Üstün, Mahmut; Boztosun, Ismail

    2017-09-01

    In cancer treatment, high energy X-rays are used which are produced by linear accelerators (LINACs). If the energy of these beams is over 8 MeV, photonuclear reactions occur between the bremsstrahlung photons and the metallic parts of the LINAC. As a result of these interactions, neutrons are also produced as secondary radiation products (γ,n) which are called photoneutrons. The study aims to map the photoneutron flux distribution within the LINAC bunker via neutron activation analysis (NAA) using indium-cadmium foils. Irradiations made at different gantry angles (0°, 90°, 180° and 270°) with a total of 91 positions in the Philips SLI-25 linear accelerator treatment room and location-based distribution of thermal neutron flux was obtained. Gamma spectrum analysis was carried out with high purity germanium (HPGe) detector. Results of the analysis showed that the maximum neutron flux in the room occurred at just above of the LINAC head (1.2x105 neutrons/cm2.s) which is compatible with an americium-beryllium (Am-Be) neutron source. There was a 90% decrease of flux at the walls and at the start of the maze with respect to the maximum neutron flux. And, just in front of the LINAC door, inside the room, neutron flux was measured less than 1% of the maximum.

  3. Analysis of the dynamics of a nutating body. [numerical analysis of displacement, velocity, and acceleration of point on mechanical drives

    NASA Technical Reports Server (NTRS)

    Anderson, W. J.

    1974-01-01

    The equations for the displacement, velocity, and acceleration of a point in a nutating body are developed. These are used to derive equations for the inertial moment developed by a nutating body of arbitrary shape. Calculations made for a previously designed nutating plate transmission indicate that that device is severely speed limited because of the very high magnitude inertial moment.

  4. Calibration of a new experimental chamber for PIXE analysis at the Accelerator Facilities Division of Atomic Energy Centre Dhaka (AECD)

    NASA Astrophysics Data System (ADS)

    Hassan, Md. Taufique; Shariff, Md. Asad; Hossein, Amzad; Abedin, Md. Joynal; Fazlul Hoque, A. K. M.; Chowdhuri, M. S.

    2015-05-01

    A new experimental chamber has been installed at the 3 MV Van de Graaff Accelerator Facilities Division in the Atomic Energy Centre, Dhaka, to perform different Ion Beam Analysis (IBA) techniques. The calibration of this new setup for Particle Induced X-ray Emission (PIXE) technique has been done using a set of thin MicroMatter standards and GUPIX (PIXE spectrum analysis software), which is explicated in this paper. The effective thicknesses of the beryllium window of the X-ray detector and of the different absorbers used were determined. For standardization, the so called instrumental constant H (product of detector solid angle and the correction factor for the setup) as function of X-ray energy were determined and stored inside the GUPIX library for further PIXE analysis.

  5. Comparison of spectral analysis of vibration using commercial knock sensor and 3-axis acceleration sensor

    NASA Astrophysics Data System (ADS)

    Zieliński, Ł.; Walczak, D.; Szczurowski, K.; Radkowski, S.

    2016-09-01

    With the development of internal combustion engines, engineers attempt to reduce the noise and vibration generated. Due to the high cost of fuel, are increasingly looking for new sources of power in order to reduce costs. In diesel engines, an increasingly popular method is the admixture of propane-butane. This follows because of the price of the fuel as well as to improve the efficiency of combustion. With the development of this type of dual fuel power seems to be a reasonable study of the effects of LPG to generate noise and vibration, as well as an attempt to evaluate the combustion process. Unfortunately, too much addition of LPG causes a phenomenon called knock consisting in abnormal, uneven, explosive combustion of fuels in reciprocating engines. This phenomenon may lead to a reduction in engine performance and permanent damage. Control of the knock detection uses vibration acceleration sensors recording the high frequency ranges. Within the framework of the research conducted by the team of authors, an attempt was made to compare the vibroacoustic signals originating from the commercial knocking sensor with a three-axis acceleration sensor. These signals were subject to a quick Fourier transform in the purpose of analysing the amplitude spectra.

  6. Acceleration of plasma flows in the closed magnetic fields: Simulation and analysis

    SciTech Connect

    Mahajan, Swadesh M.; Shatashvili, Nana L.; Mikeladze, Solomon V.; Sigua, Ketevan I.

    2006-06-15

    Within the framework of a two-fluid description, possible pathways for the generation of fast flows (dynamical as well as steady) in the closed magnetic fields are established. It is shown that a primary plasma flow (locally sub-Alfvenic) is accelerated while interacting with ambient arcade-like closed field structures. The time scale for creating reasonably fast flows (> or approx. 100 km/s) is dictated by the initial ion skin depth, while the amplification of the flow depends on local plasma {beta}. It is shown that distances over which the flows become 'fast' are {approx}0.01R{sub 0} from the interaction surface (R{sub 0} being a characteristic length of the system); later, the fast flow localizes (with dimensions < or approx. 0.05R{sub 0}) in the upper central region of the original arcade. For fixed initial temperature, the final speed (> or approx. 500 km/s) of the accelerated flow and the modification of the field structure are independent of the time duration (lifetime) of the initial flow. In the presence of dissipation, these flows are likely to play a fundamental role in the heating of the finely structured stellar atmospheres; their relevance to the solar wind is also obvious.

  7. Performance analysis and acceleration of explicit integration for large kinetic networks using batched GPU computations

    SciTech Connect

    Shyles, Daniel; Dongarra, Jack J.; Guidry, Mike W.; Tomov, Stanimire Z.; Billings, Jay Jay; Brock, Benjamin A.; Haidar Ahmad, Azzam A.

    2016-09-01

    Abstract—We demonstrate the systematic implementation of recently-developed fast explicit kinetic integration algorithms that solve efficiently N coupled ordinary differential equations (subject to initial conditions) on modern GPUs. We take representative test cases (Type Ia supernova explosions) and demonstrate two or more orders of magnitude increase in efficiency for solving such systems (of realistic thermonuclear networks coupled to fluid dynamics). This implies that important coupled, multiphysics problems in various scientific and technical disciplines that were intractable, or could be simulated only with highly schematic kinetic networks, are now computationally feasible. As examples of such applications we present the computational techniques developed for our ongoing deployment of these new methods on modern GPU accelerators. We show that similarly to many other scientific applications, ranging from national security to medical advances, the computation can be split into many independent computational tasks, each of relatively small-size. As the size of each individual task does not provide sufficient parallelism for the underlying hardware, especially for accelerators, these tasks must be computed concurrently as a single routine, that we call batched routine, in order to saturate the hardware with enough work.

  8. Analysis on weathering characteristics of volcanic rocks in Dokdo, Korea based on accelerated weatehring experiments

    NASA Astrophysics Data System (ADS)

    Woo, Ik; Song, Won-Kyong; Kim, Bok-Chul; Kang, Jinseok

    2010-05-01

    Dokdo consists of small volcanic islands located in the southern part of the East Sea. Accelerated weathering tests was performed to examine the physico-mechanical characteristics of volcanic rocks in Dokdo. Rock core specimens of trachyandesite, andesitic dyke and ash tuff were prepared, and double soxhlet extractors(DSE) and peristatic pumps were used for accelerating the weathering processes. The DSE was designed to perform cyclic leaching tests for rock core specimen using distilled water at seventy degrees centigrade. The core specimens which are classified according to pre-test weathering grades placed in the lower part of the DSE, and periodically exposed to hot distilled water at every ninety minutes. On the other hand the peristatic pumps were utilized to induce leaching by distilled or brine water at normal temperature. The physico-mechanical property changes including rock surface appearance, microscopic structure and rock strength were analyzed with the results obtained from both experiments performed for 120 days. The conducted research in this study have shown that the methodologies of artificial weathering experiments have strong capability to understand the weathering characteristics of the rocks effectively.

  9. Use of simple x-ray measurement in the performance analysis of cryogenic RF accelerator cavities

    SciTech Connect

    D. Dotson; M. Drury; R. May; C. Reece

    1996-10-01

    X-ray emission by radiofrequency (RF) resonant cavities has long been known to accelerator health physicists as a potentially serious source of radiation exposure. The authors points out the danger of klystrons and microwave cavities by stating that the radiation source term is erratic and may be unpredictable depending on microscopic surface conditions which change with time. He also states the x-ray output is a rapidly increasing function of RF input power. At Jefferson Lab, the RF cavities used to accelerate the electron beam employ superconducting technology. X-rays are emitted at high cavity gradients, and measurements of cavity x-rays are valuable for health physics purposes and provide a useful diagnostic tool for assessing cavity performance. The quality factor (Q) for superconducting RF resonant cavities used at Jefferson Lab, is typically 5 x 10{sup 9} for the nominal design gradient of 5 MVm{sup {minus}1}. This large value for Q follows from the small resistive loss in superconducting technology. The operating frequency is 1,497 MHz. In the absence of beam, the input power for a cavity is typically 750 W and the corresponding dissipated power is 2.6 W. At 5 MWm{sup {minus}1}, the input power is 3 kW fully beam loaded. At higher gradients, performance degradation tends to occur due to the onset of electron field emission from defects in the cavity.

  10. Analysis of Anderson Acceleration on a Simplified Neutronics/Thermal Hydraulics System

    SciTech Connect

    Toth, Alex; Kelley, C. T.; Slattery, Stuart R; Hamilton, Steven P; Clarno, Kevin T; Pawlowski, R. P. P.

    2015-01-01

    ABSTRACT A standard method for solving coupled multiphysics problems in light water reactors is Picard iteration, which sequentially alternates between solving single physics applications. This solution approach is appealing due to simplicity of implementation and the ability to leverage existing software packages to accurately solve single physics applications. However, there are several drawbacks in the convergence behavior of this method; namely slow convergence and the necessity of heuristically chosen damping factors to achieve convergence in many cases. Anderson acceleration is a method that has been seen to be more robust and fast converging than Picard iteration for many problems, without significantly higher cost per iteration or complexity of implementation, though its effectiveness in the context of multiphysics coupling is not well explored. In this work, we develop a one-dimensional model simulating the coupling between the neutron distribution and fuel and coolant properties in a single fuel pin. We show that this model generally captures the convergence issues noted in Picard iterations which couple high-fidelity physics codes. We then use this model to gauge potential improvements with regard to rate of convergence and robustness from utilizing Anderson acceleration as an alternative to Picard iteration.

  11. Microwave-accelerated derivatization for the simultaneous gas chromatographic-mass spectrometric analysis of natural and synthetic estrogenic steroids.

    PubMed

    Zuo, Yuegang; Zhang, Kai; Lin, Yuejuan

    2007-05-04

    A rapid microwave-accelerated derivatization process for the GC-MS analysis of steroid estrogens, estrone (E1), 17beta-estradiol (E2), estriol (E3), 17alpha-ethynylestradiol (EE2) and mestranol (MeEE2), was developed. Under microwave irradiation, the five estrogenic hormones studied were simultaneously derivatized with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA)+trimethylchlorosilane (TMCS) in pyridine solution. Effects of irradiation time (15-120 s) and power level (240-800 W) on the yield of the derivatization were investigated. The derivatization under the irradiation of 800 W microwave for 60s produced comparable results when compared with the conventional heating process in a sand bath for 30 min at 80 degrees C in terms of derivatization yield, linearity and precision for all steroid hormones tested. The calibration curves are linear between 3.00 and 3.00 x 10(2) microg mL(-1). The square of the regression coefficients (R(2)) range from 0.979 to 1.000. The applicability of the method was evaluated on spiked river and distilled water samples at two concentrations, 25.0 and 2.00 x 10(2) ng mL(-1). The recoveries obtained by using microwave heating (60s, 800 W) were similar to those by conventional heating. When combined solid-phase extraction (SPE) with the application of the microwave-accelerated derivatization proposed here, the detection limits of 0.02-0.1 ng L(-1) for the steroid hormones have been achieved. The results demonstrated that microwave-accelerated derivatization is an efficient and suitable sample preparation method for the GC-MS analysis of estrogenic steroids.

  12. 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

  13. Shielding analysis of proton therapy accelerators: a demonstration using Monte Carlo-generated source terms and attenuation lengths.

    PubMed

    Lai, Bo-Lun; Sheu, Rong-Jiun; Lin, Uei-Tyng

    2015-05-01

    Monte Carlo simulations are generally considered the most accurate method for complex accelerator shielding analysis. Simplified models based on point-source line-of-sight approximation are often preferable in practice because they are intuitive and easy to use. A set of shielding data, including source terms and attenuation lengths for several common targets (iron, graphite, tissue, and copper) and shielding materials (concrete, iron, and lead) were generated by performing Monte Carlo simulations for 100-300 MeV protons. Possible applications and a proper use of the data set were demonstrated through a practical case study, in which shielding analysis on a typical proton treatment room was conducted. A thorough and consistent comparison between the predictions of our point-source line-of-sight model and those obtained by Monte Carlo simulations for a 360° dose distribution around the room perimeter showed that the data set can yield fairly accurate or conservative estimates for the transmitted doses, except for those near the maze exit. In addition, this study demonstrated that appropriate coupling between the generated source term and empirical formulae for radiation streaming can be used to predict a reasonable dose distribution along the maze. This case study proved the effectiveness and advantage of applying the data set to a quick shielding design and dose evaluation for proton therapy accelerators.

  14. Analysis of factors responsible for the accelerated creep rupture of 12% Cr martensitic steel weld joints

    NASA Astrophysics Data System (ADS)

    Kudryavtsev, A. S.; Okhapkin, K. A.; Mikhailov, M. S.; Skutin, V. S.; Zubova, G. E.; Fedotov, B. V.

    2016-06-01

    In the process of the investigation of the heat resistance of a 0.07C-12Cr-Ni-Mo-V-Nb steel of the martensitic-ferritic class, a reduction was revealed in the long-term strength of its welded joints to below the level of the strength of the base metal. To establish the causes for the accelerated failure of the welded joints, an imitation of the thermal cycles was carried out that produce the structure of the heataffected zone using a dilatometer. In the samples with the structure that corresponds to that of the heataffected zone, a local zone of softening was revealed. The investigations of the metal structure using transmission electron microscopy have shown that the reduction in the creep rupture strength was caused by structural changes under the conditions of the thermal cycle of welding upon the staying of the steel in the temperature range between the Ac 1 and Ac 3 points.

  15. Ultra-trace analysis of 36Cl by accelerator mass spectrometry: an interlaboratory study.

    PubMed

    Merchel, S; Bremser, W; Alfimov, V; Arnold, M; Aumaître, G; Benedetti, L; Bourlès, D L; Caffee, M; Fifield, L K; Finkel, R C; Freeman, S P H T; Martschini, M; Matsushi, Y; Rood, D H; Sasa, K; Steier, P; Takahashi, T; Tamari, M; Tims, S G; Tosaki, Y; Wilcken, K M; Xu, S

    2011-07-01

    A first international (36)Cl interlaboratory comparison has been initiated. Evaluation of the final results of the eight participating accelerator mass spectrometry (AMS) laboratories on three synthetic AgCl samples with (36)Cl/Cl ratios at the 10(-11), 10(-12), and 10(-13) level shows no difference in the sense of simple statistical significance. However, more detailed statistical analyses demonstrate certain interlaboratory bias and underestimation of uncertainties by some laboratories. Following subsequent remeasurement and reanalysis of the data from some AMS facilities, the round-robin data indicate that (36)Cl/Cl data from two individual AMS laboratories can differ by up to 17%. Thus, the demand for further work on harmonising the (36)Cl-system on a worldwide scale and enlarging the improvement of measurements is obvious.

  16. Verification analysis of the Toroidal Accelerator Rotor Platform wind energy conversion system

    NASA Astrophysics Data System (ADS)

    Duffy, Robert E.

    1988-09-01

    A unique wind energy system, the Toroidal Accelerator Rotor Platform (TARP) is studied. The TARP system places the rotors in pairs on either side of a torus-shaped platform, so that the wind is forced to flow into the rotors. As the wind is forced around the form, it picks up velocity and turns the rotors faster, generating more power. By concentrating the wind's power, the TARP system can be constructed in modules using 10 foot diameter rotor blades. Mounted on a track suspension system, the rotors are able to yaw with the wind to take advantage of breezes from any direction. The basic TARP design was tested and modified in a wind tunnel. The system was then analyzed for its integration into a farm silo and as a multistacked wind power needle. It was determined that the TARP technology would be feasible for application involving sites with high wind velocities, including some sites in New York State.

  17. Analysis of accelerated failure time data with dependent censoring using auxiliary variables via nonparametric multiple imputation.

    PubMed

    Hsu, Chiu-Hsieh; Taylor, Jeremy M G; Hu, Chengcheng

    2015-08-30

    We consider the situation of estimating the marginal survival distribution from censored data subject to dependent censoring using auxiliary variables. We had previously developed a nonparametric multiple imputation approach. The method used two working proportional hazards (PH) models, one for the event times and the other for the censoring times, to define a nearest neighbor imputing risk set. This risk set was then used to impute failure times for censored observations. Here, we adapt the method to the situation where the event and censoring times follow accelerated failure time models and propose to use the Buckley-James estimator as the two working models. Besides studying the performances of the proposed method, we also compare the proposed method with two popular methods for handling dependent censoring through the use of auxiliary variables, inverse probability of censoring weighted and parametric multiple imputation methods, to shed light on the use of them. In a simulation study with time-independent auxiliary variables, we show that all approaches can reduce bias due to dependent censoring. The proposed method is robust to misspecification of either one of the two working models and their link function. This indicates that a working proportional hazards model is preferred because it is more cumbersome to fit an accelerated failure time model. In contrast, the inverse probability of censoring weighted method is not robust to misspecification of the link function of the censoring time model. The parametric imputation methods rely on the specification of the event time model. The approaches are applied to a prostate cancer dataset.

  18. DEX: Increasing the Capability of Scientific Data Analysis Pipelines by Using Efficient Bitmap Indices to Accelerate Scientific Visualization

    SciTech Connect

    Stockinger, Kurt; Shalf, John; Bethel, Wes; Wu, Kesheng

    2005-02-04

    We describe a new approach to scalable data analysis that enables scientists to manage the explosion in size and complexity of scientific data produced by experiments and simulations. Our approach uses a novel combination of efficient query technology and visualization infrastructure. The combination of bit map indexing, which is a data management technology that accelerates queries on large scientific datasets, with a visualization pipeline for generating images of abstract data results in a tool suitable for use by scientists in fields where data size and complexity poses a barrier to efficient analysis. Our architecture and implementation, which we call DEX (short for dexterous data explorer), directly addresses the problem of ''too much data'' by focusing analysis on data deemed to be ''scientifically interesting'' via a user-specified selection criteria. The architectural concepts and implementation are applicable to wide variety of scientific data analysis and visualization applications. This paper presents an architectural overview of the system along with an analysis showing substantial performance over traditional visualization pipelines. While performance gains are a significant result, even more important is the new functionality not present in any visualization analysis software--namely the ability to perform interactive, multi-dimensional queries to refine regions of interest that are later used as input to analysis or visualization.

  19. Radical Acceleration

    ERIC Educational Resources Information Center

    Gross, Miraca U. M.; Van Vliet, Helen E.

    2005-01-01

    Research has found that teachers' objections to accelerating gifted students are mainly based on a fear that acceleration will lead to social or emotional damage. Ironically, it is the academic and emotional maturity which characterizes intellectually gifted students, coupled with their high levels of academic achievement, which makes them such…

  20. RECIRCULATING ACCELERATION

    SciTech Connect

    BERG,J.S.; GARREN,A.A.; JOHNSTONE,C.

    2000-04-07

    This paper compares various types of recirculating accelerators, outlining the advantages and disadvantages of various approaches. The accelerators are characterized according to the types of arcs they use: whether there is a single arc for the entire recirculator or there are multiple arcs, and whether the arc(s) are isochronous or non-isochronous.

  1. Analysis of sonic boom measurements near shock wave extremities for flight near Mach 1.0 and for airplane accelerations

    NASA Technical Reports Server (NTRS)

    Haglund, G. T.; Kane, E. J.

    1974-01-01

    The analysis of the 14 low-altitude transonic flights showed that the prevailing meteorological consideration of the acoustic disturbances below the cutoff altitude during threshold Mach number flight has shown that a theoretical safe altitude appears to be valid over a wide range of meteorological conditions and provides a reasonable estimate of the airplane ground speed reduction to avoid sonic boom noise during threshold Mach number flight. Recent theoretical results for the acoustic pressure waves below the threshold Mach number caustic showed excellent agreement with observations near the caustic, but the predicted overpressure levels were significantly lower than those observed far from the caustic. The analysis of caustics produced by inadvertent low-magnitude accelerations during flight at Mach numbers slightly greater than the threshold Mach number showed that folds and associated caustics were produced by slight changes in the airplane ground speed. These caustic intensities ranged from 1 to 3 time the nominal steady, level flight intensity.

  2. Cluster analysis of accelerated molecular dynamics simulations: A case study of the decahedron to icosahedron transition in Pt nanoparticles

    NASA Astrophysics Data System (ADS)

    Huang, Rao; Lo, Li-Ta; Wen, Yuhua; Voter, Arthur F.; Perez, Danny

    2017-10-01

    Modern molecular-dynamics-based techniques are extremely powerful to investigate the dynamical evolution of materials. With the increase in sophistication of the simulation techniques and the ubiquity of massively parallel computing platforms, atomistic simulations now generate very large amounts of data, which have to be carefully analyzed in order to reveal key features of the underlying trajectories, including the nature and characteristics of the relevant reaction pathways. We show that clustering algorithms, such as the Perron Cluster Cluster Analysis, can provide reduced representations that greatly facilitate the interpretation of complex trajectories. To illustrate this point, clustering tools are used to identify the key kinetic steps in complex accelerated molecular dynamics trajectories exhibiting shape fluctuations in Pt nanoclusters. This analysis provides an easily interpretable coarse representation of the reaction pathways in terms of a handful of clusters, in contrast to the raw trajectory that contains thousands of unique states and tens of thousands of transitions.

  3. An accelerated buoyancy adhesion assay combined with 3-D morphometric analysis for assessing osteoblast adhesion on microgrooved substrata.

    PubMed

    Sobral, J M; Malheiro, V N; Clyne, T W; Harris, J; Rezk, R; O'Neill, W; Markaki, A E

    2016-07-01

    An accelerated negative buoyancy method has been developed to assess cell adhesion strength. This method has been used in conjunction with 3-D morphometric analysis to understand the effects of surface topology on cell response. Aligned micro-grooved surface topographies (with a range of groove depths) were produced on stainless steel 316L substrates by laser ablation. An investigation was carried out on the effect of the micro-grooved surface topography on cell adhesion strength, cell and nucleus volumes, cell phenotypic expression and attachment patterns. Increased hydrophobicity and anisotropic wettability was observed on surfaces with deeper grooves. A reduction was noted in cell volume, projected areas and adhesion sites for deeper grooves, linked to lower cell proliferation and differentiation rates and also to reduced adhesion strength. The results suggest that the centrifugation assay combined with three-dimensional cell morphometric analysis has considerable potential for obtaining improved understanding of the cell/substrate interface.

  4. SU-E-T-144: Effective Analysis of VMAT QA Generated Trajectory Log Files for Medical Accelerator Predictive Maintenance

    SciTech Connect

    Able, CM; Baydush, AH; Nguyen, C; Munley, MT; Gersh, J; Ndlovu, A; Rebo, I; Booth, J; Perez, M; Sintay, B

    2014-06-01

    Purpose: To determine the effectiveness of SPC analysis for a model predictive maintenance process that uses accelerator generated parameter and performance data contained in trajectory log files. Methods: Each trajectory file is decoded and a total of 131 axes positions are recorded (collimator jaw position, gantry angle, each MLC, etc.). This raw data is processed and either axis positions are extracted at critical points during the delivery or positional change over time is used to determine axis velocity. The focus of our analysis is the accuracy, reproducibility and fidelity of each axis. A reference positional trace of the gantry and each MLC is used as a motion baseline for cross correlation (CC) analysis. A total of 494 parameters (482 MLC related) were analyzed using Individual and Moving Range (I/MR) charts. The chart limits were calculated using a hybrid technique that included the use of the standard 3σ limits and parameter/system specifications. Synthetic errors/changes were introduced to determine the initial effectiveness of I/MR charts in detecting relevant changes in operating parameters. The magnitude of the synthetic errors/changes was based on: TG-142 and published analysis of VMAT delivery accuracy. Results: All errors introduced were detected. Synthetic positional errors of 2mm for collimator jaw and MLC carriage exceeded the chart limits. Gantry speed and each MLC speed are analyzed at two different points in the delivery. Simulated Gantry speed error (0.2 deg/sec) and MLC speed error (0.1 cm/sec) exceeded the speed chart limits. Gantry position error of 0.2 deg was detected by the CC maximum value charts. The MLC position error of 0.1 cm was detected by the CC maximum value location charts for every MLC. Conclusion: SPC I/MR evaluation of trajectory log file parameters may be effective in providing an early warning of performance degradation or component failure for medical accelerator systems.

  5. SU-E-T-495: Neutron Induced Electronics Failure Rate Analysis for a Single Room Proton Accelerator

    SciTech Connect

    Knutson, N; DeWees, T; Klein, E

    2014-06-01

    Purpose: To determine the failure rate as a function of neutron dose of the range modulator's servo motor controller system (SMCS) while shielded with Borated Polyethylene (BPE) and unshielded in a single room proton accelerator. Methods: Two experimental setups were constructed using two servo motor controllers and two motors. Each SMCS was then placed 30 cm from the end of the plugged proton accelerator applicator. The motor was then turned on and observed from outside of the vault while being irradiated to known neutron doses determined from bubble detector measurements. Anytime the motor deviated from the programmed motion a failure was recorded along with the delivered dose. The experiment was repeated using 9 cm of BPE shielding surrounding the SMCS. Results: Ten SMCS failures were recorded in each experiment. The dose per monitor unit for the unshielded SMCS was 0.0211 mSv/MU and 0.0144 mSv/MU for the shielded SMCS. The mean dose to produce a failure for the unshielded SMCS was 63.5 ± 58.3 mSv versus 17.0 ±12.2 mSv for the shielded. The mean number of MUs between failures were 2297 ± 1891 MU for the unshielded SMCS and 2122 ± 1523 MU for the shielded. A Wilcoxon Signed Ranked test showed the dose between failures were significantly different (P value = 0.044) while the number of MUs between failures were not (P value = 1.000). Statistical analysis determined a SMCS neutron dose of 5.3 mSv produces a 5% chance of failure. Depending on the workload and location of the SMCS, this failure rate could impede clinical workflow. Conclusion: BPE shielding was shown to not reduce the average failure of the SMCS and relocation of the system outside of the accelerator vault was required to lower the failure rate enough to avoid impeding clinical work flow.

  6. Theoretical and experimental analysis of a linear accelerator endowed with single feed coupler with movable short-circuit

    NASA Astrophysics Data System (ADS)

    Forno, Massimo Dal; Craievich, Paolo; Penco, Giuseppe; Vescovo, Roberto

    2013-11-01

    The front-end injection systems of the FERMI@Elettra linac produce high brightness electron beams that define the performance of the Free Electron Laser. The photoinjector mainly consists of the radiofrequency (rf) gun and of two S-band rf structures which accelerate the beam. Accelerating structures endowed with a single feed coupler cause deflection and degradation of the electron beam properties, due to the asymmetry of the electromagnetic field. In this paper, a new type of single feed structure with movable short-circuit is proposed. It has the advantage of having only one waveguide input, but we propose a novel design where the dipolar component is reduced. Moreover, the racetrack geometry allows to reduce the quadrupolar component. This paper presents the microwave design and the analysis of the particle motion inside the linac. A prototype has been machined at the Elettra facility to verify the new coupler design and the rf field has been measured by adopting the bead-pull method. The results are here presented, showing good agreement with the expectations.

  7. [Visual and auditory analyzers of human under the conditions of acceleration: comparative analysis of the genesis of disturbances].

    PubMed

    Barer, A S

    2009-01-01

    More than 500 pinpoint physiological experiments were to discern the state and genesis of visual and auditory disturbances during rotation on an 8-meter armed centrifuge at 14 g. The ample instrumentation provided a broad variety of measurements within very short intervals including acuity and angle of vision, absolute light sensitivity, critical flicker frequency, threshold of tone hearing, speech intelligibility. Examination of the eye ground blood vessels was conducted both remotely and by an ophthalmologist sitting next to a volunteered subject during rotation. Results of the experiments showed degradation of the visual function as acceleration grew and almost complete loss of vision at 12-14 g. As regards the hearing function, acoustic energy bore some loss on the way to the Corti's organ and yet hearing remained good enough to support orientation of human operator exposed to the range of acceleration that do not cause loss of consciousness. The significance of hearing retention is attested by successful experience of using aural information in laboratory studies of the effectiveness of manual space vehicle operation against 18 g. Comparative analysis of these and other laboratory data, and literature makes possible the assessment of the functional status of different components of light and acoustic energy transportation and transformation on the way to the "headquarters" and display of "weak points" of these analyzers. Our data favours the view on the retina as a blocker of the light energy transportation. Genesis of this phenomenon is associated primarily with the disturbance of circulation in a centralis retinae.

  8. Comparison Study of Electromagnet and Permanent Magnet Systems for an Accelerator Using Cost-Based Failure Modes and Effects Analysis.

    SciTech Connect

    Spencer, C

    2004-02-19

    The next generation of particle accelerators will be one-of-a-kind facilities, and to meet their luminosity goals they must have guaranteed availability over their several decade lifetimes. The Next Linear Collider (NLC) is one viable option for a 1 TeV electron-positron linear collider, it has an 85% overall availability goal. We previously showed how a traditional Failure Modes and Effects Analysis (FMEA) of a SLAC electromagnet leads to reliability-enhancing design changes. Traditional FMEA identifies failure modes with high risk but does not consider the consequences in terms of cost, which could lead to unnecessarily expensive components. We have used a new methodology, ''Life Cost-Based FMEA'', which measures risk of failure in terms of cost, in order to evaluate and compare two different technologies that might be used for the 8653 NLC magnets: electromagnets or permanent magnets. The availabilities for the two different types of magnet systems have been estimated using empirical data from SLAC's accelerator failure database plus expert opinion on permanent magnet failure modes and industry standard failure data. Labor and material costs to repair magnet failures are predicted using a Monte Carlo simulation of all possible magnet failures over a 30-year lifetime. Our goal is to maximize up-time of the NLC through magnet design improvements and the optimal combination of electromagnets and permanent magnets, while reducing magnet system lifecycle costs.

  9. Theoretical and experimental analysis of a linear accelerator endowed with single feed coupler with movable short-circuit

    SciTech Connect

    Forno, Massimo Dal; Craievich, Paolo; Penco, Giuseppe; Vescovo, Roberto

    2013-11-15

    The front-end injection systems of the FERMI@Elettra linac produce high brightness electron beams that define the performance of the Free Electron Laser. The photoinjector mainly consists of the radiofrequency (rf) gun and of two S-band rf structures which accelerate the beam. Accelerating structures endowed with a single feed coupler cause deflection and degradation of the electron beam properties, due to the asymmetry of the electromagnetic field. In this paper, a new type of single feed structure with movable short-circuit is proposed. It has the advantage of having only one waveguide input, but we propose a novel design where the dipolar component is reduced. Moreover, the racetrack geometry allows to reduce the quadrupolar component. This paper presents the microwave design and the analysis of the particle motion inside the linac. A prototype has been machined at the Elettra facility to verify the new coupler design and the rf field has been measured by adopting the bead-pull method. The results are here presented, showing good agreement with the expectations.

  10. Hyperfractionated Accelerated Radiotherapy (HART) for Anaplastic Thyroid Carcinoma: Toxicity and Survival Analysis

    SciTech Connect

    Dandekar, Prasad; Rhys-Evans, Peter; Harrington, Kevin; Nutting, Christopher; Newbold, Kate

    2009-06-01

    Purpose: Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers, and the current protocol of hyperfractionated accelerated radiotherapy was initiated to improve survival while limiting toxicities. Methods and Materials: All patients with ATC from 1991 to 2002 were accrued and received megavoltage radiotherapy from the mastoid processes to the carina up to 60 Gy in twice-daily fractions of 1.8 and 2 Gy, 6 hours apart. Results: Thirty-one patients were accrued with a median age of 69 years, and 55% were women. Debulking was performed in 26%, and total thyroidectomy, in 6%, whereas 68% received radical radiotherapy alone. Local control data were available for 27 patients: 22% had a complete response, 26% had a partial response, 15% showed progressive disease, and 37% showed static disease. Median overall survival for all 31 patients was 70 days (95% confidence interval, 40-99). There was no significant difference in median survival between patients younger (70 days) and older than 70 years (42 days), between men (70 days) and women (49days), and between patients receiving postoperative radiotherapy (77 days) and radical radiotherapy alone (35 days). Grade III or higher skin erythema was seen in 56% patients; desquamation in 21%; dysphagia in 74%; and esophagitis in 79%. Conclusion: The current protocol failed to offer a significant survival benefit, was associated with severe toxicities, and thus was discontinued. There is a suggestion that younger patients with operable disease have longer survival, but this would require a larger study to confirm it.

  11. Improved protocol and data analysis for accelerated shelf-life estimation of solid dosage forms.

    PubMed

    Waterman, Kenneth C; Carella, Anthony J; Gumkowski, Michael J; Lukulay, Patrick; MacDonald, Bruce C; Roy, Michael C; Shamblin, Sheri L

    2007-04-01

    To propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life. The concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations. Examples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions. The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.

  12. An analysis of spatially varying turbulent Prandtl number in a flow with local acceleration and deceleration

    NASA Astrophysics Data System (ADS)

    Jung, Eunbum; Lee, Wook; Kang, Seongwon; Iaccarino, Gianluca

    2015-11-01

    The turbulent Prandtl number (Prt) is an important parameter in turbulent flows used in many engineering models for heat transfer. In the present study, spatial variation of Prt in a wall-bounded turbulent flow is investigated using DNS. We derived a form of Prt applicable to a general flow configuration, using the least-square method in a manner consistent with the turbulent viscosity model in LES. For a flow subject to local acceleration and deceleration induced by the wall geometry, we performed a parametric study for the Reynolds number, Prandtl number and a geometric factor using DNS. A comparison of the data from DNS and RANS with a constant Prt indicates the potential of improved RANS predictions using the present variable Prt subject to the local flow field. Also, it is observed that the local pressure gradient has an important effect on the Prt field. From the flow statistics, a few flow variables showing higher correlations with Prt are identified. An elementary model for Prt is devised, and used for RANS prediction producing a more accurate prediction of the heat transfer rate. Corresponding author

  13. Analysis of accelerated death benefit claims at a Japanese life insurance company.

    PubMed

    Kobayashi, Miyoharu; Kudomi, Hiroyuki

    2002-01-01

    We studied accelerated death benefit (ADB) claims at the Dai-ichi Mutual Life Insurance Company (Dai-ichi Life). The ADB provision is designed to pay all or a portion of the death benefit if the insured is expected to die within 6 months. Dai-ichi Life paid 243 ADB claims and did not pay 17 ADB claims between December 1994 and March 1998. Of the 260 ADB claims, 253 (97.3%) were caused by malignant neoplasm, 2 by intracranial hemorrhage, 2 by angina pectoris, 1 by dilated cardiomyopathy, 1 by hepatic cirrhosis, and 1 by bleeding gastric ulcer. The age range of the 243 paid claims at the time when the attendant physician predicted a life expectancy below 6 months was 21.6-72.6 years (48.7 +/- 8.7 years [Mean +/- SD]). By the end of March 2000, 236 cases were followed up among the above 243 paid ADB claims. Of the 236 followed-up cases, 149 (63.1%) died within 6 months and 203 (86.0%) died within 1 year. The range of survival periods of these 236 cases was 6-1516 days (210 +/- 237 days). Of the 217 dead cases due to malignant neoplasm, 45 (20.7%) died of gastric cancer, 44 (20.3%) of lung cancer, 24 (11.1%) of liver cancer, 16 (7.4%) of colon cancer, 13 (6.0%) of rectum cancer, and 12 (5.5%) of pancreatic cancer.

  14. Stochastic Modeling and Analysis of Multiple Nonlinear Accelerated Degradation Processes through Information Fusion

    PubMed Central

    Sun, Fuqiang; Liu, Le; Li, Xiaoyang; Liao, Haitao

    2016-01-01

    Accelerated degradation testing (ADT) is an efficient technique for evaluating the lifetime of a highly reliable product whose underlying failure process may be traced by the degradation of the product’s performance parameters with time. However, most research on ADT mainly focuses on a single performance parameter. In reality, the performance of a modern product is usually characterized by multiple parameters, and the degradation paths are usually nonlinear. To address such problems, this paper develops a new s-dependent nonlinear ADT model for products with multiple performance parameters using a general Wiener process and copulas. The general Wiener process models the nonlinear ADT data, and the dependency among different degradation measures is analyzed using the copula method. An engineering case study on a tuner’s ADT data is conducted to demonstrate the effectiveness of the proposed method. The results illustrate that the proposed method is quite effective in estimating the lifetime of a product with s-dependent performance parameters. PMID:27509499

  15. Fourier analysis of Solar atmospheric numerical simulations accelerated with GPUs (CUDA).

    NASA Astrophysics Data System (ADS)

    Marur, A.

    2015-12-01

    Solar dynamics from the convection zone creates a variety of waves that may propagate through the solar atmosphere. These waves are important in facilitating the energy transfer between the sun's surface and the corona as well as propagating energy throughout the solar system. How and where these waves are dissipated remains an open question. Advanced 3D numerical simulations have furthered our understanding of the processes involved. Fourier transforms to understand the nature of the waves by finding the frequency and wavelength of these waves through the simulated atmosphere, as well as the nature of their propagation and where they get dissipated. In order to analyze the different waves produced by the aforementioned simulations and models, Fast Fourier Transform algorithms will be applied. Since the processing of the multitude of different layers of the simulations (of the order of several 100^3 grid points) would be time intensive and inefficient on a CPU, CUDA, a computing architecture that harnesses the power of the GPU, will be used to accelerate the calculations.

  16. Fusion-neutron-yield, activation measurements at the Z accelerator: design, analysis, and sensitivity.

    PubMed

    Hahn, K D; Cooper, G W; Ruiz, C L; Fehl, D L; Chandler, G A; Knapp, P F; Leeper, R J; Nelson, A J; Smelser, R M; Torres, J A

    2014-04-01

    We present a general methodology to determine the diagnostic sensitivity that is directly applicable to neutron-activation diagnostics fielded on a wide variety of neutron-producing experiments, which include inertial-confinement fusion (ICF), dense plasma focus, and ion beam-driven concepts. This approach includes a combination of several effects: (1) non-isotropic neutron emission; (2) the 1/r(2) decrease in neutron fluence in the activation material; (3) the spatially distributed neutron scattering, attenuation, and energy losses due to the fielding environment and activation material itself; and (4) temporally varying neutron emission. As an example, we describe the copper-activation diagnostic used to measure secondary deuterium-tritium fusion-neutron yields on ICF experiments conducted on the pulsed-power Z Accelerator at Sandia National Laboratories. Using this methodology along with results from absolute calibrations and Monte Carlo simulations, we find that for the diagnostic configuration on Z, the diagnostic sensitivity is 0.037% ± 17% counts/neutron per cm(2) and is ∼ 40% less sensitive than it would be in an ideal geometry due to neutron attenuation, scattering, and energy-loss effects.

  17. Analysis of a Symmetric Terahertz Dielectric-Lined Rectangular Structure for High Gradient Acceleration

    SciTech Connect

    Marshall, T. C.; Sotnikov, G. V.; Shchelkunov, S. V.; Hirshfield, J. L.

    2009-01-22

    We study, using computational methods based on analytic theory as well as a PIC code, the wakefields set up in a seven-zone symmetric rectangular THZ structure, and find that for overall transverse x/y dimensions 2.121 mmx0.6 mm, two 5-GeV drive bunches (3 nC, with x/y/z dimensions 0.3/0.3/0.12 mm{sup 3} as available at SLAC) will set up an axial wakefield {approx}350 MV/m in the witness channel, with a transformer ratio {approx}18-20. The symmetry of the structure ensures not only that small transverse forces are imposed on the witness bunch, but also that the two components of transverse force are equal and opposite at the bunch location so as to enable dynamical stabilization in an accelerator comprising many modules. Transverse forces on the drive bunch tails may allow bunches to move {approx}0.5-1 m without suffering excessive erosion.

  18. Accelerated calendar and pulse life analysis of lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Jungst, Rudolph G.; Nagasubramanian, Ganesan; Case, Herbert L.; Liaw, Bor Yann; Urbina, Angel; Paez, Thomas L.; Doughty, Daniel H.

    Sandia National Laboratories has been studying calendar and pulse discharge life of prototype high-power lithium-ion cells as part of the Advanced Technology Development (ATD) Program. One of the goals of ATD is to establish validated accelerated life test protocols for lithium-ion cells in the hybrid electric vehicle application. In order to accomplish this, aging experiments have been conducted on 18650-size cells containing a chemistry representative of these high-power designs. Loss of power and capacity are accompanied by increasing interfacial impedance at the cathode. These relationships are consistent within a given state-of-charge (SOC) over the range of storage temperatures and times. Inductive models have been used to construct detailed descriptions of the relationships between power fade and aging time and to relate power fade, capacity loss and impedance rise. These models can interpolate among the different experimental conditions and can also describe the error surface when fitting life prediction models to the data.

  19. Analysis of efficient ion acceleration with multi-picosecond LFEX laser

    NASA Astrophysics Data System (ADS)

    Iwata, Natsumi; Yogo, Akifumi; Mima, Kunioki; Tosaki, Shota; Koga, Keisuke; Nagatomo, Hideo; Kishimoto, Yasuaki; Nishimura, Hiroaki; Azechi, Horishi

    2016-10-01

    We demonstrate an efficient proton acceleration reaching 30 MeV by using high contrast, kilojoule, picosecond laser LFEX at the peak intensity of 2.3 ×1018 W/cm2. Owing to the large spot size of 70 μm FWHM, the target foil expands one-dimensionally during the multi-picosecond pulse duration time, which yields the electron heating beyond the ponderomotive scaling observed in the experiment. We present by a 1D PIC simulation that the electron temperature evolves in time while the electrons recirculate between the front and rear surfaces of the expanding plasma. A theoretical calculation for the ion maximum energy that takes the temperature evolution into account agrees with the experimental result quantitatively. Being supported by the experiment and simulation, our theoretical model for the non-isothermal plasma expansion dynamics will provide an important basis for understanding the multi-picosecond high intensity laser-plasma interactions and for various applications such as energetic ion beam generation for medical applications and fast ignition-based laser fusion.

  20. Accelerated stress testing and diagnostic analysis of degradation in CdTe solar cells

    NASA Astrophysics Data System (ADS)

    Albin, David S.

    2008-08-01

    Solar cell module reliability is inextricably linked to cell-level reliability. This is particularly so with thin-film technologies. In CdTe, reliability issues historically associate with back contact stability and the use of Cu as an extrinsic dopant. Using a simple approach by which identical cells are heated under open-circuit bias and 1-sun illumination, degradation activation energies of 0.63 and 2.94 eV in laboratory-scale CdS/CdTe devices were identified in the accelerated stress temperature range of 60 to 120 °C. At lower stress temperatures, cell performance changes were linearly correlated with changes in both fill factor (FF) and short-circuit current (Jsc). At higher stress temperatures, changes in efficiency were correlated with changes in FF and open-circuit voltage (Voc). The measured activation energy of 0.63 is associated with Cu-diffusion. During the early stage of stress testing, which may provide additional back contact annealing, improvements in FF were due to Cu-diffusion. Decreased performance observed at longer stress times (decreased FF and Voc), according to a two-diode Pspice model, were due to both increased space-charge recombination (near the junction) and decreased recombination in the bulk. Kirkendall void formation (S-outdiffusion) at the CdS/CdTe interface is given as responsible for the 2.9 eV degradation mechanism.

  1. Economic analysis of opportunities to accelerate Alzheimer’s disease research and development

    PubMed Central

    Scott, Troy J; O'Connor, Alan C; Link, Albert N; Beaulieu, Travis J

    2014-01-01

    The development of disease-modifying treatments for Alzheimer's disease (AD) faces a number of barriers. Among these are the lack of surrogate biomarkers, the exceptional size and duration of clinical trials, difficulties in identifying appropriate populations for clinical trials, and the limitations of monotherapies in addressing such a complex multifactorial disease. This study sets out to first estimate the consequent impact on the expected cost of developing disease-modifying treatments for AD and then to estimate the potential benefits of bringing together industry, academic, and government stakeholders to co-invest in, for example, developing better biomarkers and cognitive assessment tools, building out advanced registries and clinical trial-readiness cohorts, and establishing clinical trial platforms to investigate combinations of candidate drugs and biomarkers from the portfolios of multiple companies. Estimates based on interviews with experts on AD research and development suggest that the cost of one new drug is now $5.7 billion (95% confidence interval (CI) $3.7–9.5 billion) and could be reduced to $2.0 billion (95% CI $1.5–2.9 billion). The associated acceleration in the arrival of disease-modifying treatments could reduce the number of case years of dementia by 7.0 million (95% CI 4.4–9.4 million) in the United States from 2025 through 2040. PMID:24673372

  2. Pharmacokinetic analysis of 14C-ursodiol in newborn infants using accelerator mass spectrometry.

    PubMed

    Gordi, Toufigh; Baillie, Rebecca; Vuong, Le T; Abidi, Saira; Dueker, Stephen; Vasquez, Herbert; Pegis, Priscilla; Hopper, Andrew O; Power, Gordon G; Blood, Arlin B

    2014-09-01

    Pharmacokinetic studies in the neonatal population are often limited by the small volume of blood that can be collected. The high sensitivity of (14) C-accelerator mass spectrometry (AMS) enables pharmacokinetic studies to be conducted with greatly reduced sample volumes. We demonstrated the utility of AMS in infants by studying the plasma pharmacokinetic behavior of nanogram doses of (14) C-ursodiol administered as a non-perturbing microdose or as a microtracer with therapeutic doses of non-labeled ursodiol in infants. Five non-cholestatic infants were administered 3 consecutive oral microdoses of (14) C-ursodiol: 8 ng (1.0 nCi), 26 ng (3.3 nCi), and 80 ng (10 nCi) 48 hours apart. Three additional infants with cholestasis were administered a single 80 ng (10.0 nCi) oral dose of (14) C-ursodiol together with a therapeutic dose of 40 mg/kg of non-labeled ursodiol. A pharmacokinetic model describing ursodiol concentrations was developed using nonlinear mixed-effects modeling. The pharmacokinetics of ursodiol in this pilot study were best described by a two-compartment model with first-order elimination. This study demonstrates the feasibility and utility of microdose and microtrace methodology in pediatric research.

  3. Analysis and comparison between electric and magnetic power couplers for accelerators in Free Electron Lasers (FEL)

    NASA Astrophysics Data System (ADS)

    Serpico, C.; Grudiev, A.; Vescovo, R.

    2016-10-01

    Free-electron lasers represent a new and exciting class of coherent optical sources possessing broad wavelength tunability and excellent optical-beam quality. The FERMI seeded free-electron laser (FEL), located at the Elettra laboratory in Trieste, is driven by a 200 m long, S-band linac: the high energy part of the linac is equipped with 6 m long backward traveling wave (BTW) structures. The structures have small iris radius and a nose cone geometry which allows for high gradient operation. Development of new high-gradient, S-band accelerating structures for the replacement of the existing BTWs is under consideration. This paper investigates two possible solutions for the RF power couplers suitable for a linac driven FEL which require reduced wakefields effects, high operating gradient and very high reliability. The first part of the manuscript focuses on the reduction of residual field asymmetries, while in the second analyzes RF performances, the peak surface fields and the expected breakdown rate. In the conclusion, two solutions are compared and pros and cons are highlighted.

  4. Verification analysis of the toroidal accelerator rotor platform wind energy conversion system. Summary report

    SciTech Connect

    Duffy, R.E.

    1988-09-01

    Researchers at Rensselaer Polytechnic Institute have studied a unique wind energy system, the Toroidal Accelerator Rotor Platform (TARP). The TARP system places the rotors in pairs on either side of a torus-shaped platform, so that the wind is forced to flow into the rotors. As the wind is forced around the form, it picks up velocity and turns the rotors faster, generating more power. By concentrating the wind's power, the TARP system can be constructed in modules using 10-foot-diameter rotor blades. Mounted on a track suspension system, the rotors are able to yaw with the wind to take advantage of breezes from any direction. In this project, the basic TARP design was tested and modified in a wind tunnel. The system was then analyzed for its integration into a farm silo and as a multi-stacked wind power needle. It was determined that the TARP technology would be feasible for applications involving sites with high wind velocities, including some sites in New York State.

  5. Composites Associated with Pulp-Protection Material: Color-Stability Analysis after Accelerated Artificial Aging

    PubMed Central

    Cruvinel, Diogo Rodrigues; Garcia, Lucas da Fonseca Roberti; Consani, Simonides; de Carvalho Panzeri Pires-de-Souza, Fernanda

    2010-01-01

    Objectives: This study assessed the color stability of two composites associated with two pulp protectors submitted to accelerated artificial aging (AAA). Methods: 60 test specimens were made with 0.5 mm of protection material (calcium hydroxide - CH or glass ionomer cement - GIC) and 2.5 mm of restoration material (Concept or QuixFil) and divided into 3 groups (n=10) according to the type of protection material/composite, and the control group (no protection). After polishing, color readings were obtained with a spectrophotometer (PCB 6807 Byk Gardner) before and after AAA for 384 hours, and L*, a*, and b* coordinates and total color variation (ΔE) were analyzed (2-way ANOVA, Bonferroni, α=05). Results: Composites placed on CH presented lower L* levels than those on GIC, which presented higher L* values than the control group and lower b* values than those of the CH group. The Concept composite presented higher ΔE levels for all groups, differing statistically from QuixFil, except when placed on GIC. Conclusions: It was concluded that the protection material could affect the color stability and AAA is a factor that enhances this effect, depending on the type of composite used. PMID:20046473

  6. Economic analysis of opportunities to accelerate Alzheimer's disease research and development.

    PubMed

    Scott, Troy J; O'Connor, Alan C; Link, Albert N; Beaulieu, Travis J

    2014-04-01

    The development of disease-modifying treatments for Alzheimer's disease (AD) faces a number of barriers. Among these are the lack of surrogate biomarkers, the exceptional size and duration of clinical trials, difficulties in identifying appropriate populations for clinical trials, and the limitations of monotherapies in addressing such a complex multifactorial disease. This study sets out to first estimate the consequent impact on the expected cost of developing disease-modifying treatments for AD and then to estimate the potential benefits of bringing together industry, academic, and government stakeholders to co-invest in, for example, developing better biomarkers and cognitive assessment tools, building out advanced registries and clinical trial-readiness cohorts, and establishing clinical trial platforms to investigate combinations of candidate drugs and biomarkers from the portfolios of multiple companies. Estimates based on interviews with experts on AD research and development suggest that the cost of one new drug is now $5.7 billion (95% confidence interval (CI) $3.7-9.5 billion) and could be reduced to $2.0 billion (95% CI $1.5-2.9 billion). The associated acceleration in the arrival of disease-modifying treatments could reduce the number of case years of dementia by 7.0 million (95% CI 4.4-9.4 million) in the United States from 2025 through 2040.

  7. A Bayesian approach to joint analysis of multivariate longitudinal data and parametric accelerated failure time.

    PubMed

    Luo, Sheng

    2014-02-20

    Impairment caused by Parkinson's disease (PD) is multidimensional (e.g., sensoria, functions, and cognition) and progressive. Its multidimensional nature precludes a single outcome to measure disease progression. Clinical trials of PD use multiple categorical and continuous longitudinal outcomes to assess the treatment effects on overall improvement. A terminal event such as death or dropout can stop the follow-up process. Moreover, the time to the terminal event may be dependent on the multivariate longitudinal measurements. In this article, we consider a joint random-effects model for the correlated outcomes. A multilevel item response theory model is used for the multivariate longitudinal outcomes and a parametric accelerated failure time model is used for the failure time because of the violation of proportional hazard assumption. These two models are linked via random effects. The Bayesian inference via MCMC is implemented in 'BUGS' language. Our proposed method is evaluated by a simulation study and is applied to DATATOP study, a motivating clinical trial to determine if deprenyl slows the progression of PD. © 2013 The authors. Statistics in Medicine published by John Wiley & Sons, Ltd.

  8. Two-Locus Heterogeneity Cannot Be Distinguished from Two-Locus Epistasis on the Basis of Affected-Sib-Pair Data

    PubMed Central

    Vieland, Veronica J.; Huang, Jian

    2003-01-01

    The observation of multiple linkage signals in the course of conducting genome screens for complex disorders raises the question of whether distinct genes represent independent causes of disease (heterogeneity) or whether they interact to produce the phenotype of interest (epistasis); and there has been a corresponding interest in statistical methods for detecting and/or exploiting the distinction between these two possibilities. At the same time, researchers are increasingly relying on affected-sib-pair (ASP) data. Here, we demonstrate an apparently unrecognized fact about two-locus (2L) mode