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Sample records for large-scale genetic studies

  1. Next generation analytic tools for large scale genetic epidemiology studies of complex diseases.

    PubMed

    Mechanic, Leah E; Chen, Huann-Sheng; Amos, Christopher I; Chatterjee, Nilanjan; Cox, Nancy J; Divi, Rao L; Fan, Ruzong; Harris, Emily L; Jacobs, Kevin; Kraft, Peter; Leal, Suzanne M; McAllister, Kimberly; Moore, Jason H; Paltoo, Dina N; Province, Michael A; Ramos, Erin M; Ritchie, Marylyn D; Roeder, Kathryn; Schaid, Daniel J; Stephens, Matthew; Thomas, Duncan C; Weinberg, Clarice R; Witte, John S; Zhang, Shunpu; Zöllner, Sebastian; Feuer, Eric J; Gillanders, Elizabeth M

    2012-01-01

    Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled "Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases" on September 15-16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. © 2011 Wiley Periodicals, Inc.

  2. Next Generation Analytic Tools for Large Scale Genetic Epidemiology Studies of Complex Diseases

    PubMed Central

    Mechanic, Leah E.; Chen, Huann-Sheng; Amos, Christopher I.; Chatterjee, Nilanjan; Cox, Nancy J.; Divi, Rao L.; Fan, Ruzong; Harris, Emily L.; Jacobs, Kevin; Kraft, Peter; Leal, Suzanne M.; McAllister, Kimberly; Moore, Jason H.; Paltoo, Dina N.; Province, Michael A.; Ramos, Erin M.; Ritchie, Marylyn D.; Roeder, Kathryn; Schaid, Daniel J.; Stephens, Matthew; Thomas, Duncan C.; Weinberg, Clarice R.; Witte, John S.; Zhang, Shunpu; Zöllner, Sebastian; Feuer, Eric J.; Gillanders, Elizabeth M.

    2012-01-01

    Over the past several years, genome-wide association studies (GWAS) have succeeded in identifying hundreds of genetic markers associated with common diseases. However, most of these markers confer relatively small increments of risk and explain only a small proportion of familial clustering. To identify obstacles to future progress in genetic epidemiology research and provide recommendations to NIH for overcoming these barriers, the National Cancer Institute sponsored a workshop entitled “Next Generation Analytic Tools for Large-Scale Genetic Epidemiology Studies of Complex Diseases” on September 15–16, 2010. The goal of the workshop was to facilitate discussions on (1) statistical strategies and methods to efficiently identify genetic and environmental factors contributing to the risk of complex disease; and (2) how to develop, apply, and evaluate these strategies for the design, analysis, and interpretation of large-scale complex disease association studies in order to guide NIH in setting the future agenda in this area of research. The workshop was organized as a series of short presentations covering scientific (gene-gene and gene-environment interaction, complex phenotypes, and rare variants and next generation sequencing) and methodological (simulation modeling and computational resources and data management) topic areas. Specific needs to advance the field were identified during each session and are summarized. PMID:22147673

  3. Approaches to Investigating Complex Genetic Traits in a Large Scale Inbred Mouse Aging Study

    PubMed Central

    Sundberg, John P.; Berndt, Annerose; Sundberg, Beth A.; Silva, Kathleen A.; Kennedy, Victoria; Smith, Richard S.; Cooper, Timothy K.; Schofield, Paul N.

    2017-01-01

    Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytical tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, using histopathology, the type and diversity of spontaneous diseases aging mice develop. Eighteen inbred strains have had their genomes sequenced and many others have been partially sequenced to provide large repositories of data on genetic variation between the strains. This vast amount of genomic information can be utilized in genome-wide association studies (GWAS) to find candidate genes that are involved in the pathogenesis of spontaneous diseases. We present here, as an illustration, a GWAS of the genetic associations of age-related intestinal amyloidosis which implicates three candidate genes Tram1, Sf3b5, and Stx11. Many of the age-related mouse diseases are similar, if not identical, to human diseases and therefore the genetic discoveries have direct translational benefit. Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions. PMID:26936752

  4. Approaches to Investigating Complex Genetic Traits in a Large-Scale Inbred Mouse Aging Study.

    PubMed

    Sundberg, J P; Berndt, A; Sundberg, B A; Silva, K A; Kennedy, V; Smith, R S; Cooper, T K; Schofield, P N

    2016-03-01

    Inbred mice are a unique model system for studying aging because of the genetic homogeneity within inbred strains, the short life span of mice relative to humans, and the rich array of analytic tools that are available. A large-scale aging study was conducted on 28 inbred strains representing great genetic diversity to determine, via histopathology, the type and diversity of spontaneous diseases that aging mice develop. A total of 20 885 different diagnoses were made, with an average of 12 diagnoses per mouse in the study. Eighteen inbred strains have had their genomes sequenced, and many others have been partially sequenced to provide large repositories of data on genetic variation among the strains. This vast amount of genomic information can be utilized in genome-wide association studies to find candidate genes that are involved in the pathogenesis of spontaneous diseases. As an illustration, this article presents a genome-wide association study of the genetic associations of age-related intestinal amyloidosis, which implicated 3 candidate genes: translocating chain-associated membrane protein 1 (Tram1); splicing factor 3b, subunit 5 (Sf3b5); and syntaxin 11 (Stx11). Representative photomicrographs are available on the Mouse Tumor Biology Database and Pathbase to serve as a reference when evaluating inbred mice used in other genetic or experimental studies to rule out strain background lesions. Many of the age-related mouse diseases are similar, if not identical, to human diseases; therefore, the genetic discoveries have direct translational benefit. © The Author(s) 2016.

  5. Genetic interplay between human longevity and metabolic pathways - a large-scale eQTL study.

    PubMed

    Häsler, Robert; Venkatesh, Geetha; Tan, Qihua; Flachsbart, Friederike; Sinha, Anupam; Rosenstiel, Philip; Lieb, Wolfgang; Schreiber, Stefan; Christensen, Kaare; Christiansen, Lene; Nebel, Almut

    2017-08-01

    Human longevity is a complex phenotype influenced by genetic and environmental components. Unraveling the contribution of genetic vs. nongenetic factors to longevity is a challenging task. Here, we conducted a large-scale RNA-sequencing-based expression quantitative trait loci study (eQTL) with subsequent heritability analysis. The investigation was performed on blood samples from 244 individuals from Germany and Denmark, representing various age groups including long-lived subjects up to the age of 104 years. Our eQTL-based approach revealed for the first time that human longevity is associated with a depletion of metabolic pathways in a genotype-dependent and independent manner. Further analyses indicated that 20% of the differentially expressed genes are influenced by genetic variants in cis. The subsequent study of twins showed that the transcriptional activity of a third of the differentially regulated genes is heritable. These findings suggest that longevity-associated biological processes such as altered metabolism are, to a certain extent, also the driving force of longevity rather than just a consequence of old age. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  6. Spitting for Science: Danish High School Students Commit to a Large-Scale Self-Reported Genetic Study

    PubMed Central

    Athanasiadis, Georgios; Jørgensen, Frank G.; Cheng, Jade Y.; Kjærgaard, Peter C.; Schierup, Mikkel H.; Mailund, Thomas

    2016-01-01

    Scientific outreach delivers science to the people. But it can also deliver people to the science. In this work, we report our experience from a large-scale public engagement project promoting genomic literacy among Danish high school students with the additional benefit of collecting data for studying the genetic makeup of the Danish population. Not only did we confirm that students have a great interest in their genetic past, but we were also gratified to see that, with the right motivation, adolescents can provide high-quality data for genetic studies. PMID:27571202

  7. Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study.

    PubMed

    Khemiri, L; Kuja-Halkola, R; Larsson, H; Jayaram-Lindström, N

    2016-04-01

    Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity. Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985. The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31-57%] for males and 62% (95% CI 52-72%) for females. For impulsivity, the heritability was 33% (95% CI 30-36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23-0.58) in males and 0.20 (95% CI 0.07-0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47-117%) for males and 53% (95% CI 19-86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors. The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.

  8. A non-human primate system for large-scale genetic studies of complex traits

    PubMed Central

    Jasinska, Anna J.; Lin, Michelle K.; Service, Susan; Choi, Oi-Wa; DeYoung, Joseph; Grujic, Olivera; Kong, Sit-Yee; Jung, Yoon; Jorgensen, Mathew J.; Fairbanks, Lynn A.; Turner, Trudy; Cantor, Rita M.; Wasserscheid, Jessica; Dewar, Ken; Warren, Wesley; Wilson, Richard K.; Weinstock, George; Jentsch, J. David; Freimer, Nelson B.

    2012-01-01

    Non-human primates provide genetic model systems biologically intermediate between humans and other mammalian model organisms. Populations of Caribbean vervet monkeys (Chlorocebus aethiops sabaeus) are genetically homogeneous and large enough to permit well-powered genetic mapping studies of quantitative traits relevant to human health, including expression quantitative trait loci (eQTL). Previous transcriptome-wide investigation in an extended vervet pedigree identified 29 heritable transcripts for which levels of expression in peripheral blood correlate strongly with expression levels in the brain. Quantitative trait linkage analysis using 261 microsatellite markers identified significant (n = 8) and suggestive (n = 4) linkages for 12 of these transcripts, including both cis- and trans-eQTL. Seven transcripts, located on different chromosomes, showed maximum linkage to markers in a single region of vervet chromosome 9; this observation suggests the possibility of a master trans-regulator locus in this region. For one cis-eQTL (at B3GALTL, beta-1,3-glucosyltransferase), we conducted follow-up single nucleotide polymorphism genotyping and fine-scale association analysis in a sample of unrelated Caribbean vervets, localizing this eQTL to a region of <200 kb. These results suggest the value of pedigree and population samples of the Caribbean vervet for linkage and association mapping studies of quantitative traits. The imminent whole genome sequencing of many of these vervet samples will enhance the power of such investigations by providing a comprehensive catalog of genetic variation. PMID:22556363

  9. A Large-scale genetic association study of esophageal adenocarcinoma risk

    PubMed Central

    Liu, Chen-yu; Wu, Michael C.; Chen, Feng; Ter-Minassian, Monica; Asomaning, Kofi; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Heist, Rebecca S.; Kulke, Matthew H.; Lin, Xihong; Liu, Geoffrey; Christiani, David C.

    2010-01-01

    The incidence of esophageal adenocarcinoma (EA) has been increasing rapidly, particularly among white males, over the past few decades in the USA. However, the etiology of EA and the striking male predominance is not fully explained by known risk factors. To identify susceptible genes for EA risk, we conducted a pathway-based candidate gene association study on 335 Caucasian EA cases and 319 Caucasian controls. A total of 1330 single-nucleotide polymorphisms (SNPs) selected from 354 genes were analyzed using an Illumina GoldenGate assay. The genotyped common SNPs include missense and exonic SNPs, SNPs within untranslated regions and 2 kb 5′ of the gene, and tagSNPs for genes with little functional information available. Logistic regression adjusted for potential confounders was used to assess the genetic effect of each SNP on EA risk. We also tested gene–gender interactions using the likelihood ratio tests. We found that the genetic variants in the apoptosis pathway were significantly associated with EA risk after correcting for multiple comparisons. SNPs of rs3127075 in Caspase-7 (CASP7) and rs4661636 in Caspase-9 (CASP9) genes that play a critical role in apoptosis were found to be associated with an increased risk of EA. A protective effect of SNP rs572483 in the progesterone receptor (PGR) gene was observed among women carrying the variant G allele [adjusted odds ratio (OR) = 0.19; 95% confidence interval (CI) = 0.08–0.46] but was not observed among men (adjusted OR = 1.38; 95% CI = 0.95–2.00). In conclusion, this study suggests that the genetic variants of CASP7 and CASP9 in the apoptosis pathway may be important predictive markers for EA susceptibility and that PGR in the sex hormone signaling pathway may be associated with the gender differences in EA risk. PMID:20453000

  10. A Large-scale genetic association study of esophageal adenocarcinoma risk.

    PubMed

    Liu, Chen-Yu; Wu, Michael C; Chen, Feng; Ter-Minassian, Monica; Asomaning, Kofi; Zhai, Rihong; Wang, Zhaoxi; Su, Li; Heist, Rebecca S; Kulke, Matthew H; Lin, Xihong; Liu, Geoffrey; Christiani, David C

    2010-07-01

    The incidence of esophageal adenocarcinoma (EA) has been increasing rapidly, particularly among white males, over the past few decades in the USA. However, the etiology of EA and the striking male predominance is not fully explained by known risk factors. To identify susceptible genes for EA risk, we conducted a pathway-based candidate gene association study on 335 Caucasian EA cases and 319 Caucasian controls. A total of 1330 single-nucleotide polymorphisms (SNPs) selected from 354 genes were analyzed using an Illumina GoldenGate assay. The genotyped common SNPs include missense and exonic SNPs, SNPs within untranslated regions and 2 kb 5' of the gene, and tagSNPs for genes with little functional information available. Logistic regression adjusted for potential confounders was used to assess the genetic effect of each SNP on EA risk. We also tested gene-gender interactions using the likelihood ratio tests. We found that the genetic variants in the apoptosis pathway were significantly associated with EA risk after correcting for multiple comparisons. SNPs of rs3127075 in Caspase-7 (CASP7) and rs4661636 in Caspase-9 (CASP9) genes that play a critical role in apoptosis were found to be associated with an increased risk of EA. A protective effect of SNP rs572483 in the progesterone receptor (PGR) gene was observed among women carrying the variant G allele [adjusted odds ratio (OR) = 0.19; 95% confidence interval (CI) = 0.08-0.46] but was not observed among men (adjusted OR = 1.38; 95% CI = 0.95-2.00). In conclusion, this study suggests that the genetic variants of CASP7 and CASP9 in the apoptosis pathway may be important predictive markers for EA susceptibility and that PGR in the sex hormone signaling pathway may be associated with the gender differences in EA risk.

  11. Assessing the Probability that a Finding Is Genuine for Large-Scale Genetic Association Studies.

    PubMed

    Kuo, Chia-Ling; Vsevolozhskaya, Olga A; Zaykin, Dmitri V

    2015-01-01

    Genetic association studies routinely involve massive numbers of statistical tests accompanied by P-values. Whole genome sequencing technologies increased the potential number of tested variants to tens of millions. The more tests are performed, the smaller P-value is required to be deemed significant. However, a small P-value is not equivalent to small chances of a spurious finding and significance thresholds may fail to serve as efficient filters against false results. While the Bayesian approach can provide a direct assessment of the probability that a finding is spurious, its adoption in association studies has been slow, due in part to the ubiquity of P-values and the automated way they are, as a rule, produced by software packages. Attempts to design simple ways to convert an association P-value into the probability that a finding is spurious have been met with difficulties. The False Positive Report Probability (FPRP) method has gained increasing popularity. However, FPRP is not designed to estimate the probability for a particular finding, because it is defined for an entire region of hypothetical findings with P-values at least as small as the one observed for that finding. Here we propose a method that lets researchers extract probability that a finding is spurious directly from a P-value. Considering the counterpart of that probability, we term this method POFIG: the Probability that a Finding is Genuine. Our approach shares FPRP's simplicity, but gives a valid probability that a finding is spurious given a P-value. In addition to straightforward interpretation, POFIG has desirable statistical properties. The POFIG average across a set of tentative associations provides an estimated proportion of false discoveries in that set. POFIGs are easily combined across studies and are immune to multiple testing and selection bias. We illustrate an application of POFIG method via analysis of GWAS associations with Crohn's disease.

  12. Assessing the Probability that a Finding Is Genuine for Large-Scale Genetic Association Studies

    PubMed Central

    Kuo, Chia-Ling; Vsevolozhskaya, Olga A.; Zaykin, Dmitri V.

    2015-01-01

    Genetic association studies routinely involve massive numbers of statistical tests accompanied by P-values. Whole genome sequencing technologies increased the potential number of tested variants to tens of millions. The more tests are performed, the smaller P-value is required to be deemed significant. However, a small P-value is not equivalent to small chances of a spurious finding and significance thresholds may fail to serve as efficient filters against false results. While the Bayesian approach can provide a direct assessment of the probability that a finding is spurious, its adoption in association studies has been slow, due in part to the ubiquity of P-values and the automated way they are, as a rule, produced by software packages. Attempts to design simple ways to convert an association P-value into the probability that a finding is spurious have been met with difficulties. The False Positive Report Probability (FPRP) method has gained increasing popularity. However, FPRP is not designed to estimate the probability for a particular finding, because it is defined for an entire region of hypothetical findings with P-values at least as small as the one observed for that finding. Here we propose a method that lets researchers extract probability that a finding is spurious directly from a P-value. Considering the counterpart of that probability, we term this method POFIG: the Probability that a Finding is Genuine. Our approach shares FPRP's simplicity, but gives a valid probability that a finding is spurious given a P-value. In addition to straightforward interpretation, POFIG has desirable statistical properties. The POFIG average across a set of tentative associations provides an estimated proportion of false discoveries in that set. POFIGs are easily combined across studies and are immune to multiple testing and selection bias. We illustrate an application of POFIG method via analysis of GWAS associations with Crohn's disease. PMID:25955023

  13. An assessment of the Irish population for large-scale genetic mapping studies involving epilepsy and other complex diseases.

    PubMed

    O'Dushlaine, Colm T; Dolan, Ciara; Weale, Michael E; Stanton, Alice; Croke, David T; Kalviainen, Reetta; Eriksson, Kai; Kantanen, Anne-Mari; Gibson, Rachel A; Hosford, David; Sisodiya, Sanjay M; Gill, Michael; Corvin, Aiden P; Morris, Derek W; Delanty, Norman; Cavalleri, Gianpiero L

    2008-02-01

    The recent completion of the International HapMap Project has rapidly advanced our understanding of linkage disequilibrium (LD) in the human genome. Today, tagging SNPs (tSNPs) can be quickly and easily selected and consequently HapMap data are regularly applied to both small- and large-scale genetic mapping studies. However, to correctly interpret the application of HapMap-derived tSNPs in a genetic mapping study, an understanding of how well HapMap data represents LD in the study population is critical. The Irish population had not previously been characterised in this way. Here, we do so using a set of 4424 SNPs selected from 279 candidate genes for epilepsy genotyped across 1118 healthy individuals from the Irish, British, Finnish and Australian populations. By considering the Irish population alongside surrounding European populations, our results confirm that the HapMap European-derived population accurately estimates patterning of LD in European descent populations. The Irish population appears notably well matched to the European HapMap population, and is markedly similar to the neighbouring British population. Although we were unable to detect significant substructure within the Irish population (a favourable result for genetic mapping), methods for controlling stratification should always be incorporated. This analysis therefore confirms that the genetic architecture of the Irish population is well suited to the study of complex traits and that tSNPs selected using the HapMap data can be confidently applied to the Irish population.

  14. 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

  15. Large-scale candidate gene study to identify genetic risk factors predictive of paliperidone treatment response in patients with schizophrenia.

    PubMed

    Wang, Dai; Fu, Dong-Jing; Wu, Xiaodong; Shapiro, Alice; Favis, Reyna; Savitz, Adam; Chung, Hedy; Alphs, Larry; Gopal, Srihari; Haas, Magali; Cohen, Nadine; Li, Qingqin

    2015-04-01

    Clinical response to antipsychotic medications can vary markedly in patients with schizophrenia. Identifying genetic variants associated with treatment response could help optimize patient care and outcome. To this end, we carried out a large-scale candidate gene study to identify genetic risk factors predictive of paliperidone efficacy. A central nervous system custom chip containing single nucleotide polymorphisms from 1204 candidate genes was utilized to genotype a discovery cohort of 684 schizophrenia patients from four clinical studies of paliperidone extended-release and paliperidone palmitate. Variants predictive of paliperidone efficacy were identified and further tested in four independent replication cohorts of schizophrenic patients (N=2856). We identified an SNP in ERBB4 that may contribute toward differential treatment response to paliperidone. The association trended in the same direction as the discovery cohort in two of the four replication cohorts, but ultimately did not survive multiple testing corrections. The association was not replicated in the other two independent cohorts. We also report several SNPs in well-known schizophrenia candidate genes that show suggestive associations with paliperidone efficacy. These preliminary findings suggest that genetic variation in the ERBB4 gene may differentially affect treatment response to paliperidone in individuals with schizophrenia. They implicate the neuregulin 1 (NRG1)-ErbB4 pathway for modulating antipsychotic response. However, these findings were not robustly reproduced in replication cohorts.

  16. Combining semi-automated image analysis techniques with machine learning algorithms to accelerate large-scale genetic studies.

    PubMed

    Atkinson, Jonathan A; Lobet, Guillaume; Noll, Manuel; Meyer, Patrick E; Griffiths, Marcus; Wells, Darren M

    2017-10-01

    Genetic analyses of plant root systems require large datasets of extracted architectural traits. To quantify such traits from images of root systems, researchers often have to choose between automated tools (that are prone to error and extract only a limited number of architectural traits) or semi-automated ones (that are highly time consuming). We trained a Random Forest algorithm to infer architectural traits from automatically extracted image descriptors. The training was performed on a subset of the dataset, then applied to its entirety. This strategy allowed us to (i) decrease the image analysis time by 73% and (ii) extract meaningful architectural traits based on image descriptors. We also show that these traits are sufficient to identify the quantitative trait loci that had previously been discovered using a semi-automated method. We have shown that combining semi-automated image analysis with machine learning algorithms has the power to increase the throughput of large-scale root studies. We expect that such an approach will enable the quantification of more complex root systems for genetic studies. We also believe that our approach could be extended to other areas of plant phenotyping. © The Authors 2017. Published by Oxford University Press.

  17. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof-of-concept and roadmap for future studies

    PubMed Central

    Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Shugart, Yin Yao; Ho, Yvonne YW; Martin, Nicholas G; Wright, Margaret J

    2016-01-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between schizophrenia cases and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. The current study provides proof-of-concept (albeit based on a limited set of structural brain measures), and defines a roadmap for future studies investigating the genetic covariance between structural/functional brain phenotypes and risk for psychiatric disorders. PMID:26854805

  18. Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk

    PubMed Central

    Zhang, Ben; Jia, Wei-Hua; Matsuda, Koichi; Kweon, Sun-Seog; Matsuo, Keitaro; Xiang, Yong-Bing; Shin, Aesun; Jee, Sun Ha; Kim, Dong-Hyun; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Li, Chun; Li, Bingshan; Guo, Yan; Ren, Zefang; Ji, Bu-Tian; Pan, Zhi-Zhong; Takahashi, Atsushi; Shin, Min-Ho; Matsuda, Fumihiko; Gao, Yu-Tang; Oh, Jae Hwan; Kim, Soriul; Ahn, Yoon-Ok; Chan, Andrew T; Chang-Claude, Jenny; Slattery, Martha L.; Gruber, Stephen B.; Schumacher, Fredrick R.; Stenzel, Stephanie L.; Casey, Graham; Kim, Hyeong-Rok; Jeong, Jin-Young; Park, Ji Won; Li, Hong-Lan; Hosono, Satoyo; Cho, Sang-Hee; Kubo, Michiaki; Shu, Xiao-Ou; Zeng, Yi-Xin; Zheng, Wei

    2014-01-01

    Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted the largest genome-wide association study in East Asians with 14,963 CRC cases and 31,945 controls and identified six new loci associated with CRC risk (P = 3.42 × 10−8 to 9.22 × 10−21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcription regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9) and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC loci. Our study provides insights into the genetic basis of CRC and suggests new biological pathways. PMID:24836286

  19. Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.

    PubMed

    Zhang, Ben; Jia, Wei-Hua; Matsuda, Koichi; Kweon, Sun-Seog; Matsuo, Keitaro; Xiang, Yong-Bing; Shin, Aesun; Jee, Sun Ha; Kim, Dong-Hyun; Cai, Qiuyin; Long, Jirong; Shi, Jiajun; Wen, Wanqing; Yang, Gong; Zhang, Yanfeng; Li, Chun; Li, Bingshan; Guo, Yan; Ren, Zefang; Ji, Bu-Tian; Pan, Zhi-Zhong; Takahashi, Atsushi; Shin, Min-Ho; Matsuda, Fumihiko; Gao, Yu-Tang; Oh, Jae Hwan; Kim, Soriul; Ahn, Yoon-Ok; Chan, Andrew T; Chang-Claude, Jenny; Slattery, Martha L; Gruber, Stephen B; Schumacher, Fredrick R; Stenzel, Stephanie L; Casey, Graham; Kim, Hyeong-Rok; Jeong, Jin-Young; Park, Ji Won; Li, Hong-Lan; Hosono, Satoyo; Cho, Sang-Hee; Kubo, Michiaki; Shu, Xiao-Ou; Zeng, Yi-Xin; Zheng, Wei

    2014-06-01

    Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10(-8) to 9.22 × 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.

  20. Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study.

    PubMed

    Martins, M; Williams, A H; Comeau, M; Marion, M; Ziegler, J T; Freedman, B I; Merrill, J T; Glenn, S B; Kelly, J A; Sivils, K M; James, J A; Guthridge, J M; Alarcón-Riquelme, M E; Bae, S-C; Kim, J-H; Kim, D; Anaya, J-M; Boackle, S A; Criswell, L A; Kimberly, R P; Alarcón, G S; Brown, E E; Vilá, L M; Petri, M A; Ramsey-Goldman, R; Niewold, T B; Tsao, B P; Gilkeson, G S; Kamen, D L; Jacob, C O; Stevens, A M; Gaffney, P M; Harley, J B; Langefeld, C D; Fesel, C

    2015-03-01

    A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

  1. New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

    PubMed

    De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

    2002-06-01

    Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

  2. Large-Scale PV Integration Study

    SciTech Connect

    Lu, Shuai; Etingov, Pavel V.; Diao, Ruisheng; Ma, Jian; Samaan, Nader A.; Makarov, Yuri V.; Guo, Xinxin; Hafen, Ryan P.; Jin, Chunlian; Kirkham, Harold; Shlatz, Eugene; Frantzis, Lisa; McClive, Timothy; Karlson, Gregory; Acharya, Dhruv; Ellis, Abraham; Stein, Joshua; Hansen, Clifford; Chadliev, Vladimir; Smart, Michael; Salgo, Richard; Sorensen, Rahn; Allen, Barbara; Idelchik, Boris

    2011-07-29

    This research effort evaluates the impact of large-scale photovoltaic (PV) and distributed generation (DG) output on NV Energy’s electric grid system in southern Nevada. It analyzes the ability of NV Energy’s generation to accommodate increasing amounts of utility-scale PV and DG, and the resulting cost of integrating variable renewable resources. The study was jointly funded by the United States Department of Energy and NV Energy, and conducted by a project team comprised of industry experts and research scientists from Navigant Consulting Inc., Sandia National Laboratories, Pacific Northwest National Laboratory and NV Energy.

  3. Genetic variants determining survival and fertility in an adverse African environment: a population-based large-scale candidate gene association study

    PubMed Central

    Koopman, Jacob J.E.; Pijpe, Jeroen; Böhringer, Stefan; van Bodegom, David; Eriksson, Ulrika K.; Sanchez-Faddeev, Hernando; Ziem, Juventus B.; Zwaan, Bas; Slagboom, P. Eline; de Knijff, Peter; Westendorp, Rudi G.J.

    2016-01-01

    Human survival probability and fertility decline strongly with age. These life history traits have been shaped by evolution. However, research has failed to uncover a consistent genetic determination of variation in survival and fertility. As an explanation, such genetic determinants have been selected in adverse environments, in which humans have lived during most of their history, but are almost exclusively studied in populations in modern affluent environments. Here, we present a large-scale candidate gene association study in a rural African population living in an adverse environment. In 4387 individuals, we studied 4052 SNPs in 148 genes that have previously been identified as possible determinants of survival or fertility in animals or humans. We studied their associations with survival comparing newborns, middle-age adults, and old individuals. In women, we assessed their associations with reported and observed numbers of children. We found no statistically significant associations of these SNPs with survival between the three age groups nor with women's reported and observed fertility. Population stratification was unlikely to explain these results. Apart from a lack of power, we hypothesise that genetic heterogeneity of complex phenotypes and gene-environment interactions prevent the identification of genetic variants explaining variation in survival and fertility in humans. PMID:27356285

  4. A large-scale genetic association study to evaluate the contribution of Omi/HtrA2 (PARK13) to Parkinson's disease.

    PubMed

    Krüger, Rejko; Sharma, Manu; Riess, Olaf; Gasser, Thomas; Van Broeckhoven, Christine; Theuns, Jessie; Aasly, Jan; Annesi, Grazia; Bentivoglio, Anna Rita; Brice, Alexis; Djarmati, Ana; Elbaz, Alexis; Farrer, Matthew; Ferrarese, Carlo; Gibson, J Mark; Hadjigeorgiou, Georgios M; Hattori, Nobutaka; Ioannidis, John P A; Jasinska-Myga, Barbara; Klein, Christine; Lambert, Jean-Charles; Lesage, Suzanne; Lin, Juei-Jueng; Lynch, Timothy; Mellick, George D; de Nigris, Francesa; Opala, Grzegorz; Prigione, Alessandro; Quattrone, Aldo; Ross, Owen A; Satake, Wataru; Silburn, Peter A; Tan, Eng King; Toda, Tatsushi; Tomiyama, Hiroyuki; Wirdefeldt, Karin; Wszolek, Zbigniew; Xiromerisiou, Georgia; Maraganore, Demetrius M

    2011-03-01

    High-profile studies have provided conflicting results regarding the involvement of the Omi/HtrA2 gene in Parkinson's disease (PD) susceptibility. Therefore, we performed a large-scale analysis of the association of common Omi/HtrA2 variants in the Genetic Epidemiology of Parkinson's disease (GEO-PD) consortium. GEO-PD sites provided clinical and genetic data including affection status, gender, ethnicity, age at study, age at examination (all subjects); age at onset and family history of PD (patients). Genotyping was performed for the five most informative SNPs spanning the Omi/HtrA2 gene in approximately 2-3 kb intervals (rs10779958, rs2231250, rs72470544, rs1183739, rs2241028). Fixed as well as random effect models were used to provide summary risk estimates of Omi/HtrA2 variants. The 20 GEO-PD sites provided data for 6378 cases and 8880 controls. No overall significant associations for the five Omi/HtrA2 SNPs and PD were observed using either fixed effect or random effect models. The summary odds ratios ranged between 0.98 and 1.08 and the estimates of between-study heterogeneity were not large (non-significant Q statistics for all 5 SNPs; I(2) estimates 0-28%). Trends for association were seen for participants of Scandinavian descent for rs2241028 (OR 1.41, p=0.04) and for rs1183739 for age at examination (cut-off 65 years; OR 1.17, p=0.02), but these would not be significant after adjusting for multiple comparisons and their Bayes factors were only modest. This largest association study performed to define the role of any gene in the pathogenesis of Parkinson's disease revealed no overall strong association of Omi/HtrA2 variants with PD in populations worldwide.

  5. Large scale study of tooth enamel

    SciTech Connect

    Bodart, F.; Deconninck, G.; Martin, M.Th.

    1981-04-01

    Human tooth enamel contains traces of foreign elements. The presence of these elements is related to the history and the environment of the human body and can be considered as the signature of perturbations which occur during the growth of a tooth. A map of the distribution of these traces on a large scale sample of the population will constitute a reference for further investigations of environmental effects. One hundred eighty samples of teeth were first analysed using PIXE, backscattering and nuclear reaction techniques. The results were analysed using statistical methods. Correlations between O, F, Na, P, Ca, Mn, Fe, Cu, Zn, Pb and Sr were observed and cluster analysis was in progress. The techniques described in the present work have been developed in order to establish a method for the exploration of very large samples of the Belgian population.

  6. Robust regression for large-scale neuroimaging studies.

    PubMed

    Fritsch, Virgile; Da Mota, Benoit; Loth, Eva; Varoquaux, Gaël; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Brühl, Rüdiger; Butzek, Brigitte; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Lemaitre, Hervé; Mann, Karl; Nees, Frauke; Paus, Tomas; Schad, Daniel J; Schümann, Gunter; Frouin, Vincent; Poline, Jean-Baptiste; Thirion, Bertrand

    2015-05-01

    Multi-subject datasets used in neuroimaging group studies have a complex structure, as they exhibit non-stationary statistical properties across regions and display various artifacts. While studies with small sample sizes can rarely be shown to deviate from standard hypotheses (such as the normality of the residuals) due to the poor sensitivity of normality tests with low degrees of freedom, large-scale studies (e.g. >100 subjects) exhibit more obvious deviations from these hypotheses and call for more refined models for statistical inference. Here, we demonstrate the benefits of robust regression as a tool for analyzing large neuroimaging cohorts. First, we use an analytic test based on robust parameter estimates; based on simulations, this procedure is shown to provide an accurate statistical control without resorting to permutations. Second, we show that robust regression yields more detections than standard algorithms using as an example an imaging genetics study with 392 subjects. Third, we show that robust regression can avoid false positives in a large-scale analysis of brain-behavior relationships with over 1500 subjects. Finally we embed robust regression in the Randomized Parcellation Based Inference (RPBI) method and demonstrate that this combination further improves the sensitivity of tests carried out across the whole brain. Altogether, our results show that robust procedures provide important advantages in large-scale neuroimaging group studies. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Genetic invalidation of Lp-PLA2 as a therapeutic target: Large-scale study of five functional Lp-PLA2-lowering alleles.

    PubMed

    Gregson, John M; Freitag, Daniel F; Surendran, Praveen; Stitziel, Nathan O; Chowdhury, Rajiv; Burgess, Stephen; Kaptoge, Stephen; Gao, Pei; Staley, James R; Willeit, Peter; Nielsen, Sune F; Caslake, Muriel; Trompet, Stella; Polfus, Linda M; Kuulasmaa, Kari; Kontto, Jukka; Perola, Markus; Blankenberg, Stefan; Veronesi, Giovanni; Gianfagna, Francesco; Männistö, Satu; Kimura, Akinori; Lin, Honghuang; Reilly, Dermot F; Gorski, Mathias; Mijatovic, Vladan; Munroe, Patricia B; Ehret, Georg B; Thompson, Alex; Uria-Nickelsen, Maria; Malarstig, Anders; Dehghan, Abbas; Vogt, Thomas F; Sasaoka, Taishi; Takeuchi, Fumihiko; Kato, Norihiro; Yamada, Yoshiji; Kee, Frank; Müller-Nurasyid, Martina; Ferrières, Jean; Arveiler, Dominique; Amouyel, Philippe; Salomaa, Veikko; Boerwinkle, Eric; Thompson, Simon G; Ford, Ian; Wouter Jukema, J; Sattar, Naveed; Packard, Chris J; Shafi Majumder, Abdulla Al; Alam, Dewan S; Deloukas, Panos; Schunkert, Heribert; Samani, Nilesh J; Kathiresan, Sekar; Nordestgaard, Børge G; Saleheen, Danish; Howson, Joanna Mm; Di Angelantonio, Emanuele; Butterworth, Adam S; Danesh, John

    2017-03-01

    Aims Darapladib, a potent inhibitor of lipoprotein-associated phospholipase A2 (Lp-PLA2), has not reduced risk of cardiovascular disease outcomes in recent randomized trials. We aimed to test whether Lp-PLA2 enzyme activity is causally relevant to coronary heart disease. Methods In 72,657 patients with coronary heart disease and 110,218 controls in 23 epidemiological studies, we genotyped five functional variants: four rare loss-of-function mutations (c.109+2T > C (rs142974898), Arg82His (rs144983904), Val279Phe (rs76863441), Gln287Ter (rs140020965)) and one common modest-impact variant (Val379Ala (rs1051931)) in PLA2G7, the gene encoding Lp-PLA2. We supplemented de-novo genotyping with information on a further 45,823 coronary heart disease patients and 88,680 controls in publicly available databases and other previous studies. We conducted a systematic review of randomized trials to compare effects of darapladib treatment on soluble Lp-PLA2 activity, conventional cardiovascular risk factors, and coronary heart disease risk with corresponding effects of Lp-PLA2-lowering alleles. Results Lp-PLA2 activity was decreased by 64% ( p = 2.4 × 10(-25)) with carriage of any of the four loss-of-function variants, by 45% ( p < 10(-300)) for every allele inherited at Val279Phe, and by 2.7% ( p = 1.9 × 10(-12)) for every allele inherited at Val379Ala. Darapladib 160 mg once-daily reduced Lp-PLA2 activity by 65% ( p < 10(-300)). Causal risk ratios for coronary heart disease per 65% lower Lp-PLA2 activity were: 0.95 (0.88-1.03) with Val279Phe; 0.92 (0.74-1.16) with carriage of any loss-of-function variant; 1.01 (0.68-1.51) with Val379Ala; and 0.95 (0.89-1.02) with darapladib treatment. Conclusions In a large-scale human genetic study, none of a series of Lp-PLA2-lowering alleles was related to coronary heart disease risk, suggesting that Lp-PLA2 is unlikely to be a causal risk factor.

  8. Large-scale studies of marked birds in North America

    USGS Publications Warehouse

    Tautin, J.; Metras, L.; Smith, G.

    1999-01-01

    The first large-scale, co-operative, studies of marked birds in North America were attempted in the 1950s. Operation Recovery, which linked numerous ringing stations along the east coast in a study of autumn migration of passerines, and the Preseason Duck Ringing Programme in prairie states and provinces, conclusively demonstrated the feasibility of large-scale projects. The subsequent development of powerful analytical models and computing capabilities expanded the quantitative potential for further large-scale projects. Monitoring Avian Productivity and Survivorship, and Adaptive Harvest Management are current examples of truly large-scale programmes. Their exemplary success and the availability of versatile analytical tools are driving changes in the North American bird ringing programme. Both the US and Canadian ringing offices are modifying operations to collect more and better data to facilitate large-scale studies and promote a more project-oriented ringing programme. New large-scale programmes such as the Cornell Nest Box Network are on the horizon.

  9. A study of MLFMA for large-scale scattering problems

    NASA Astrophysics Data System (ADS)

    Hastriter, Michael Larkin

    This research is centered in computational electromagnetics with a focus on solving large-scale problems accurately in a timely fashion using first principle physics. Error control of the translation operator in 3-D is shown. A parallel implementation of the multilevel fast multipole algorithm (MLFMA) was studied as far as parallel efficiency and scaling. The large-scale scattering program (LSSP), based on the ScaleME library, was used to solve ultra-large-scale problems including a 200lambda sphere with 20 million unknowns. As these large-scale problems were solved, techniques were developed to accurately estimate the memory requirements. Careful memory management is needed in order to solve these massive problems. The study of MLFMA in large-scale problems revealed significant errors that stemmed from inconsistencies in constants used by different parts of the algorithm. These were fixed to produce the most accurate data possible for large-scale surface scattering problems. Data was calculated on a missile-like target using both high frequency methods and MLFMA. This data was compared and analyzed to determine possible strategies to increase data acquisition speed and accuracy through multiple computation method hybridization.

  10. The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative Efforts on the Precipice of Discovery

    PubMed Central

    Georgitsi, Marianthi; Willsey, A. Jeremy; Mathews, Carol A.; State, Matthew; Scharf, Jeremiah M.; Paschou, Peristera

    2016-01-01

    Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive. However, multiple resources and large-scale projects are coming together, launching a new era in the field and bringing us on the verge of discovery. The large-scale efforts outlined in this report are complementary and represent a range of different approaches to the study of disorders with complex inheritance. The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has focused on large families, parent-proband trios and cases for large case-control designs such as genomewide association studies (GWAS), copy number variation (CNV) scans, and exome/genome sequencing. TIC Genetics targets rare, large effect size mutations in simplex trios, and multigenerational families. The European Multicentre Tics in Children Study (EMTICS) seeks to elucidate gene-environment interactions including the involvement of infection and immune mechanisms in TS etiology. Finally, TS-EUROTRAIN, a Marie Curie Initial Training Network, aims to act as a platform to unify large-scale projects in the field and to educate the next generation of experts. Importantly, these complementary large-scale efforts are joining forces to uncover the full range of genetic variation and environmental risk factors for TS, holding great promise for identifying definitive TS susceptibility genes and shedding light into the complex pathophysiology of this disorder. PMID:27536211

  11. Acoustic Studies of the Large Scale Ocean Circulation

    NASA Technical Reports Server (NTRS)

    Menemenlis, Dimitris

    1999-01-01

    Detailed knowledge of ocean circulation and its transport properties is prerequisite to an understanding of the earth's climate and of important biological and chemical cycles. Results from two recent experiments, THETIS-2 in the Western Mediterranean and ATOC in the North Pacific, illustrate the use of ocean acoustic tomography for studies of the large scale circulation. The attraction of acoustic tomography is its ability to sample and average the large-scale oceanic thermal structure, synoptically, along several sections, and at regular intervals. In both studies, the acoustic data are compared to, and then combined with, general circulation models, meteorological analyses, satellite altimetry, and direct measurements from ships. Both studies provide complete regional descriptions of the time-evolving, three-dimensional, large scale circulation, albeit with large uncertainties. The studies raise serious issues about existing ocean observing capability and provide guidelines for future efforts.

  12. Transgenic dairy cattle: genetic engineering on a large scale.

    PubMed

    Wall, R J; Kerr, D E; Bondioli, K R

    1997-09-01

    Amid the explosion of fundamental knowledge generated from transgenic animal models, a small group of scientists has been producing transgenic livestock with goals of improving animal production efficiency and generating new products. The ability to modify mammary-specific genes provides an opportunity to pursue several distinctly different avenues of research. The objective of the emerging gene "pharming" industry is to produce pharmaceuticals for treating human diseases. It is argued that mammary glands are an ideal site for producing complex bioactive proteins that can be cost effectively harvested and purified. Consequently, during the past decade, approximately a dozen companies have been created to capture the US market for pharmaceuticals produced from transgenic bioreactors estimated at $3 billion annually. Several products produced in this way are now in human clinical trials. Another research direction, which has been widely discussed but has received less attention in the laboratory, is genetic engineering of the bovine mammary gland to alter the composition of milk destined for human consumption. Proposals include increasing or altering endogenous proteins, decreasing fat, and altering milk composition to resemble that of human milk. Initial studies using transgenic mice to investigate the feasibility of enhancing manufacturing properties of milk have been encouraging. The potential profitability of gene "pharming" seems clear, as do the benefits of transgenic cows producing milk that has been optimized for food products. To take full advantage of enhanced milk, it may be desirable to restructure the method by which dairy producers are compensated. However, the cost of producing functional transgenic cattle will remain a severe limitation to realizing the potential of transgenic cattle until inefficiencies of transgenic technology are overcome. These inefficiencies include low rates of gene integration, poor embryo survival, and unpredictable transgene

  13. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

    PubMed

    Winkler, Thomas W; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B; Ferreira, Teresa; Heard-Costa, Nancy L; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M; Jansen, Rick; Westra, Harm-Jan; White, Charles C; Absher, Devin; Ahluwalia, Tarunveer S; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L; de Craen, Anton J M; Bis, Joshua C; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W K; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E; Jackson, Anne U; Jacobs, Kevin B; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E; Lahti, Jari; Mateo Leach, Irene; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A F; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L; Montasser, May E; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W; Renström, Frida; Rizzi, Federica; Rose, Lynda M; Ryan, Kathy A; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L; Wang, Sophie R; Wang, Zhaoming; Wild, Sarah H; Willenborg, Christina; Wilson, James F; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A; Bakker, Stephan J L; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L; Boyd, Heather A; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S; Claudi-Boehm, Simone; Cole, John; Collins, Francis S; de Geus, Eco J C; de Groot, Lisette C P G M; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G; Friedrich, Nele; Gejman, Pablo V; Gigante, Bruna; Glorioso, Nicola; Go, Alan S; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C; Hansen, Torben; Harris, Tamara B; Hartman, Catharina A; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T; Heath, Andrew C; Henders, Anjali K; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L; Hutri-Kähönen, Nina; Hysi, Pirro G; Illig, Thomas; De Jager, Philip L; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K; McArdle, Wendy L; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W; Morris, Andrew P; Narisu, Narisu; Nelis, Mari; Ong, Ken K; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M; Rice, Treva K; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R; Sarzynski, Mark A; Scholtens, Salome; Scott, Robert A; Scott, William R; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P Eline; Smit, Jan H; Sparsø, Thomas H; Stirrups, Kathleen; Stolk, Ronald P; Stringham, Heather M; Swertz, Morris A; Swift, Amy J; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M; Waldenberger, Melanie; Walker, Ryan W; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F; Zillikens, M Carola; van Dijk, Suzanne C; van Schoor, Natasja M; Asselbergs, Folkert W; de Bakker, Paul I W; Beckmann, Jacques S; Beilby, John; Bennett, David A; Bergman, Richard N; Bergmann, Sven; Böger, Carsten A; Boehm, Bernhard O; Boerwinkle, Eric; Boomsma, Dorret I; Bornstein, Stefan R; Bottinger, Erwin P; Bouchard, Claude; Chambers, John C; Chanock, Stephen J; Chasman, Daniel I; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G; Evans, Denis A; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W; Froguel, Philippe; Gansevoort, Ron T; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V; Hveem, Kristian; James, Alan L; Jordan, Joanne M; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A L M; Kivimaki, Mika; Knekt, Paul B; Koistinen, Heikki A; Kooner, Jaspal S; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D; Moll, Frans L; Murray, Jeffrey C; Musk, Arthur W; Nieminen, Markku S; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J; Oostra, Ben A; Palmer, Lyle J; Pankow, James S; Pasterkamp, Gerard; Pedersen, Nancy L; Pedersen, Oluf; Penninx, Brenda W; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P; Psaty, Bruce M; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M; Rioux, John D; Rivadeneira, Fernando; Rotter, Jerome I; Rudan, Igor; den Ruijter, Hester M; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E H; Shuldiner, Alan R; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I A; Spector, Tim D; Staessen, Jan A; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G; Uusitupa, Matti; Verbeek, André L M; Vermeulen, Sita H; Viikari, Jorma S; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J; Cupples, L Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E; Rao, D C; Abecasis, Goncalo R; Assimes, Themistocles L; Barroso, Inês; Berndt, Sonja I; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S; Groop, Leif C; Hunter, David J; Ingelsson, Erik; Kaplan, Robert C; McCarthy, Mark I; Mohlke, Karen L; O'Connell, Jeffrey R; Schlessinger, David; Strachan, David P; Stefansson, Kari; van Duijn, Cornelia M; Hirschhorn, Joel N; Lindgren, Cecilia M; Heid, Iris M; North, Kari E; Borecki, Ingrid B; Kutalik, Zoltán; Loos, Ruth J F

    2015-10-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

  14. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

    PubMed Central

    Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove; Kilpeläinen, Tuomas O.; Lu, Yingchang; Mägi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rüeger, Sina; Teumer, Alexander; Ehret, Georg B.; Ferreira, Teresa; Heard-Costa, Nancy L.; Karjalainen, Juha; Lagou, Vasiliki; Mahajan, Anubha; Neinast, Michael D.; Prokopenko, Inga; Simino, Jeannette; Teslovich, Tanya M.; Jansen, Rick; Westra, Harm-Jan; White, Charles C.; Absher, Devin; Ahluwalia, Tarunveer S.; Ahmad, Shafqat; Albrecht, Eva; Alves, Alexessander Couto; Bragg-Gresham, Jennifer L.; de Craen, Anton J. M.; Bis, Joshua C.; Bonnefond, Amélie; Boucher, Gabrielle; Cadby, Gemma; Cheng, Yu-Ching; Chiang, Charleston W. K.; Delgado, Graciela; Demirkan, Ayse; Dueker, Nicole; Eklund, Niina; Eiriksdottir, Gudny; Eriksson, Joel; Feenstra, Bjarke; Fischer, Krista; Frau, Francesca; Galesloot, Tessel E.; Geller, Frank; Goel, Anuj; Gorski, Mathias; Grammer, Tanja B.; Gustafsson, Stefan; Haitjema, Saskia; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Jackson, Anne U.; Jacobs, Kevin B.; Johansson, Åsa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; Lehne, Benjamin; Liu, Youfang; Lo, Ken Sin; Lorentzon, Mattias; Luan, Jian'an; Madden, Pamela A. F.; Mangino, Massimo; McKnight, Barbara; Medina-Gomez, Carolina; Monda, Keri L.; Montasser, May E.; Müller, Gabriele; Müller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renström, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stančáková, Alena; Steinthorsdottir, Valgerdur; Strawbridge, Rona J.; Sung, Yun Ju; Tachmazidou, Ioanna; Tanaka, Toshiko; Thorleifsson, Gudmar; Trompet, Stella; Pervjakova, Natalia; Tyrer, Jonathan P.; Vandenput, Liesbeth; van der Laan, Sander W; van der Velde, Nathalie; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Vlachopoulou, Efthymia; Waite, Lindsay L.; Wang, Sophie R.; Wang, Zhaoming; Wild, Sarah H.; Willenborg, Christina; Wilson, James F.; Wong, Andrew; Yang, Jian; Yengo, Loïc; Yerges-Armstrong, Laura M.; Yu, Lei; Zhang, Weihua; Zhao, Jing Hua; Andersson, Ehm A.; Bakker, Stephan J. L.; Baldassarre, Damiano; Banasik, Karina; Barcella, Matteo; Barlassina, Cristina; Bellis, Claire; Benaglio, Paola; Blangero, John; Blüher, Matthias; Bonnet, Fabrice; Bonnycastle, Lori L.; Boyd, Heather A.; Bruinenberg, Marcel; Buchman, Aron S; Campbell, Harry; Chen, Yii-Der Ida; Chines, Peter S.; Claudi-Boehm, Simone; Cole, John; Collins, Francis S.; de Geus, Eco J. C.; de Groot, Lisette C. P. G. M.; Dimitriou, Maria; Duan, Jubao; Enroth, Stefan; Eury, Elodie; Farmaki, Aliki-Eleni; Forouhi, Nita G.; Friedrich, Nele; Gejman, Pablo V.; Gigante, Bruna; Glorioso, Nicola; Go, Alan S.; Gottesman, Omri; Gräßler, Jürgen; Grallert, Harald; Grarup, Niels; Gu, Yu-Mei; Broer, Linda; Ham, Annelies C.; Hansen, Torben; Harris, Tamara B.; Hartman, Catharina A.; Hassinen, Maija; Hastie, Nicholas; Hattersley, Andrew T.; Heath, Andrew C.; Henders, Anjali K.; Hernandez, Dena; Hillege, Hans; Holmen, Oddgeir; Hovingh, Kees G; Hui, Jennie; Husemoen, Lise L.; Hutri-Kähönen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jørgensen, Torben; Jukema, J. Wouter; Juonala, Markus; Kanoni, Stavroula; Karaleftheri, Maria; Khaw, Kay Tee; Kinnunen, Leena; Kittner, Steven J.; Koenig, Wolfgang; Kolcic, Ivana; Kovacs, Peter; Krarup, Nikolaj T.; Kratzer, Wolfgang; Krüger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindström, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stéphane; Luben, Robert; Lyssenko, Valeriya; Männistö, Satu; Magnusson, Patrik K.; McArdle, Wendy L.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Montgomery, Grant W.; Morris, Andrew P.; Narisu, Narisu; Nelis, Mari; Ong, Ken K.; Palotie, Aarno; Pérusse, Louis; Pichler, Irene; Pilia, Maria G.; Pouta, Anneli; Rheinberger, Myriam; Ribel-Madsen, Rasmus; Richards, Marcus; Rice, Kenneth M.; Rice, Treva K.; Rivolta, Carlo; Salomaa, Veikko; Sanders, Alan R.; Sarzynski, Mark A.; Scholtens, Salome; Scott, Robert A.; Scott, William R.; Sebert, Sylvain; Sengupta, Sebanti; Sennblad, Bengt; Seufferlein, Thomas; Silveira, Angela; Slagboom, P. Eline; Smit, Jan H.; Sparsø, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A; Swift, Amy J.; Syvänen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Tönjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J.; Völker, Uwe; Vohl, Marie-Claude; Vonk, Judith M.; Waldenberger, Melanie; Walker, Ryan W.; Wennauer, Roman; Widén, Elisabeth; Willemsen, Gonneke; Wilsgaard, Tom; Wright, Alan F.; Zillikens, M. Carola; van Dijk, Suzanne C.; van Schoor, Natasja M.; Asselbergs, Folkert W.; de Bakker, Paul I. W.; Beckmann, Jacques S.; Beilby, John; Bennett, David A.; Bergman, Richard N.; Bergmann, Sven; Böger, Carsten A.; Boehm, Bernhard O.; Boerwinkle, Eric; Boomsma, Dorret I.; Bornstein, Stefan R.; Bottinger, Erwin P.; Bouchard, Claude; Chambers, John C.; Chanock, Stephen J.; Chasman, Daniel I.; Cucca, Francesco; Cusi, Daniele; Dedoussis, George; Erdmann, Jeanette; Eriksson, Johan G.; Evans, Denis A.; de Faire, Ulf; Farrall, Martin; Ferrucci, Luigi; Ford, Ian; Franke, Lude; Franks, Paul W.; Froguel, Philippe; Gansevoort, Ron T.; Gieger, Christian; Grönberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliövaara, Markku; Hengstenberg, Christian; Hicks, Andrew A; Hingorani, Aroon; Hofman, Albert; Hu, Frank; Huikuri, Heikki V.; Hveem, Kristian; James, Alan L.; Jordan, Joanne M.; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Kathiresan, Sekar; Kiemeney, Lambertus A. L. M.; Kivimaki, Mika; Knekt, Paul B.; Koistinen, Heikki A.; Kooner, Jaspal S.; Koskinen, Seppo; Kuusisto, Johanna; Maerz, Winfried; Martin, Nicholas G; Laakso, Markku; Lakka, Timo A.; Lehtimäki, Terho; Lettre, Guillaume; Levinson, Douglas F.; Lind, Lars; Lokki, Marja-Liisa; Mäntyselkä, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D.; Moll, Frans L.; Murray, Jeffrey C.; Musk, Arthur W.; Nieminen, Markku S.; Njølstad, Inger; Ohlsson, Claes; Oldehinkel, Albertine J.; Oostra, Ben A.; Palmer, Lyle J; Pankow, James S.; Pasterkamp, Gerard; Pedersen, Nancy L.; Pedersen, Oluf; Penninx, Brenda W.; Perola, Markus; Peters, Annette; Polašek, Ozren; Pramstaller, Peter P.; Psaty, Bruce M.; Qi, Lu; Quertermous, Thomas; Raitakari, Olli T.; Rankinen, Tuomo; Rauramaa, Rainer; Ridker, Paul M.; Rioux, John D.; Rivadeneira, Fernando; Rotter, Jerome I.; Rudan, Igor; den Ruijter, Hester M.; Saltevo, Juha; Sattar, Naveed; Schunkert, Heribert; Schwarz, Peter E. H.; Shuldiner, Alan R.; Sinisalo, Juha; Snieder, Harold; Sørensen, Thorkild I. A.; Spector, Tim D.; Staessen, Jan A.; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, André G.; Uusitupa, Matti; Verbeek, André L. M.; Vermeulen, Sita H.; Viikari, Jorma S.; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Waeber, Gérard; Walker, Mark; Wallaschofski, Henri; Wareham, Nicholas J.; Watkins, Hugh; Zeggini, Eleftheria; Chakravarti, Aravinda; Clegg, Deborah J.; Cupples, L. Adrienne; Gordon-Larsen, Penny; Jaquish, Cashell E.; Rao, D. C.; Abecasis, Goncalo R.; Assimes, Themistocles L.; Barroso, Inês; Berndt, Sonja I.; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; Hunter, David J.; Ingelsson, Erik; Kaplan, Robert C.; McCarthy, Mark I.; Mohlke, Karen L.; O'Connell, Jeffrey R.; Schlessinger, David; Strachan, David P.; Stefansson, Kari; van Duijn, Cornelia M.; Hirschhorn, Joel N.; Lindgren, Cecilia M.; Heid, Iris M.; North, Kari E.; Borecki, Ingrid B.; Kutalik, Zoltán; Loos, Ruth J. F.

    2015-01-01

    Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape. PMID:26426971

  15. Lessons from Large-Scale Renewable Energy Integration Studies: Preprint

    SciTech Connect

    Bird, L.; Milligan, M.

    2012-06-01

    In general, large-scale integration studies in Europe and the United States find that high penetrations of renewable generation are technically feasible with operational changes and increased access to transmission. This paper describes other key findings such as the need for fast markets, large balancing areas, system flexibility, and the use of advanced forecasting.

  16. Improving AFLP analysis of large-scale patterns of genetic variation--a case study with the Central African lianas Haumania spp (Marantaceae) showing interspecific gene flow.

    PubMed

    Ley, A C; Hardy, O J

    2013-04-01

    AFLP markers are often used to study patterns of population genetic variation and gene flow because they offer a good coverage of the nuclear genome, but the reliability of AFLP scoring is critical. To assess interspecific gene flow in two African rainforest liana species (Haumania danckelmaniana, H. liebrechtsiana) where previous evidence of chloroplast captures questioned the importance of hybridization and species boundaries, we developed new AFLP markers and a novel approach to select reliable bands from their degree of reproducibility. The latter is based on the estimation of the broad-sense heritability of AFLP phenotypes, an improvement over classical scoring error rates, which showed that the polymorphism of most AFLP bands was affected by a substantial nongenetic component. Therefore, using a quantitative genetics framework, we also modified an existing estimator of pairwise kinship coefficient between individuals correcting for the limited heritability of markers. Bayesian clustering confirms the recognition of the two Haumania species. Nevertheless, the decay of the relatedness between individuals of distinct species with geographic distance demonstrates that hybridization affects the nuclear genome. In conclusion, although we showed that AFLP markers might be substantially affected by nongenetic factors, their analysis using the new methods developed considerably advanced our understanding of the pattern of gene flow in our model species.

  17. FVGWAS: Fast Voxelwise Genome Wide Association Analysis of Large-scale Imaging Genetic Data 1

    PubMed Central

    Huang, Meiyan; Nichols, Thomas; Huang, Chao; Yang, Yu; Lu, Zhaohua; Feng, Qianjing; Knickmeyer, Rebecca C; Zhu, Hongtu

    2015-01-01

    More and more large-scale imaging genetic studies are being widely conducted to collect a rich set of imaging, genetic, and clinical data to detect putative genes for complexly inherited neuropsychiatric and neurodegenerative disorders. Several major big-data challenges arise from testing genome-wide (NC > 12 million known variants) associations with signals at millions of locations (NV ~ 106) in the brain from thousands of subjects (n ~ 103). The aim of this paper is to develop a Fast Voxelwise Genome Wide Association analysiS (FVGWAS) framework to e ciently carry out whole-genome analyses of whole-brain data. FVGWAS consists of three components including a heteroscedastic linear model, a global sure independence screening (G-SIS) procedure, and a detection procedure based on wild bootstrap methods. Specifically, for standard linear association, the computational complexity is O(nNV NC) for voxelwise genome wide association analysis (VGWAS) method compared with O((NC + NV)n2) for FVGWAS. Simulation studies show that FVGWAS is an effcient method of searching sparse signals in an extremely large search space, while controlling for the family-wise error rate. Finally, we have successfully applied FVGWAS to a large-scale imaging genetic data analysis of ADNI data with 708 subjects, 193,275 voxels in RAVENS maps, and 501,584 SNPs, and the total processing time was 203,645 seconds for a single CPU. Our FVG-WAS may be a valuable statistical toolbox for large-scale imaging genetic analysis as the field is rapidly advancing with ultra-high-resolution imaging and whole-genome sequencing. PMID:26025292

  18. Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence

    PubMed Central

    Yoon, Dankyu; Kim, Young-Jin; Cui, Wen-Yan; Van der Vaart, Andrew; Shin Cho, Yoon; Lee, Jong-Young; Ma, Jennie Z.; Payne, Thomas J.; Li, Ming D.; Park, Taesung

    2014-01-01

    Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p valuemeta = 6.40 × 10−6; rs2349433, p valuemeta = 5.57 × 10−6), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p valuemeta = 2.30 × 10−6) and the other at 7q31.1 (rs848353, p valuemeta = 9.16 × 10−8). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples. PMID:22006218

  19. Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.

    PubMed

    Yoon, Dankyu; Kim, Young-Jin; Cui, Wen-Yan; Van der Vaart, Andrew; Cho, Yoon Shin; Lee, Jong-Young; Ma, Jennie Z; Payne, Thomas J; Li, Ming D; Park, Taesung

    2012-06-01

    Diseases related to smoking are the second leading cause of death in the world. Cigarette smoking is a risk factor for several diseases such as cancer and cardiovascular and respiratory disorders. Despite increasing evidence of genetic determination, the susceptibility genes and loci underlying various aspects of smoking behavior are largely unknown. Moreover, almost all reported genome-wide association studies (GWASs) have been performed on samples of European origin, limiting the applicability of the results to other ethnic populations. In this first GWAS on smoking behavior in an Asian population, after analyzing 8,842 DNA samples from the Korea Association Resource project with 352,228 single nucleotide polymorphisms (SNPs) genotyped for each sample, we identified 8 SNPs significantly associated with smoking initiation (SI) and 4 with nicotine dependence (ND). Because of the current unavailability of an independent Asian smoking sample, we replicated the discoveries in independent samples of European-American and African-American origin. Of the 12 SNPs examined in the replicated samples, we identified two SNPs, in the regulator of G-protein signaling 17 gene (rs7747583, p value(meta) = 6.40 × 10(-6); rs2349433, p value(meta) = 5.57 × 10(-6)), associated with SI. Also, we found two SNPs significantly associated with ND; one in the FERM domain containing 4A (rs4424567, p value(meta) = 2.30 × 10(-6)) and the other at 7q31.1 (rs848353, p value(meta) = 9.16 × 10(-8)). These SNPs represent novel targets for examination of smoking behavior and warrant further investigation using independent samples.

  20. Comparative study of large-scale nonlinear optimization methods

    SciTech Connect

    Alemzadeh, S.A.

    1987-01-01

    Solving large-scale nonlinear optimization problems has been one of the active research areas for the last twenty years. Several heuristic algorithms with codes have been developed and implemented since 1966. This study explores the motivation and basic mathematical ideas leading to the development of MINOS-1.0, GRG-2,and MINOS-5.0 algorithms and their codes. The reliability, accuracy, and complexity of the algorithms and software depend upon their use of the gradient, Jacobian, and the Hessian. MINOS-1.0 and GRG-2 incorporate all of the input and output features, while MINOS-1.0 is not able to handle the nonlinearly constrained problems, and GRG-2 is not able to handle large-scale problems, MINOS-5.0 is a robust and an efficient software that incorporates all input, output features.

  1. Simplified DGS procedure for large-scale genome structural study.

    PubMed

    Jung, Yong-Chul; Xu, Jia; Chen, Jun; Kim, Yeong; Winchester, David; Wang, San Ming

    2009-11-01

    Ditag genome scanning (DGS) uses next-generation DNA sequencing to sequence the ends of ditag fragments produced by restriction enzymes. These sequences are compared to known genome sequences to determine their structure. In order to use DGS for large-scale genome structural studies, we have substantially revised the original protocol by replacing the in vivo genomic DNA cloning with in vitro adaptor ligation, eliminating the ditag concatemerization steps, and replacing the 454 sequencer with Solexa or SOLiD sequencers for ditag sequence collection. This revised protocol further increases genome coverage and resolution and allows DGS to be used to analyze multiple genomes simultaneously.

  2. Validity of large-scale reading tests: A phenotypic and behaviour-genetic analysis

    PubMed Central

    Grasby, Katrina L; Byrne, Brian; Olson, Richard K

    2016-01-01

    Each year, all Australian students in grades 3, 5, 7, and 9 sit nationwide large-scale tests in literacy and numeracy, which have their validity frequently questioned. We compared the performance of Grade 3 twins on these large-scale reading tests with their performance on three individually administered literacy tests in comprehension, word reading and vocabulary within a genetically sensitive design. Comprehension, word reading, and vocabulary accounted for a substantial amount of the variance in school reading tests. Performance on large-scale reading tests and individually administered tests was moderately to substantially heritable and the same genes contributed to performance in both types of test. These results confirm that large-scale school reading tests measure, at least in part, the literacy skills tapped by individual tests that are frequently considered to be the “gold-standard” in testing. PMID:27721516

  3. A Large-Scale Genetic Association Study Confirms IL12B and Leads to the Identification of IL23R as Psoriasis-Risk Genes

    PubMed Central

    Cargill, Michele ; Schrodi, Steven J. ; Chang, Monica ; Garcia, Veronica E. ; Brandon, Rhonda ; Callis, Kristina P. ; Matsunami, Nori ; Ardlie, Kristin G. ; Civello, Daniel ; Catanese, Joseph J. ; Leong, Diane U. ; Panko, Jackie M. ; McAllister, Linda B. ; Hansen, Christopher B. ; Papenfuss, Jason ; Prescott, Stephen M. ; White, Thomas J. ; Leppert, Mark F. ; Krueger, Gerald G. ; Begovich, Ann B. 

    2007-01-01

    We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3′-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR]common 0.64, combined P [Pcomb]=7.85×10-10). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located ∼60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (ORcommon 1.40, Pcomb=8.11×10-9) and a less frequent protective haplotype (ORcommon 0.58, Pcomb=5.65×10-12), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (ORcommon 1.44, Pcomb=3.13×10-6). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (ORcommon 1.66, Pcomb=1.33×10-8). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis pathogenesis. PMID:17236132

  4. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes.

    PubMed

    Cargill, Michele; Schrodi, Steven J; Chang, Monica; Garcia, Veronica E; Brandon, Rhonda; Callis, Kristina P; Matsunami, Nori; Ardlie, Kristin G; Civello, Daniel; Catanese, Joseph J; Leong, Diane U; Panko, Jackie M; McAllister, Linda B; Hansen, Christopher B; Papenfuss, Jason; Prescott, Stephen M; White, Thomas J; Leppert, Mark F; Krueger, Gerald G; Begovich, Ann B

    2007-02-01

    We performed a multitiered, case-control association study of psoriasis in three independent sample sets of white North American individuals (1,446 cases and 1,432 controls) with 25,215 genecentric single-nucleotide polymorphisms (SNPs) and found a highly significant association with an IL12B 3'-untranslated-region SNP (rs3212227), confirming the results of a small Japanese study. This SNP was significant in all three sample sets (odds ratio [OR](common) 0.64, combined P [Pcomb]=7.85x10(-10)). A Monte Carlo simulation to address multiple testing suggests that this association is not a type I error. The coding regions of IL12B were resequenced in 96 individuals with psoriasis, and 30 additional IL12B-region SNPs were genotyped. Haplotypes were estimated, and genotype-conditioned analyses identified a second risk allele (rs6887695) located approximately 60 kb upstream of the IL12B coding region that exhibited association with psoriasis after adjustment for rs3212227. Together, these two SNPs mark a common IL12B risk haplotype (OR(common) 1.40, Pcomb=8.11x10(-9)) and a less frequent protective haplotype (OR(common) 0.58, Pcomb=5.65x10(-12)), which were statistically significant in all three studies. Since IL12B encodes the common IL-12p40 subunit of IL-12 and IL-23, we individually genotyped 17 SNPs in the genes encoding the other chains of these cytokines (IL12A and IL23A) and their receptors (IL12RB1, IL12RB2, and IL23R). Haplotype analyses identified two IL23R missense SNPs that together mark a common psoriasis-associated haplotype in all three studies (OR(common) 1.44, Pcomb=3.13x10(-6)). Individuals homozygous for both the IL12B and the IL23R predisposing haplotypes have an increased risk of disease (OR(common) 1.66, Pcomb=1.33x10(-8)). These data, and the previous observation that administration of an antibody specific for the IL-12p40 subunit to patients with psoriasis is highly efficacious, suggest that these genes play a fundamental role in psoriasis

  5. Practical considerations for large-scale gut microbiome studies.

    PubMed

    Vandeputte, Doris; Tito, Raul Y; Vanleeuwen, Rianne; Falony, Gwen; Raes, Jeroen

    2017-08-01

    First insights on the human gut microbiome have been gained from medium-sized, cross-sectional studies. However, given the modest portion of explained variance of currently identified covariates and the small effect size of gut microbiota modulation strategies, upscaling seems essential for further discovery and characterisation of the multiple influencing factors and their relative contribution. In order to guide future research projects and standardisation efforts, we here review currently applied collection and preservation methods for gut microbiome research. We discuss aspects such as sample quality, applicable omics techniques, user experience and time and cost efficiency. In addition, we evaluate the protocols of a large-scale microbiome cohort initiative, the Flemish Gut Flora Project, to give an idea of perspectives, and pitfalls of large-scale faecal sampling studies. Although cryopreservation can be regarded as the gold standard, freezing protocols generally require more resources due to cold chain management. However, here we show that much can be gained from an optimised transport chain and sample aliquoting before freezing. Other protocols can be useful as long as they preserve the microbial signature of a sample such that relevant conclusions can be drawn regarding the research question, and the obtained data are stable and reproducible over time. © FEMS 2017.

  6. A study of synthetic large scales in turbulent boundary layers

    NASA Astrophysics Data System (ADS)

    Duvvuri, Subrahmanyam; Luhar, Mitul; Barnard, Casey; Sheplak, Mark; McKeon, Beverley

    2013-11-01

    Synthetic spanwise-constant spatio-temporal disturbances are excited in a turbulent boundary layer through a spatially impulsive patch of dynamic wall-roughness. The downstream flow response is studied through hot wire anemometry, pressure measurements at the wall and direct measurements of wall-shear-stress made using a novel micro-machined capacitive floating element sensor. These measurements are phase-locked to the input perturbation to recover the synthetic large-scale motion and characterize its structure and wall signature. The phase relationship between the synthetic large scale and small scale activity provides further insights into the apparent amplitude modulation effect between them, and the dynamics of wall-bounded turbulent flows in general. Results from these experiments will be discussed in the context of the critical-layer behavior revealed by the resolvent analysis of McKeon & Sharma (J Fluid Mech, 2010), and compared with similar earlier work by Jacobi & McKeon (J Fluid Mech, 2011). Model predictions are shown to be in broad agreement with experiments. The support of AFOSR grant #FA 9550-12-1-0469, Resnick Institute Graduate Research Fellowship (S.D.) and Sandia Graduate Fellowship (C.B.) are gratefully acknowledged.

  7. Studies on Editing Patterns in Large-scale Wikis

    NASA Astrophysics Data System (ADS)

    Boulain, Philip; Shadbolt, Nigel; Gibbins, Nicholas

    Wiki systems have developed over the past years as lightweight, community-editable, web-based hypertext systems. With the emergence of Semantic Wikis, these collections of interlinked documents have also gained a dual role as ad-hoc RDF graphs. However, their roots lie at the limited hypertext capabilities of the World Wide Web: embedded links, without support for composite objects or transclusion. In this chapter, we present experimental evidence that hyperstructure changes, as opposed to content changes, form a substantial proportion of editing effort on a large-scale wiki.We then follow this with a in-detail experiment, studying how individual editors work to edit articles on the wiki. These experiments are set in the wider context of a study of how the technologies developed during decades of hypertext research may be applied to improve management of wiki document structure and, with semantic wikis, knowledge structure.

  8. Compromising genetic diversity in the wild: Unmonitored large-scale release of plants and animals

    Treesearch

    Linda Laikre; Michael K. Schwartz; Robin S. Waples; Nils Ryman; F. W. Allendorf; C. S. Baker; D. P. Gregovich; M. M. Hansen; J. A. Jackson; K. C. Kendall; K. McKelvey; M. C. Neel; I. Olivieri; R. Short Bull; J. B. Stetz; D. A. Tallmon; C. D. Vojta; D. M. Waller

    2010-01-01

    Large-scale exploitation of wild animals and plants through fishing, hunting and logging often depends on augmentation through releases of translocated or captively raised individuals. Such releases are performed worldwide in vast numbers. Augmentation can be demographically and economically beneficial but can also cause four types of adverse genetic change to wild...

  9. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

    PubMed

    Thompson, Paul M; Stein, Jason L; Medland, Sarah E; Hibar, Derrek P; Vasquez, Alejandro Arias; Renteria, Miguel E; Toro, Roberto; Jahanshad, Neda; Schumann, Gunter; Franke, Barbara; Wright, Margaret J; Martin, Nicholas G; Agartz, Ingrid; Alda, Martin; Alhusaini, Saud; Almasy, Laura; Almeida, Jorge; Alpert, Kathryn; Andreasen, Nancy C; Andreassen, Ole A; Apostolova, Liana G; Appel, Katja; Armstrong, Nicola J; Aribisala, Benjamin; Bastin, Mark E; Bauer, Michael; Bearden, Carrie E; Bergmann, Orjan; Binder, Elisabeth B; Blangero, John; Bockholt, Henry J; Bøen, Erlend; Bois, Catherine; Boomsma, Dorret I; Booth, Tom; Bowman, Ian J; Bralten, Janita; Brouwer, Rachel M; Brunner, Han G; Brohawn, David G; Buckner, Randy L; Buitelaar, Jan; Bulayeva, Kazima; Bustillo, Juan R; Calhoun, Vince D; Cannon, Dara M; Cantor, Rita M; Carless, Melanie A; Caseras, Xavier; Cavalleri, Gianpiero L; Chakravarty, M Mallar; Chang, Kiki D; Ching, Christopher R K; Christoforou, Andrea; Cichon, Sven; Clark, Vincent P; Conrod, Patricia; Coppola, Giovanni; Crespo-Facorro, Benedicto; Curran, Joanne E; Czisch, Michael; Deary, Ian J; de Geus, Eco J C; den Braber, Anouk; Delvecchio, Giuseppe; Depondt, Chantal; de Haan, Lieuwe; de Zubicaray, Greig I; Dima, Danai; Dimitrova, Rali; Djurovic, Srdjan; Dong, Hongwei; Donohoe, Gary; Duggirala, Ravindranath; Dyer, Thomas D; Ehrlich, Stefan; Ekman, Carl Johan; Elvsåshagen, Torbjørn; Emsell, Louise; Erk, Susanne; Espeseth, Thomas; Fagerness, Jesen; Fears, Scott; Fedko, Iryna; Fernández, Guillén; Fisher, Simon E; Foroud, Tatiana; Fox, Peter T; Francks, Clyde; Frangou, Sophia; Frey, Eva Maria; Frodl, Thomas; Frouin, Vincent; Garavan, Hugh; Giddaluru, Sudheer; Glahn, David C; Godlewska, Beata; Goldstein, Rita Z; Gollub, Randy L; Grabe, Hans J; Grimm, Oliver; Gruber, Oliver; Guadalupe, Tulio; Gur, Raquel E; Gur, Ruben C; Göring, Harald H H; Hagenaars, Saskia; Hajek, Tomas; Hall, Geoffrey B; Hall, Jeremy; Hardy, John; Hartman, Catharina A; Hass, Johanna; Hatton, Sean N; Haukvik, Unn K; Hegenscheid, Katrin; Heinz, Andreas; Hickie, Ian B; Ho, Beng-Choon; Hoehn, David; Hoekstra, Pieter J; Hollinshead, Marisa; Holmes, Avram J; Homuth, Georg; Hoogman, Martine; Hong, L Elliot; Hosten, Norbert; Hottenga, Jouke-Jan; Hulshoff Pol, Hilleke E; Hwang, Kristy S; Jack, Clifford R; Jenkinson, Mark; Johnston, Caroline; Jönsson, Erik G; Kahn, René S; Kasperaviciute, Dalia; Kelly, Sinead; Kim, Sungeun; Kochunov, Peter; Koenders, Laura; Krämer, Bernd; Kwok, John B J; Lagopoulos, Jim; Laje, Gonzalo; Landen, Mikael; Landman, Bennett A; Lauriello, John; Lawrie, Stephen M; Lee, Phil H; Le Hellard, Stephanie; Lemaître, Herve; Leonardo, Cassandra D; Li, Chiang-Shan; Liberg, Benny; Liewald, David C; Liu, Xinmin; Lopez, Lorna M; Loth, Eva; Lourdusamy, Anbarasu; Luciano, Michelle; Macciardi, Fabio; Machielsen, Marise W J; Macqueen, Glenda M; Malt, Ulrik F; Mandl, René; Manoach, Dara S; Martinot, Jean-Luc; Matarin, Mar; Mather, Karen A; Mattheisen, Manuel; Mattingsdal, Morten; Meyer-Lindenberg, Andreas; McDonald, Colm; McIntosh, Andrew M; McMahon, Francis J; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Milaneschi, Yuri; Mohnke, Sebastian; Montgomery, Grant W; Morris, Derek W; Moses, Eric K; Mueller, Bryon A; Muñoz Maniega, Susana; Mühleisen, Thomas W; Müller-Myhsok, Bertram; Mwangi, Benson; Nauck, Matthias; Nho, Kwangsik; Nichols, Thomas E; Nilsson, Lars-Göran; Nugent, Allison C; Nyberg, Lars; Olvera, Rene L; Oosterlaan, Jaap; Ophoff, Roel A; Pandolfo, Massimo; Papalampropoulou-Tsiridou, Melina; Papmeyer, Martina; Paus, Tomas; Pausova, Zdenka; Pearlson, Godfrey D; Penninx, Brenda W; Peterson, Charles P; Pfennig, Andrea; Phillips, Mary; Pike, G Bruce; Poline, Jean-Baptiste; Potkin, Steven G; Pütz, Benno; Ramasamy, Adaikalavan; Rasmussen, Jerod; Rietschel, Marcella; Rijpkema, Mark; Risacher, Shannon L; Roffman, Joshua L; Roiz-Santiañez, Roberto; Romanczuk-Seiferth, Nina; Rose, Emma J; Royle, Natalie A; Rujescu, Dan; Ryten, Mina; Sachdev, Perminder S; Salami, Alireza; Satterthwaite, Theodore D; Savitz, Jonathan; Saykin, Andrew J; Scanlon, Cathy; Schmaal, Lianne; Schnack, Hugo G; Schork, Andrew J; Schulz, S Charles; Schür, Remmelt; Seidman, Larry; Shen, Li; Shoemaker, Jody M; Simmons, Andrew; Sisodiya, Sanjay M; Smith, Colin; Smoller, Jordan W; Soares, Jair C; Sponheim, Scott R; Sprooten, Emma; Starr, John M; Steen, Vidar M; Strakowski, Stephen; Strike, Lachlan; Sussmann, Jessika; Sämann, Philipp G; Teumer, Alexander; Toga, Arthur W; Tordesillas-Gutierrez, Diana; Trabzuni, Daniah; Trost, Sarah; Turner, Jessica; Van den Heuvel, Martijn; van der Wee, Nic J; van Eijk, Kristel; van Erp, Theo G M; van Haren, Neeltje E M; van 't Ent, Dennis; van Tol, Marie-Jose; Valdés Hernández, Maria C; Veltman, Dick J; Versace, Amelia; Völzke, Henry; Walker, Robert; Walter, Henrik; Wang, Lei; Wardlaw, Joanna M; Weale, Michael E; Weiner, Michael W; Wen, Wei; Westlye, Lars T; Whalley, Heather C; Whelan, Christopher D; White, Tonya; Winkler, Anderson M; Wittfeld, Katharina; Woldehawariat, Girma; Wolf, Christiane; Zilles, David; Zwiers, Marcel P; Thalamuthu, Anbupalam; Schofield, Peter R; Freimer, Nelson B; Lawrence, Natalia S; Drevets, Wayne

    2014-06-01

    The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

  10. Experiment study of large-scale magnetorheological fluid damper

    NASA Astrophysics Data System (ADS)

    Guan, Xinchun; Li, Jinhai; Ou, Jinping

    2005-05-01

    Due to their character of low power requirement, rapid-response and large force, the dampers that made based on the special rheologic performance of magnetorheological fluid (MRF) have shown to be one kind of ideal semi-active vibration control devices for civil engineering structures and vehicles. In this paper, the character of magnetic circuit of MRF damper was firstly studied; based on above results, a large-scale MRF damper whose adjustable multiple is about 16 and maximum damping force is about 170kN was then designed and tested. Experimental results show that, under lower electrical current, same or opposite of electric current direction of multi-coils winding on the piston do not influence damping performance of MRF damper; however, under higher electrical current, inverse connecting of adjacent coils is apt to improve damping force of MRF damper.

  11. Large-scale genetic structuring of a widely distributed carnivore--the Eurasian lynx (Lynx lynx).

    PubMed

    Rueness, Eli K; Naidenko, Sergei; Trosvik, Pål; Stenseth, Nils Chr

    2014-01-01

    Over the last decades the phylogeography and genetic structure of a multitude of species inhabiting Europe and North America have been described. The flora and fauna of the vast landmasses of north-eastern Eurasia are still largely unexplored in this respect. The Eurasian lynx is a large felid that is relatively abundant over much of the Russian sub-continent and the adjoining countries. Analyzing 148 museum specimens collected throughout its range over the last 150 years we have described the large-scale genetic structuring in this highly mobile species. We have investigated the spatial genetic patterns using mitochondrial DNA sequences (D-loop and cytochrome b) and 11 microsatellite loci, and describe three phylogenetic clades and a clear structuring along an east-west gradient. The most likely scenario is that the contemporary Eurasian lynx populations originated in central Asia and that parts of Europe were inhabited by lynx during the Pleistocene. After the Last Glacial Maximum (LGM) range expansions lead to colonization of north-western Siberia and Scandinavia from the Caucasus and north-eastern Siberia from a refugium further east. No evidence of a Berinigan refugium could be detected in our data. We observed restricted gene flow and suggest that future studies of the Eurasian lynx explore to what extent the contemporary population structure may be explained by ecological variables.

  12. Large-Scale Genetic Structuring of a Widely Distributed Carnivore - The Eurasian Lynx (Lynx lynx)

    PubMed Central

    Rueness, Eli K.; Naidenko, Sergei; Trosvik, Pål; Stenseth, Nils Chr.

    2014-01-01

    Over the last decades the phylogeography and genetic structure of a multitude of species inhabiting Europe and North America have been described. The flora and fauna of the vast landmasses of north-eastern Eurasia are still largely unexplored in this respect. The Eurasian lynx is a large felid that is relatively abundant over much of the Russian sub-continent and the adjoining countries. Analyzing 148 museum specimens collected throughout its range over the last 150 years we have described the large-scale genetic structuring in this highly mobile species. We have investigated the spatial genetic patterns using mitochondrial DNA sequences (D-loop and cytochrome b) and 11 microsatellite loci, and describe three phylogenetic clades and a clear structuring along an east-west gradient. The most likely scenario is that the contemporary Eurasian lynx populations originated in central Asia and that parts of Europe were inhabited by lynx during the Pleistocene. After the Last Glacial Maximum (LGM) range expansions lead to colonization of north-western Siberia and Scandinavia from the Caucasus and north-eastern Siberia from a refugium further east. No evidence of a Berinigan refugium could be detected in our data. We observed restricted gene flow and suggest that future studies of the Eurasian lynx explore to what extent the contemporary population structure may be explained by ecological variables. PMID:24695745

  13. Large scale molecular dynamics study of polymer-surfactant complex

    NASA Astrophysics Data System (ADS)

    Goswami, Monojoy; Sumpter, Bobby

    2012-02-01

    In this work, we study the self-assembly of cationic polyelectrolytes mediated by anionic surfactants in dilute or semi-dilute and gel states. The understanding of the dilute system is a requirement for the understanding of gel states. The importance of polyelectrolyte with oppositely charged colloidal particles can be found in biological systems, such as immobilization of enzymes in polyelectrolyte complexes or nonspecific association of DNA with protein. With the same understanding, interaction of surfactants with polyelectrolytes shows intriguing phenomena that are important for both in academic research as well as industrial applications. Many useful properties of PE surfactant complexes come from the highly ordered structures of surfactant self-assembly inside the PE aggregate. We do large scale molecular dynamics simulation using LAMMPS to understand the structure and dynamics of PE-surfactant systems. Our investigation shows highly ordered ring-string structures that have been observed experimentally in biological systems. We will investigate many different properties of PE-surfactant complexation which will be helpful for pharmaceutical, engineering and biological applications.

  14. River Seepage Conductance in Large-Scale Regional Studies.

    PubMed

    Morel-Seytoux, Hubert J; Miller, Calvin D; Miracapillo, Cinzia; Mehl, Steffen

    2016-12-20

    Flow exchange between surface and groundwater is of great importance be it for beneficial allocation and use of water resources or for the proper exercise of water rights. In large-scale regional studies, most numerical models use coarse grid sizes, which make it difficult to provide an accurate depiction of the phenomenon. In particular, a somewhat arbitrary leakance coefficient in a third type (i.e., Cauchy, General Head) boundary condition is used to calculate the seepage discharge as a function of the difference of head in the river and in the aquifer, whose value is often found by calibration. A different approach is presented to analytically estimate that leakance coefficient. It is shown that a simple equivalence can be deduced from the analytical solution for the empirical coefficient, so that it provides the accuracy of the analytical solution while the model maintains a very coarse grid, treating the water-table aquifer as a single calculation layer. Relating the empirical leakance coefficient to the exact conductance, derived from physical principles, provides a physical basis for the leakance coefficient. Factors such as normalized wetted perimeter, degree of penetration of the river, presence of a clogging layer, and anisotropy can be included with little computational demand. In addition the river coefficient in models such as MODFLOW, for example, can be easily modified when grid size is changed without need for recalibration.

  15. The genetics revolution in rheumatology: large scale genomic arrays and genetic mapping.

    PubMed

    Eyre, Stephen; Orozco, Gisela; Worthington, Jane

    2017-07-01

    Susceptibility to rheumatic diseases, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, juvenile idiopathic arthritis and psoriatic arthritis, includes a large genetic component. Understanding how an individual's genetic background influences disease onset and outcome can lead to a better understanding of disease biology, improved diagnosis and treatment, and, ultimately, to disease prevention or cure. The past decade has seen great progress in the identification of genetic variants that influence the risk of rheumatic diseases. The challenging task of unravelling the function of these variants is ongoing. In this Review, the major insights from genetic studies, gained from advances in technology, bioinformatics and study design, are discussed in the context of rheumatic disease. In addition, pivotal genetic studies in the main rheumatic diseases are highlighted, with insights into how these studies have changed the way we view these conditions in terms of disease overlap, pathways of disease and potential new therapeutic targets. Finally, the limitations of genetic studies, gaps in our knowledge and ways in which current genetic knowledge can be fully translated into clinical benefit are examined.

  16. Achieving online consent to participation in large-scale gene-environment studies: a tangible destination.

    PubMed

    Wood, Fiona; Kowalczuk, Jenny; Elwyn, Glyn; Mitchell, Clive; Gallacher, John

    2011-08-01

    Population based genetics studies are dependent on large numbers of individuals in the pursuit of small effect sizes. Recruiting and consenting a large number of participants is both costly and time consuming. We explored whether an online consent process for large-scale genetics studies is acceptable for prospective participants using an example online genetics study. We conducted semi-structured interviews with 42 members of the public stratified by age group, gender and newspaper readership (a measure of social status). Respondents were asked to use a website designed to recruit for a large-scale genetic study. After using the website a semi-structured interview was conducted to explore opinions and any issues they would have. Responses were analysed using thematic content analysis. The majority of respondents said they would take part in the research (32/42). Those who said they would decline to participate saw fewer benefits from the research, wanted more information and expressed a greater number of concerns about the study. Younger respondents had concerns over time commitment. Middle aged respondents were concerned about privacy and security. Older respondents were more altruistic in their motivation to participate. Common themes included trust in the authenticity of the website, security of personal data, curiosity about their own genetic profile, operational concerns and a desire for more information about the research. Online consent to large-scale genetic studies is likely to be acceptable to the public. The online consent process must establish trust quickly and effectively by asserting authenticity and credentials, and provide access to a range of information to suit different information preferences.

  17. Compromising genetic diversity in the wild: unmonitored large-scale release of plants and animals.

    PubMed

    Laikre, Linda; Schwartz, Michael K; Waples, Robin S; Ryman, Nils

    2010-09-01

    Large-scale exploitation of wild animals and plants through fishing, hunting and logging often depends on augmentation through releases of translocated or captively raised individuals. Such releases are performed worldwide in vast numbers. Augmentation can be demographically and economically beneficial but can also cause four types of adverse genetic change to wild populations: (1) loss of genetic variation, (2) loss of adaptations, (3) change of population composition, and (4) change of population structure. While adverse genetic impacts are recognized and documented in fisheries, little effort is devoted to actually monitoring them. In forestry and wildlife management, genetic risks associated with releases are largely neglected. We outline key features of programs to effectively monitor consequences of such releases on natural populations. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Large Scale Single Nucleotide Polymorphism Study of PD Susceptibility

    DTIC Science & Technology

    2005-03-01

    identification of eight genetic loci in the familial PD, the results of intensive investigations of polymorphisms in dozens of genes related to sporadic, late...1) investigate the association between classical, sporadic PD and 2386 SNPs in 23 genes implicated in the pathogenesis of PD; (2) construct...addition, experiences derived from this study may be applied in other complex disorders for the identification of susceptibility genes , as well as in genome

  19. Large-Scale periodic solar velocities: An observational study

    NASA Technical Reports Server (NTRS)

    Dittmer, P. H.

    1977-01-01

    Observations of large-scale solar velocities were made using the mean field telescope and Babcock magnetograph of the Stanford Solar Observatory. Observations were made in the magnetically insensitive ion line at 5124 A, with light from the center (limb) of the disk right (left) circularly polarized, so that the magnetograph measures the difference in wavelength between center and limb. Computer calculations are made of the wavelength difference produced by global pulsations for spherical harmonics up to second order and of the signal produced by displacing the solar image relative to polarizing optics or diffraction grating.

  20. Prediction of monthly rainfall on homogeneous monsoon regions of India based on large scale circulation patterns using Genetic Programming

    NASA Astrophysics Data System (ADS)

    Kashid, Satishkumar S.; Maity, Rajib

    2012-08-01

    SummaryPrediction of Indian Summer Monsoon Rainfall (ISMR) is of vital importance for Indian economy, and it has been remained a great challenge for hydro-meteorologists due to inherent complexities in the climatic systems. The Large-scale atmospheric circulation patterns from tropical Pacific Ocean (ENSO) and those from tropical Indian Ocean (EQUINOO) are established to influence the Indian Summer Monsoon Rainfall. The information of these two large scale atmospheric circulation patterns in terms of their indices is used to model the complex relationship between Indian Summer Monsoon Rainfall and the ENSO as well as EQUINOO indices. However, extracting the signal from such large-scale indices for modeling such complex systems is significantly difficult. Rainfall predictions have been done for 'All India' as one unit, as well as for five 'homogeneous monsoon regions of India', defined by Indian Institute of Tropical Meteorology. Recent 'Artificial Intelligence' tool 'Genetic Programming' (GP) has been employed for modeling such problem. The Genetic Programming approach is found to capture the complex relationship between the monthly Indian Summer Monsoon Rainfall and large scale atmospheric circulation pattern indices - ENSO and EQUINOO. Research findings of this study indicate that GP-derived monthly rainfall forecasting models, that use large-scale atmospheric circulation information are successful in prediction of All India Summer Monsoon Rainfall with correlation coefficient as good as 0.866, which may appears attractive for such a complex system. A separate analysis is carried out for All India Summer Monsoon rainfall for India as one unit, and five homogeneous monsoon regions, based on ENSO and EQUINOO indices of months of March, April and May only, performed at end of month of May. In this case, All India Summer Monsoon Rainfall could be predicted with 0.70 as correlation coefficient with somewhat lesser Correlation Coefficient (C.C.) values for different

  1. Genetic weighted k-means algorithm for clustering large-scale gene expression data.

    PubMed

    Wu, Fang-Xiang

    2008-05-28

    The traditional (unweighted) k-means is one of the most popular clustering methods for analyzing gene expression data. However, it suffers three major shortcomings. It is sensitive to initial partitions, its result is prone to the local minima, and it is only applicable to data with spherical-shape clusters. The last shortcoming means that we must assume that gene expression data at the different conditions follow the independent distribution with the same variances. Nevertheless, this assumption is not true in practice. In this paper, we propose a genetic weighted K-means algorithm (denoted by GWKMA), which solves the first two problems and partially remedies the third one. GWKMA is a hybridization of a genetic algorithm (GA) and a weighted K-means algorithm (WKMA). In GWKMA, each individual is encoded by a partitioning table which uniquely determines a clustering, and three genetic operators (selection, crossover, mutation) and a WKM operator derived from WKMA are employed. The superiority of the GWKMA over the k-means is illustrated on a synthetic and two real-life gene expression datasets. The proposed algorithm has general application to clustering large-scale biological data such as gene expression data and peptide mass spectral data.

  2. A new way to protect privacy in large-scale genome-wide association studies

    PubMed Central

    Kamm, Liina; Bogdanov, Dan; Laur, Sven; Vilo, Jaak

    2013-01-01

    Motivation: Increased availability of various genotyping techniques has initiated a race for finding genetic markers that can be used in diagnostics and personalized medicine. Although many genetic risk factors are known, key causes of common diseases with complex heritage patterns are still unknown. Identification of such complex traits requires a targeted study over a large collection of data. Ideally, such studies bring together data from many biobanks. However, data aggregation on such a large scale raises many privacy issues. Results: We show how to conduct such studies without violating privacy of individual donors and without leaking the data to third parties. The presented solution has provable security guarantees. Contact: jaak.vilo@ut.ee Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23413435

  3. Evaluating Large-Scale Studies to Accurately Appraise Children's Performance

    ERIC Educational Resources Information Center

    Ernest, James M.

    2012-01-01

    Educational policy is often developed using a top-down approach. Recently, there has been a concerted shift in policy for educators to develop programs and research proposals that evolve from "scientific" studies and focus less on their intuition, aided by professional wisdom. This article analyzes several national and international…

  4. Computational and experimental studies on large scale solar heating

    NASA Astrophysics Data System (ADS)

    Peltola, S.

    The experimental part of the work deals mainly with the experiences gained from the Kerava Solar Village (KSV) but some additional remarks are presented from international studies. The measured thermal performance of the KSV heating system indicates considerably poorer performance than original design values. Reasons for this are studied by means of computational analyses. Fundamental problems with KSV systems was too small storage size with respect both to installed collector area and connected load. From an operational point of view, the frequent heat pump failures were the most severe problem. Computational tools for large solar heating system design and analyses are presented. Numerical models developed in this work, the KERCONT and SUPERSOL, are validated with measured performance from the KSV indicating reasonably good accuracy. The tools have been applied for detecting KSV heating system problems and for finding solutions for them as well as for re-design of the system. More general analyses are presented on the applicability of the KSV system principle in other load sizes and locations. A new approach for preliminary studies on Central Solar Heating Plants with Seasonal Storage (CSHPSS) is described. The analytical model, SOLCHIPS, is shown to be a very effective tool for pre-design studies. The validity of SOLCHIPS approach is studied by comparing the results against results from validated numerical model, MINSUN. In the last part of the work, preliminary results from numerical simulations of summer time district solar heating with short term storage are presented. According to the analyses, these systems should provide heat at or below the cost achievable with seasonal storage systems.

  5. Large scale study of multiple-molecule queries.

    PubMed

    Nasr, Ramzi J; Swamidass, S Joshua; Baldi, Pierre F

    2009-06-04

    In ligand-based screening, as well as in other chemoinformatics applications, one seeks to effectively search large repositories of molecules in order to retrieve molecules that are similar typically to a single molecule lead. However, in some case, multiple molecules from the same family are available to seed the query and search for other members of the same family.Multiple-molecule query methods have been less studied than single-molecule query methods. Furthermore, the previous studies have relied on proprietary data and sometimes have not used proper cross-validation methods to assess the results. In contrast, here we develop and compare multiple-molecule query methods using several large publicly available data sets and background. We also create a framework based on a strict cross-validation protocol to allow unbiased benchmarking for direct comparison in future studies across several performance metrics. Fourteen different multiple-molecule query methods were defined and benchmarked using: (1) 41 publicly available data sets of related molecules with similar biological activity; and (2) publicly available background data sets consisting of up to 175,000 molecules randomly extracted from the ChemDB database and other sources. Eight of the fourteen methods were parameter free, and six of them fit one or two free parameters to the data using a careful cross-validation protocol. All the methods were assessed and compared for their ability to retrieve members of the same family against the background data set by using several performance metrics including the Area Under the Accumulation Curve (AUAC), Area Under the Curve (AUC), F1-measure, and BEDROC metrics.Consistent with the previous literature, the best parameter-free methods are the MAX-SIM and MIN-RANK methods, which score a molecule to a family by the maximum similarity, or minimum ranking, obtained across the family. One new parameterized method introduced in this study and two previously defined methods

  6. Large scale study of multiple-molecule queries

    PubMed Central

    2009-01-01

    Background In ligand-based screening, as well as in other chemoinformatics applications, one seeks to effectively search large repositories of molecules in order to retrieve molecules that are similar typically to a single molecule lead. However, in some case, multiple molecules from the same family are available to seed the query and search for other members of the same family. Multiple-molecule query methods have been less studied than single-molecule query methods. Furthermore, the previous studies have relied on proprietary data and sometimes have not used proper cross-validation methods to assess the results. In contrast, here we develop and compare multiple-molecule query methods using several large publicly available data sets and background. We also create a framework based on a strict cross-validation protocol to allow unbiased benchmarking for direct comparison in future studies across several performance metrics. Results Fourteen different multiple-molecule query methods were defined and benchmarked using: (1) 41 publicly available data sets of related molecules with similar biological activity; and (2) publicly available background data sets consisting of up to 175,000 molecules randomly extracted from the ChemDB database and other sources. Eight of the fourteen methods were parameter free, and six of them fit one or two free parameters to the data using a careful cross-validation protocol. All the methods were assessed and compared for their ability to retrieve members of the same family against the background data set by using several performance metrics including the Area Under the Accumulation Curve (AUAC), Area Under the Curve (AUC), F1-measure, and BEDROC metrics. Consistent with the previous literature, the best parameter-free methods are the MAX-SIM and MIN-RANK methods, which score a molecule to a family by the maximum similarity, or minimum ranking, obtained across the family. One new parameterized method introduced in this study and two

  7. The Study of Clusters of Galaxies and Large Scale Structures

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Many research projects have been initiated and completed under support of this program. The results are summarized below. The work on the ROSAT Deep Survey has been successfully completed. A number of interesting results have been established within this joint MPE, Cal Tech, JHU, ST ScI, ESO collaboration. First, a very large fraction, 70-80 percent, of the X-ray background has been directly resolved into point sources. We have derived a new log N-log S for X-ray sources and have measured a source density of 970 sources per square degree at a limiting flux level. Care was taken in these studies to accurately model and measure the effects of sources confusion. This was possible because of our observing strategy which included both deep PSPC and HRI observations. No evidence of a population of narrow emission line galaxies has been established but some evidence for the evolution of low luminosity AGN (Seyfert galaxies) has been reported. The work on the ROSAT All Sky Survey Northern Cluster Survey has been substantially concluded but the publication of the list has been held up by the need to analyze newly re-calibrated data. This should result in publication over the next year. During the past year we have submitted a paper to the Astrophysical Journal which utilized a sample of clusters originally selected from the ROSAT All-sky survey at redshifts greater than 0.3. This sample was studied with ASCA to determine temperature and luminosity.

  8. The Study of Clusters of Galaxies and Large Scale Structures

    NASA Technical Reports Server (NTRS)

    1998-01-01

    The work on the ROSAT Deep Survey has been successfully completed. A number of interesting results have been established within this joint MPE, Cal Tech, JHU, ST Scl, ESO collaboration. First, a very large fraction, 70-80 percent, of the X-ray background has been directly resolved into point sources. We have derived a new log N-log S for X- ray sources and have measured a source density of 970 sources per square degree at a limiting flux level of 10(exp -15)/erg s sq cm (0.5-2.0 keV). Care was taken in these studies to accurately model and measure the effects of sources confusion. This was possible because of our observing strategy which included both deep PSPC and HRI observations. In the last year we initiated work in the design and development of the Next Generation Space Telescope.

  9. A large scale flume for hydro-environmental studies

    NASA Astrophysics Data System (ADS)

    Gomez, Jose Alfonso; Giráldez, Juan Vicente; Castro-Orgaz, Oscar; Casalí, Javier; Hermosín, Maria del Carmen; Mateos, Luciano

    2013-04-01

    The understanding of key hydrologic processes such as, water erosion, rill network development or agrochemical transport, requires controlled experiments at the appropriate scale. This is the reason for experimentation at flume scale in hydro-environmental research, used for many decades in this field. This communication presents a research infrastructure, recently completed in its first stage, consisting of a large flume for studying soil water erosion, sediment transport, and environmental processes such as the transport of different substances (salts, fertilizers, herbicides, carbon, …) rather dissolved or absorbed with the sediment. It is located at the Institute for Sustainable Agriculture (CSIC) in Córdoba, Spain. The flume is 0.6 m deep, 12 m long, and 6 m wide. It may be divided longitudinally into three channels (6 m long, 1 m wide). The slope of the flume can be regulated from 0 % to 20 %. The device allows studying free surface flows over movable beds with different conditions of sediment transport by supplying clear or sediment-laden water from its head system. The head system consists of three triangular weirs for accurate measurement of water flow, three stilling tanks at the entrance of the flume, and three vibratory hoppers for applying sediments at pre-set rates. The water can be re-circulated, the maximum inflow is then about 30 l s-1, or evacuated, then the inflow is limited to about 20 l s-1. The infrastructure is within a shelter with an area of 400 m2 and height 8.7 m. The area of the shelter allows in-door mechanical preparation of soil and sediments. The height of the shelter will allow the installation of the rainfall simulator and a light rail crane in a second stage, not started yet. Several experiments have been planned at IAS-CSIC already, particularly investigation of the water erosion and sediment transport processes in concentrated flows under different soil conditions, as well as hydrodynamics aspects of suspended and bed

  10. HIV-1 genetic diversity and primary drug resistance mutations before large-scale access to antiretroviral therapy, Republic of Congo.

    PubMed

    Niama, Fabien Roch; Vidal, Nicole; Diop-Ndiaye, Halimatou; Nguimbi, Etienne; Ahombo, Gabriel; Diakabana, Philippe; Bayonne Kombo, Édith Sophie; Mayengue, Pembe Issamou; Kobawila, Simon-Charles; Parra, Henri Joseph; Toure-Kane, Coumba

    2017-07-05

    In this work, we investigated the genetic diversity of HIV-1 and the presence of mutations conferring antiretroviral drug resistance in 50 drug-naïve infected persons in the Republic of Congo (RoC). Samples were obtained before large-scale access to HAART in 2002 and 2004. To assess the HIV-1 genetic recombination, the sequencing of the pol gene encoding a protease and partial reverse transcriptase was performed and analyzed with updated references, including newly characterized CRFs. The assessment of drug resistance was conducted according to the WHO protocol. Among the 50 samples analyzed for the pol gene, 50% were classified as intersubtype recombinants, charring complex structures inside the pol fragment. Five samples could not be classified (noted U). The most prevalent subtypes were G with 10 isolates and D with 11 isolates. One isolate of A, J, H, CRF05, CRF18 and CRF37 were also found. Two samples (4%) harboring the mutations M230L and Y181C associated with the TAMs M41L and T215Y, respectively, were found. This first study in the RoC, based on WHO classification, shows that the threshold of transmitted drug resistance before large-scale access to antiretroviral therapy is 4%.

  11. Caught you: threats to confidentiality due to the public release of large-scale genetic data sets

    PubMed Central

    2010-01-01

    Background Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. Discussion The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Summary Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public. PMID:21190545

  12. Caught you: threats to confidentiality due to the public release of large-scale genetic data sets.

    PubMed

    Wjst, Matthias

    2010-12-29

    Large-scale genetic data sets are frequently shared with other research groups and even released on the Internet to allow for secondary analysis. Study participants are usually not informed about such data sharing because data sets are assumed to be anonymous after stripping off personal identifiers. The assumption of anonymity of genetic data sets, however, is tenuous because genetic data are intrinsically self-identifying. Two types of re-identification are possible: the "Netflix" type and the "profiling" type. The "Netflix" type needs another small genetic data set, usually with less than 100 SNPs but including a personal identifier. This second data set might originate from another clinical examination, a study of leftover samples or forensic testing. When merged to the primary, unidentified set it will re-identify all samples of that individual. Even with no second data set at hand, a "profiling" strategy can be developed to extract as much information as possible from a sample collection. Starting with the identification of ethnic subgroups along with predictions of body characteristics and diseases, the asthma kids case as a real-life example is used to illustrate that approach. Depending on the degree of supplemental information, there is a good chance that at least a few individuals can be identified from an anonymized data set. Any re-identification, however, may potentially harm study participants because it will release individual genetic disease risks to the public.

  13. Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept.

    PubMed

    Franke, Barbara; Stein, Jason L; Ripke, Stephan; Anttila, Verneri; Hibar, Derrek P; van Hulzen, Kimm J E; Arias-Vasquez, Alejandro; Smoller, Jordan W; Nichols, Thomas E; Neale, Michael C; McIntosh, Andrew M; Lee, Phil; McMahon, Francis J; Meyer-Lindenberg, Andreas; Mattheisen, Manuel; Andreassen, Ole A; Gruber, Oliver; Sachdev, Perminder S; Roiz-Santiañez, Roberto; Saykin, Andrew J; Ehrlich, Stefan; Mather, Karen A; Turner, Jessica A; Schwarz, Emanuel; Thalamuthu, Anbupalam; Yao, Yin; Ho, Yvonne Y W; Martin, Nicholas G; Wright, Margaret J; O'Donovan, Michael C; Thompson, Paul M; Neale, Benjamin M; Medland, Sarah E; Sullivan, Patrick F

    2016-03-01

    Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders.

  14. Discovery and mapping of a new expressed sequence tag-single nucleotide polymorphism and simple sequence repeat panel for large-scale genetic studies and breeding of Theobroma cacao L.

    PubMed Central

    Allegre, Mathilde; Argout, Xavier; Boccara, Michel; Fouet, Olivier; Roguet, Yolande; Bérard, Aurélie; Thévenin, Jean Marc; Chauveau, Aurélie; Rivallan, Ronan; Clement, Didier; Courtois, Brigitte; Gramacho, Karina; Boland-Augé, Anne; Tahi, Mathias; Umaharan, Pathmanathan; Brunel, Dominique; Lanaud, Claire

    2012-01-01

    Theobroma cacao is an economically important tree of several tropical countries. Its genetic improvement is essential to provide protection against major diseases and improve chocolate quality. We discovered and mapped new expressed sequence tag-single nucleotide polymorphism (EST-SNP) and simple sequence repeat (SSR) markers and constructed a high-density genetic map. By screening 149 650 ESTs, 5246 SNPs were detected in silico, of which 1536 corresponded to genes with a putative function, while 851 had a clear polymorphic pattern across a collection of genetic resources. In addition, 409 new SSR markers were detected on the Criollo genome. Lastly, 681 new EST-SNPs and 163 new SSRs were added to the pre-existing 418 co-dominant markers to construct a large consensus genetic map. This high-density map and the set of new genetic markers identified in this study are a milestone in cocoa genomics and for marker-assisted breeding. The data are available at http://tropgenedb.cirad.fr. PMID:22210604

  15. Integrative approaches for large-scale transcriptome-wide association studies.

    PubMed

    Gusev, Alexander; Ko, Arthur; Shi, Huwenbo; Bhatia, Gaurav; Chung, Wonil; Penninx, Brenda W J H; Jansen, Rick; de Geus, Eco J C; Boomsma, Dorret I; Wright, Fred A; Sullivan, Patrick F; Nikkola, Elina; Alvarez, Marcus; Civelek, Mete; Lusis, Aldons J; Lehtimäki, Terho; Raitoharju, Emma; Kähönen, Mika; Seppälä, Ilkka; Raitakari, Olli T; Kuusisto, Johanna; Laakso, Markku; Price, Alkes L; Pajukanta, Päivi; Pasaniuc, Bogdan

    2016-03-01

    Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome-wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ∼ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.

  16. A large-scale genetic screen for mutants with altered salicylic acid accumulation in Arabidopsis.

    PubMed

    Ding, Yezhang; Shaholli, Danjela; Mou, Zhonglin

    2014-01-01

    Salicylic acid (SA) is a key defense signal molecule against biotrophic and hemibiotrophic pathogens in plants, but how SA is synthesized in plant cells still remains elusive. Identification of new components involved in pathogen-induced SA accumulation would help address this question. To this end, we performed a large-scale genetic screen for mutants with altered SA accumulation during pathogen infection in Arabidopsis using a bacterial biosensor Acinetobacter sp. ADPWH_lux-based SA quantification method. A total of 35,000 M2 plants in the npr1-3 mutant background have been individually analyzed for the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326-induced SA accumulation. Among the mutants isolated, 19 had SA levels lower than npr1 (sln) and two exhibited increased SA accumulation in npr1 (isn). Complementation tests revealed that seven of the sln mutants are new alleles of eds5/sid1, two are sid2/eds16 alleles, one is allelic to pad4, and the remaining seven sln and two isn mutants are new non-allelic SA accumulation mutants. Interestingly, a large group of mutants (in the npr1-3 background), in which Psm ES4326-induced SA levels were similar to those in the wild-type Columbia plants, were identified, suggesting that the signaling network fine-tuning pathogen-induced SA accumulation is complex. We further characterized the sln1 single mutant and found that Psm ES4326-induced defense responses were compromised in this mutant. These defense response defects could be rescued by exogenous SA, suggesting that SLN1 functions upstream of SA. The sln1 mutation was mapped to a region on the north arm of chromosome I, which contains no known genes regulating pathogen-induced SA accumulation, indicating that SLN1 likely encodes a new regulator of SA biosynthesis. Thus, the new sln and isn mutants identified in this genetic screen are valuable for dissecting the molecular mechanisms underlying pathogen-induced SA accumulation in plants.

  17. Improving Disease Prediction by Incorporating Family Disease History in Risk Prediction Models with Large-Scale Genetic Data.

    PubMed

    Gim, Jungsoo; Kim, Wonji; Kwak, Soo Heon; Choi, Hosik; Park, Changyi; Park, Kyong Soo; Kwon, Sunghoon; Park, Taesung; Won, Sungho

    2017-09-12

    Despite the many successes of genome-wide association studies (GWAS), the known susceptibility variants identified by GWAS have modest effect sizes, leading to notable skepticism about the effectiveness of building a risk prediction model from large-scale genetic data. However, in contrast to genetic variants, the family history of diseases has been largely accepted as an important risk factor in clinical diagnosis and risk prediction. Nevertheless, the complicated structures of the family history of diseases have limited their application in clinical practice. Here, we developed a new method that enables incorporation of the general family history of diseases with a liability threshold model, and propose a new analysis strategy for risk prediction with penalized regression analysis that incorporates both large numbers of genetic variants and clinical risk factors. Application of our model to type 2 diabetes (T2D) in the Korean population (1846 cases and 1846 controls) demonstrated that single nucleotide polymorphisms accounted for 32.5% of the variation explained by the predicted risk scores in the test data set, and incorporation of family history led to an additional 6.3% improvement in prediction. Our results illustrate that the family medical history is valuable information on the variation of complex diseases and improves prediction performance. Copyright © 2017, Genetics.

  18. Identification of plant stress-responsive determinants in Arabidopsis by large-scale forward genetic screens.

    PubMed

    Koiwa, Hisashi; Bressan, Ray A; Hasegawa, Paul M

    2006-01-01

    All plants sense and adapt to adverse environmental conditions, however, crop plants exhibit less genetic diversity for abiotic stress tolerance than do wild relatives indicating that a genetic basis exists for stress adaptability. Model plant genetic systems and the plethora of molecular genetic resources that are currently available are greatly enhancing our ability to identify abiotic stress-responsive genetic determinants. Forward genetic screens of T-DNA mutagenized Arabidopsis thaliana populations in the genetic background of ecotypes C24(RD29a-LUC) and Col-0 gl1 sos3-1 were carried out to begin an exhaustive search for such determinants. The C24(RD29a-LUC) screens identified mutants with altered salt/osmotic stress sensitivity or mutants with altered expression of the salt/osmotic/cold/ABA-responsive RD29a gene. Also, mutations that alter the NaCl sensitivity of sos3-1 were screened for potential genetic suppressors or enhancers of salt-stress responses mediated by SOS3. In total, more than 250 000 independent insertion lines were screened and greater than 200 individual mutants that exhibited altered stress/ABA responses were recovered. Although several of these mutants have been reported, most have not yet been studied in detail. Notable examples include novel alleles of SOS1 and mutations to genes encoding the STT3a subunit of the oligosaccharyltransferase, syntaxin, RNA polymerase II CTD phosphatases, transcription factors, ABA biosynthetic enzyme, Na+ transporter HKT1, and SUMO E3 ligase. The stress-specific phenotypes of mutations to genes that are involved in many basic cellular functions provide indication of the wide range of control mechanisms in cellular homeostasis that are involved in stress adaptation.

  19. Large-scale natural disturbance alters genetic population structure of the sailfin molly, Poecilia latipinna.

    PubMed

    Apodaca, Joseph J; Trexler, Joel C; Jue, Nathaniel K; Schrader, Matthew; Travis, Joseph

    2013-02-01

    Many inferences about contemporary rates of gene flow are based on the assumption that the observed genetic structure among populations is stable. Recent studies have uncovered several cases in which this assumption is tenuous. Most of those studies have focused on the effects that regular environmental fluctuations can have on genetic structure and gene flow patterns. Occasional catastrophic disturbances could also alter either the distribution of habitat or the spatial distribution of organisms in a way that affects population structure. However, evidence of such effects is sparse in the literature because it is difficult to obtain. Hurricanes, in particular, have the potential to exert dramatic effects on population structure of organisms found on islands or coral reefs or in near shore and coastal habitats. Here we draw on a historic genetic data set and new data to suggest that the genetic structure of sailfin molly (Poecilia latipinna) populations in north Florida was altered dramatically by an unusually large and uncommon type of storm surge associated with Hurricane Dennis in 2005. We compare the spatial pattern of genetic variation in these populations after Hurricane Dennis to the patterns described in an earlier study in this same area. We use comparable genetic data from another region of Florida, collected in the same two periods, to estimate the amount of change expected from typical temporal variation in population structure. The comparative natural history of sailfin mollies in these two regions indicates that the change in population structure produced by the storm surge is not the result of many local extinctions with recolonization from a few refugia but emerged from a pattern of mixing and redistribution.

  20. Large-scale genetic perturbations reveal regulatory networks and an abundance of gene-specific repressors.

    PubMed

    Kemmeren, Patrick; Sameith, Katrin; van de Pasch, Loes A L; Benschop, Joris J; Lenstra, Tineke L; Margaritis, Thanasis; O'Duibhir, Eoghan; Apweiler, Eva; van Wageningen, Sake; Ko, Cheuk W; van Heesch, Sebastiaan; Kashani, Mehdi M; Ampatziadis-Michailidis, Giannis; Brok, Mariel O; Brabers, Nathalie A C H; Miles, Anthony J; Bouwmeester, Diane; van Hooff, Sander R; van Bakel, Harm; Sluiters, Erik; Bakker, Linda V; Snel, Berend; Lijnzaad, Philip; van Leenen, Dik; Groot Koerkamp, Marian J A; Holstege, Frank C P

    2014-04-24

    To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the varying responsiveness to genetic perturbation. The data are assembled into a genetic perturbation network that shows different connectivities for different classes of regulators. Four feed-forward loop (FFL) types are overrepresented, including incoherent type 2 FFLs that likely represent feedback. Systematic transcription factor classification shows a surprisingly high abundance of gene-specific repressors, suggesting that yeast chromatin is not as generally restrictive to transcription as is often assumed. The data set is useful for studying individual genes and for discovering properties of an entire regulatory system.

  1. Integrative approaches for large-scale transcriptome-wide association studies

    PubMed Central

    Gusev, Alexander; Ko, Arthur; Shi, Huwenbo; Bhatia, Gaurav; Chung, Wonil; Penninx, Brenda W J H; Jansen, Rick; de Geus, Eco JC; Boomsma, Dorret I; Wright, Fred A; Sullivan, Patrick F; Nikkola, Elina; Alvarez, Marcus; Civelek, Mete; Lusis, Aldons J.; Lehtimäki, Terho; Raitoharju, Emma; Kähönen, Mika; Seppälä, Ilkka; Raitakari, Olli T.; Kuusisto, Johanna; Laakso, Markku; Price, Alkes L.; Pajukanta, Päivi; Pasaniuc, Bogdan

    2016-01-01

    Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. Here, we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated to complex traits. We leverage expression imputation to perform a transcriptome wide association scan (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ~3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits. PMID:26854917

  2. Effects of Large-Scale Releases on the Genetic Structure of Red Sea Bream (Pagrus major, Temminck et Schlegel) Populations in Japan.

    PubMed

    Blanco Gonzalez, Enrique; Aritaki, Masato; Knutsen, Halvor; Taniguchi, Nobuhiko

    2015-01-01

    Large-scale hatchery releases are carried out for many marine fish species worldwide; nevertheless, the long-term effects of this practice on the genetic structure of natural populations remains unclear. The lack of knowledge is especially evident when independent stock enhancement programs are conducted simultaneously on the same species at different geographical locations, as occurs with red sea bream (Pagrus major, Temminck et Schlegel) in Japan. In this study, we examined the putative effects of intensive offspring releases on the genetic structure of red sea bream populations along the Japanese archipelago by genotyping 848 fish at fifteen microsatellite loci. Our results suggests weak but consistent patterns of genetic divergence (F(ST) = 0.002, p < 0.001). Red sea bream in Japan appeared spatially structured with several patches of distinct allelic composition, which corresponded to areas receiving an important influx of fish of hatchery origin, either released intentionally or from unintentional escapees from aquaculture operations. In addition to impacts upon local populations inhabiting semi-enclosed embayments, large-scale releases (either intentionally or from unintentional escapes) appeared also to have perturbed genetic structure in open areas. Hence, results of the present study suggest that independent large-scale marine stock enhancement programs conducted simultaneously on one species at different geographical locations may compromise native genetic structure and lead to patchy patterns in population genetic structure.

  3. Effects of Large-Scale Releases on the Genetic Structure of Red Sea Bream (Pagrus major, Temminck et Schlegel) Populations in Japan

    PubMed Central

    Blanco Gonzalez, Enrique; Aritaki, Masato; Knutsen, Halvor; Taniguchi, Nobuhiko

    2015-01-01

    Large-scale hatchery releases are carried out for many marine fish species worldwide; nevertheless, the long-term effects of this practice on the genetic structure of natural populations remains unclear. The lack of knowledge is especially evident when independent stock enhancement programs are conducted simultaneously on the same species at different geographical locations, as occurs with red sea bream (Pagrus major, Temminck et Schlegel) in Japan. In this study, we examined the putative effects of intensive offspring releases on the genetic structure of red sea bream populations along the Japanese archipelago by genotyping 848 fish at fifteen microsatellite loci. Our results suggests weak but consistent patterns of genetic divergence (FST = 0.002, p < 0.001). Red sea bream in Japan appeared spatially structured with several patches of distinct allelic composition, which corresponded to areas receiving an important influx of fish of hatchery origin, either released intentionally or from unintentional escapees from aquaculture operations. In addition to impacts upon local populations inhabiting semi-enclosed embayments, large-scale releases (either intentionally or from unintentional escapes) appeared also to have perturbed genetic structure in open areas. Hence, results of the present study suggest that independent large-scale marine stock enhancement programs conducted simultaneously on one species at different geographical locations may compromise native genetic structure and lead to patchy patterns in population genetic structure. PMID:25993089

  4. Expert and self-assessment of lifetime symptoms and diagnosis of major depressive disorder in large-scale genetic studies in the general population: comparison of a clinical interview and a self-administered checklist

    PubMed Central

    Martin, Jessica; Streit, Fabian; Treutlein, Jens; Lang, Maren; Frank, Josef; Forstner, Andreas J.; Degenhardt, Franziska; Witt, Stephanie H.; Schulze, Thomas G.; Cichon, Sven; Nöthen, Markus M.; Rietschel, Marcella

    2017-01-01

    Major depression disorder (MDD) is a complex neuropsychiatric disorder and an increasing number of genetic risk variants are being identified. Investigation of their influence in the general population requires accurate and efficient assessment of depressive symptoms. Here, clinical interviews conducted by clinicians are the gold standard. We investigated whether valid and reliable clinical phenotypes can be obtained efficiently using self-administered instruments. Lifetime depressive symptoms and lifetime MDD diagnosis were assessed in 464 population-based individuals using a clinical interview and a structured, self-administered checklist. Analyses were carried out of the following: (i) intraclass correlations (ICC) between checklist and interview; (ii) sensitivity/specificity of the checklist; and (iii) the association of interview and checklist with a positive family history of MDD (FH-MDD+). The correspondence of the self-administered checklist with the clinical interview was good for most depressive symptoms (ICC=0.60–0.80) and moderate for MDD diagnosis (ICC=0.45). With the consecutive inclusion of MDD diagnostic criteria, sensitivity decreased from 0.67 to 0.46, whereas specificity remained high (0.95). For checklist and interview, strong associations were found between FH-MDD+ and most depressive symptoms and MDD diagnosis (all odds ratio≥1.83). The self-administered checklist showed high reliability for both the assessment of lifetime depressive symptoms and screening for individuals with no lifetime diagnosis of MDD. However, attention is warranted when the aim is to identify MDD cases. The positive association between depressive symptomatology and FH-MDD+ indicates the usefulness of both instruments to assess patients in genetic studies. Our data suggest that the more time-efficient and cost-efficient self-administered instruments also allow for the assessment of depressive symptoms accurate enough to investigate the influence of MDD genetic risk

  5. Large-scale discovery of novel genetic causes of developmental disorders.

    PubMed

    2015-03-12

    Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.

  6. Systematic large-scale study of the inheritance mode of Mendelian disorders provides new insight into human diseasome.

    PubMed

    Hao, Dapeng; Wang, Guangyu; Yin, Zuojing; Li, Chuanxing; Cui, Yan; Zhou, Meng

    2014-11-01

    One important piece of information about the human Mendelian disorders is the mode of inheritance. Recent studies of human genetic diseases on a large scale have provided many novel insights into the underlying molecular mechanisms. However, most successful analyses ignored the mode of inheritance of diseases, which severely limits our understanding of human disease mechanisms relating to the mode of inheritance at the large scale. Therefore, we here conducted a systematic large-scale study of the inheritance mode of Mendelian disorders, to bring new insight into human diseases. Our analyses include the comparison between dominant and recessive disease genes on both genomic and proteomic characteristics, Mendelian mutations, protein network properties and disease connections on both the genetic and the population levels. We found that dominant disease genes are more functionally central, topological central and more sensitive to disease outcome. On the basis of these findings, we suggested that dominant diseases should have higher genetic heterogeneity and should have more comprehensive connections with each other compared with recessive diseases, a prediction we confirm by disease network and disease comorbidity.

  7. Genetic effects of a large-scale Spartina alterniflora (smooth cordgrass) dieback and recovery in the northern Gulf of Mexico

    USGS Publications Warehouse

    Edwards, K.R.; Travis, S.E.; Proffitt, C.E.

    2005-01-01

    A large-scale dieback event struck marshes along the northwestern Gulf of Mexico coast during summer 2000, in apparent response to a prolonged and severe drought. Along the Louisiana coast, large areas of the dominant marsh species, Spartina alterniflora, turned brown, followed by death of at least the aboveground structures or entire plant mortality. Key ecological and genetic measures were studied in a dieback-affected marsh in southwest Louisiana (C83 marsh, Sabine National Wildlife Refuge), for which existed predieback ecologic and genetic datasets. Effects on genetic diversity only were studied in a second set of sites in southeastern Louisiana (near Bay Junop), where the dieback was more widespread. We hypothesized that stem density, live aboveground biomass, and genetic diversity would be significantly reduced compared to predieback conditions and to nearby unaffected marshes. Stem densities and biomass levels approached predieback conditions 14 months after first observance of the dieback in the Sabine marsh and were similar to or exceeded the same measures for a nearby unaffected marsh. DNA extracted from leaf samples in the Sabine and Bay Junop sites was used to construct genotype profiles using AFLPs and analyzed using the complement of Simpson's Index (1-D), the richness measure G/N, average heterozygosity ???H???, and the estimated proportion of polymorphic genes ???P???. Genetic diversity was relatively unaffected by the dieback at either the Sabine or Bay Junop sites. Evidence from field observations and the results of the genetic analyses suggest that seedling recruitment is an important factor in the recovery of both the Bay Junop and C83 sites, although re-growth from surviving below-ground rhizomes appeared to dominate recovery at the latter site. Survival of below-ground structures, leading to the rapid recovery observed, indicates a high level of resilience of the Sabine marsh to drought-induced stress. Still, the genetic diversity of S

  8. Large-scale targeted sequencing comparison highlights extreme genetic heterogeneity in nephronophthisis-related ciliopathies

    PubMed Central

    Schueler, Markus; Halbritter, Jan; Phelps, Ian G.; Braun, Daniela A.; Otto, Edgar A.; Porath, Jonathan D.; Gee, Heon Yung; Shendure, Jay; O’Roak, Brian J.; Lawson, Jennifer A.; Soliman, Neveen A.; Nabhan, Marwa M.; Doherty, Dan; Hildebrandt, Friedhelm

    2016-01-01

    The term nephronophthisis-related ciliopathies (NPHP-RC) describes a group of rare autosomal-recessive cystic kidney diseases, characterized by broad genetic and clinical heterogeneity. NPHP-RC is frequently associated with extrarenal manifestations and accounts for the majority of genetically caused chronic kidney disease (CKD) during childhood and adolescence. Generation of a molecular diagnosis has been impaired by this broad genetic heterogeneity. However, recently developed high-throughput exon sequencing techniques represent powerful and efficient tools to screen large cohorts for dozens of causative genes. Therefore, we performed massively multiplexed targeted sequencing using the modified molecular inversion probe (MIPs) strategy in an international cohort of 384 patients diagnosed with NPHP-RC. As a result, we established the molecular diagnoses in 81/384 unrelated individuals (21.1%). We detected 127 likely disease-causing mutations in 18 of 34 evaluated NPHP-RC genes, 22 of which were novel. We further compared a subgroup of current findings to the results of a previous study in which we used an array-based microfluidic PCR technology in the same cohort. While 78 likely disease-causing mutations were previously detected by the array-based microfluidic PCR, the MIPs approach identified 94 likely pathogenic mutations. Compared to the previous approach, MIPs re-detected 66 out of 78 variants and 28 previously unidentified variants, for a total of 94 variants. In summary, we demonstrate that the modified MIPs technology is a useful approach to screen large cohorts for a multitude of established NPHP genes in order to identify the underlying molecular cause. Combined application of two independent library preparation and sequencing techniques, however, may still be indicated for Mendelian diseases with extensive genetic heterogeneity in order to further increase diagnostic sensitivity. PMID:26673778

  9. Rare Variants Association Analysis in Large-Scale Sequencing Studies at the Single Locus Level

    PubMed Central

    Lu, Wenbin; Tzeng, Jung-Ying

    2016-01-01

    Genetic association analyses of rare variants in next-generation sequencing (NGS) studies are fundamentally challenging due to the presence of a very large number of candidate variants at extremely low minor allele frequencies. Recent developments often focus on pooling multiple variants to provide association analysis at the gene instead of the locus level. Nonetheless, pinpointing individual variants is a critical goal for genomic researches as such information can facilitate the precise delineation of molecular mechanisms and functions of genetic factors on diseases. Due to the extreme rarity of mutations and high-dimensionality, significances of causal variants cannot easily stand out from those of noncausal ones. Consequently, standard false-positive control procedures, such as the Bonferroni and false discovery rate (FDR), are often impractical to apply, as a majority of the causal variants can only be identified along with a few but unknown number of noncausal variants. To provide informative analysis of individual variants in large-scale sequencing studies, we propose the Adaptive False-Negative Control (AFNC) procedure that can include a large proportion of causal variants with high confidence by introducing a novel statistical inquiry to determine those variants that can be confidently dispatched as noncausal. The AFNC provides a general framework that can accommodate for a variety of models and significance tests. The procedure is computationally efficient and can adapt to the underlying proportion of causal variants and quality of significance rankings. Extensive simulation studies across a plethora of scenarios demonstrate that the AFNC is advantageous for identifying individual rare variants, whereas the Bonferroni and FDR are exceedingly over-conservative for rare variants association studies. In the analyses of the CoLaus dataset, AFNC has identified individual variants most responsible for gene-level significances. Moreover, single-variant results

  10. A Large-Scale Study of the Characteristics of Asperger Syndrome

    ERIC Educational Resources Information Center

    Myles, Brenda Smith; Lee, Hyo Jung; Smith, Sheila M.; Tien, Kai-Chien; Chou, Yu-Chi; Swanson, Terri Cooper; Hudson, Jill

    2007-01-01

    This article presents the results of a large-scale study of the characteristics of 156 individuals with Asperger Syndrome (AS) ages 12 to 18. Specifically, cognitive (intellectual, empathizing, systemizing), adaptive behavior, behavior, temperament, and sensory profiles of study participants are overviewed. These characteristics are discussed as…

  11. A Fundamental Study for Efficient Implementaion of Online Collaborative Activities in Large-Scale Classes

    ERIC Educational Resources Information Center

    Matsuba, Ryuichi; Suzuki, Yusei; Kubota, Shin-Ichiro; Miyazaki, Makoto

    2015-01-01

    We study tactics for writing skills development through cross-disciplinary learning in online large-scale classes, and particularly are interested in implementation of online collaborative activities such as peer reviewing of writing. The goal of our study is to carry out collaborative works efficiently via online effectively in large-scale…

  12. Large-scale genetic survey provides insights into the captive management and reintroduction of giant pandas.

    PubMed

    Shan, Lei; Hu, Yibo; Zhu, Lifeng; Yan, Li; Wang, Chengdong; Li, Desheng; Jin, Xuelin; Zhang, Chenglin; Wei, Fuwen

    2014-10-01

    The captive genetic management of threatened species strives to preserve genetic diversity and avoid inbreeding to ensure populations remain available, healthy, and viable for future reintroduction. Determining and responding to the genetic status of captive populations is therefore paramount to these programs. Here, we genotyped 19 microsatellite loci for 240 captive giant pandas (Ailuropoda melanoleuca) (∼64% of the captive population) from four breeding centers, Wolong (WL), Chengdu (CD), Louguantai (LGT), and Beijing (BJ), and analyzed 655 bp of mitochondrial DNA control region sequence for 220 of these animals. High levels of genetic diversity and low levels of inbreeding were estimated in the breeding centers, indicating that the captive population is genetically healthy and deliberate further genetic input from wild animals is unnecessary. However, the LGT population faces a higher risk of inbreeding, and significant genetic structure was detected among breeding centers, with LGT-CD and WL-BJ clustering separately. Based on these findings, we highlight that: 1) the LGT population should be managed as an independent captive population to resemble the genetic distinctness of their Qinling Mountain origins; 2) exchange between CD and WL should be encouraged because of similar wild founder sources; 3) the selection of captive individuals for reintroduction should consider their geographic origin, genetic background, and genetic contribution to wild populations; and 4) combining our molecular genetic data with existing pedigree data will better guide giant panda breeding and further reduce inbreeding into the future.

  13. Nurture Groups: A Large-Scale, Controlled Study of Effects on Development and Academic Attainment

    ERIC Educational Resources Information Center

    Reynolds, Sue; MacKay, Tommy; Kearney, Maura

    2009-01-01

    Nurture groups have contributed to inclusive practices in primary schools in the UK for some time now and have frequently been the subject of articles in this journal. This large-scale, controlled study of nurture groups across 32 schools in the City of Glasgow provides further evidence for their effectiveness in addressing the emotional…

  14. Study of large-scale mixing in developing wakes behind streamlined bodies

    NASA Technical Reports Server (NTRS)

    Ramaprian, B. R.; Kalale, K. P. L.; Jovic, S.; Kaushik, S.

    1984-01-01

    Heat-tagging and conditional sampling techniques were used to study the large scale mixing process in the developing wake behind a streamlined body. The results were used to understand the manner in which the large eddy length scale evolves from a value appropriate to a boundary layer to that appropriate to the asymptotic far-wake.

  15. Soil physical properties of agricultural systems in a large-scale study

    USDA-ARS?s Scientific Manuscript database

    A large-scale field study was performed to determine the effects of agricultural management systems on soil physical properties, including their spatial and temporal variations. Replicates were established in 1998 at the Center for Environmental Farming Systems, Goldsboro, North Carolina; replicates...

  16. LARGE SCALE CARCINOGEN DOSE RESPONSE STUDIES WITH JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    To investigate the responses to low carcinogen doses in animal models, large sample sizes are needed and it is an advantage if the model has a low spontaneous tumor rate. Three large scale dose response studies were conducted using Japanese medaka and the carcinogen diethylnitros...

  17. Home Language and Language Proficiency; A Large-Scale Longitudinal Study in Dutch Primary Schools.

    ERIC Educational Resources Information Center

    Driessen, Geert; van der Slik, Frans; De Bot, Kees

    2002-01-01

    Reports on a large-scale longitudinal study into the development of language proficiency of Dutch primary school children aged 7-10. Data on language proficiency and a range of background variables were analyzed. Results suggest that while immigrant children develop their language skill in Dutch considerably over 2 years, they are nonetheless…

  18. LARGE SCALE CARCINOGEN DOSE RESPONSE STUDIES WITH JAPANESE MEDAKA (ORYZIAS LATIPES)

    EPA Science Inventory

    To investigate the responses to low carcinogen doses in animal models, large sample sizes are needed and it is an advantage if the model has a low spontaneous tumor rate. Three large scale dose response studies were conducted using Japanese medaka and the carcinogen diethylnitros...

  19. Home Language and Language Proficiency; A Large-Scale Longitudinal Study in Dutch Primary Schools.

    ERIC Educational Resources Information Center

    Driessen, Geert; van der Slik, Frans; De Bot, Kees

    2002-01-01

    Reports on a large-scale longitudinal study into the development of language proficiency of Dutch primary school children aged 7-10. Data on language proficiency and a range of background variables were analyzed. Results suggest that while immigrant children develop their language skill in Dutch considerably over 2 years, they are nonetheless…

  20. Effects of large-scale nonstationarity on parametric maps. A study of rest perfusion CASL data.

    PubMed

    Viviani, Roberto

    2011-02-01

    This study investigates the emergence of characteristic patterns in clusters thresholded at uncorrected significance levels, using as a case study rest perfusion images obtained with the continuous arterial spin labelling technique (CASL). The origin of these patterns is traced back to the existence of large-scale spatial covariance, a violation of the stationarity assumption on the spatial distribution of residual errors. It is shown that in the presence of large-scale covariance, several principles or intuitions common among experimenters when evaluating the inferential strength of their analyses are not applicable. Thresholded maps and clusters are confounded by the spatial patterns of large-scale covariance, irrespective of the existence of a true effect, as shown in t maps constructed by resampling groups at random from a large pool of volumes. Filtering clusters according to their size made the problem worse, and corrections on cluster size based on random field theory models of smoothness had only a minor impact on their tendency to appear in characteristic locations. A formal analysis shows that the large-scale covariance at the origin of these problems is retained in the parametric map irrespective of sample size. Therefore, neither sample independence nor sample size protect from replications of effects being confounded by replications of the spatial covariance of residual errors. In contrast, cluster peaks were not affected by large-scale covariance but only by local differences in smoothness levels, as predicted by random field theory for the distribution of maxima, highlighting the different inferential robustness of cluster-based and maxima-based statistics. A framework is provided to generalize these results to mixed effects models with nested random effects, applicable also to activation studies. Large-scale nonstationarity is most problematic when the variance source at the origin of the characteristic patterns is not specific to a function or

  1. Temperature dependence of large-scale water retention curves: Acase study

    SciTech Connect

    Liu, Hui-Hai; Bodvarsson, G.S.; Dane, J.H.

    2001-10-26

    A local-scale model for temperature-dependence of water-retention curves may be applicable to large scales. Consideration of this temperature dependence is important for modeling unsaturated flow and transport in the subsurface in numerous cases. Although significant progress has been made in understanding and modeling this temperature effect, almost all the previous studies have been limited to small scales (on the order of several centimeters). Numerical experiments were used to investigate the possibility of extending a local-scale model for the temperature-dependence of water retention curves to large scales (on the order of meters). Temperature effects on large-scale hydraulic properties are of interest in many practical applications. Numerical experiment results indicate that the local-scale model can indeed be applicable to large-scale problems for special porous media with high air entry values. A typical porous medium of this kind is the porous tuff matrix in the unsaturated zone of Yucca Mountain, Nevada, the proposed geologic disposal site for national high-level nuclear wastes. Whether this finding can approximately hold for general cases needs to be investigated in future studies.

  2. Using DNA barcoding and phylogenetics to identify Antarctic invertebrate larvae: Lessons from a large scale study.

    PubMed

    Heimeier, Dorothea; Lavery, Shane; Sewell, Mary A

    2010-01-01

    Ecological studies of the diversity and distribution of marine planktonic larvae are increasingly depending on molecular methods for accurate taxonomic identification. The greater coverage of reference marine species on genetic databases such as GenBank and BoLD (Barcoding of Life Data Systems; www.boldystems.org); together with the decreasing costs for DNA sequencing have made large scale larval identification studies using molecular methods more feasible. Here, we present the development and implementation of a practical molecular approach to identify over 2000 individual marine invertebrate larvae that were collected in the Ross Sea, Antarctica, during the austral summer over five years (2002-2007) as part of the LGP (Latitudinal Gradient Project). Larvae for molecular ID were morphologically identified to belong to the Phyla Mollusca, Echinodermata, Nemertea and Annelida (Class Polychaeta), but also included unidentified early developmental stages which could not be assigned a specific taxon (e.g., eggs, blastulae). The use of a 100μm mesh plankton net makes this one of the first larval identification studies to simultaneously consider both embryos and larvae. Molecular identification methods included amplification of up to three molecular loci for each specimen, a pre-identification step using BLAST with GenBank, phylogenetic reconstructions and cross-validation of assigned Molecular Operational Taxonomic Units (MOTUs). This combined approach of morphological and molecular methods assigned about 700 individuals to 53 MOTUs, which were identified to the lowest possible taxonomic level. During the course of this long-term study we identified several procedural difficulties, including issues with the collection of larvae, locus amplification, contamination, assignment and validation of MOTUs. The practical guidelines that we describe here should greatly assist other researchers to conduct reliable molecular identification studies of larvae in the future

  3. Large-Scale Wind Integration Studies in the United States: Preliminary Results

    SciTech Connect

    Milligan, M.; Lew, D.; Corbus, D.; Piwko, R.; Miller, N.; Clark, K.; Jordan, G.; Freeman, L.; Zavadil, B.; Schuerger, M.

    2009-01-01

    The National Renewable Energy Laboratory, under the sponsorship of the U.S. Department of Energy, is managing two large-scale wind integration studies. The Western Wind and Solar Integration Study (WWSIS) covers the footprint of WestConnect, a group of transmission owners that covers most of Colorado, New Mexico, Arizona, Nevada, and Wyoming. The Eastern Wind Integration and Transmission Study (EWITS) covers a large part of the Eastern Interconnection, and leverages a large-scale transmission study known as the Joint Coordinated System Plan (JCSP). Both studies analyze the impact of 20-30% wind energy penetration within the study footprint based on energy. This paper discusses key results that have emerged so far from each study, focusing primarily on simulation results based on hourly production simulations. Results from both studies show that high wind penetrations can be successfully integrated into the power system, but depend on sufficient transmission and significant changes in operations.

  4. Large-scale spatial and temporal genetic diversity of feline calicivirus.

    PubMed

    Coyne, Karen P; Christley, Rob M; Pybus, Oliver G; Dawson, Susan; Gaskell, Rosalind M; Radford, Alan D

    2012-10-01

    Feline calicivirus (FCV) is an important pathogen of domestic cats and a frequently used model of human caliciviruses. Here we use an epidemiologically rigorous sampling framework to describe for the first time the phylodynamics of a calicivirus at regional and national scales. A large number of FCV strains cocirculated in the United Kingdom at the national and community levels, with no strain comprising more than 5% and 14% of these populations, respectively. The majority of strains exhibited a relatively restricted geographical range, with only two strains (one field virus and one vaccine virus) spreading further than 100 km. None of the field strains were identified outside the United Kingdom. Temporally, while some strains persisted locally for the majority of the study, others may have become locally extinct. Evolutionary analysis revealed a radial phylogeny with little bootstrap support for nodes above the strain level. In most cases, spatially and temporally diverse strains intermingled in the phylogeny. Together, these data suggest that current FCV evolution is not associated with selective competition among strains. Rather, the genetic and antigenic landscape in each geographical location is highly complex, with many strains cocirculating. These variants likely exist at the community level by a combination of de novo evolution and occasional gene flow from the wider national population. This complexity provides a benchmark, for the first time, against which vaccine cross-protection at both local and national levels can be judged.

  5. Large-Scale Spatial and Temporal Genetic Diversity of Feline Calicivirus

    PubMed Central

    Coyne, Karen P.; Christley, Rob M.; Pybus, Oliver G.; Dawson, Susan; Gaskell, Rosalind M.

    2012-01-01

    Feline calicivirus (FCV) is an important pathogen of domestic cats and a frequently used model of human caliciviruses. Here we use an epidemiologically rigorous sampling framework to describe for the first time the phylodynamics of a calicivirus at regional and national scales. A large number of FCV strains cocirculated in the United Kingdom at the national and community levels, with no strain comprising more than 5% and 14% of these populations, respectively. The majority of strains exhibited a relatively restricted geographical range, with only two strains (one field virus and one vaccine virus) spreading further than 100 km. None of the field strains were identified outside the United Kingdom. Temporally, while some strains persisted locally for the majority of the study, others may have become locally extinct. Evolutionary analysis revealed a radial phylogeny with little bootstrap support for nodes above the strain level. In most cases, spatially and temporally diverse strains intermingled in the phylogeny. Together, these data suggest that current FCV evolution is not associated with selective competition among strains. Rather, the genetic and antigenic landscape in each geographical location is highly complex, with many strains cocirculating. These variants likely exist at the community level by a combination of de novo evolution and occasional gene flow from the wider national population. This complexity provides a benchmark, for the first time, against which vaccine cross-protection at both local and national levels can be judged. PMID:22855496

  6. Problems in setting up an executing large-scale psychiatric epidemiological studies.

    PubMed

    Offord, D R; Boyle, M H

    1986-01-01

    This paper focuses on problems that can be encountered in conceptualizing, executing and writing up large-scale psychiatric epidemiological studies. It makes no attempt to cover fundamental issues of design and analysis, rather it centers on problems associated with projects of considerable size. In the conceptual area, it discusses the prerequisites to be considered before deciding to launch such a study. It notes the administrative and scientific uses of epidemiological studies and considers the strengths and weaknesses of large-scale studies to address those concerns. Issues in carrying out such studies are discussed including decisions about study design, sampling method and instrumentation. All are dependent on the central purpose of the study but trade-offs between feasibility and scientific rigor are always present. Data collection and analysis problems highlighted in large-scale studies are examined. They include the difficulty, in the former, of adequately motivating and supervising field personnel and, in the latter, of dealing with problems that accompany missing data and complicated sampling strategies. Potential problems in data access and use and writing up the results are seen as arising from the presence of a large investigative team with diverse interests. Lastly, the comparative worth of these studies is considered.

  7. A large scale analysis of genetic variants within putative miRNA binding sites in prostate cancer

    PubMed Central

    Stegeman, Shane; Amankwah, Ernest; Klein, Kerenaftali; O’Mara, Tracy A.; Kim, Donghwa; Lin, Hui-Yi; Permuth-Wey, Jennifer; Sellers, Thomas A.; Srinivasan, Srilakshmi; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Olama, Ali Amin Al; Benlloch, Sara; Muir, Kenneth; Giles, Graham G.; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A.; Schleutker, Johanna; Nordestgaard, Børge G.; Travis, Ruth C.; Neal, David; Pharoah, Paul; Khaw, Kay-Tee; Stanford, Janet L.; Blot, William J.; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S.; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Kaneva, Radka; Teixeira, Manuel R.; Consortium, PRACTICAL; Spurdle, Amanda B.; Clements, Judith A.; Park, Jong Y.; Batra, Jyotsna

    2015-01-01

    Prostate cancer is the second most common malignancy among men worldwide. Genome-wide association studies (GWAS) have identified 100 risk variants for prostate cancer, which can explain ~33% of the familial risk of the disease. We hypothesized that a comprehensive analysis of genetic variations found within the 3′ UTR of genes predicted to affect miRNA binding (miRSNPs) can identify additional prostate cancer risk variants. We investigated the association between 2,169 miRSNPs and prostate cancer risk in a large-scale analysis of 22,301 cases and 22,320 controls of European ancestry from 23 participating studies. Twenty-two miRSNPs were associated (p<2.3×10−5) with risk of prostate cancer, 10 of which were within the 7 genes previously not mapped by GWASs. Further, using miRNA mimics and reporter gene assays, we showed that miR-3162-5p has specific affinity for the KLK3 rs1058205 miRSNP T-allele whilst miR-370 has greater affinity for the VAMP8 rs1010 miRSNP A-allele, validating their functional role. Significance Findings from this large association study suggest that a focus on miRSNPs, including functional evaluation, can identify candidate risk loci below currently accepted statistical levels of genome-wide significance. Studies of miRNAs and their interactions with SNPs could provide further insights into the mechanisms of prostate cancer risk. PMID:25691096

  8. A study of energetic large-scale structures in turbulent boundary layer

    NASA Astrophysics Data System (ADS)

    Wu, Yanhua

    2014-04-01

    This study established the connection in turbulent boundary layers between the first two dominant proper orthogonal decomposition (POD) modes and the instantaneous large-scale turbulence structures. The velocity fields consistent with the signature velocity fields of the hairpin vortex packets in two-dimensional PIV (particle image velocimetry) measurement planes are observed as the major contributors to the first two POD modes. Another kind of equally important turbulence structure is the large region of Q4 vectors, which may possibly be obtained by slicing the outskirts of the three-dimensional structure of the hairpin vortex packet by PIV planes. The streamwise Reynolds normal stress, Reynolds shear stress, and the length scales of the two-point velocity correlation coefficients ρuu and ρuv are noticeably decreased without those large-scale turbulence structures contributing significantly to the first POD mode. Similarity of these results is observed at a higher Reynolds number.

  9. Experimental study of large-scale pulsations of a fluidized bed

    SciTech Connect

    Glinskii, V.A.; Protod'yakonov, I.O.; Chesnokov, Yu.G.

    1980-01-01

    In experimental investigations of the hydrodynamics of fluidized beds, study of large- and small-scale pulsations of the most important characteristics of the fluidized bed: voidage, hydraulic resistance, velocities of the gaseous and solid phases, etc., is of considerable interest. The character of these pulsations is determined by the heterogeneity of the structure of the fluidized bed, due to the presence of channels, bubbles, stagnant zones, and circulation currents. The object of the present work was experimental study of fluctuations of the height h of the surface of a fluidized bed, with simultaneous recording of the corresponding fluctuations of the hydraulic resistance ..delta..P of the bed. The existence of a direct connection between large-scale pulsations of the hydraulic resistance ..delta..P of the fluidized bed and large-scale pulsations of the bed height h is demonstrated in the paper. It is proved on this basis that large-scale pulsations of h and ..delta..P can be described by equations of the same type. The coefficients of the equation are determined from experimental data on pulsations, and its solutions for different fluidization regimes are analyzed.

  10. Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells.

    PubMed

    Weinberg, Benjamin H; Pham, N T Hang; Caraballo, Leidy D; Lozanoski, Thomas; Engel, Adrien; Bhatia, Swapnil; Wong, Wilson W

    2017-05-01

    Engineered genetic circuits for mammalian cells often require extensive fine-tuning to perform as intended. We present a robust, general, scalable system, called 'Boolean logic and arithmetic through DNA excision' (BLADE), to engineer genetic circuits with multiple inputs and outputs in mammalian cells with minimal optimization. The reliability of BLADE arises from its reliance on recombinases under the control of a single promoter, which integrates circuit signals on a single transcriptional layer. We used BLADE to build 113 circuits in human embryonic kidney and Jurkat T cells and devised a quantitative, vector-proximity metric to evaluate their performance. Of 113 circuits analyzed, 109 functioned (96.5%) as intended without optimization. The circuits, which are available through Addgene, include a 3-input, two-output full adder; a 6-input, one-output Boolean logic look-up table; circuits with small-molecule-inducible control; and circuits that incorporate CRISPR-Cas9 to regulate endogenous genes. BLADE enables execution of sophisticated cellular computation in mammalian cells, with applications in cell and tissue engineering.

  11. Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.

    PubMed

    Lapteva, Natalia; Parihar, Robin; Rollins, Lisa A; Gee, Adrian P; Rooney, Cliona M

    2016-01-01

    Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells. These methodologies are good manufacturing practice (GMP) compliant and could be used for clinical-grade product manufacturing.

  12. Large-scale diversification without genetic isolation in nematode symbionts of figs

    PubMed Central

    Susoy, Vladislav; Herrmann, Matthias; Kanzaki, Natsumi; Kruger, Meike; Nguyen, Chau N.; Rödelsperger, Christian; Röseler, Waltraud; Weiler, Christian; Giblin-Davis, Robin M.; Ragsdale, Erik J.; Sommer, Ralf J.

    2016-01-01

    Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig-associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity. PMID:26824073

  13. Large-scale diversification without genetic isolation in nematode symbionts of figs.

    PubMed

    Susoy, Vladislav; Herrmann, Matthias; Kanzaki, Natsumi; Kruger, Meike; Nguyen, Chau N; Rödelsperger, Christian; Röseler, Waltraud; Weiler, Christian; Giblin-Davis, Robin M; Ragsdale, Erik J; Sommer, Ralf J

    2016-01-01

    Diversification is commonly understood to be the divergence of phenotypes accompanying that of lineages. In contrast, alternative phenotypes arising from a single genotype are almost exclusively limited to dimorphism in nature. We report a remarkable case of macroevolutionary-scale diversification without genetic divergence. Upon colonizing the island-like microecosystem of individual figs, symbiotic nematodes of the genus Pristionchus accumulated a polyphenism with up to five discrete adult morphotypes per species. By integrating laboratory and field experiments with extensive genotyping of individuals, including the analysis of 49 genomes from a single species, we show that rapid filling of potential ecological niches is possible without diversifying selection on genotypes. This uncoupling of morphological diversification and speciation in fig-associated nematodes has resulted from a remarkable expansion of discontinuous developmental plasticity.

  14. Large-Scale Identification of Putative Exported Proteins in Candida albicans by Genetic Selection

    PubMed Central

    Monteoliva, L.; López Matas, M.; Gil, C.; Nombela, C.; Pla, J.

    2002-01-01

    In all living organisms, secreted proteins play essential roles in different processes. Of special interest is the construction of the fungal cell wall, since this structure is absent from mammalian cells. The identification of the proteins involved in its biogenesis is therefore a primary goal in antifungal research. To perform a systematic identification of such proteins in Candida albicans, we carried out a genetic screening in which in-frame fusions with an intracellular allele of invertase gene SUC2 of Saccharomyces cerevisiae can be used to select and identify putatively exported proteins in the heterologous host S. cerevisiae. Eighty-three clones were selected, including 11 previously identified genes from C. albicans as well as 41 C. albicans genes that encode proteins homologous to already described proteins from related organisms. They include enzymes involved in cell wall synthesis and protein secretion. We also found membrane receptors and transporters presumably related to the interaction of C. albicans with the environment as well as extracellular enzymes and proteins involved in different morphological transitions. In addition, 11 C. albicans open reading frames (ORFs) identified in this screening encode proteins homologous to unknown or putative proteins, while 5 ORFs encode novel secreted proteins without known homologues in other organisms. This screening procedure therefore not only identifies a set of targets of interest in antifungal research but also provides new clues for understanding the topological locations of many proteins involved in processes relevant to the pathogenicity of this microorganism. PMID:12456000

  15. Large-scale identification of putative exported proteins in Candida albicans by genetic selection.

    PubMed

    Monteoliva, L; Matas, M López; Gil, C; Nombela, C; Pla, J

    2002-08-01

    In all living organisms, secreted proteins play essential roles in different processes. Of special interest is the construction of the fungal cell wall, since this structure is absent from mammalian cells. The identification of the proteins involved in its biogenesis is therefore a primary goal in antifungal research. To perform a systematic identification of such proteins in Candida albicans, we carried out a genetic screening in which in-frame fusions with an intracellular allele of invertase gene SUC2 of Saccharomyces cerevisiae can be used to select and identify putatively exported proteins in the heterologous host S. cerevisiae. Eighty-three clones were selected, including 11 previously identified genes from C. albicans as well as 41 C. albicans genes that encode proteins homologous to already described proteins from related organisms. They include enzymes involved in cell wall synthesis and protein secretion. We also found membrane receptors and transporters presumably related to the interaction of C. albicans with the environment as well as extracellular enzymes and proteins involved in different morphological transitions. In addition, 11 C. albicans open reading frames (ORFs) identified in this screening encode proteins homologous to unknown or putative proteins, while 5 ORFs encode novel secreted proteins without known homologues in other organisms. This screening procedure therefore not only identifies a set of targets of interest in antifungal research but also provides new clues for understanding the topological locations of many proteins involved in processes relevant to the pathogenicity of this microorganism.

  16. How to assess common somatic symptoms in large-scale studies: a systematic review of questionnaires.

    PubMed

    Zijlema, Wilma L; Stolk, Ronald P; Löwe, Bernd; Rief, Winfried; White, Peter D; Rosmalen, Judith G M

    2013-06-01

    Many questionnaires for assessment of common somatic symptoms or functional somatic symptoms are available and their use differs greatly among studies. The prevalence and incidence of symptoms are partially determined by the methods used to assess them. As a result, comparison across studies is difficult. This article describes a systematic review of self-report questionnaires for somatic symptoms for use in large-scale studies and recommends two questionnaires for use in such studies. A literature search was performed in the databases Medline, PsycINFO and EMBASE. Articles that reported the development, evaluation, or review of a self-report somatic symptom measure were included. Instrument evaluation was based on validity and reliability, and their fitness for purpose in large scale studies, according to the PhenX criteria. The literature search identified 40 questionnaires. The number of items within the questionnaires ranged from 5 to 78 items. In 70% of the questionnaires, headaches were included, followed by nausea/upset stomach (65%), shortness of breath/breathing trouble (58%), dizziness (55%), and (low) back pain/backaches (55%). Data on validity and reliability were reported and used for evaluation. Questionnaires varied regarding usability and burden to participants, and relevance to a variety of populations and regions. Based on our criteria, the Patient Health Questionnaire-15 and the Symptom Checklist-90 somatization scale seem the most fit for purpose for use in large-scale studies. These two questionnaires have well-established psychometric properties, contain relevant symptoms, are relatively short, and are available in multiple languages. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. What drivers phenotypic divergence in Leymus chinensis (Poaceae) on large-scale gradient, climate or genetic differentiation?

    NASA Astrophysics Data System (ADS)

    Yuan, Shan; Ma, Linna; Guo, Chengyuan; Wang, Renzhong

    2016-05-01

    Elucidating the driving factors among-population divergence is an important task in evolutionary biology, however the relative contribution from natural selection and neutral genetic differentiation has been less debated. A manipulation experiment was conducted to examine whether the phenotypic divergence of Leymus chinensis depended on climate variations or genetic differentiations at 18 wild sites along a longitudinal gradient from 114 to 124°E in northeast China and at common garden condition of transplantation. Demographical, morphological and physiological phenotypes of 18 L. chinensis populations exhibited significant divergence along the gradient, but these divergent variations narrowed significantly at the transplantation. Moreover, most of the phenotypes were significantly correlated with mean annual precipitation and temperature in wild sites, suggesting that climatic variables played vital roles in phenotypic divergence of the species. Relative greater heterozygosity (HE), genotype evenness (E) and Shannon-Wiener diversity (I) in western group of populations suggested that genetic differentiation also drove phenotypic divergence of the species. However, neutral genetic differentiation (FST = 0.041) was greatly lower than quantitative differentiation (QST = 0.199), indicating that divergent selection/climate variable was the main factor in determining the phenotypic divergence of the species along the large-scale gradient.

  18. What drivers phenotypic divergence in Leymus chinensis (Poaceae) on large-scale gradient, climate or genetic differentiation?

    PubMed Central

    Yuan, Shan; Ma, Linna; Guo, Chengyuan; Wang, Renzhong

    2016-01-01

    Elucidating the driving factors among-population divergence is an important task in evolutionary biology, however the relative contribution from natural selection and neutral genetic differentiation has been less debated. A manipulation experiment was conducted to examine whether the phenotypic divergence of Leymus chinensis depended on climate variations or genetic differentiations at 18 wild sites along a longitudinal gradient from 114 to 124°E in northeast China and at common garden condition of transplantation. Demographical, morphological and physiological phenotypes of 18 L. chinensis populations exhibited significant divergence along the gradient, but these divergent variations narrowed significantly at the transplantation. Moreover, most of the phenotypes were significantly correlated with mean annual precipitation and temperature in wild sites, suggesting that climatic variables played vital roles in phenotypic divergence of the species. Relative greater heterozygosity (HE), genotype evenness (E) and Shannon-Wiener diversity (I) in western group of populations suggested that genetic differentiation also drove phenotypic divergence of the species. However, neutral genetic differentiation (FST = 0.041) was greatly lower than quantitative differentiation (QST = 0.199), indicating that divergent selection/climate variable was the main factor in determining the phenotypic divergence of the species along the large-scale gradient. PMID:27195668

  19. Higher Education Teachers' Descriptions of Their Own Learning: A Large-Scale Study of Finnish Universities of Applied Sciences

    ERIC Educational Resources Information Center

    Töytäri, Aija; Piirainen, Arja; Tynjälä, Päivi; Vanhanen-Nuutinen, Liisa; Mäki, Kimmo; Ilves, Vesa

    2016-01-01

    In this large-scale study, higher education teachers' descriptions of their own learning were examined with qualitative analysis involving application of principles of phenomenographic research. This study is unique: it is unusual to use large-scale data in qualitative studies. The data were collected through an e-mail survey sent to 5960 teachers…

  20. Higher Education Teachers' Descriptions of Their Own Learning: A Large-Scale Study of Finnish Universities of Applied Sciences

    ERIC Educational Resources Information Center

    Töytäri, Aija; Piirainen, Arja; Tynjälä, Päivi; Vanhanen-Nuutinen, Liisa; Mäki, Kimmo; Ilves, Vesa

    2016-01-01

    In this large-scale study, higher education teachers' descriptions of their own learning were examined with qualitative analysis involving application of principles of phenomenographic research. This study is unique: it is unusual to use large-scale data in qualitative studies. The data were collected through an e-mail survey sent to 5960 teachers…

  1. Innovative approaches to estimate individual usual dietary intake in large-scale epidemiological studies.

    PubMed

    Conrad, Johanna; Nöthlings, Ute

    2017-02-06

    Valid estimation of usual dietary intake in epidemiological studies is a topic of present interest. The aim of the present paper is to review recent literature on innovative approaches focussing on: (1) the requirements to assess usual intake and (2) the application in large-scale settings. Recently, a number of technology-based self-administered tools have been developed, including short-term instruments such as web-based 24-h recalls, mobile food records or simple closed-ended questionnaires that assess the food intake of the previous 24 h. Due to their advantages in terms of feasibility and cost-effectiveness these tools may be superior to conventional assessment methods in large-scale settings. New statistical methods have been developed to combine dietary information from repeated 24-h dietary recalls and FFQ. Conceptually, these statistical methods presume that the usual food intake of a subject equals the probability of consuming a food on a given day, multiplied by the average amount of intake of that food on a typical consumption day. Repeated 24-h recalls from the same individual provide information on consumption probability and amount. In addition, the FFQ can add information on intake frequency of rarely consumed foods. It has been suggested that this combined approach may provide high-quality dietary information. A promising direction for estimation of usual intake in large-scale settings is the integration of both statistical methods and new technologies. Studies are warranted to assess the validity of estimated usual intake in comparison with biomarkers.

  2. Transitioning a home telehealth project into a sustainable, large-scale service: a qualitative study.

    PubMed

    Wade, Victoria A; Taylor, Alan D; Kidd, Michael R; Carati, Colin

    2016-05-16

    This study was a component of the Flinders Telehealth in the Home project, which tested adding home telehealth to existing rehabilitation, palliative care and geriatric outreach services. Due to the known difficulty of transitioning telehealth projects services, a qualitative study was conducted to produce a preferred implementation approach for sustainable and large-scale operations, and a process model that offers practical advice for achieving this goal. Initially, semi-structured interviews were conducted with senior clinicians, health service managers and policy makers, and a thematic analysis of the interview transcripts was undertaken to identify the range of options for ongoing operations, plus the factors affecting sustainability. Subsequently, the interviewees and other decision makers attended a deliberative forum in which participants were asked to select a preferred model for future implementation. Finally, all data from the study was synthesised by the researchers to produce a process model. 19 interviews with senior clinicians, managers, and service development staff were conducted, finding strong support for home telehealth but a wide diversity of views on governance, models of clinical care, technical infrastructure operations, and data management. The deliberative forum worked through these options and recommended a collaborative consortium approach for large-scale implementation. The process model proposes that the key factor for large-scale implementation is leadership support, which is enabled by 1) showing solutions to the problems of service demand, budgetary pressure and the relationship between hospital and primary care, 2) demonstrating how home telehealth aligns with health service policies, and 3) achieving clinician acceptance through providing evidence of benefit and developing new models of clinical care. Two key actions to enable change were marketing telehealth to patients, clinicians and policy-makers, and building a community of

  3. A Feasibility Study on Operating Large Scale Compressed Air Energy Storage in Porous Formations

    NASA Astrophysics Data System (ADS)

    Wang, B.; Pfeiffer, W. T.; Li, D.; Bauer, S.

    2015-12-01

    Compressed air energy storage (CAES) in porous formations has been considered as one promising option of large scale energy storage for decades. This study, hereby, aims at analyzing the feasibility of operating large scale CAES in porous formations and evaluating the performance of underground porous gas reservoirs. To address these issues quantitatively, a hypothetic CAES scenario with a typical anticline structure in northern Germany was numerically simulated. Because of the rapid growth in photovoltaics, the period of extraction in a daily cycle was set to the early morning and the late afternoon in order to bypass the massive solar energy production around noon. The gas turbine scenario was defined referring to the specifications of the Huntorf CAES power plant. The numerical simulations involved two stages, i.e. initial fill and cyclic operation, and both were carried out using the Eclipse E300 simulator (Schlumberger). Pressure loss in the gas wells was post analyzed using an analytical solution. The exergy concept was applied to evaluate the potential energy amount stored in the specific porous formation. The simulation results show that porous formations prove to be a feasible solution of large scale CAES. The initial fill with shut-in periods determines the spatial distribution of the gas phase and helps to achieve higher gas saturation around the wells, and thus higher deliverability. The performance evaluation shows that the overall exergy flow of stored compressed air is also determined by the permeability, which directly affects the deliverability of the gas reservoir and thus the number of wells required.

  4. Food peptidomics: large scale analysis of small bioactive peptides--a pilot study.

    PubMed

    Lahrichi, Sabine L; Affolter, Michael; Zolezzi, Irma Silva; Panchaud, Alexandre

    2013-08-02

    Food peptidomics deals in part with the identification and quantification of nutritionally relevant peptides which are called bioactive peptides. This category of peptides comprises large, medium to small peptides. However, small peptides (2-6 amino acids) represent by far the largest category. Such molecules sit at the interface of both the world of proteomics and small molecule. The purpose of this study was to evaluate the feasibility of developing an LC-MSMS based method to measure such small peptides at a large scale that is representative of the hundreds of known small bioactive peptides. In order to do that we selected a very complex and homogeneous peptide set in terms of chemical and physical properties. This peptide set comprised only di, tri- and tetrapeptides made out of the three branched chain amino acids (valine, leucine and isoleucine). Results showed that at least 60% of these 117 peptides can be uniquely identified although many are isobaric and co-eluting. Moreover, identical results were obtained when spiked into a complex matrix, i.e. hydrolyzed whey protein. In conclusion, these results support the feasibility of a large scale approach and open the door to further development for all potential small bioactive peptides known so far. Bioactive peptides are a key category of molecules for functional food application. Most known bioactive peptides are small (less than 5 amino acids) and hence represent a challenge in terms of analysis when using current proteomics techniques. Therefore development of the food peptidomics field through high throughput large scale assays for these molecules is mandatory in the future to better conduct research in this field. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Coupling large scale hydrologic-reservoir-hydraulic models for impact studies in data sparse regions

    NASA Astrophysics Data System (ADS)

    O'Loughlin, Fiachra; Neal, Jeff; Wagener, Thorsten; Bates, Paul; Freer, Jim; Woods, Ross; Pianosi, Francesca; Sheffied, Justin

    2017-04-01

    As hydraulic modelling moves to increasingly large spatial domains it has become essential to take reservoirs and their operations into account. Large-scale hydrological models have been including reservoirs for at least the past two decades, yet they cannot explicitly model the variations in spatial extent of reservoirs, and many reservoirs operations in hydrological models are not undertaken during the run-time operation. This requires a hydraulic model, yet to-date no continental scale hydraulic model has directly simulated reservoirs and their operations. In addition to the need to include reservoirs and their operations in hydraulic models as they move to global coverage, there is also a need to link such models to large scale hydrology models or land surface schemes. This is especially true for Africa where the number of river gauges has consistently declined since the middle of the twentieth century. In this study we address these two major issues by developing: 1) a coupling methodology for the VIC large-scale hydrological model and the LISFLOOD-FP hydraulic model, and 2) a reservoir module for the LISFLOOD-FP model, which currently includes four sets of reservoir operating rules taken from the major large-scale hydrological models. The Volta Basin, West Africa, was chosen to demonstrate the capability of the modelling framework as it is a large river basin ( 400,000 km2) and contains the largest man-made lake in terms of area (8,482 km2), Lake Volta, created by the Akosombo dam. Lake Volta also experiences a seasonal variation in water levels of between two and six metres that creates a dynamic shoreline. In this study, we first run our coupled VIC and LISFLOOD-FP model without explicitly modelling Lake Volta and then compare these results with those from model runs where the dam operations and Lake Volta are included. The results show that we are able to obtain variation in the Lake Volta water levels and that including the dam operations and Lake Volta

  6. Constructing large-scale genetic maps using an evolutionary strategy algorithm.

    PubMed Central

    Mester, D; Ronin, Y; Minkov, D; Nevo, E; Korol, A

    2003-01-01

    This article is devoted to the problem of ordering in linkage groups with many dozens or even hundreds of markers. The ordering problem belongs to the field of discrete optimization on a set of all possible orders, amounting to n!/2 for n loci; hence it is considered an NP-hard problem. Several authors attempted to employ the methods developed in the well-known traveling salesman problem (TSP) for multilocus ordering, using the assumption that for a set of linked loci the true order will be the one that minimizes the total length of the linkage group. A novel, fast, and reliable algorithm developed for the TSP and based on evolution-strategy discrete optimization was applied in this study for multilocus ordering on the basis of pairwise recombination frequencies. The quality of derived maps under various complications (dominant vs. codominant markers, marker misclassification, negative and positive interference, and missing data) was analyzed using simulated data with approximately 50-400 markers. High performance of the employed algorithm allows systematic treatment of the problem of verification of the obtained multilocus orders on the basis of computing-intensive bootstrap and/or jackknife approaches for detecting and removing questionable marker scores, thereby stabilizing the resulting maps. Parallel calculation technology can easily be adopted for further acceleration of the proposed algorithm. Real data analysis (on maize chromosome 1 with 230 markers) is provided to illustrate the proposed methodology. PMID:14704202

  7. Resting behaviour, ecology and genetics of malaria vectors in large scale agricultural areas of Western Kenya.

    PubMed

    Githeko, A K; Service, M W; Mbogo, C M; Atieli, F K

    1996-12-01

    In Kenya indoor and outdoor resting densities of Anopheles arabiensis and Anopheles funestus at the Ahero rice irrigation scheme, and Anopheles gambiae s.s., An. arabiensis and An. funestus at the Miwani sugar belt were assessed for 13 months by pyrethrum spray collections in houses and granaries. The vector's house leaving behaviour was evaluated with exit traps and it was noted that early exophily (i.e., deliberate) was not detected in any of the vectors. Assortative indoor/outdoor resting behaviour was studied by a capture-mark-release-recapture method and showed that in An. arabiensis both indoor and outdoor resting traits were present in the same individuals. Samples of half-gravid female An. gambiae s.l. were chromosomally identified either as Anopheles gambiae s.s. or An. arabiensis and in a subsample chromosomal inversions were read. Anopheles gambiae s.s. and An. arabiensis had the 2Rb inversion but in addition the 2La inversion was found in An. gambiae s.s. and this is an indication of low chromosomal variation. At Ahero An. arabiensis was most abundant when the rice crop was immature and An. funestus when the crop was mature. This succession of vectors facilitated the transmission of malaria throughout the year. At Miwani, An. gambiae s.l. population peaked during the long rains but the proportion of An. arabiensis was highest during the dry season. The indoor resting density of males of the three vector species was less than half of the females.

  8. Coalescent-based method for learning parameters of admixture events from large-scale genetic variation data.

    PubMed

    Tsai, Ming-Chi; Blelloch, Guy; Ravi, R; Schwartz, Russell

    2013-01-01

    Detecting and quantifying the timing and the genetic contributions of parental populations to a hybrid population is an important but challenging problem in reconstructing evolutionary histories from genetic variation data. With the advent of high throughput genotyping technologies, new methods suitable for large-scale data are especially needed. Furthermore, existing methods typically assume the assignment of individuals into subpopulations is known, when that itself is a difficult problem often unresolved for real data. Here, we propose a novel method that combines prior work for inferring non reticulate population structures with an MCMC scheme for sampling over admixture scenarios to both identify population assignments and learn divergence times and admixture proportions for those populations using genome-scale admixed genetic variation data. We validated our method using coalescent simulations and a collection of real bovine and human variation data. On simulated sequences, our methods show better accuracy and faster run time than leading competitive methods in estimating admixture fractions and divergence times. Analysis on the real data further shows our methods to be effective at matching our best current knowledge about the relevant populations.

  9. Large-Scale Brain Networks of the Human Left Temporal Pole: A Functional Connectivity MRI Study

    PubMed Central

    Pascual, Belen; Masdeu, Joseph C.; Hollenbeck, Mark; Makris, Nikos; Insausti, Ricardo; Ding, Song-Lin; Dickerson, Bradford C.

    2015-01-01

    The most rostral portion of the human temporal cortex, the temporal pole (TP), has been described as “enigmatic” because its functional neuroanatomy remains unclear. Comparative anatomy studies are only partially helpful, because the human TP is larger and cytoarchitectonically more complex than in nonhuman primates. Considered by Brodmann as a single area (BA 38), the human TP has been recently parceled into an array of cytoarchitectonic subfields. In order to clarify the functional connectivity of subregions of the TP, we undertook a study of 172 healthy adults using resting-state functional connectivity MRI. Remarkably, a hierarchical cluster analysis performed to group the seeds into distinct subsystems according to their large-scale functional connectivity grouped 87.5% of the seeds according to the recently described cytoarchitectonic subregions of the TP. Based on large-scale functional connectivity, there appear to be 4 major subregions of the TP: 1) dorsal, with predominant connectivity to auditory/somatosensory and language networks; 2) ventromedial, predominantly connected to visual networks; 3) medial, connected to paralimbic structures; and 4) anterolateral, connected to the default-semantic network. The functional connectivity of the human TP, far more complex than its known anatomic connectivity in monkey, is concordant with its hypothesized role as a cortical convergence zone. PMID:24068551

  10. Scaling up explanation generation: Large-scale knowledge bases and empirical studies

    SciTech Connect

    Lester, J.C.; Porter, B.W.

    1996-12-31

    To explain complex phenomena, an explanation system must be able to select information from a formal representation of domain knowledge, organize the selected information into multisentential discourse plans, and realize the discourse plans in text. Although recent years have witnessed significant progress in the development of sophisticated computational mechanisms for explanation, empirical results have been limited. This paper reports on a seven year effort to empirically study explanation generation from semantically rich, large-scale knowledge bases. We first describe Knight, a robust explanation system that constructs multi-sentential and multi-paragraph explanations from the Biology Knowledge Base, a large-scale knowledge base in the domain of botanical anatomy, physiology, and development. We then introduce the Two Panel evaluation methodology and describe how Knight`s performance was assessed with this methodology in the most extensive empirical evaluation conducted on an explanation system. In this evaluation, Knight scored within {open_quotes}half a grade{close_quote} of domain experts, and its performance exceeded that of one of the domain experts.

  11. Numerical study of large-scale vorticity generation in shear-flow turbulence.

    PubMed

    Käpylä, Petri J; Mitra, Dhrubaditya; Brandenburg, Axel

    2009-01-01

    Simulations of stochastically forced shear-flow turbulence in a shearing-periodic domain are used to study the spontaneous generation of large-scale flow patterns in the direction perpendicular to the plane of the shear. Based on an analysis of the resulting large-scale velocity correlations it is argued that the mechanism behind this phenomenon could be the mean-vorticity dynamo effect pioneered by Elperin, Kleeorin, and Rogachevskii [Phys. Rev. E 68, 016311 (2003)]. This effect is based on the anisotropy of the eddy viscosity tensor. One of its components may be able to replenish cross-stream mean flows by acting upon the streamwise component of the mean flow. Shear, in turn, closes the loop by acting upon the cross-stream mean flow to produce stronger streamwise mean flows. The diagonal component of the eddy viscosity is found to be of the order of the rms turbulent velocity divided by the wave number of the energy-carrying eddies.

  12. Large-scale and spatio-temporal extreme rain events over India: a hydrometeorological study

    NASA Astrophysics Data System (ADS)

    Ranade, Ashwini; Singh, Nityanand

    2014-02-01

    Frequency, intensity, areal extent (AE) and duration of rain spells during summer monsoon exhibit large intra-seasonal and inter-annual variations. Important features of the monsoon period large-scale wet spells over India have been documented. A main monsoon wet spell (MMWS) occurs over the country from 18 June to 16 September, during which, 26.5 % of the area receives rainfall 26.3 mm/day. Detailed characteristics of the MMWS period large-scale extreme rain events (EREs) and spatio-temporal EREs (ST-EREs), each concerning rainfall intensity (RI), AE and rainwater (RW), for 1 to 25 days have been studied using 1° gridded daily rainfall (1951-2007). In EREs, `same area' (grids) is continuously wet, whereas in ST-EREs, `any area' on the mean under wet condition for specified durations is considered. For the different extremes, second-degree polynomial gave excellent fit to increase in values from distribution of annual maximum RI and RW series with increase in duration. Fluctuations of RI, AE, RW and date of occurrence (or start) of the EREs and the ST-EREs did not show any significant trend. However, fluctuations of 1° latitude-longitude grid annual and spatial maximum rainfall showed highly significant increasing trend for 1 to 5 days, and unprecedented rains on 26-27 July 2005 over Mumbai could be a realization of this trend. The Asia-India monsoon intensity significantly influences the MMWS RW.

  13. Challenges of cardiac image analysis in large-scale population-based studies.

    PubMed

    Medrano-Gracia, Pau; Cowan, Brett R; Suinesiaputra, Avan; Young, Alistair A

    2015-03-01

    Large-scale population-based imaging studies of preclinical and clinical heart disease are becoming possible due to the advent of standardized robust non-invasive imaging methods and infrastructure for big data analysis. This gives an exciting opportunity to gain new information about the development and progression of heart disease across population groups. However, the large amount of image data and prohibitive time required for image analysis present challenges for obtaining useful derived data from the images. Automated analysis tools for cardiac image analysis are only now becoming available. This paper reviews the challenges and possible solutions to the analysis of big imaging data in population studies. We also highlight the potential of recent large epidemiological studies using cardiac imaging to discover new knowledge on heart health and well-being.

  14. The Application of PERT to Large-Scale Educational Research and Evaluation Studies

    ERIC Educational Resources Information Center

    Case, C. Marston

    1969-01-01

    Discusses four points related to the coordination and management of large scale educational research projects: 1) the need for "project visibility; 2) the basic features of a Project Evaluation and Review Technique (PERT) chart; 3) recommendations for implementing PERT; and 4) an application of PERT to a large scale project at Educational…

  15. Case Study: Commercialization of sweet sorghum juice clarification for large-scale syrup manufacture

    USDA-ARS?s Scientific Manuscript database

    The precipitation and burning of insoluble granules of starch from sweet sorghum juice on heating coils prevented the large scale manufacture of syrup at a new industrial plant in Missouri, USA. To remove insoluble starch granules, a series of small and large-scale experiments were conducted at the...

  16. Large scale hydrological studies for the benefit of water resources management - looking up or down?

    NASA Astrophysics Data System (ADS)

    Tallaksen, Lena M.

    2017-04-01

    Hydrological information at the macro scale has become increasingly available through the establishment of global archives of hydrological observations (e.g. the Global Runoff Data Centre) and the development of hydrological models for the purpose of water resource assessments and climate change impact studies at the global and continental scale. As such, it has contributed to improved knowledge of the present state of global water resources and variability across large spatial domains, the role of terrestrial hydrology in earth system models and the influence of climate variability and change on continental hydrology, including extremes. Recent advances include among other, improved representation of subsurface hydrology and land-surface atmosphere feedback processes. Models are further adapted to multiple sources of input data, including remote sensing products, which in turn has facilitated the development of global and continental scale flood and drought monitoring and forecasting systems (e.g. the European Flood Awareness System and the Global Integrated Drought Monitoring and Prediction System). Nevertheless, there are several challenges related to large-scale modelling due to limited data for ground truth (e.g. soil moisture, groundwater, streamflow), large differences in data availability and quality across regions, sub grid variability, downscaled and bias-corrected climate data as driving force, etc. Limitations that have questioned the usefulness of large-scale model simulations for water resource management and policy making at various scales. Still, one can argue that such models represent a useful source of information, particular for continental-scale hydrological assessments and evidence-based policy making at the EU level, as up-to-date, consistent hydrological data are not easily available across national borders. Transfer of knowledge across scales is essential to improve hydrologic predictions at different spatial scales in an ever

  17. Large-scale shell model study of the newly found isomer in 136La

    NASA Astrophysics Data System (ADS)

    Teruya, E.; Yoshinaga, N.; Higashiyama, K.; Nishibata, H.; Odahara, A.; Shimoda, T.

    2016-07-01

    The doubly-odd nucleus 136La is theoretically studied in terms of a large-scale shell model. The energy spectrum and transition rates are calculated and compared with the most updated experimental data. The isomerism is investigated for the first 14+ state, which was found to be an isomer in the previous study [Phys. Rev. C 91, 054305 (2015), 10.1103/PhysRevC.91.054305]. It is found that the 14+ state becomes an isomer due to a band crossing of two bands with completely different configurations. The yrast band with the (ν h11/2 -1⊗π h11 /2 ) configuration is investigated, revealing a staggering nature in M 1 transition rates.

  18. The assessment of individual usual food intake in large-scale prospective studies.

    PubMed

    Illner, Anne-Kathrin; Nöthlings, Ute; Wagner, Karen; Ward, Heather; Boeing, Heiner

    2010-01-01

    Recent research has called into question the current practice to estimate individual usual food intake in large-scale studies. In such studies, usual food intake has been defined as diet over the past year. The aim of this review is to summarise the concepts of dietary assessment methods providing food intake data over this time period. A conceptualised framework is given to help researchers to understand the more recent developments to improve dietary assessment in large-scale prospective studies, and also to help to spot the gaps that need to be addressed in future methodological research. The conceptual framework illustrates the current options for the assessment of an individual's food consumption over 1 year. Ideally, a person's food intake on each day of this year should be assessed. Due to participants' burden, and organisational and financial constraints, however, the options are limited to directly requesting the long-term average (e.g. food frequency questionnaires), or selecting a few days with detailed food consumption measurements (e.g. 24-hour dietary recalls) or using snapshot techniques (e.g. barcode scanning of purchases). It seems necessary and important to further evaluate the performance of statistical modelling of the individual usual food intake from all available sources. Future dietary assessment might profit from the growing prominence of internet and telecommunication technologies to further enhance the available data on food consumption for each study participant. Research is crucial to investigate the performance of innovative assessment tools. However, the self-reported nature of the data itself will always lead to bias.

  19. 3D fully convolutional networks for subcortical segmentation in MRI: A large-scale study.

    PubMed

    Dolz, Jose; Desrosiers, Christian; Ben Ayed, Ismail

    2017-04-24

    This study investigates a 3D and fully convolutional neural network (CNN) for subcortical brain structure segmentation in MRI. 3D CNN architectures have been generally avoided due to their computational and memory requirements during inference. We address the problem via small kernels, allowing deeper architectures. We further model both local and global context by embedding intermediate-layer outputs in the final prediction, which encourages consistency between features extracted at different scales and embeds fine-grained information directly in the segmentation process. Our model is efficiently trained end-to-end on a graphics processing unit (GPU), in a single stage, exploiting the dense inference capabilities of fully CNNs. We performed comprehensive experiments over two publicly available datasets. First, we demonstrate a state-of-the-art performance on the ISBR dataset. Then, we report a large-scale multi-site evaluation over 1112 unregistered subject datasets acquired from 17 different sites (ABIDE dataset), with ages ranging from 7 to 64 years, showing that our method is robust to various acquisition protocols, demographics and clinical factors. Our method yielded segmentations that are highly consistent with a standard atlas-based approach, while running in a fraction of the time needed by atlas-based methods and avoiding registration/normalization steps. This makes it convenient for massive multi-site neuroanatomical imaging studies. To the best of our knowledge, our work is the first to study subcortical structure segmentation on such large-scale and heterogeneous data. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Study of Large Scale Jet in M 87 at the Multi-Wavebands

    NASA Astrophysics Data System (ADS)

    Meng, D.-M.; Wang, C.-C.; Zhou, H.-Y.

    2007-09-01

    The large scale jet of the radio galaxy M87 has been observed in high resolution at radio and optical wavelengths as well as X-ray band, the spectra of the knots are commonly believed to be generated from synchrotron emission. The authors study spectra of the knots in the jet at multi-wavebands by using Kardashev-Packolczyk radiation model, and obtain the corresponding Doppler factor. Combined with superluminal motion, they derive the Lorentz factor and the angle to the line of sight for individual knots. Their results show that M87 has a slightly bend as well as a moderated relativistic jet. They also find that the bulk velocity of its jet decelerates as it flows out.

  1. Australia Antigen: Large-Scale Purification from Human Serum and Biochemical Studies of Its Proteins

    PubMed Central

    Gerin, J. L.; Holland, P. V.; Purcell, R. H.

    1971-01-01

    Biophysical techniques are described for the large-scale isolation of Australia antigen (Au) from unit quantities of human serum by using the batch-type zonal centrifuge rotors. A three-step procedure involving isopycnic banding of the particle in CsCl density gradients and rate-zonal centrifugation on sucrose gradients resulted in a highly purified Au preparation which was used for biochemical studies of Au proteins and as immunizing antigen for the production of reagent antiserum in animals. The spherical form of Au, which was devoid of detectable nucleic acid, was composed of two major proteins (AuP1 and AuP2) and a minor protein (AuP3) of 26,000, 32,000, and 40,000 molecular weight, respectively, as determined by acrylamide gel electrophoresis. The significance of these findings to the possibility of Au subtypes is discussed. PMID:5105002

  2. A case study of large-scale structure in a 'hot' model universe

    NASA Technical Reports Server (NTRS)

    Centrella, Joan M.; Gallagher, John S., III; Melott, Adrian L.; Bushouse, Howard A.

    1988-01-01

    Large-scale structure is studied in an Omega(0) = 1 model universe filled with 'hot' dark matter. A particle mesh computer code is used to calculate the development of gravitational instabilities in 64-cubed mass clouds on a 64-cubed three-dimensional grid over an expansion factor of about 1000. The present epoch is identified by matching the slope of the model particle-particle two-point correlation function with that obtained from observations of galaxies, and the model then corresponds to a cubical sample of the universe of about 105/h Mpc on a side. Properties of the simulated universe are investigated by casting the model quantities into observer's coordinates and comparing the results with observations of the spatial and velocity distributions of luminous matter. It is concluded based on simple arguments that current limits on the time of galaxy formation do not rule out 'hot' dark matter.

  3. Proteomics studies confirm the presence of alternative protein isoforms on a large scale

    PubMed Central

    Tress, Michael L; Bodenmiller, Bernd; Aebersold, Ruedi; Valencia, Alfonso

    2008-01-01

    Background Alternative splicing of messenger RNA permits the formation of a wide range of mature RNA transcripts and has the potential to generate a diverse spectrum of functional proteins. Although there is extensive evidence for large scale alternative splicing at the transcript level, there have been no comparable studies demonstrating the existence of alternatively spliced protein isoforms. Results Recent advances in proteomics technology have allowed us to carry out a comprehensive identification of protein isoforms in Drosophila. The analysis of this proteomic data confirmed the presence of multiple alternative gene products for over a hundred Drosophila genes. Conclusions We demonstrate that proteomics techniques can detect the expression of stable alternative splice isoforms on a genome-wide scale. Many of these alternative isoforms are likely to have regions that are disordered in solution, and specific proteomics methodologies may be required to identify these peptides. PMID:19017398

  4. Biomass logistics analysis for large scale biofuel production: case study of loblolly pine and switchgrass.

    PubMed

    Lu, Xiaoming; Withers, Mitch R; Seifkar, Navid; Field, Randall P; Barrett, Steven R H; Herzog, Howard J

    2015-05-01

    The objective of this study was to assess the costs, energy consumption and greenhouse gas (GHG) emissions throughout the biomass supply chain for large scale biofuel production. Two types of energy crop were considered, switchgrass and loblolly pine, as representative of herbaceous and woody biomass. A biomass logistics model has been developed to estimate the feedstock supply system from biomass production through transportation. Biomass in the form of woodchip, bale and pellet was investigated with road, railway and waterway transportation options. Our analysis indicated that the farm or forest gate cost is lowest for loblolly pine whole tree woodchip at $39.7/dry tonne and highest for switchgrass round bale at $72.3/dry tonne. Switchgrass farm gate GHG emissions is approximately 146kgCO2e/dry tonne, about 4 times higher than loblolly pine. The optimum biomass transportation mode and delivered form are determined by the tradeoff between fixed and variable costs for feedstock shipment.

  5. Climatic Consequences of a Large-Scale Desertification in Northeast Brazil: A GCM Simulation Study.

    NASA Astrophysics Data System (ADS)

    Oyama, Marcos Daisuke; Nobre, Carlos Afonso

    2004-08-01

    The climatic impacts of a large-scale desertification in northeast Brazil (NEB) are assessed by using the Center for Weather Forecasting and Climate Studies Center for Ocean Land Atmosphere Studies (CPTEC COLA) AGCM. Two numerical runs are performed. In the control run, NEB is covered by its natural vegetation (most of NEB is covered by a xeromorphic vegetation known as caatinga); in the desertification run, NEB vegetation is changed to desert (bare soil). Each run consists of five 1-yr numerical integrations. The results for NEB wet season (March May) are analyzed. Desertification results in hydrological cycle weakening: precipitation, evapotranspiration, moisture convergence, and runoff decrease. Surface net radiation decreases and this reduction is almost evenly divided between sensible and latent heat flux. Atmospheric diabatic heating decreases and subsidence anomalies confined at lower atmospheric levels are found. The climatic impacts result from the cooperative action of feedback processes related to albedo increase, plant transpiration suppression, and roughness length decrease. On a larger scale, desertification leads to precipitation increase in the oceanic belt close to the northernmost part of NEB (NNEB). In the NEB NNEB dipole, the anomalies of vertical motion and atmospheric circulation are confined to lower atmospheric levels, that is, 850 700 hPa. At these levels, circulation anomalies resemble the linear baroclinic response of a shallow atmospheric layer (850 700 hPa) to a tropical heat sink placed over NEB at the middle-layer level. Therefore, NEB climate does show sensitivity to a vegetation change to desert. The present work shows the possibility of significant and pronounced climate impacts, on both regional and large scales, if the environmental degradation in NEB continues unchecked.


  6. Anatomically Detailed and Large-Scale Simulations Studying Synapse Loss and Synchrony Using NeuroBox

    PubMed Central

    Breit, Markus; Stepniewski, Martin; Grein, Stephan; Gottmann, Pascal; Reinhardt, Lukas; Queisser, Gillian

    2016-01-01

    The morphology of neurons and networks plays an important role in processing electrical and biochemical signals. Based on neuronal reconstructions, which are becoming abundantly available through databases such as NeuroMorpho.org, numerical simulations of Hodgkin-Huxley-type equations, coupled to biochemical models, can be performed in order to systematically investigate the influence of cellular morphology and the connectivity pattern in networks on the underlying function. Development in the area of synthetic neural network generation and morphology reconstruction from microscopy data has brought forth the software tool NeuGen. Coupling this morphology data (either from databases, synthetic, or reconstruction) to the simulation platform UG 4 (which harbors a neuroscientific portfolio) and VRL-Studio, has brought forth the extendible toolbox NeuroBox. NeuroBox allows users to perform numerical simulations on hybrid-dimensional morphology representations. The code basis is designed in a modular way, such that e.g., new channel or synapse types can be added to the library. Workflows can be specified through scripts or through the VRL-Studio graphical workflow representation. Third-party tools, such as ImageJ, can be added to NeuroBox workflows. In this paper, NeuroBox is used to study the electrical and biochemical effects of synapse loss vs. synchrony in neurons, to investigate large morphology data sets within detailed biophysical simulations, and used to demonstrate the capability of utilizing high-performance computing infrastructure for large scale network simulations. Using new synapse distribution methods and Finite Volume based numerical solvers for compartment-type models, our results demonstrate how an increase in synaptic synchronization can compensate synapse loss at the electrical and calcium level, and how detailed neuronal morphology can be integrated in large-scale network simulations. PMID:26903818

  7. Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans

    PubMed Central

    Uhl, M.Andrew; Biery, Matt; Craig, Nancy; Johnson, Alexander D.

    2003-01-01

    Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large-scale loss-of-function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single-cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approxim ately one-third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens. PMID:12773383

  8. Haploinsufficiency-based large-scale forward genetic analysis of filamentous growth in the diploid human fungal pathogen C.albicans.

    PubMed

    Uhl, M Andrew; Biery, Matt; Craig, Nancy; Johnson, Alexander D

    2003-06-02

    Candida albicans is the most prevalent human fungal pathogen. Here, we take advantage of haploinsufficiency and transposon mutagenesis to perform large-scale loss-of-function genetic screen in this organism. We identified mutations in 146 genes that affect the switch between its single-cell (yeast) form and filamentous forms of growth; this switch appears central to the virulence of C.albicans. The encoded proteins include those involved in nutrient sensing, signal transduction, transcriptional control, cytoskeletal organization and cell wall construction. Approximately one-third of the genes identified in the screen lack homologs in Saccharomyces cerevisiae and other model organisms and thus constitute candidate antifungal drug targets. These results illustrate the value of performing forward genetic studies in bona fide pathogens.

  9. Large-scale SNP discovery and construction of a high-density genetic map of Colossoma macropomum through genotyping-by-sequencing

    PubMed Central

    Nunes, José de Ribamar da Silva; Liu, Shikai; Pértille, Fábio; Perazza, Caio Augusto; Villela, Priscilla Marqui Schmidt; de Almeida-Val, Vera Maria Fonseca; Hilsdorf, Alexandre Wagner Silva; Liu, Zhanjiang; Coutinho, Luiz Lehmann

    2017-01-01

    Colossoma macropomum, or tambaqui, is the largest native Characiform species found in the Amazon and Orinoco river basins, yet few resources for genetic studies and the genetic improvement of tambaqui exist. In this study, we identified a large number of single-nucleotide polymorphisms (SNPs) for tambaqui and constructed a high-resolution genetic linkage map from a full-sib family of 124 individuals and their parents using the genotyping by sequencing method. In all, 68,584 SNPs were initially identified using minimum minor allele frequency (MAF) of 5%. Filtering parameters were used to select high-quality markers for linkage analysis. We selected 7,734 SNPs for linkage mapping, resulting in 27 linkage groups with a minimum logarithm of odds (LOD) of 8 and maximum recombination fraction of 0.35. The final genetic map contains 7,192 successfully mapped markers that span a total of 2,811 cM, with an average marker interval of 0.39 cM. Comparative genomic analysis between tambaqui and zebrafish revealed variable levels of genomic conservation across the 27 linkage groups which allowed for functional SNP annotations. The large-scale SNP discovery obtained here, allowed us to build a high-density linkage map in tambaqui, which will be useful to enhance genetic studies that can be applied in breeding programs. PMID:28387238

  10. Large scale wildlife monitoring studies: statistical methods for design and analysis

    USGS Publications Warehouse

    Pollock, K.H.; Nichols, J.D.; Simons, T.R.; Farnsworth, G.L.; Bailey, L.L.; Sauer, J.R.

    2002-01-01

    Techniques for estimation of absolute abundance of wildlife populations have received a lot of attention in recent years. The statistical research has been focused on intensive small-scale studies. Recently, however, wildlife biologists have desired to study populations of animals at very large scales for monitoring purposes. Population indices are widely used in these extensive monitoring programs because they are inexpensive compared to estimates of absolute abundance. A crucial underlying assumption is that the population index (C) is directly proportional to the population density (D). The proportionality constant, b, is simply the probability of 'detection' for animals in the survey. As spatial and temporal comparisons of indices are crucial, it is necessary to also assume that the probability of detection is constant over space and time. Biologists intuitively recognize this when they design rigid protocols for the studies where the indices are collected. Unfortunately, however in many field studios the assumption is clearly invalid. We believe that the estimation of detection probability should be built into the monitoring design through a double sampling approach. A large sample of points provides an abundance index, and a smaller sub-sample of the same points is used to estimate detection probability. There is an important need for statistical research on the design and analysis of these complex studies. Some basic concepts based on actual avian, amphibian, and fish monitoring studies are presented in this article.

  11. Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

    PubMed

    Saxena, Richa; Elbers, Clara C; Guo, Yiran; Peter, Inga; Gaunt, Tom R; Mega, Jessica L; Lanktree, Matthew B; Tare, Archana; Castillo, Berta Almoguera; Li, Yun R; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Böhm, Bernhard O; Braund, Peter S; Burton, Paul R; Chandrupatla, Hareesh R; Clarke, Robert; Cooper-DeHoff, Rhonda M; Crook, Errol D; Davey-Smith, George; Day, Ian N; de Boer, Anthonius; de Groot, Mark C H; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S; Furlong, Clement E; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A; Glessner, Joseph T; Goel, Anuj; Gong, Yan; Grant, Struan F A; Grobbee, Diederick E; Hastie, Claire; Humphries, Steve E; Kim, Cecilia E; Kivimaki, Mika; Kleber, Marcus; Meisinger, Christa; Kumari, Meena; Langaee, Taimour Y; Lawlor, Debbie A; Li, Mingyao; Lobmeyer, Maximilian T; Maitland-van der Zee, Anke-Hilse; Meijs, Matthijs F L; Molony, Cliona M; Morrow, David A; Murugesan, Gurunathan; Musani, Solomon K; Nelson, Christopher P; Newhouse, Stephen J; O'Connell, Jeffery R; Padmanabhan, Sandosh; Palmen, Jutta; Patel, Sanjey R; Pepine, Carl J; Pettinger, Mary; Price, Thomas S; Rafelt, Suzanne; Ranchalis, Jane; Rasheed, Asif; Rosenthal, Elisabeth; Ruczinski, Ingo; Shah, Sonia; Shen, Haiqing; Silbernagel, Günther; Smith, Erin N; Spijkerman, Annemieke W M; Stanton, Alice; Steffes, Michael W; Thorand, Barbara; Trip, Mieke; van der Harst, Pim; van der A, Daphne L; van Iperen, Erik P A; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V; Verweij, Niek; Wolffenbuttel, Bruce H R; Young, Taylor; Zafarmand, M Hadi; Zmuda, Joseph M; Boehnke, Michael; Altshuler, David; McCarthy, Mark; Kao, W H Linda; Pankow, James S; Cappola, Thomas P; Sever, Peter; Poulter, Neil; Caulfield, Mark; Dominiczak, Anna; Shields, Denis C; Bhatt, Deepak L; Bhatt, Deepak; Zhang, Li; Curtis, Sean P; Danesh, John; Casas, Juan P; van der Schouw, Yvonne T; Onland-Moret, N Charlotte; Doevendans, Pieter A; Dorn, Gerald W; Farrall, Martin; FitzGerald, Garret A; Hamsten, Anders; Hegele, Robert; Hingorani, Aroon D; Hofker, Marten H; Huggins, Gordon S; Illig, Thomas; Jarvik, Gail P; Johnson, Julie A; Klungel, Olaf H; Knowler, William C; Koenig, Wolfgang; März, Winfried; Meigs, James B; Melander, Olle; Munroe, Patricia B; Mitchell, Braxton D; Bielinski, Susan J; Rader, Daniel J; Reilly, Muredach P; Rich, Stephen S; Rotter, Jerome I; Saleheen, Danish; Samani, Nilesh J; Schadt, Eric E; Shuldiner, Alan R; Silverstein, Roy; Kottke-Marchant, Kandice; Talmud, Philippa J; Watkins, Hugh; Asselbergs, Folkert W; Asselbergs, Folkert; de Bakker, Paul I W; McCaffery, Jeanne; Wijmenga, Cisca; Sabatine, Marc S; Wilson, James G; Reiner, Alex; Bowden, Donald W; Hakonarson, Hakon; Siscovick, David S; Keating, Brendan J

    2012-03-09

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  12. Influenza epidemic spread simulation for Poland — a large scale, individual based model study

    NASA Astrophysics Data System (ADS)

    Rakowski, Franciszek; Gruziel, Magdalena; Bieniasz-Krzywiec, Łukasz; Radomski, Jan P.

    2010-08-01

    In this work a construction of an agent based model for studying the effects of influenza epidemic in large scale (38 million individuals) stochastic simulations, together with the resulting various scenarios of disease spread in Poland are reported. Simple transportation rules were employed to mimic individuals’ travels in dynamic route-changing schemes, allowing for the infection spread during a journey. Parameter space was checked for stable behaviour, especially towards the effective infection transmission rate variability. Although the model reported here is based on quite simple assumptions, it allowed to observe two different types of epidemic scenarios: characteristic for urban and rural areas. This differentiates it from the results obtained in the analogous studies for the UK or US, where settlement and daily commuting patterns are both substantially different and more diverse. The resulting epidemic scenarios from these ABM simulations were compared with simple, differential equations based, SIR models - both types of the results displaying strong similarities. The pDYN software platform developed here is currently used in the next stage of the project employed to study various epidemic mitigation strategies.

  13. A large-scale proteogenomics study of apicomplexan pathogens—Toxoplasma gondii and Neospora caninum

    PubMed Central

    Krishna, Ritesh; Xia, Dong; Sanderson, Sanya; Shanmugasundram, Achchuthan; Vermont, Sarah; Bernal, Axel; Daniel-Naguib, Gianluca; Ghali, Fawaz; Brunk, Brian P; Roos, David S; Wastling, Jonathan M; Jones, Andrew R

    2015-01-01

    Proteomics data can supplement genome annotation efforts, for example being used to confirm gene models or correct gene annotation errors. Here, we present a large-scale proteogenomics study of two important apicomplexan pathogens: Toxoplasma gondii and Neospora caninum. We queried proteomics data against a panel of official and alternate gene models generated directly from RNASeq data, using several newly generated and some previously published MS datasets for this meta-analysis. We identified a total of 201 996 and 39 953 peptide-spectrum matches for T. gondii and N. caninum, respectively, at a 1% peptide FDR threshold. This equated to the identification of 30 494 distinct peptide sequences and 2921 proteins (matches to official gene models) for T. gondii, and 8911 peptides/1273 proteins for N. caninum following stringent protein-level thresholding. We have also identified 289 and 140 loci for T. gondii and N. caninum, respectively, which mapped to RNA-Seq-derived gene models used in our analysis and apparently absent from the official annotation (release 10 from EuPathDB) of these species. We present several examples in our study where the RNA-Seq evidence can help in correction of the current gene model and can help in discovery of potential new genes. The findings of this study have been integrated into the EuPathDB. The data have been deposited to the ProteomeXchange with identifiers PXD000297and PXD000298. PMID:25867681

  14. The merger remnant NGC 3610 and its globular cluster system: a large-scale study

    NASA Astrophysics Data System (ADS)

    Bassino, Lilia P.; Caso, Juan P.

    2017-04-01

    We present a photometric study of the prototype merger remnant NGC 3610 and its globular cluster (GC) system, based on new Gemini/GMOS and Advanced Camera for Surveys/Hubble Space Telescope archival images. Thanks to the large field of view of our GMOS data, larger than previous studies, we are able to detect a 'classical' bimodal GC colour distribution, corresponding to metal-poor and metal-rich GCs, at intermediate radii and a small subsample of likely young clusters of intermediate colours, mainly located in the outskirts. The extent of the whole GC system is settled as about 40 kpc. The GC population is quite poor, about 500 ± 110 members that corresponds to a low total specific frequency SN ∼ 0.8. The effective radii of a cluster sample are determined, including those of two spectroscopically confirmed young and metal-rich clusters, that are in the limit between GC and UCD sizes and brightness. The large-scale galaxy surface-brightness profile can be decomposed as an inner embedded disc and an outer spheroid, determining for both larger extents than earlier research (10 and 30 kpc, respectively). We detect boxy isophotes, expected in merger remnants, and show a wealth of fine-structure in the surface-brightness distribution with unprecedented detail, coincident with the outer spheroid. The lack of symmetry in the galaxy colour map adds a new piece of evidence to the recent merger scenario of NGC 3610.

  15. Simulating large-scale pedestrian movement using CA and event driven model: Methodology and case study

    NASA Astrophysics Data System (ADS)

    Li, Jun; Fu, Siyao; He, Haibo; Jia, Hongfei; Li, Yanzhong; Guo, Yi

    2015-11-01

    Large-scale regional evacuation is an important part of national security emergency response plan. Large commercial shopping area, as the typical service system, its emergency evacuation is one of the hot research topics. A systematic methodology based on Cellular Automata with the Dynamic Floor Field and event driven model has been proposed, and the methodology has been examined within context of a case study involving the evacuation within a commercial shopping mall. Pedestrians walking is based on Cellular Automata and event driven model. In this paper, the event driven model is adopted to simulate the pedestrian movement patterns, the simulation process is divided into normal situation and emergency evacuation. The model is composed of four layers: environment layer, customer layer, clerk layer and trajectory layer. For the simulation of movement route of pedestrians, the model takes into account purchase intention of customers and density of pedestrians. Based on evacuation model of Cellular Automata with Dynamic Floor Field and event driven model, we can reflect behavior characteristics of customers and clerks at the situations of normal and emergency evacuation. The distribution of individual evacuation time as a function of initial positions and the dynamics of the evacuation process is studied. Our results indicate that the evacuation model using the combination of Cellular Automata with Dynamic Floor Field and event driven scheduling can be used to simulate the evacuation of pedestrian flows in indoor areas with complicated surroundings and to investigate the layout of shopping mall.

  16. The merger remnant NGC 3610 and its globular cluster system: a large-scale study

    NASA Astrophysics Data System (ADS)

    Bassino, Lilia P.; Caso, Juan P.

    2017-01-01

    We present a photometric study of the prototype merger remnant NGC 3610 and its globular cluster (GC) system, based on new GEMINI/GMOS and ACS/HST archival images. Thanks to the large FOV of our GMOS data, larger than previous studies, we are able to detect a `classical' bimodal GC colour distribution, correponding metal-poor and metal-rich GCs, at intermediate radii and a small subsample of likely young clusters of intermediate colours, mainly located in the outskirts. The extent of the whole GC system is settled as about 40 kpc. The GC population is quite poor, about 500 ± 110 members that corresponds to a low total specific frequency SN ˜ 0.8. The effective radii of a cluster sample are determined, including those of two spectroscopically confirmed young and metal-rich clusters, that are in the limit between GC and UCD sizes and brightness. The large-scale galaxy surface-brightness profile can be decomposed as an inner embedded disc and an outer spheroid, determining for both larger extents than earlier research (10 kpc and 30 kpc, respectively). We detect boxy isophotes, expected in merger remnants, and show a wealth of fine-structure in the surface-brightness distribution with unprecedented detail, coincident with the outer spheroid. The lack of symmetry in the galaxy colour map adds a new piece of evidence to the recent merger scenario of NGC 3610.

  17. A study of the large-scale infrared emission from a selected dark cloud

    NASA Technical Reports Server (NTRS)

    Young, Erick T.

    1990-01-01

    An investigation of the infrared emission energetics and embedded population in the rho Ophiuchi dark cloud is summarized. With a distance of approximately 140 pc, the rho Ophiuchi cloud is one of the closest regions of recent star formation. It is also one of the best studied such regions with numerous observations at all wavelengths. The IRAS data of the cloud provided a new glimpse of the overall structure of the cloud. In particular, the interaction of radiation from the Sco-Oph OB Association on the external heating of the cloud was very evident on Skyflux and Survey Co-Add images produced by IRAS. The infrared survey also revealed a number of new embedded sources in the cloud which have subsequently been observed from the ground. An earlier study explored the overall energetics of the cloud using the IRAS data. The main conclusions of that work were: (1) the overall luminosity of the cloud is well explained by the emission of the known B-stars, HD 147889, SR-3, and S1, along with a 15 percent contribution from the external radiation field; (2) the dust physical temperatures were significantly lower than the observed CO gas temperatures; and (3) dust grains are heated to only 10 percent to 20 percent of the total depth into the cloud. This analysis is extended by drawing on data from large-scale CO maps and from near-infrared surveys of the embedded population.

  18. Progress of large-scale air-sea interaction studies in China

    NASA Astrophysics Data System (ADS)

    Pu, Shuzhen; Zhao, Jinping; Yu, Weidong; Zhao, Yongping; Yang, Bo

    2004-06-01

    This paper summarizes the progress of large-scale air-sea interaction studies that has been achieved in China in the four-year period from July 1998 to July 2002, including seven aspects in the area of the air-sea interaction, namely air-sea interaction related to the tropical Pacific Ocean, monsoon-related air-sea interaction, air-sea interaction in the north Pacific Ocean, air-sea interaction in the Indian Ocean, air-sea interactions in the global oceans, field experiments, and oceanic cruise surveys. However more attention has been paid to the first and the second aspects because a large number of papers in the reference literature for preparing and organizing this paper are concentrated in the tropical Pacific Ocean, such as the ENSO process with its climatic effects and dynamics, and the monsoon-related air-sea interaction. The literature also involves various phenomena with their different time and spatial scales such as intraseasonal, annual, interannual, and interdecadal variabilities in the atmosphere/ocean interaction system, reflecting the contemporary themes in the four-year period at the beginning of an era from the post-TOGA to CLIVAR studies. Apparently, it is a difficult task to summarize the great progress in this area, as it is extracted from a large quantity of literature, although the authors tried very hard.

  19. A study of residence time distribution using radiotracer technique in the large scale plant facility

    NASA Astrophysics Data System (ADS)

    Wetchagarun, S.; Tippayakul, C.; Petchrak, A.; Sukrod, K.; Khoonkamjorn, P.

    2017-06-01

    As the demand for troubleshooting of large industrial plants increases, radiotracer techniques, which have capability to provide fast, online and effective detections to plant problems, have been continually developed. One of the good potential applications of the radiotracer for troubleshooting in a process plant is the analysis of Residence Time Distribution (RTD). In this paper, the study of RTD in a large scale plant facility using radiotracer technique was presented. The objective of this work is to gain experience on the RTD analysis using radiotracer technique in a “larger than laboratory” scale plant setup which can be comparable to the real industrial application. The experiment was carried out at the sedimentation tank in the water treatment facility of Thailand Institute of Nuclear Technology (Public Organization). Br-82 was selected to use in this work due to its chemical property, its suitable half-life and its on-site availability. NH4Br in the form of aqueous solution was injected into the system as the radiotracer. Six NaI detectors were placed along the pipelines and at the tank in order to determine the RTD of the system. The RTD and the Mean Residence Time (MRT) of the tank was analysed and calculated from the measured data. The experience and knowledge attained from this study is important for extending this technique to be applied to industrial facilities in the future.

  20. A study of the large-scale infrared emission from a selected dark cloud

    NASA Technical Reports Server (NTRS)

    Young, Erick T.

    1993-01-01

    An investigation of the infrared emission energetics and embedded population in the rho Ophiuchi dark cloud is summarized. With a distance of approximately 140 pc, the rho Ophiuchi cloud is one of the closest regions of recent star formation. It is also one of the best studied such regions with numerous observations at all wavelengths. The Infrared Astronomy Satellite (IRAS) data of the cloud provided a new glimpse of the overall structure of the cloud. In particular, the interaction of radiation from the Sco-Oph OB Association on the external heating of the cloud was very evident on Skyflux and Survey CO-Add images produced by IRAS. The infrared survey also revealed a number of new embedded sources in the cloud which have subsequently been observed from the ground. In earlier study, the overall energies of the cloud using the IRAS data was explored. The main conclusions of that work were: (1) the overall luminosity of the cloud is well explained by the emission of the known B-stars, HD 147889, SR-3, and S1, along with a 15 percent contribution from the external radiation field; (2) the dust physical temperatures were significantly lower than the observed CO gas temperatures; and (3) dust grains are heated to only 10 percent to 20 percent of the total depth into the cloud. This analysis was extended by drawing on data from large-scale CO maps of Loren (1989) and from near-infrared surveys of the embedded population.

  1. Forcing the statistical regionalization method WETTREG with large scale models of different resolution: A sensitivity study

    NASA Astrophysics Data System (ADS)

    Spekat, A.; Baumgart, S.; Kreienkamp, F.; Enke, W.

    2010-09-01

    The statistical regionalization method WETTREG is making use of the assumption that future climate changes are linked to changes in large scale atmospheric patterns. The frequency distributions of those patterns and their time-dependency are identified in the output fields of dynamical climate models and applied to force WETTREG. Thus, the magnitude and the time evolution of high-resolution climate signals for time horizons far into the 21st century can be computed. The model results employed to force WETTREG include the GCMS ECHAM5C, HadCM3C and CNRM. Additionally results from the dynamical regional models CLM, DMI, HadRM, RACMO and REMO, nested into one or more of these global models, are used in their pattern-generating capacity to force WETTREG. The study yield insight concerning the forcing-dependent sensitivity of WETTREG as well as the bandwidth of climate change signals. Recent results for the German State of Hesse will be presented in an intercomparison study.

  2. NV Energy Large-Scale Photovoltaic Integration Study: Intra-Hour Dispatch and AGC Simulation

    SciTech Connect

    Lu, Shuai; Etingov, Pavel V.; Meng, Da; Guo, Xinxin; Jin, Chunlian; Samaan, Nader A.

    2013-01-02

    The uncertainty and variability with photovoltaic (PV) generation make it very challenging to balance power system generation and load, especially under high penetration cases. Higher reserve requirements and more cycling of conventional generators are generally anticipated for large-scale PV integration. However, whether the existing generation fleet is flexible enough to handle the variations and how well the system can maintain its control performance are difficult to predict. The goal of this project is to develop a software program that can perform intra-hour dispatch and automatic generation control (AGC) simulation, by which the balancing operations of a system can be simulated to answer the questions posed above. The simulator, named Electric System Intra-Hour Operation Simulator (ESIOS), uses the NV Energy southern system as a study case, and models the system’s generator configurations, AGC functions, and operator actions to balance system generation and load. Actual dispatch of AGC generators and control performance under various PV penetration levels can be predicted by running ESIOS. With data about the load, generation, and generator characteristics, ESIOS can perform similar simulations and assess variable generation integration impacts for other systems as well. This report describes the design of the simulator and presents the study results showing the PV impacts on NV Energy real-time operations.

  3. Guidelines for Large-Scale Sequence-Based Complex Trait Association Studies: Lessons Learned from the NHLBI Exome Sequencing Project.

    PubMed

    Auer, Paul L; Reiner, Alex P; Wang, Gao; Kang, Hyun Min; Abecasis, Goncalo R; Altshuler, David; Bamshad, Michael J; Nickerson, Deborah A; Tracy, Russell P; Rich, Stephen S; Leal, Suzanne M

    2016-10-06

    Massively parallel whole-genome sequencing (WGS) data have ushered in a new era in human genetics. These data are now being used to understand the role of rare variants in complex traits and to advance the goals of precision medicine. The technological and computing advances that have enabled us to generate WGS data on thousands of individuals have also outpaced our ability to perform analyses in scientifically and statistically rigorous and thoughtful ways. The past several years have witnessed the application of whole-exome sequencing (WES) to complex traits and diseases. From our analysis of NHLBI Exome Sequencing Project (ESP) data, not only have a number of important disease and complex trait association findings emerged, but our collective experience offers some valuable lessons for WGS initiatives. These include caveats associated with generating automated pipelines for quality control and analysis of rare variants; the importance of studying minority populations; sample size requirements and efficient study designs for identifying rare-variant associations; and the significance of incidental findings in population-based genetic research. With the ESP as an example, we offer guidance and a framework on how to conduct a large-scale association study in the era of WGS.

  4. Large-scale epitaxial growth kinetics of graphene: A kinetic Monte Carlo study

    SciTech Connect

    Jiang, Huijun; Hou, Zhonghuai

    2015-08-28

    Epitaxial growth via chemical vapor deposition is considered to be the most promising way towards synthesizing large area graphene with high quality. However, it remains a big theoretical challenge to reveal growth kinetics with atomically energetic and large-scale spatial information included. Here, we propose a minimal kinetic Monte Carlo model to address such an issue on an active catalyst surface with graphene/substrate lattice mismatch, which facilitates us to perform large scale simulations of the growth kinetics over two dimensional surface with growth fronts of complex shapes. A geometry-determined large-scale growth mechanism is revealed, where the rate-dominating event is found to be C{sub 1}-attachment for concave growth-front segments and C{sub 5}-attachment for others. This growth mechanism leads to an interesting time-resolved growth behavior which is well consistent with that observed in a recent scanning tunneling microscopy experiment.

  5. An experimental study of heat transfer in a large-scale turbine rotor passage

    NASA Technical Reports Server (NTRS)

    Blair, Michael F.

    1992-01-01

    An experimental study of the heat transfer distribution in a turbine rotor passage was conducted in a large-scale, ambient temperature, rotating turbine model. Heat transfer was measured for both the full-span suction and pressure surfaces of the airfoil as well as for the hub endwall surface. The objective of this program was to document the effects of flow three-dimensionality on the heat transfer in a rotating blade row (vs a stationary cascade). Of particular interest were the effects of the hub and tip secondary flows, tip leakage and the leading-edge horseshoe vortex system. The effect of surface roughness on the passage heat transfer was also investigated. Midspan results are compared with both smooth-wall and rough-wall finite-difference two-dimensional heat transfer predictions. Contour maps of Stanton number for both the rotor airfoil and endwall surfaces revealed numerous regions of high heat transfer produced by the three-dimensional flows within the rotor passage. Of particular importance are regions of local enhancement (as much as 100 percent over midspan values) produced on the airfoil suction surface by the secondary flows and tip-leakage vortices and on the hub endwall by the leading-edge horseshoe vortex system.

  6. Prospective large-scale field study generates predictive model identifying major contributors to colony losses.

    PubMed

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J R; Ballam, Joan M

    2015-04-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health.

  7. Large-Scale Recombinant Expression and Purification of Human Tyrosinase Suitable for Structural Studies

    PubMed Central

    Lai, Xuelei; Soler-Lopez, Montserrat; Wichers, Harry J.

    2016-01-01

    Human tyrosinase (TYR) is a glycoprotein that initiates the first two reactions in the melanin biosynthesis pathway. Mutations in its encoding gene cause Oculocutaneous Albinism type I (OCA1), the most severe form of albinism, which is a group of autosomal recessive disorders characterized by reduced or absent production of melanin in skin, hair and eyes. Despite extensive structural and characterization studies of its homologues in lower eukaryotic organisms, the catalytic mechanism of human TYR and the molecular basis of OCA1 are largely unknown. In this work, we have carried out a large-scale recombinant expression of TYR that has enabled us to obtain high yields of pure and active protein, required for crystallization trials and screening of skin whitening agents, which is highly demanded in the cosmetic industry. Addition of an N-terminal honeybee melittin signal peptide for secretion of the produced protein into the (protein-free) medium, as well as a cleavable His-tag at the C-terminus, was crucial for increasing the yield of pure protein. We have successfully crystallized two TYR variants, in both glycosylated and deglycosylated forms, showing preliminary X-ray diffraction patterns at 3.5 Å resolution. Hence, we have established an expression and purification protocol suitable for the crystal structure determination of human TYR, which will give unique atomic insight into the nature and conformation of the residues that shape the substrate binding pocket that will ultimately lead to efficient compound design. PMID:27551823

  8. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies.

    PubMed

    Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H; Michel, Jennifer Carlisle; Claxton, Derek P; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K Christopher; Gouaux, Eric

    2014-11-01

    Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in overexpression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol, we show how to use small-scale transient transfection and fluorescence-detection size-exclusion chromatography (FSEC) experiments using a GFP-His8-tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI(-) (N-acetylglucosaminyltransferase I-negative) cells in suspension culture and overexpress the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl) for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks.

  9. Screening and large-scale expression of membrane proteins in mammalian cells for structural studies

    PubMed Central

    Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H.; Michel, Jennifer Carlisle; Claxton, Derek P.; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K. Christopher; Gouaux, Eric

    2014-01-01

    Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in over-expression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol we show how to use small-scale transient transfection and fluorescence-detection, size-exclusion chromatography (FSEC) experiments using a GFP-His8 tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI− (N-acetylglucosaminyltransferase I-negative) cells in suspension culture, and over-express the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl), for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks. PMID:25299155

  10. Cooling rate dependence of solidification for liquid aluminium: a large-scale molecular dynamics simulation study.

    PubMed

    Hou, Z Y; Dong, K J; Tian, Z A; Liu, R S; Wang, Z; Wang, J G

    2016-06-29

    The effect of the cooling rate on the solidification process of liquid aluminium is studied using a large-scale molecular dynamics method. It is found that there are various types of short-range order (SRO) structures in the liquid, among which the icosahedral (ICO)-like structures are dominant. These SRO structures are in dynamic fluctuation and transform each other. The effect of the cooling rate on the microstructure is very weak at high temperatures and in supercooled liquids, and it appears only below the liquid-solid transition temperature. Fast cooling rates favour the formation of amorphous structures with ICO-like features, while slow cooling rates favour the formation of FCC crystalline structures. Furthermore, FCC and HCP structures can coexist in crystalline structures. It is also found that nanocrystalline aluminium can be achieved at appropriate cooling rates, and its formation mechanism is thoroughly investigated by tracing the evolution of nanoclusters. The arrangement of FCC and HCP atoms in the nanograins displays various twinned structures as observed using visualization analysis, which is different from the layering or phase separation structures observed in the solidification of Lennard-Jones fluids and some metal liquids.

  11. Tropical and extratropical forcing of the large-scale circulation - A diagnostic study

    NASA Technical Reports Server (NTRS)

    Lau, K. M.; Boyle, J. S.

    1987-01-01

    Seasonal anomalies in the large-scale circulation are studied in relation to seasonal-mean tropical forcing and extratropical transient-eddy forcing using nine years of tropical-wind and outgoing-longwave-radiation (OLR) data. Results show that in the interannual time scale, extreme swings in anomalous convection over the maritime continent of Indonesia/Borneo and the equatorial central Pacific are linked, respectively, by an east-west seesaw or a dipole pattern, identified with major fluctuations of the Pacific Walker circulation. It is found that extratropical circulation anomalies are related to the fluctuation of this dipole heat source. The overall extratropical circulation seems to be more responsive to the dipole heating with enhanced convection over the maritime continent. While the characteristics of the transient eddies, especially near the exit region of the East Asia jet stream, change substantially between maximum or minimum convection episodes, these transient eddies (defined as transients from the seasonal mean) appear to be unimportant in forcing the seasonal mean circulation anomalies.

  12. Prospective Large-Scale Field Study Generates Predictive Model Identifying Major Contributors to Colony Losses

    PubMed Central

    Kielmanowicz, Merav Gleit; Inberg, Alex; Lerner, Inbar Maayan; Golani, Yael; Brown, Nicholas; Turner, Catherine Louise; Hayes, Gerald J. R.; Ballam, Joan M.

    2015-01-01

    Over the last decade, unusually high losses of colonies have been reported by beekeepers across the USA. Multiple factors such as Varroa destructor, bee viruses, Nosema ceranae, weather, beekeeping practices, nutrition, and pesticides have been shown to contribute to colony losses. Here we describe a large-scale controlled trial, in which different bee pathogens, bee population, and weather conditions across winter were monitored at three locations across the USA. In order to minimize influence of various known contributing factors and their interaction, the hives in the study were not treated with antibiotics or miticides. Additionally, the hives were kept at one location and were not exposed to potential stress factors associated with migration. Our results show that a linear association between load of viruses (DWV or IAPV) in Varroa and bees is present at high Varroa infestation levels (>3 mites per 100 bees). The collection of comprehensive data allowed us to draw a predictive model of colony losses and to show that Varroa destructor, along with bee viruses, mainly DWV replication, contributes to approximately 70% of colony losses. This correlation further supports the claim that insufficient control of the virus-vectoring Varroa mite would result in increased hive loss. The predictive model also indicates that a single factor may not be sufficient to trigger colony losses, whereas a combination of stressors appears to impact hive health. PMID:25875764

  13. Analyzing large-scale conservation interventions with Bayesian hierarchical models: a case study of supplementing threatened Pacific salmon

    PubMed Central

    Scheuerell, Mark D; Buhle, Eric R; Semmens, Brice X; Ford, Michael J; Cooney, Tom; Carmichael, Richard W

    2015-01-01

    Myriad human activities increasingly threaten the existence of many species. A variety of conservation interventions such as habitat restoration, protected areas, and captive breeding have been used to prevent extinctions. Evaluating the effectiveness of these interventions requires appropriate statistical methods, given the quantity and quality of available data. Historically, analysis of variance has been used with some form of predetermined before-after control-impact design to estimate the effects of large-scale experiments or conservation interventions. However, ad hoc retrospective study designs or the presence of random effects at multiple scales may preclude the use of these tools. We evaluated the effects of a large-scale supplementation program on the density of adult Chinook salmon Oncorhynchus tshawytscha from the Snake River basin in the northwestern United States currently listed under the U.S. Endangered Species Act. We analyzed 43 years of data from 22 populations, accounting for random effects across time and space using a form of Bayesian hierarchical time-series model common in analyses of financial markets. We found that varying degrees of supplementation over a period of 25 years increased the density of natural-origin adults, on average, by 0–8% relative to nonsupplementation years. Thirty-nine of the 43 year effects were at least two times larger in magnitude than the mean supplementation effect, suggesting common environmental variables play a more important role in driving interannual variability in adult density. Additional residual variation in density varied considerably across the region, but there was no systematic difference between supplemented and reference populations. Our results demonstrate the power of hierarchical Bayesian models to detect the diffuse effects of management interventions and to quantitatively describe the variability of intervention success. Nevertheless, our study could not address whether ecological

  14. Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

    PubMed Central

    Saxena, Richa; Elbers, Clara C.; Guo, Yiran; Peter, Inga; Gaunt, Tom R.; Mega, Jessica L.; Lanktree, Matthew B.; Tare, Archana; Castillo, Berta Almoguera; Li, Yun R.; Johnson, Toby; Bruinenberg, Marcel; Gilbert-Diamond, Diane; Rajagopalan, Ramakrishnan; Voight, Benjamin F.; Balasubramanyam, Ashok; Barnard, John; Bauer, Florianne; Baumert, Jens; Bhangale, Tushar; Böhm, Bernhard O.; Braund, Peter S.; Burton, Paul R.; Chandrupatla, Hareesh R.; Clarke, Robert; Cooper-DeHoff, Rhonda M.; Crook, Errol D.; Davey-Smith, George; Day, Ian N.; de Boer, Anthonius; de Groot, Mark C.H.; Drenos, Fotios; Ferguson, Jane; Fox, Caroline S.; Furlong, Clement E.; Gibson, Quince; Gieger, Christian; Gilhuijs-Pederson, Lisa A.; Glessner, Joseph T.; Goel, Anuj; Gong, Yan; Grant, Struan F.A.; Grobbee, Diederick E.; Hastie, Claire; Humphries, Steve E.; Kim, Cecilia E.; Kivimaki, Mika; Kleber, Marcus; Meisinger, Christa; Kumari, Meena; Langaee, Taimour Y.; Lawlor, Debbie A.; Li, Mingyao; Lobmeyer, Maximilian T.; Maitland-van der Zee, Anke-Hilse; Meijs, Matthijs F.L.; Molony, Cliona M.; Morrow, David A.; Murugesan, Gurunathan; Musani, Solomon K.; Nelson, Christopher P.; Newhouse, Stephen J.; O'Connell, Jeffery R.; Padmanabhan, Sandosh; Palmen, Jutta; Patel, Sanjey R.; Pepine, Carl J.; Pettinger, Mary; Price, Thomas S.; Rafelt, Suzanne; Ranchalis, Jane; Rasheed, Asif; Rosenthal, Elisabeth; Ruczinski, Ingo; Shah, Sonia; Shen, Haiqing; Silbernagel, Günther; Smith, Erin N.; Spijkerman, Annemieke W.M.; Stanton, Alice; Steffes, Michael W.; Thorand, Barbara; Trip, Mieke; van der Harst, Pim; van der A, Daphne L.; van Iperen, Erik P.A.; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Wolffenbuttel, Bruce H.R.; Young, Taylor; Zafarmand, M. Hadi; Zmuda, Joseph M.; Boehnke, Michael; Altshuler, David; McCarthy, Mark; Kao, W.H. Linda; Pankow, James S.; Cappola, Thomas P.; Sever, Peter; Poulter, Neil; Caulfield, Mark; Dominiczak, Anna; Shields, Denis C.; Bhatt, Deepak L.; Zhang, Li; Curtis, Sean P.; Danesh, John; Casas, Juan P.; van der Schouw, Yvonne T.; Onland-Moret, N. Charlotte; Doevendans, Pieter A.; Dorn, Gerald W.; Farrall, Martin; FitzGerald, Garret A.; Hamsten, Anders; Hegele, Robert; Hingorani, Aroon D.; Hofker, Marten H.; Huggins, Gordon S.; Illig, Thomas; Jarvik, Gail P.; Johnson, Julie A.; Klungel, Olaf H.; Knowler, William C.; Koenig, Wolfgang; März, Winfried; Meigs, James B.; Melander, Olle; Munroe, Patricia B.; Mitchell, Braxton D.; Bielinski, Susan J.; Rader, Daniel J.; Reilly, Muredach P.; Rich, Stephen S.; Rotter, Jerome I.; Saleheen, Danish; Samani, Nilesh J.; Schadt, Eric E.; Shuldiner, Alan R.; Silverstein, Roy; Kottke-Marchant, Kandice; Talmud, Philippa J.; Watkins, Hugh; Asselbergs, Folkert W.; de Bakker, Paul I.W.; McCaffery, Jeanne; Wijmenga, Cisca; Sabatine, Marc S.; Wilson, James G.; Reiner, Alex; Bowden, Donald W.; Hakonarson, Hakon; Siscovick, David S.; Keating, Brendan J.

    2012-01-01

    To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with ∼2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 × 10−9) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p < 2.4 × 10−6). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 × 10−7) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 × 10−15). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 × 10−8). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups. PMID:22325160

  15. RACORO Continental Boundary Layer Cloud Investigations: 1. Case Study Development and Ensemble Large-Scale Forcings

    NASA Technical Reports Server (NTRS)

    Vogelmann, Andrew M.; Fridlind, Ann M.; Toto, Tami; Endo, Satoshi; Lin, Wuyin; Wang, Jian; Feng, Sha; Zhang, Yunyan; Turner, David D.; Liu, Yangang; hide

    2015-01-01

    Observation-based modeling case studies of continental boundary layer clouds have been developed to study cloudy boundary layers, aerosol influences upon them, and their representation in cloud- and global-scale models. Three 60 h case study periods span the temporal evolution of cumulus, stratiform, and drizzling boundary layer cloud systems, representing mixed and transitional states rather than idealized or canonical cases. Based on in situ measurements from the Routine AAF (Atmospheric Radiation Measurement (ARM) Aerial Facility) CLOWD (Clouds with Low Optical Water Depth) Optical Radiative Observations (RACORO) field campaign and remote sensing observations, the cases are designed with a modular configuration to simplify use in large-eddy simulations (LES) and single-column models. Aircraft measurements of aerosol number size distribution are fit to lognormal functions for concise representation in models. Values of the aerosol hygroscopicity parameter, kappa, are derived from observations to be approximately 0.10, which are lower than the 0.3 typical over continents and suggestive of a large aerosol organic fraction. Ensemble large-scale forcing data sets are derived from the ARM variational analysis, European Centre for Medium-Range Weather Forecasts, and a multiscale data assimilation system. The forcings are assessed through comparison of measured bulk atmospheric and cloud properties to those computed in "trial" large-eddy simulations, where more efficient run times are enabled through modest reductions in grid resolution and domain size compared to the full-sized LES grid. Simulations capture many of the general features observed, but the state-of-the-art forcings were limited at representing details of cloud onset, and tight gradients and high-resolution transients of importance. Methods for improving the initial conditions and forcings are discussed. The cases developed are available to the general modeling community for studying continental boundary

  16. A large-scale multicentre cerebral diffusion tensor imaging study in amyotrophic lateral sclerosis.

    PubMed

    Müller, Hans-Peter; Turner, Martin R; Grosskreutz, Julian; Abrahams, Sharon; Bede, Peter; Govind, Varan; Prudlo, Johannes; Ludolph, Albert C; Filippi, Massimo; Kassubek, Jan

    2016-06-01

    Damage to the cerebral tissue structural connectivity associated with amyotrophic lateral sclerosis (ALS), which extends beyond the motor pathways, can be visualised by diffusion tensor imaging (DTI). The effective translation of DTI metrics as biomarker requires its application across multiple MRI scanners and patient cohorts. A multicentre study was undertaken to assess structural connectivity in ALS within a large sample size. 442 DTI data sets from patients with ALS (N=253) and controls (N=189) were collected for this retrospective study, from eight international ALS-specialist clinic sites. Equipment and DTI protocols varied across the centres. Fractional anisotropy (FA) maps of the control participants were used to establish correction matrices to pool data, and correction algorithms were applied to the FA maps of the control and ALS patient groups. Analysis of data pooled from all centres, using whole-brain-based statistical analysis of FA maps, confirmed the most significant alterations in the corticospinal tracts, and captured additional significant white matter tract changes in the frontal lobe, brainstem and hippocampal regions of the ALS group that coincided with postmortem neuropathological stages. Stratification of the ALS group for disease severity (ALS functional rating scale) confirmed these findings. This large-scale study overcomes the challenges associated with processing and analysis of multiplatform, multicentre DTI data, and effectively demonstrates the anatomical fingerprint patterns of changes in a DTI metric that reflect distinct ALS disease stages. This success paves the way for the use of DTI-based metrics as read-out in natural history, prognostic stratification and multisite disease-modifying studies in ALS. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  17. RACORO Continental Boundary Layer Cloud Investigations: 1. Case Study Development and Ensemble Large-Scale Forcings

    NASA Technical Reports Server (NTRS)

    Vogelmann, Andrew M.; Fridlind, Ann M.; Toto, Tami; Endo, Satoshi; Lin, Wuyin; Wang, Jian; Feng, Sha; Zhang, Yunyan; Turner, David D.; Liu, Yangang; Li, Zhijin; Xie, Shaocheng; Ackerman, Andrew S.; Zhang, Minghua; Khairoutdinov, Marat

    2015-01-01

    Observation-based modeling case studies of continental boundary layer clouds have been developed to study cloudy boundary layers, aerosol influences upon them, and their representation in cloud- and global-scale models. Three 60 h case study periods span the temporal evolution of cumulus, stratiform, and drizzling boundary layer cloud systems, representing mixed and transitional states rather than idealized or canonical cases. Based on in situ measurements from the Routine AAF (Atmospheric Radiation Measurement (ARM) Aerial Facility) CLOWD (Clouds with Low Optical Water Depth) Optical Radiative Observations (RACORO) field campaign and remote sensing observations, the cases are designed with a modular configuration to simplify use in large-eddy simulations (LES) and single-column models. Aircraft measurements of aerosol number size distribution are fit to lognormal functions for concise representation in models. Values of the aerosol hygroscopicity parameter, kappa, are derived from observations to be approximately 0.10, which are lower than the 0.3 typical over continents and suggestive of a large aerosol organic fraction. Ensemble large-scale forcing data sets are derived from the ARM variational analysis, European Centre for Medium-Range Weather Forecasts, and a multiscale data assimilation system. The forcings are assessed through comparison of measured bulk atmospheric and cloud properties to those computed in "trial" large-eddy simulations, where more efficient run times are enabled through modest reductions in grid resolution and domain size compared to the full-sized LES grid. Simulations capture many of the general features observed, but the state-of-the-art forcings were limited at representing details of cloud onset, and tight gradients and high-resolution transients of importance. Methods for improving the initial conditions and forcings are discussed. The cases developed are available to the general modeling community for studying continental boundary

  18. Understanding Participation in E-Learning in Organizations: A Large-Scale Empirical Study of Employees

    ERIC Educational Resources Information Center

    Garavan, Thomas N.; Carbery, Ronan; O'Malley, Grace; O'Donnell, David

    2010-01-01

    Much remains unknown in the increasingly important field of e-learning in organizations. Drawing on a large-scale survey of employees (N = 557) who had opportunities to participate in voluntary e-learning activities, the factors influencing participation in e-learning are explored in this empirical paper. It is hypothesized that key variables…

  19. DNS study of large-scale structures in a separated turbulent boundary layer

    NASA Astrophysics Data System (ADS)

    Abe, Hiroyuki; Mizobuchi, Yasuhiro; Matsuo, Yuichi

    2011-11-01

    Direct numerical simulations (DNSs) of a separated flat-plate turbulent boundary layer have been carried out. The inlet data are prescribed by DNSs of a zero-pressure-gradient turbulent boundary layer with the rescaling-recycling method; blowing and suction are imposed at the upper boundary for producing a separation bubble. The Reynolds numbers at the inlet are set to be Reθ =300, 600 and 900, where Reθ is the Reynolds number based on the freestream velocity and the momentum thickness. Particular attention is given to large- scale structures existing in a separated region. Results indicate that large-scale organized structures of the streamwise velocity fluctuation appear in a detached shear layer when a large separated region is formed. The latter structures consist of positive and negative regions alternating in the spanwise direction with a spacing of about 2 ~ 3δ99 (δ99 denotes the 99% boundary layer thickness at the inlet), which become more apparent with increasing Reynolds number. They are most likely associated with large-scale spanwise meandering of the separation line. There is also close relationship between the large-scale structures and vortical structures, the latter tending to form vortex clusters where hairpin-like vortices are also observed.

  20. Science: The Salters' Approach--A Case Study of the Process of Large Scale Curriculum Development.

    ERIC Educational Resources Information Center

    Campbell, Bob; And Others

    1994-01-01

    Analyzes the process of large scale curriculum development. Locates the projects and their development within the range of approaches advocated in science education and considers the practical decisions taken during the development in relation to theories of curriculum development and change. (ZWH)

  1. Numerics-Characteristics-Asymptotics: A Case Study from Large Scale Ocean Circulation

    ERIC Educational Resources Information Center

    Hodnett, P. F.; Courtney, C.

    2007-01-01

    This paper uses a partial differential equation which occurs in a reduced model of large scale circulation in an ocean basin as an educational vehicle through which to demonstrate the usefulness of a set of mathematical techniques in analysing the equation. A parameter occurring in the equation does in reality vary from very small through…

  2. Understanding Participation in E-Learning in Organizations: A Large-Scale Empirical Study of Employees

    ERIC Educational Resources Information Center

    Garavan, Thomas N.; Carbery, Ronan; O'Malley, Grace; O'Donnell, David

    2010-01-01

    Much remains unknown in the increasingly important field of e-learning in organizations. Drawing on a large-scale survey of employees (N = 557) who had opportunities to participate in voluntary e-learning activities, the factors influencing participation in e-learning are explored in this empirical paper. It is hypothesized that key variables…

  3. Numerics-Characteristics-Asymptotics: A Case Study from Large Scale Ocean Circulation

    ERIC Educational Resources Information Center

    Hodnett, P. F.; Courtney, C.

    2007-01-01

    This paper uses a partial differential equation which occurs in a reduced model of large scale circulation in an ocean basin as an educational vehicle through which to demonstrate the usefulness of a set of mathematical techniques in analysing the equation. A parameter occurring in the equation does in reality vary from very small through…

  4. Celiac disease markers in patients with liver diseases: a single center large scale screening study.

    PubMed

    Drastich, Pavel; Honsová, Eva; Lodererová, Alena; Jarešová, Marcela; Pekáriková, Aneta; Hoffmanová, Iva; Tučková, Ludmila; Tlaskalová-Hogenová, Helena; Spičák, Julius; Sánchez, Daniel

    2012-11-21

    To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases. Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy. We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients: 4 with autoimmune hepatitis type I, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type I. We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.

  5. Observational and Model Studies of Large-Scale Mixing Processes in the Stratosphere

    NASA Technical Reports Server (NTRS)

    Bowman, Kenneth P.

    1997-01-01

    The following is the final technical report for grant NAGW-3442, 'Observational and Model Studies of Large-Scale Mixing Processes in the Stratosphere'. Research efforts in the first year concentrated on transport and mixing processes in the polar vortices. Three papers on mixing in the Antarctic were published. The first was a numerical modeling study of wavebreaking and mixing and their relationship to the period of observed stratospheric waves (Bowman). The second paper presented evidence from TOMS for wavebreaking in the Antarctic (Bowman and Mangus 1993). The third paper used Lagrangian trajectory calculations from analyzed winds to show that there is very little transport into the Antarctic polar vortex prior to the vortex breakdown (Bowman). Mixing is significantly greater at lower levels. This research helped to confirm theoretical arguments for vortex isolation and data from the Antarctic field experiments that were interpreted as indicating isolation. A Ph.D. student, Steve Dahlberg, used the trajectory approach to investigate mixing and transport in the Arctic. While the Arctic vortex is much more disturbed than the Antarctic, there still appears to be relatively little transport across the vortex boundary at 450 K prior to the vortex breakdown. The primary reason for the absence of an ozone hole in the Arctic is the earlier warming and breakdown of the vortex compared to the Antarctic, not replenishment of ozone by greater transport. Two papers describing these results have appeared (Dahlberg and Bowman; Dahlberg and Bowman). Steve Dahlberg completed his Ph.D. thesis (Dahlberg and Bowman) and is now teaching in the Physics Department at Concordia College. We also prepared an analysis of the QBO in SBUV ozone data (Hollandsworth et al.). A numerical study in collaboration with Dr. Ping Chen investigated mixing by barotropic instability, which is the probable origin of the 4-day wave in the upper stratosphere (Bowman and Chen). The important result from

  6. Observational and Model Studies of Large-Scale Mixing Processes in the Stratosphere

    NASA Technical Reports Server (NTRS)

    Bowman, Kenneth P.

    1997-01-01

    The following is the final technical report for grant NAGW-3442, 'Observational and Model Studies of Large-Scale Mixing Processes in the Stratosphere'. Research efforts in the first year concentrated on transport and mixing processes in the polar vortices. Three papers on mixing in the Antarctic were published. The first was a numerical modeling study of wavebreaking and mixing and their relationship to the period of observed stratospheric waves (Bowman). The second paper presented evidence from TOMS for wavebreaking in the Antarctic (Bowman and Mangus 1993). The third paper used Lagrangian trajectory calculations from analyzed winds to show that there is very little transport into the Antarctic polar vortex prior to the vortex breakdown (Bowman). Mixing is significantly greater at lower levels. This research helped to confirm theoretical arguments for vortex isolation and data from the Antarctic field experiments that were interpreted as indicating isolation. A Ph.D. student, Steve Dahlberg, used the trajectory approach to investigate mixing and transport in the Arctic. While the Arctic vortex is much more disturbed than the Antarctic, there still appears to be relatively little transport across the vortex boundary at 450 K prior to the vortex breakdown. The primary reason for the absence of an ozone hole in the Arctic is the earlier warming and breakdown of the vortex compared to the Antarctic, not replenishment of ozone by greater transport. Two papers describing these results have appeared (Dahlberg and Bowman; Dahlberg and Bowman). Steve Dahlberg completed his Ph.D. thesis (Dahlberg and Bowman) and is now teaching in the Physics Department at Concordia College. We also prepared an analysis of the QBO in SBUV ozone data (Hollandsworth et al.). A numerical study in collaboration with Dr. Ping Chen investigated mixing by barotropic instability, which is the probable origin of the 4-day wave in the upper stratosphere (Bowman and Chen). The important result from

  7. Large-Scale Crowdsourced Study for Tone-Mapped HDR Pictures.

    PubMed

    Kundu, Debarati; Ghadiyaram, Deepti; Bovik, Alan C; Evans, Brian L

    2017-10-01

    Measuring digital picture quality, as perceived by human observers, is increasingly important in many applications in which humans are the ultimate consumers of visual information. Standard dynamic range (SDR) images provide 8 b/color/pixel. High dynamic range (HDR) images, usually created from multiple exposures of the same scene, can provide 16 or 32 b/color/pixel, but need to be tonemapped to SDR for display on standard monitors. Multiexposure fusion (MEF) techniques bypass HDR creation by fusing an exposure stack directly to SDR images to achieve aesthetically pleasing luminance and color distributions. Many HDR and MEF databases have a relatively small number of images and human opinion scores, obtained under stringently controlled conditions, thereby limiting realistic viewing. Moreover, many of these databases are intended to compare tone-mapping algorithms, rather than being specialized for developing and comparing image quality assessment models. To overcome these challenges, we conducted a massively crowdsourced online subjective study. The primary contributions described in this paper are: 1) the new ESPL-LIVE HDR Image Database that we created containing diverse images obtained by tone-mapping operators and MEF algorithms, with and without post-processing; 2) a large-scale subjective study that we conducted using a crowdsourced platform to gather more than 300 000 opinion scores on 1811 images from over 5000 unique observers; and 3) a detailed study of the correlation performance of the state-of-the-art no-reference image quality assessment algorithms against human opinion scores of these images. The database is available at http://signal.ece.utexas.edu/%7Edebarati/HDRDatabase.zip.

  8. Design and methodology of the Shanghai child and adolescent large-scale eye study (SCALE).

    PubMed

    He, Xiangui; Zhao, Rong; Sankaridurg, Padmaja; Zhu, Jianfeng; John, Thomas; Ma, Yingyan; Lu, Lina; Lv, Minzhi; Smith, Earl L; Resnikoff, Serge; Naidoo, Kovin; Zou, Haidong; Xu, Xun

    2017-09-12

    Nearly half of children suffering vision impairment reside in China with myopia accounting for the vast majority. To describe the design and methodology of the Shanghai Child and Adolescent Large-scale Eye Study (SCALE). The SCALE was a city wide, school-based, prospective survey. Children and adolescents aged 4 to 14 years from kindergarten (middle and senior), primary schools and junior high schools of all 17 districts and counties of the city of Shanghai, China were examined in 2012-2013. Each enrolled child underwent vision assessment (distance visual acuity; uncorrected and with corrective device if worn) and their parent/carer completed a questionnaire designed to elicit risk factors associated with myopia. Additionally, non-cycloplegic autorefraction and ocular axial length was measured in a sub-set of the larger sample.. Prevalence and the associated factors of vision impairment, myopia and high myopia in Shanghai. In 2012-2013, a total of 910,245 of the eligible 1,196,763 children and adolescents identified from census (76%, mean age 9.0 ± 2.7 years (4- 14 years)) were enrolled with visual acuity screened in the city of Shanghai. Of these, 610,952 children (67% of the entire sample) underwent non-cycloplegic autorefraction and 219,188 (24% of the entire sample) had both non-cycloplegic autorefraction and axial length measurements. The study results will provide insights on the burden of vision impairment, myopia and high myopia in children and adolescents in a metropolitan area of China, and contribute to the policies and strategies to address and limit the burden. This article is protected by copyright. All rights reserved.

  9. Temperature dependence of dimerization and dewetting of large-scale hydrophobes: a molecular dynamics study.

    PubMed

    Zangi, Ronen; Berne, B J

    2008-07-24

    We studied by molecular dynamics simulations the temperature dependence of hydrophobic association and drying transition of large-scale solutes. Similar to the behavior of small solutes, we found the association process to be characterized by a large negative heat capacity change. The origin of this large change in heat capacity is the high fragility of hydrogen bonds between water molecules at the interface with hydrophobic solutes; an increase in temperature breaks more hydrogen bonds at the interface than in the bulk. With increasing temperature, both entropy and enthalpy changes for association strongly decrease, while the change in free energy weakly varies, exhibiting a small minimum at high temperatures. At around T=Ts=360 K, the change in entropy is zero, a behavior similar to the solvation of small nonpolar solutes. Unexpectedly, we find that at Ts, there is still a substantial orientational ordering of the interfacial water molecules relative to the bulk. Nevertheless, at this point, the change in entropy vanishes due to a compensating contribution of translational entropy. Thus, at Ts, there is rotational order and translational disorder of the interfacial water relative to bulk water. In addition, we studied the temperature dependence of the drying-wetting transition. By calculating the contact angle of water on the hydrophobic surface at different temperatures, we compared the critical distance observed in the simulations with the critical distance predicted by macroscopic theory. Although the deviations of the predicted from the observed values are very small (8-23%), there seems to be an increase in the deviations with an increase in temperature. We suggest that these deviations emerge due to increased fluctuations, characterizing finite systems, as the temperature increases.

  10. The R3/R5 impoundment study: a large-scale management experiment

    USGS Publications Warehouse

    Lyons, J.E.; Laskowski, H.P.; Runge, M.C.; Lor, S.; Kendall, W.L.; Talbott, S.

    2005-01-01

    Managed wetlands provide a broad spectrum of resources to migratory waterbirds (shorebirds, wading birds, and waterfowl) throughout the annual cycle. Successful conservation and management of waterbirds depends on integrated approaches that (1) incorporate larger spatial and temporal scales than traditional approaches to wetland management, and (2) use experimental designs to reduce uncertainty about the response of the systems to management. In a previous experiment on USFWS National Wildlife Refuges in the Northeast, we explored the effects of water-level management on migratory shorebirds in spring. We documented regional patterns of shorebird use of Refuge wetlands and showed that across the region, a slow drawdown was superior to 2 alternatives. USGS and USFWS have now cooperatively undertaken an expanded study focusing on 3 waterbird guilds in the context of the complete annual cycle and over a larger spatial extent. For this 3-yr study, now in its first year, 2 impoundments were selected at each of 23 NWRs across the Northeast and Upper Midwest Regions. Two experimental treatments (annual water regimes focused on early-season or late-season drawdowns) are being applied each year in a cross-over design. This experimental design will increase our understanding of cross-seasonal interactions which result from specific hydrologic regimes aimed at a particular waterbird guild. Monitoring will allow waterbird responses to be linked with direct effects of water management on plant and invertebrate populations. Results of this large-scale experiment will be used to motivate formal adaptive management of wetlands and waterbirds at refuges following completion of this experiment.

  11. LUCI: A facility at DUSEL for large-scale experimental study of geologic carbon sequestration

    SciTech Connect

    Peters, C. A.; Dobson, P.F.; Oldenburg, C.M.; Wang, J. S. Y.; Onstott, T.C.; Scherer, G.W.; Freifeld, B.M.; Ramakrishnan, T.S.; Stabinski, E.L.; Liang, K.; Verma, S.

    2010-10-01

    LUCI, the Laboratory for Underground CO{sub 2} Investigations, is an experimental facility being planned for the DUSEL underground laboratory in South Dakota, USA. It is designed to study vertical flow of CO{sub 2} in porous media over length scales representative of leakage scenarios in geologic carbon sequestration. The plan for LUCI is a set of three vertical column pressure vessels, each of which is {approx}500 m long and {approx}1 m in diameter. The vessels will be filled with brine and sand or sedimentary rock. Each vessel will have an inner column to simulate a well for deployment of down-hole logging tools. The experiments are configured to simulate CO{sub 2} leakage by releasing CO{sub 2} into the bottoms of the columns. The scale of the LUCI facility will permit measurements to study CO{sub 2} flow over pressure and temperature variations that span supercritical to subcritical gas conditions. It will enable observation or inference of a variety of relevant processes such as buoyancy-driven flow in porous media, Joule-Thomson cooling, thermal exchange, viscous fingering, residual trapping, and CO{sub 2} dissolution. Experiments are also planned for reactive flow of CO{sub 2} and acidified brines in caprock sediments and well cements, and for CO{sub 2}-enhanced methanogenesis in organic-rich shales. A comprehensive suite of geophysical logging instruments will be deployed to monitor experimental conditions as well as provide data to quantify vertical resolution of sensor technologies. The experimental observations from LUCI will generate fundamental new understanding of the processes governing CO{sub 2} trapping and vertical migration, and will provide valuable data to calibrate and validate large-scale model simulations.

  12. Studying large-scale programmes to improve patient safety in whole care systems: challenges for research.

    PubMed

    Benn, Jonathan; Burnett, Susan; Parand, Anam; Pinto, Anna; Iskander, Sandra; Vincent, Charles

    2009-12-01

    Large-scale national and multi-institutional patient safety improvement programmes are being developed in the health care systems of several countries to address problems in the reliability of care delivered to patients. Drawing upon popular collaborative improvement models, these campaigns are ambitious in their aims to improve patient safety in macro-level systems such as whole health care organisations. This article considers the methodological issues involved in conducting research and evaluation of these programmes. Several specific research challenges are outlined, which result from the complexity of longitudinal, multi-level intervention programmes and the variable, highly sociotechnical care systems, with which they interact. Organisational-level improvement programmes are often underspecified due to local variations in context and organisational readiness for improvement work. The result is variable implementation patterns and local adaptations. Programme effects span levels and other boundaries within a system, vary dynamically or are cumulative over time and are problematic to understand in terms of cause and effect, where concurrent external influences exist and the impact upon study endpoints may be mediated by a range of organisational and social factors. We outline the methodological approach to research in the United Kingdom Safer Patients Initiative, to exemplify how some of the challenges for research in this area can be met through a multi-method, longitudinal research design. Specifically, effective research designs must be sensitive to complex variation, through employing multiple qualitative and quantitative measures, collect data over time to understand change and utilise descriptive techniques to capture specific interactions between programme and context for implementation. When considering the long-term, sustained impact of an improvement programme, researchers must consider how to define and measure the capability for continuous safe and

  13. [The benefit of large-scale cohort studies for health research: the example of the German National Cohort].

    PubMed

    Ahrens, Wolfgang; Jöckel, K-H

    2015-08-01

    The prospective nature of large-scale epidemiological multi-purpose cohort studies with long observation periods facilitates the search for complex causes of diseases, the analysis of the natural history of diseases and the identification of novel pre-clinical markers of disease. The German National Cohort (GNC) is a population-based, highly standardised and in-depth phenotyped cohort. It shall create the basis for new strategies for risk assessment and identification, early diagnosis and prevention of multifactorial diseases. The GNC is the largest population-based cohort study in Germany to date. In the year 2014 the examination of 200,000 women and men aged 20-69 years started in 18 study centers. The study facilitates the investigation of the etiology of chronic diseases in relation to lifestyle, genetic, socioeconomic, psychosocial and environmental factors. By this the GNC creates the basis for the development of methods for early diagnosis and prevention of these diseases. Cardiovascular and respiratory diseases, cancer, diabetes, neurodegenerative/-psychiatric diseases, musculoskeletal and infectious diseases are in focus of this study. Due to its mere size, the study could be characterized as a Big Data project. We deduce that this is not the case.

  14. A Study on Fast Gates for Large-Scale Quantum Simulation with Trapped Ions

    NASA Astrophysics Data System (ADS)

    Taylor, Richard L.; Bentley, Christopher D. B.; Pedernales, Julen S.; Lamata, Lucas; Solano, Enrique; Carvalho, André R. R.; Hope, Joseph J.

    2017-04-01

    Large-scale digital quantum simulations require thousands of fundamental entangling gates to construct the simulated dynamics. Despite success in a variety of small-scale simulations, quantum information processing platforms have hitherto failed to demonstrate the combination of precise control and scalability required to systematically outmatch classical simulators. We analyse how fast gates could enable trapped-ion quantum processors to achieve the requisite scalability to outperform classical computers without error correction. We analyze the performance of a large-scale digital simulator, and find that fidelity of around 70% is realizable for π-pulse infidelities below 10-5 in traps subject to realistic rates of heating and dephasing. This scalability relies on fast gates: entangling gates faster than the trap period.

  15. A feasibility study of large-scale photobiological hydrogen production utilizing mariculture-raised cyanobacteria.

    PubMed

    Sakurai, Hidehiro; Masukawa, Hajime; Kitashima, Masaharu; Inoue, Kazuhito

    2010-01-01

    In order to decrease CO(2) emissions from the burning of fossil fuels, the development of new renewable energy sources sufficiently large in quantity is essential. To meet this need, we propose large-scale H(2) production on the sea surface utilizing cyanobacteria. Although many of the relevant technologies are in the early stage of development, this chapter briefly examines the feasibility of such H(2) production, in order to illustrate that under certain conditions large-scale photobiological H(2) production can be viable. Assuming that solar energy is converted to H(2) at 1.2% efficiency, the future cost of H(2) can be estimated to be about 11 (pipelines) and 26.4 (compression and marine transportation) cents kWh(-1), respectively.

  16. A Study on Fast Gates for Large-Scale Quantum Simulation with Trapped Ions

    PubMed Central

    Taylor, Richard L.; Bentley, Christopher D. B.; Pedernales, Julen S.; Lamata, Lucas; Solano, Enrique; Carvalho, André R. R.; Hope, Joseph J.

    2017-01-01

    Large-scale digital quantum simulations require thousands of fundamental entangling gates to construct the simulated dynamics. Despite success in a variety of small-scale simulations, quantum information processing platforms have hitherto failed to demonstrate the combination of precise control and scalability required to systematically outmatch classical simulators. We analyse how fast gates could enable trapped-ion quantum processors to achieve the requisite scalability to outperform classical computers without error correction. We analyze the performance of a large-scale digital simulator, and find that fidelity of around 70% is realizable for π-pulse infidelities below 10−5 in traps subject to realistic rates of heating and dephasing. This scalability relies on fast gates: entangling gates faster than the trap period. PMID:28401945

  17. Exploring the feasibility of using copy number variants as genetic markers through large-scale whole genome sequencing experiments

    USDA-ARS?s Scientific Manuscript database

    Copy number variants (CNV) are large scale duplications or deletions of genomic sequence that are caused by a diverse set of molecular phenomena that are distinct from single nucleotide polymorphism (SNP) formation. Due to their different mechanisms of formation, CNVs are often difficult to track us...

  18. Large Scale Numerical Modelling to Study the Dispersion of Persistent Toxic Substances Over Europe

    NASA Astrophysics Data System (ADS)

    Aulinger, A.; Petersen, G.

    2003-12-01

    For the past two decades environmental research at the GKSS Research Centre has been concerned with airborne pollutants with adverse effects on human health. The research was mainly focused on investigating the dispersion and deposition of heavy metals like lead and mercury over Europe by means of numerical modelling frameworks. Lead, in particular, served as a model substance to study the relationship between emissions and human exposition. The major source of airborne lead in Germany was fuel combustion until the 1980ies when its use as gasoline additive declined due to political decisions. Since then, the concentration of lead in ambient air and the deposition rates decreased in the same way as the consumption of leaded fuel. These observations could further be related to the decrease of lead concentrations in human blood measured during medical studies in several German cities. Based on the experience with models for heavy metal transport and deposition we have now started to turn our research focus to organic substances, e.g. PAHs. PAHs have been recognized as significant air borne carcinogens for several decades. However, it is not yet possible to precisely quantify the risk of human exposure to those compounds. Physical and chemical data, known from literature, describing the partitioning of the compounds between particle and gas phase and their degradation in the gas phase are implemented in a tropospheric chemistry module. In this way, the fate of PAHs in the atmosphere due to different particle type and size and different meteorological conditions is tested before carrying out large-scale and long-time studies. First model runs have been carried out for Benzo(a)Pyrene as one of the principal carcinogenic PAHs. Up to now, nearly nothing is known about degradation reactions of particle bound BaP. Thus, they could not be taken into account in the model so far. On the other hand, the proportion of BaP in the gas phase has to be considered at higher ambient

  19. Reproducible Large-Scale Neuroimaging Studies with the OpenMOLE Workflow Management System.

    PubMed

    Passerat-Palmbach, Jonathan; Reuillon, Romain; Leclaire, Mathieu; Makropoulos, Antonios; Robinson, Emma C; Parisot, Sarah; Rueckert, Daniel

    2017-01-01

    OpenMOLE is a scientific workflow engine with a strong emphasis on workload distribution. Workflows are designed using a high level Domain Specific Language (DSL) built on top of Scala. It exposes natural parallelism constructs to easily delegate the workload resulting from a workflow to a wide range of distributed computing environments. OpenMOLE hides the complexity of designing complex experiments thanks to its DSL. Users can embed their own applications and scale their pipelines from a small prototype running on their desktop computer to a large-scale study harnessing distributed computing infrastructures, simply by changing a single line in the pipeline definition. The construction of the pipeline itself is decoupled from the execution context. The high-level DSL abstracts the underlying execution environment, contrary to classic shell-script based pipelines. These two aspects allow pipelines to be shared and studies to be replicated across different computing environments. Workflows can be run as traditional batch pipelines or coupled with OpenMOLE's advanced exploration methods in order to study the behavior of an application, or perform automatic parameter tuning. In this work, we briefly present the strong assets of OpenMOLE and detail recent improvements targeting re-executability of workflows across various Linux platforms. We have tightly coupled OpenMOLE with CARE, a standalone containerization solution that allows re-executing on a Linux host any application that has been packaged on another Linux host previously. The solution is evaluated against a Python-based pipeline involving packages such as scikit-learn as well as binary dependencies. All were packaged and re-executed successfully on various HPC environments, with identical numerical results (here prediction scores) obtained on each environment. Our results show that the pair formed by OpenMOLE and CARE is a reliable solution to generate reproducible results and re-executable pipelines. A

  20. Reproducible Large-Scale Neuroimaging Studies with the OpenMOLE Workflow Management System

    PubMed Central

    Passerat-Palmbach, Jonathan; Reuillon, Romain; Leclaire, Mathieu; Makropoulos, Antonios; Robinson, Emma C.; Parisot, Sarah; Rueckert, Daniel

    2017-01-01

    OpenMOLE is a scientific workflow engine with a strong emphasis on workload distribution. Workflows are designed using a high level Domain Specific Language (DSL) built on top of Scala. It exposes natural parallelism constructs to easily delegate the workload resulting from a workflow to a wide range of distributed computing environments. OpenMOLE hides the complexity of designing complex experiments thanks to its DSL. Users can embed their own applications and scale their pipelines from a small prototype running on their desktop computer to a large-scale study harnessing distributed computing infrastructures, simply by changing a single line in the pipeline definition. The construction of the pipeline itself is decoupled from the execution context. The high-level DSL abstracts the underlying execution environment, contrary to classic shell-script based pipelines. These two aspects allow pipelines to be shared and studies to be replicated across different computing environments. Workflows can be run as traditional batch pipelines or coupled with OpenMOLE's advanced exploration methods in order to study the behavior of an application, or perform automatic parameter tuning. In this work, we briefly present the strong assets of OpenMOLE and detail recent improvements targeting re-executability of workflows across various Linux platforms. We have tightly coupled OpenMOLE with CARE, a standalone containerization solution that allows re-executing on a Linux host any application that has been packaged on another Linux host previously. The solution is evaluated against a Python-based pipeline involving packages such as scikit-learn as well as binary dependencies. All were packaged and re-executed successfully on various HPC environments, with identical numerical results (here prediction scores) obtained on each environment. Our results show that the pair formed by OpenMOLE and CARE is a reliable solution to generate reproducible results and re-executable pipelines. A

  1. Design optimization studies for large-scale contoured beam deployable satellite antennas

    NASA Astrophysics Data System (ADS)

    Tanaka, Hiroaki

    2006-05-01

    Satellite communications systems over the past two decades have become more sophisticated and evolved new applications that require much higher flux densities. These new requirements to provide high data rate services to very small user terminals have in turn led to the need for large aperture space antenna systems with higher gain. Conventional parabolic reflectors constructed of metal have become, over time, too massive to support these new missions in a cost effective manner and also have posed problems of fitting within the constrained volume of launch vehicles. Designers of new space antenna systems have thus begun to explore new design options. These design options for advanced space communications networks include such alternatives as inflatable antennas using polyimide materials, antennas constructed of piezo-electric materials, phased array antenna systems (especially in the EHF bands) and deployable antenna systems constructed of wire mesh or cabling systems. This article updates studies being conducted in Japan of such deployable space antenna systems [H. Tanaka, M.C. Natori, Shape control of space antennas consisting of cable networks, Acta Astronautica 55 (2004) 519-527]. In particular, this study shows how the design of such large-scale deployable antenna systems can be optimized based on various factors including the frequency bands to be employed with such innovative reflector design. In particular, this study investigates how contoured beam space antennas can be effective by constructed out of so-called cable networks or mesh-like reflectors. This design can be accomplished via "plane wave synthesis" and by the "force density method" and then to iterate the design to achieve the optimum solution. We have concluded that the best design is achieved by plane wave synthesis. Further, we demonstrate that the nodes on the reflector are best determined by a pseudo-inverse calculation of the matrix that can be interpolated so as to achieve the minimum

  2. Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in large-scale study.

    PubMed

    Wu, Tao; Zhang, Zhigang; Liu, Bin; Hou, Dezhi; Liang, Yun; Zhang, Jie; Shi, Peng

    2013-10-01

    Elucidating gut microbiota among gallstone patients as well as the complex bacterial colonization of cholesterol gallstones may help in both the prediction and subsequent lowered risk of cholelithiasis. To this end, we studied the composition of bacterial communities of gut, bile, and gallstones from 29 gallstone patients as well as the gut of 38 normal individuals, examining and analyzing some 299, 217 bacterial 16S rRNA gene sequences from 120 samples. First, as compared with normal individuals, in gallstone patients there were significant (P < 0.001) increases of gut bacterial phylum Proteobacteria and decreases of three gut bacterial genera, Faecalibacterium, Lachnospira, and Roseburia. Second, about 70% of gut bacterial operational taxonomic units (OTUs) from gallstone patients were detectable in the biliary tract and bacteria diversity of biliary tract was significantly (P < 0.001) higher than that of gut. Third, analysis of the biliary tract core microbiome (represented by 106 bacteria OTUs) among gallstone patients showed that 33.96% (36/106) of constituents can be matched to known bacterial species (15 of which have publicly available genomes). A genome-wide search of MDR, BSH, bG, and phL genes purpotedly associated with the formation of cholesterol gallstones showed that all 15 species with known genomes (e.g., Propionibacterium acnes, Bacteroides vulgates, and Pseudomonas putida) contained at least contained one of the four genes. This finding could potentially provide underlying information needed to explain the association between biliary tract microbiota and the formation of cholesterol gallstones. To the best of our knowledge, this is the first study to discover gut microbiota dysbiosis among gallstone patients, the presence of which may be a key contributor to the complex bacteria community assembly linked with the presence of cholesterol gallstones. Likewise, this study also provides the first large-scale glimpse of biliary tract microbiota

  3. International Large-Scale Assessment Studies and Educational Policy-Making in Chile: Contexts and Dimensions of Influence

    ERIC Educational Resources Information Center

    Cox, Cristián; Meckes, Lorena

    2016-01-01

    Since the 1990s, Chile has participated in all major international large-scale assessment studies (ILSAs) of the IEA and OECD, as well as the regional ones conducted by UNESCO in Latin America, after it had been involved in the very first international Science Study in 1970-1971. This article examines the various ways in which these studies have…

  4. International Large-Scale Assessment Studies and Educational Policy-Making in Chile: Contexts and Dimensions of Influence

    ERIC Educational Resources Information Center

    Cox, Cristián; Meckes, Lorena

    2016-01-01

    Since the 1990s, Chile has participated in all major international large-scale assessment studies (ILSAs) of the IEA and OECD, as well as the regional ones conducted by UNESCO in Latin America, after it had been involved in the very first international Science Study in 1970-1971. This article examines the various ways in which these studies have…

  5. Development of Large-Scale Forcing Data for GoAmazon2014/5 Cloud Modeling Studies

    NASA Astrophysics Data System (ADS)

    Tang, S.; Xie, S.; Zhang, Y.; Schumacher, C.; Upton, H. M.; Ahlgrimm, M.; Feng, Z.

    2015-12-01

    The Observations and Modeling of the Green Ocean 2014-2015 (GoAmazon2014/5) field campaign is an international collaborated experiment conducted near Manaus, Brazil from January 2014 through December 2015. This experiment is designed to enable the study of aerosols, tropical clouds, convections and their interactions. To support modeling studies of these processes with data collected from the GoAmazon2014/5 campaign, we have developed a large-scale forcing data (e.g., vertical velocities and advective tendencies) during the second intensive operational period (IOP) of GoAmazon2014/5 from 1 Sep to 10 Oct, 2014. The method used in this study is the constrained variational analysis method in which the large-scale state fields are constrained by the surface and top-of-atmosphere observations (e.g. surface precipitation and outgoing longwave radiation) to conserve column-integrated mass, moisture and dry static energy. To address potential uncertainties in the derived forcing data due to uncertainties in surface precipitation, two sets of large-scale forcing data are developed based on the ECMWF analysis constrained by the two precipitation products respectively from SIPAM radar and TRMM 3B42 products. Our initial analysis shows large differences in these two precipitation products, which causes considerable differences in the derived large-scale forcing data. Potential uncertainties in the large-scale forcing data to other surface constraints such as surface latent and sensible fluxes will be explored. The characteristics of the large-scale forcing structures for selected cases will be discussed.

  6. Consanguinity profile in the Gaza Strip of Palestine: large-scale community-based study.

    PubMed

    Sirdah, Mahmoud M

    2014-02-01

    Consanguineous marriages which have been practiced throughout history continue to be practiced within different ethnic, religious and social groups to varying degrees with highest prevalences in North Africa, Middle East and central and south Asia. In the Gaza Strip of Palestine, little is known about the consanguinity profile, so the present large-scale study aims to explore the consanguinity profile of two generations using data from the β-thalassemia premarital screening program. Sociodemographic data analysis included 156,635 (141,200 males and 15,435 females) persons and their parents, representing 141,200 couples who were referred to the Thalassemia and Hemophilia Center for premarital testing. In addition, the consanguinity characteristics of parents of 217 transfusion-dependent β-thalassemic non-sibling patients were analyzed. Results revealed a significant decrease in the overall prevalence of consanguineous (first- and second-cousin) marriages between the previous (fathers') generation (45.2%) and the current (groom/bride) generation (39.9%). Among the five governorates of the Gaza Strip, records of Gaza Governorate revealed the lowest occurrence (36.9% current generation and 42.1% previous generation) of consanguineous marriages, as compared to all others. Consanguineous marriages are significantly higher in semi-urban areas (41.6%) than in urban areas (39.1%) in the current generation (previous generation, 46.4% vs 44.7%, respectively). Compound consanguinity (two generation) and a single level of consanguinity were seen in 20.7% and 43.7%, respectively, of the cases. The average age of those with first-cousin marriages is significantly lower (22.4±4.4 years) than those with second-cousin marriages (24.3±6.1 years) and the non-consanguineous (26.5±8.2 years). The rate of consanguineous marriages among never married people (42.2%) is significantly much higher than the rate of people with multiple marriages (18.1%). About 74.7% of the non

  7. Oceanographic Processes in Chilean Fjords of Patagonia: From small to large-scale studies

    NASA Astrophysics Data System (ADS)

    Iriarte, José L.; Pantoja, Silvio; Daneri, Giovanni

    2014-12-01

    Subantarctic ecosystems, such as the inner shelf of southern Chile (41-55°S), are characterized by a complex system of fjords, channels, gulf, estuaries, bays, and are affected by physical regimes that may strongly modulate biological productivity. Rhythms and rates of primary production in these highly fluctuating fjord environments depend to a large extent on the timing and magnitude of nutrient supply and light availability for primary producers. In such complex fjord systems, the interaction between oceanic waters and freshwater from multiple sources (e.g., rivers, surface and groundwater runoff, snow/glacier melting, and precipitation) produces strong vertical and horizontal gradients in salinity, density, organic and inorganic nutrient ratios and light availability (Pickard, 1971; Dávila et al., 2002; Silva and Palma 2006; Jacob et al., 2014). The vertical structure of the water column (stratified/mixed), modulated by the seasonal and inter-annual changes of the pycnocline may affect biomass and composition of pelagic and benthic assemblages, and ultimately spatial and temporal patterns of carbon fluxes (the 'Biological Pump'), and biogeochemical balances in this large region. In addition, the region is particularly vulnerable to climate change and anthropogenic influences (Iriarte et al., 2010). Remote and large-scale climatic-oceanographic phenomena (e.g., ENSO and Southern Annular Mode) and global climate trends may alter freshwater discharge of large rivers such as the Puelo and Palena, as has also been suggested for the Baker River located between Patagonian Ice fields and other northern fjords shown by paleo-oceanographic (Sepúlveda et al., 2009; Rebolledo et al., 2011) and dendrochronological studies (Lara et al., 2008). Although changes in climate are expected to alter the regional atmospheric forcing such as the West Wind Drift (Quintana and Aceituno, 2012; Garreaud et al., 2013) and the local ocean circulation in this region, including the

  8. Prevalence of Psychotropic Drug Use in Adults with Intellectual Disability: Positive and Negative Findings from a Large Scale Study

    ERIC Educational Resources Information Center

    Tsiouris, John A.; Kim, Soh-Yule; Brown, W. Ted; Pettinger, Jill; Cohen, Ira L.

    2013-01-01

    The use of psychotropics by categories and the reason for their prescription was investigated in a large scale study of 4,069 adults with ID, including those with autism spectrum disorder, in New York State. Similar to other studies it was found that 58 % (2,361/4,069) received one or more psychotropics. Six percent received typical, 6 % received…

  9. Prevalence of Psychotropic Drug Use in Adults with Intellectual Disability: Positive and Negative Findings from a Large Scale Study

    ERIC Educational Resources Information Center

    Tsiouris, John A.; Kim, Soh-Yule; Brown, W. Ted; Pettinger, Jill; Cohen, Ira L.

    2013-01-01

    The use of psychotropics by categories and the reason for their prescription was investigated in a large scale study of 4,069 adults with ID, including those with autism spectrum disorder, in New York State. Similar to other studies it was found that 58 % (2,361/4,069) received one or more psychotropics. Six percent received typical, 6 % received…

  10. Large-Scale Field Study of Landfill Covers at Sandia National Laboratories

    SciTech Connect

    Dwyer, S.F.

    1998-09-01

    A large-scale field demonstration comparing final landfill cover designs has been constructed and is currently being monitored at Sandia National Laboratories in Albuquerque, New Mexico. Two conventional designs (a RCRA Subtitle `D' Soil Cover and a RCRA Subtitle `C' Compacted Clay Cover) were constructed side-by-side with four alternative cover test plots designed for dry environments. The demonstration is intended to evaluate the various cover designs based on their respective water balance performance, ease and reliability of construction, and cost. This paper presents an overview of the ongoing demonstration.

  11. The Mathematics of Motion in Middle School: Findings from a Large Scale Study

    NASA Astrophysics Data System (ADS)

    Roschelle, Jeremy

    2006-12-01

    The SimCalc Project (http://www.simcalc.umassd.edu) has developed an integration of technology and curriculum based upon learning science principles and aimed at democratizing access to the mathematics of change and variation. Beginning in middle school, we introduce the topics of proportionality, function, and rate of change though multiple representations. In a large scale randomized experiment, we are testing replacement units based upon this approach with approximately 100 7th grade and 80 8th grade teachers. This talk will discuss results from our work and implications for science instruction, for example, for the feasibility of a physics-first sequence beginning in 9th grade.

  12. Large-scale international study enhances understanding of an emerging acne population: adult females.

    PubMed

    Dréno, B; Thiboutot, D; Layton, A M; Berson, D; Perez, M; Kang, S

    2015-06-01

    study represents the first objective assessment of the facial distribution of acne lesions in adult women presenting to the dermatology office. The data surprisingly indicate that the acne distribution in almost 90% of cases is similar to that seen in adolescent acne. The stereotype of adult female acne being due to hormonal disturbances presenting as inflammatory acne localized only to the mandibular area was not found in the majority of this large group. The large majority (93.7%) of women had facial comedones. We recommend that the general treatment approach for adult acne should include agents that target each of the acne lesion subtypes. Subgroup analyses of recent large-scale controlled clinical trials have shown that many adult women respond well to standard first-line acne therapy. © 2014 European Academy of Dermatology and Venereology.

  13. Large-scale screening in sporadic amyotrophic lateral sclerosis identifies genetic modifiers in C9orf72 repeat carriers.

    PubMed

    Dekker, Annelot M; Seelen, Meinie; van Doormaal, Perry T C; van Rheenen, Wouter; Bothof, Reinoud J P; van Riessen, Tim; Brands, William J; van der Kooi, Anneke J; de Visser, Marianne; Voermans, Nicol C; Pasterkamp, R Jeroen; Veldink, Jan H; van den Berg, Leonard H; van Es, Michael A

    2016-03-01

    Sporadic amyotrophic lateral sclerosis (ALS) is considered to be a complex disease with multiple genetic risk factors contributing to the pathogenesis. Identification of genetic risk factors that co-occur frequently could provide relevant insight into underlying mechanisms of motor neuron degeneration. To dissect the genetic architecture of sporadic ALS, we undertook a large sequencing study in 755 apparently sporadic ALS cases and 959 controls, analyzing 10 ALS genes: SOD1, C9orf72, TARDBP, FUS, ANG, CHMP2B, ATXN2, NIPA1, SMN1, and UNC13A. We observed sporadic cases with multiple genetic risk variants in 4.1% compared with 1.3% in controls. The overall difference was not in excess of what is to be expected by chance (binomial test, p = 0.59). We did, however, observe a higher frequency than expected of C9orf72 repeat carriers with co-occurring susceptibility variants (ATXN2, NIPA1, and SMN1; p = 0.001), which is mainly because of the co-occurrence of NIPA1 repeats in 15% of C9orf72 repeat carriers (p = 0.006). Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Sensitivity study of large-scale particle image velocimetry measurement of river discharge using numerical simulation

    NASA Astrophysics Data System (ADS)

    Hauet, Alexandre; Creutin, Jean-Dominique; Belleudy, Philippe

    2008-01-01

    SummaryThis study deals with the uncertainty of large-scale particle image velocimetry (LSPIV) measurements in rivers. LSPIV belongs to the methods of local remote sensing of rivers, like Radar- and Lidar-based techniques. These methods have many potential advantages, in comparison with classical river gauging, but they have a fundamental drawback: they are indirect measurements. As such they need to be assessed in reference to direct measurements. A first validation method consists in the comparison of LSPIV measurements with classic gauging results, in field and laboratory experiments. Unfortunately, in both cases, it is impossible in practice to control all the parameters and to distinguish the impact of the various error sources. In the present study we propose a more theoretical assessment of LSPIV potential through numerical simulation. The idea is simply to mathematically formulate the present state of knowledge of the measurement including both the physics of the phenomenon (the illuminated river) and the physics of the sensor (the camera and the PIV tracking). The dilemma about when to start this type of simulation is the following: The simulation is satisfactory if we can validate it which means to be able to compare simulations and observations over a wide range of conditions. The simulation is useful to get preliminary insights about the most important measurement conditions to organize validation studies. Our simulator is composed of three blocks: The river block represents the unidirectional river flow by the association of the EDM model and a theoretical vertical velocity profile giving a 3D velocity distribution. This hydraulic model is complemented by features representing free surface tracers, the illumination of the free-surface (shadows and sun reflection) and the effect of the wind. The camera block transforms the river state parameters into raster images according to the intrinsic and extrinsic parameters of the camera. The LSPIV analysis

  15. Assessing the utility of confirmatory studies following identification of large-scale genomic imbalances by microarray.

    PubMed

    Sanmann, Jennifer N; Pickering, Diane L; Golden, Denae M; Stevens, Jadd M; Hempel, Thomas E; Althof, Pamela A; Wiggins, Michele L; Starr, Lois J; Davé, Bhavana J; Sanger, Warren G

    2015-11-01

    The identification of clinically relevant genomic dosage anomalies assists in accurate diagnosis, prognosis, and medical management of affected individuals. Technological advancements within the field, such as the advent of microarray, have markedly increased the resolution of detection; however, clinical laboratories have maintained conventional techniques for confirmation of genomic imbalances identified by microarray to ensure diagnostic accuracy. In recent years the utility of this confirmatory testing of large-scale aberrations has been questioned but has not been scientifically addressed. We retrospectively reviewed 519 laboratory cases with genomic imbalances meeting reportable criteria by microarray and subsequently confirmed with a second technology, primarily fluorescence in situ hybridization. All genomic imbalances meeting reportable criteria detected by microarray were confirmed with a second technology. Microarray analysis generated no false-positive results. Confirmatory testing of large-scale genomic imbalances (deletion of ≥150 kb, duplication of ≥500 kb) solely for the purpose of microarray verification may be unwarranted. In some cases, however, adjunct testing is necessary to overcome limitations inherent to microarray. A recommended clinical strategy for adjunct testing following identified genomic imbalances using microarray is detailed.

  16. [Study on large-scale regional laser detection methods for water vapor concentration].

    PubMed

    He, Ying; Zhang, Yu-Jun; Wang, Li-Ming; You, Kun; Zhou, Yi; Sun, Xiao-Min; Liu, Zhen-Min

    2013-03-01

    Water vapor is an important meteorological parameter in the atmosphere, TDLAS direct absorption technology combined with open-path monitoring was used in order to achieve large-scale regional atmospheric water vapor concentration detection with high sensitivity, high accuracy and fast response, and to correct the remote sensing data. The large-scale regional laser detection system for water vapor was designed and the absorption line of water vapor molecules near 1.27 microm was chosen as the goal line. The system performance was verified in conjunction with a multiple reflection cell, that the system limit sensitivity was 14.803 mmol.mol-1 in optical path of 40 m. The continuous field experiment in 1,420 m optical path at the Yucheng Integrated Experimental Station, CAS was completed with this system which worked stably. Then the measured data was compared with the data of a gas analyzer LI-7500 in eddy correlation observation system at the same site, and the data consistency was good. A new method for water vapor concentration monitoring in the complex field of non-uniform underlying surface was provided.

  17. A Confirmatory Approach to Examining the Factor Structure of the Strengths and Difficulties Questionnaire (SDQ): A Large Scale Cohort Study

    ERIC Educational Resources Information Center

    Niclasen, Janni; Skovgaard, Anne Mette; Andersen, Anne-Marie Nybo; Somhovd, Mikael Julius; Obel, Carsten

    2013-01-01

    The aim of this study was to examine the factor structure of the Strengths and Difficulties Questionnaire (SDQ) using a Structural Confirmatory Factor Analytic approach. The Danish translation of the SDQ was distributed to 71,840 parents and teachers of 5-7 and 10-12-year-old boys and girls from four large scale cohorts. Three theoretical models…

  18. An Exploratory Study of Student-Paced versus Teacher-Paced Accommodations for Large-Scale Math Tests.

    ERIC Educational Resources Information Center

    Hollenbeck, Keith; Rozek-Tedesco, Marick A.; Tindal, Gerald; Glasgow, Aaron

    2000-01-01

    This study examined whether a teacher-paced video (TPV) accommodation or a student-paced computer (SPC) accommodation provided differential access for student with disabilities versus their general education peers on a large-scale math test. It found that although both pacing accommodations significantly influenced mean scores, the SPC…

  19. Achievement of Immigrant Students in Mathematics and Academic Hebrew in Israeli School: A Large-Scale Evaluation Study

    ERIC Educational Resources Information Center

    Levin, Tamar; Shohamy, Elana

    2008-01-01

    This article reports findings obtained from a large-scale national study (299 schools; 2761 students) that examined academic achievements of immigrants in Israeli schools. It focused on two distinct groups of immigrant students--those from the former USSR and from Ethiopia, in two subject areas--mathematics and academic language (Hebrew), and in…

  20. Use of large-scale silvicultural studies to evaluate management options in Pacific Northwest forests of the United States.

    Treesearch

    Stephen E. Reutebuch; Constance A. Harrington; David D. Marshall; Leslie C. Brodie

    2004-01-01

    A suite of large-scale silvicultural experiments has been established to develop and assess operational silviculture options for the Pacific Northwest Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco vat. menziesii) forests. This paper summarizes three such studies that focus on three major stages in the life of managed stands...

  1. A Confirmatory Approach to Examining the Factor Structure of the Strengths and Difficulties Questionnaire (SDQ): A Large Scale Cohort Study

    ERIC Educational Resources Information Center

    Niclasen, Janni; Skovgaard, Anne Mette; Andersen, Anne-Marie Nybo; Somhovd, Mikael Julius; Obel, Carsten

    2013-01-01

    The aim of this study was to examine the factor structure of the Strengths and Difficulties Questionnaire (SDQ) using a Structural Confirmatory Factor Analytic approach. The Danish translation of the SDQ was distributed to 71,840 parents and teachers of 5-7 and 10-12-year-old boys and girls from four large scale cohorts. Three theoretical models…

  2. Studying Teacher Selection of Resources in an Ultra-Large Scale Interactive System: Does Metadata Guide the Way?

    ERIC Educational Resources Information Center

    Abramovich, Samuel; Schunn, Christian

    2012-01-01

    Ultra-large-scale interactive systems on the Internet have begun to change how teachers prepare for instruction, particularly in regards to resource selection. Consequently, it is important to look at how teachers are currently selecting resources beyond content or keyword search. We conducted a two-part observational study of an existing popular…

  3. Cohort Profile of the Goals Study: A Large-Scale Research of Physical Activity in Dutch Students

    ERIC Educational Resources Information Center

    de Groot, Renate H. M.; van Dijk, Martin L.; Kirschner, Paul A.

    2015-01-01

    The GOALS study (Grootschalig Onderzoek naar Activiteiten van Limburgse Scholieren [Large-scale Research of Activities in Dutch Students]) was set up to investigate possible associations between different forms of physical activity and inactivity with cognitive performance, academic achievement and mental well-being. It was conducted at a…

  4. Cohort Profile of the Goals Study: A Large-Scale Research of Physical Activity in Dutch Students

    ERIC Educational Resources Information Center

    de Groot, Renate H. M.; van Dijk, Martin L.; Kirschner, Paul A.

    2015-01-01

    The GOALS study (Grootschalig Onderzoek naar Activiteiten van Limburgse Scholieren [Large-scale Research of Activities in Dutch Students]) was set up to investigate possible associations between different forms of physical activity and inactivity with cognitive performance, academic achievement and mental well-being. It was conducted at a…

  5. Use of Large-Scale Data Sets to Study Educational Pathways of American Indian and Alaska Native Students

    ERIC Educational Resources Information Center

    Faircloth, Susan C.; Alcantar, Cynthia M.; Stage, Frances K.

    2014-01-01

    This chapter discusses issues and challenges encountered in using large-scale data sets to study educational experiences and subsequent outcomes for American Indian and Alaska Native (AI/AN) students. In this chapter, we argue that the linguistic and cultural diversity of Native peoples, coupled with the legal and political ways in which education…

  6. Use of Large-Scale Data Sets to Study Educational Pathways of American Indian and Alaska Native Students

    ERIC Educational Resources Information Center

    Faircloth, Susan C.; Alcantar, Cynthia M.; Stage, Frances K.

    2014-01-01

    This chapter discusses issues and challenges encountered in using large-scale data sets to study educational experiences and subsequent outcomes for American Indian and Alaska Native (AI/AN) students. In this chapter, we argue that the linguistic and cultural diversity of Native peoples, coupled with the legal and political ways in which education…

  7. Studying Teacher Selection of Resources in an Ultra-Large Scale Interactive System: Does Metadata Guide the Way?

    ERIC Educational Resources Information Center

    Abramovich, Samuel; Schunn, Christian

    2012-01-01

    Ultra-large-scale interactive systems on the Internet have begun to change how teachers prepare for instruction, particularly in regards to resource selection. Consequently, it is important to look at how teachers are currently selecting resources beyond content or keyword search. We conducted a two-part observational study of an existing popular…

  8. Phenotyping of subjects for large scale studies on patients with IBS.

    PubMed

    Boeckxstaens, G E; Drug, V; Dumitrascu, D; Farmer, A D; Hammer, J; Hausken, T; Niesler, B; Pohl, D; Pojskic, L; Polster, A; Simren, M; Goebel-Stengel, M; Van Oudenhove, L; Vassallo, M; Wensaas, K-A; Aziz, Q; Houghton, L A

    2016-08-01

    Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life-time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a 'large' pool of IBS patients across Europe and even the world however, might help identify sub-populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi-centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four-year dialogue amongst experts associated with the European COST action BM1106 GENIEUR (www.GENIEUR.eu). © 2016 John Wiley & Sons Ltd.

  9. Large scale patterns of genetic variation and differentiation in sugar maple from tropical Central America to temperate North America.

    PubMed

    Vargas-Rodriguez, Yalma L; Platt, William J; Urbatsch, Lowell E; Foltz, David W

    2015-11-19

    Geological events in the latter Cenozoic have influenced the distribution, abundance and genetic structure of tree populations in temperate and tropical North America. The biogeographical history of temperate vegetation that spans large ranges of latitude is complex, involving multiple latitudinal shifts that might have occurred via different migration routes. We determined the regional structuring of genetic variation of sugar maple (Acer saccharum subsp. saccharum) and its only subspecies in tropical America (Acer saccharum subsp. skutchii) using nuclear and chloroplast data. The studied populations span a geographic range from Maine, USA (46°N), to El Progreso, Guatemala (15°N). We examined genetic subdivisions, explored the locations of ancestral haplotypes, analyzed genetic data to explore the presence of a single or multiple glacial refugia, and tested whether genetic lineages are temporally consistent with a Pleistocene or older divergence. Nuclear and chloroplast data indicated that populations in midwestern USA and western Mexico were highly differentiated from populations in the rest of the sites. The time of the most recent common ancestor of the western Mexico haplotype lineage was dated to the Pliocene (5.9 Ma, 95% HPD: 4.3-7.3 Ma). Splits during the Pleistocene separated the rest of the phylogroups. The most frequent and widespread haplotype occurred in half of the sites (Guatemala, eastern Mexico, southeastern USA, and Ohio). Our data also suggested that multiple Pleistocene refugia (tropics-southeastern USA, midwestern, and northeastern USA), but not western Mexico (Jalisco), contributed to post-glacial northward expansion of ranges. Current southern Mexican and Guatemalan populations have reduced population sizes, genetic bottlenecks and tend toward homozygosity, as indicated using nuclear and chloroplast markers. The divergence of western Mexican populations from the rest of the sugar maples likely resulted from orographic and volcanic barriers

  10. The Korean Gastric Cancer Cohort Study: Study Protocol and Brief Results of a Large-Scale Prospective Cohort Study

    PubMed Central

    Eom, Bang Wool; Kim, Young-Woo; Nam, Byung-Ho; Ryu, Keun Won; Jeong, Hyun-Yong; Park, Young-Kyu; Lee, Young-Joon; Yang, Han-Kwang; Yu, Wansik; Yook, Jeong-Hwan; Song, Geun Am; Youn, Sei-Jin; Kim, Heung Up; Noh, Sung-Hoon; Park, Sung Bae; Yang, Doo-Hyun; Kim, Sung

    2016-01-01

    Purpose This study aimed to establish a large-scale database of patients with gastric cancer to facilitate the development of a national-cancer management system and a comprehensive cancer control policy. Materials and Methods An observational prospective cohort study on gastric cancer was initiated in 2010. A total of 14 cancer centers throughout the country and 152 researchers were involved in this study. Patient enrollment began in January 2011, and data regarding clinicopathological characteristics, life style-related factors, quality of life, as well as diet diaries were collected. Results In total, 4,963 patients were enrolled until December 2014, and approximately 5% of all Korean patients with gastric cancer annually were included. The mean age was 58.2±11.5 years, and 68.2% were men. The number of patients in each stage was as follows: 3,394 patients (68.4%) were in stage IA/B; 514 patients (10.4%), in stage IIA/B; 469 patients (9.5%), in stage IIIA/B/C; and 127 patients (2.6%), in stage IV. Surgical treatment was performed in 3,958 patients (79.8%), endoscopic resection was performed in 700 patients (14.1%), and 167 patients (3.4%) received palliative chemotherapy. The response rate for the questionnaire on the quality of life was 95%; however, diet diaries were only collected for 27% of patients. Conclusions To provide comprehensive information on gastric cancer for patients, physicians, and government officials, a large-scale database of Korean patients with gastric cancer was established. Based on the findings of this cohort study, an effective cancer management system and national cancer control policy could be developed. PMID:27752396

  11. Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells.

    PubMed

    DeBoever, Christopher; Li, He; Jakubosky, David; Benaglio, Paola; Reyna, Joaquin; Olson, Katrina M; Huang, Hui; Biggs, William; Sandoval, Efren; D'Antonio, Matteo; Jepsen, Kristen; Matsui, Hiroko; Arias, Angelo; Ren, Bing; Nariai, Naoki; Smith, Erin N; D'Antonio-Chronowska, Agnieszka; Farley, Emma K; Frazer, Kelly A

    2017-04-06

    In this study, we used whole-genome sequencing and gene expression profiling of 215 human induced pluripotent stem cell (iPSC) lines from different donors to identify genetic variants associated with RNA expression for 5,746 genes. We were able to predict causal variants for these expression quantitative trait loci (eQTLs) that disrupt transcription factor binding and validated a subset of them experimentally. We also identified copy-number variant (CNV) eQTLs, including some that appear to affect gene expression by altering the copy number of intergenic regulatory regions. In addition, we were able to identify effects on gene expression of rare genic CNVs and regulatory single-nucleotide variants and found that reactivation of gene expression on the X chromosome depends on gene chromosomal position. Our work highlights the value of iPSCs for genetic association analyses and provides a unique resource for investigating the genetic regulation of gene expression in pluripotent cells. Published by Elsevier Inc.

  12. Enhanced ICP for the Registration of Large-Scale 3D Environment Models: An Experimental Study.

    PubMed

    Han, Jianda; Yin, Peng; He, Yuqing; Gu, Feng

    2016-02-15

    One of the main applications of mobile robots is the large-scale perception of the outdoor environment. One of the main challenges of this application is fusing environmental data obtained by multiple robots, especially heterogeneous robots. This paper proposes an enhanced iterative closest point (ICP) method for the fast and accurate registration of 3D environmental models. First, a hierarchical searching scheme is combined with the octree-based ICP algorithm. Second, an early-warning mechanism is used to perceive the local minimum problem. Third, a heuristic escape scheme based on sampled potential transformation vectors is used to avoid local minima and achieve optimal registration. Experiments involving one unmanned aerial vehicle and one unmanned surface vehicle were conducted to verify the proposed technique. The experimental results were compared with those of normal ICP registration algorithms to demonstrate the superior performance of the proposed method.

  13. Enhanced ICP for the Registration of Large-Scale 3D Environment Models: An Experimental Study

    PubMed Central

    Han, Jianda; Yin, Peng; He, Yuqing; Gu, Feng

    2016-01-01

    One of the main applications of mobile robots is the large-scale perception of the outdoor environment. One of the main challenges of this application is fusing environmental data obtained by multiple robots, especially heterogeneous robots. This paper proposes an enhanced iterative closest point (ICP) method for the fast and accurate registration of 3D environmental models. First, a hierarchical searching scheme is combined with the octree-based ICP algorithm. Second, an early-warning mechanism is used to perceive the local minimum problem. Third, a heuristic escape scheme based on sampled potential transformation vectors is used to avoid local minima and achieve optimal registration. Experiments involving one unmanned aerial vehicle and one unmanned surface vehicle were conducted to verify the proposed technique. The experimental results were compared with those of normal ICP registration algorithms to demonstrate the superior performance of the proposed method. PMID:26891298

  14. Dealing with missing values in large-scale studies: microarray data imputation and beyond.

    PubMed

    Aittokallio, Tero

    2010-03-01

    High-throughput biotechnologies, such as gene expression microarrays or mass-spectrometry-based proteomic assays, suffer from frequent missing values due to various experimental reasons. Since the missing data points can hinder downstream analyses, there exists a wide variety of ways in which to deal with missing values in large-scale data sets. Nowadays, it has become routine to estimate (or impute) the missing values prior to the actual data analysis. After nearly a decade since the publication of the first missing value imputation methods for gene expression microarray data, new imputation approaches are still being developed at an increasing rate. However, what is lagging behind is a systematic and objective evaluation of the strengths and weaknesses of the different approaches when faced with different types of data sets and experimental questions. In this review, the present strategies for missing value imputation and the measures for evaluating their performance are described. The imputation methods are first reviewed in the context of gene expression microarray data, since most of the methods have been developed for estimating gene expression levels; then, we turn to other large-scale data sets that also suffer from the problems posed by missing values, together with pointers to possible imputation approaches in these settings. Along with a description of the basic principles behind the different imputation approaches, the review tries to provide practical guidance for the users of high-throughput technologies on how to choose the imputation tool for their data and questions, and some additional research directions for the developers of imputation methodologies.

  15. International Comparative Studies in Education: Descriptions of Selected Large-Scale Assessments and Case Studies.

    ERIC Educational Resources Information Center

    National Academy of Sciences - National Research Council, Washington, DC. Commission on Behavioral and Social Sciences and Education.

    Since its inception in 1988, the Board on International Comparative Studies in Education (BICSE) has monitored U.S. participation in those cross national comparative studies in education that are funded by its sponsors, the National Science Foundation and the National Center for Education Statistics. This set of international study descriptions…

  16. Construction of a high-density genetic map for sesame based on large scale marker development by specific length amplified fragment (SLAF) sequencing

    PubMed Central

    2013-01-01

    Background The genetics and molecular biology of sesame has only recently begun to be studied even though sesame is an important oil seed crop. A high-density genetic map for sesame has not been published yet due to a lack of sufficient molecular markers. Specific length amplified fragment sequencing (SLAF-seq) is a recently developed high-resolution strategy for large-scale de novo SNP discovery and genotyping. SLAF-seq was employed in this study to obtain sufficient markers to construct a high-density genetic map for sesame. Results In total, 28.21 Gb of data containing 201,488,285 pair-end reads was obtained after sequencing. The average coverage for each SLAF marker was 23.48-fold in the male parent, 23.38-fold in the female parent, and 14.46-fold average in each F2 individual. In total, 71,793 high-quality SLAFs were detected of which 3,673 SLAFs were polymorphic and 1,272 of the polymorphic markers met the requirements for use in the construction of a genetic map. The final map included 1,233 markers on the 15 linkage groups (LGs) and was 1,474.87 cM in length with an average distance of 1.20 cM between adjacent markers. To our knowledge, this map is the densest genetic linkage map to date for sesame. 'SNP_only’ markers accounted for 87.51% of the markers on the map. A total of 205 markers on the map showed significant (P < 0.05) segregation distortion. Conclusions We report here the first high-density genetic map for sesame. The map was constructed using an F2 population and the SLAF-seq approach, which allowed the efficient development of a large number of polymorphic markers in a short time. Results of this study will not only provide a platform for gene/QTL fine mapping, map-based gene isolation, and molecular breeding for sesame, but will also serve as a reference for positioning sequence scaffolds on a physical map, to assist in the process of assembling the sesame genome sequence. PMID:24060091

  17. Construction of a high-density genetic map for sesame based on large scale marker development by specific length amplified fragment (SLAF) sequencing.

    PubMed

    Zhang, Yanxin; Wang, Linhai; Xin, Huaigen; Li, Donghua; Ma, Chouxian; Ding, Xia; Hong, Weiguo; Zhang, Xiurong

    2013-09-24

    The genetics and molecular biology of sesame has only recently begun to be studied even though sesame is an important oil seed crop. A high-density genetic map for sesame has not been published yet due to a lack of sufficient molecular markers. Specific length amplified fragment sequencing (SLAF-seq) is a recently developed high-resolution strategy for large-scale de novo SNP discovery and genotyping. SLAF-seq was employed in this study to obtain sufficient markers to construct a high-density genetic map for sesame. In total, 28.21 Gb of data containing 201,488,285 pair-end reads was obtained after sequencing. The average coverage for each SLAF marker was 23.48-fold in the male parent, 23.38-fold in the female parent, and 14.46-fold average in each F2 individual. In total, 71,793 high-quality SLAFs were detected of which 3,673 SLAFs were polymorphic and 1,272 of the polymorphic markers met the requirements for use in the construction of a genetic map. The final map included 1,233 markers on the 15 linkage groups (LGs) and was 1,474.87 cM in length with an average distance of 1.20 cM between adjacent markers. To our knowledge, this map is the densest genetic linkage map to date for sesame. 'SNP_only' markers accounted for 87.51% of the markers on the map. A total of 205 markers on the map showed significant (P < 0.05) segregation distortion. We report here the first high-density genetic map for sesame. The map was constructed using an F2 population and the SLAF-seq approach, which allowed the efficient development of a large number of polymorphic markers in a short time. Results of this study will not only provide a platform for gene/QTL fine mapping, map-based gene isolation, and molecular breeding for sesame, but will also serve as a reference for positioning sequence scaffolds on a physical map, to assist in the process of assembling the sesame genome sequence.

  18. The Asthma Mobile Health Study, a large-scale clinical observational study using ResearchKit.

    PubMed

    Chan, Yu-Feng Yvonne; Wang, Pei; Rogers, Linda; Tignor, Nicole; Zweig, Micol; Hershman, Steven G; Genes, Nicholas; Scott, Erick R; Krock, Eric; Badgeley, Marcus; Edgar, Ron; Violante, Samantha; Wright, Rosalind; Powell, Charles A; Dudley, Joel T; Schadt, Eric E

    2017-04-01

    The feasibility of using mobile health applications to conduct observational clinical studies requires rigorous validation. Here, we report initial findings from the Asthma Mobile Health Study, a research study, including recruitment, consent, and enrollment, conducted entirely remotely by smartphone. We achieved secure bidirectional data flow between investigators and 7,593 participants from across the United States, including many with severe asthma. Our platform enabled prospective collection of longitudinal, multidimensional data (e.g., surveys, devices, geolocation, and air quality) in a subset of users over the 6-month study period. Consistent trending and correlation of interrelated variables support the quality of data obtained via this method. We detected increased reporting of asthma symptoms in regions affected by heat, pollen, and wildfires. Potential challenges with this technology include selection bias, low retention rates, reporting bias, and data security. These issues require attention to realize the full potential of mobile platforms in research and patient care.

  19. Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum.

    PubMed

    Peel, Alison J; Baker, Kate S; Hayman, David T S; Suu-Ire, Richard; Breed, Andrew C; Gembu, Guy-Crispin; Lembo, Tiziana; Fernández-Loras, Andrés; Sargan, David R; Fooks, Anthony R; Cunningham, Andrew A; Wood, James L N

    2016-08-01

    Bats, including African straw-coloured fruit bats (Eidolon helvum), have been highlighted as reservoirs of many recently emerged zoonotic viruses. This common, widespread and ecologically important species was the focus of longitudinal and continent-wide studies of the epidemiological and ecology of Lagos bat virus, henipaviruses and Achimota viruses. Here we present a spatial, morphological, demographic, genetic and serological dataset encompassing 2827 bats from nine countries over an 8-year period. Genetic data comprises cytochrome b mitochondrial sequences (n=608) and microsatellite genotypes from 18 loci (n=544). Tooth-cementum analyses (n=316) allowed derivation of rare age-specific serologic data for a lyssavirus, a henipavirus and two rubulaviruses. This dataset contributes a substantial volume of data on the ecology of E. helvum and its viruses and will be valuable for a wide range of studies, including viral transmission dynamic modelling in age-structured populations, investigation of seasonal reproductive asynchrony in wide-ranging species, ecological niche modelling, inference of island colonisation history, exploration of relationships between island and body size, and various spatial analyses of demographic, morphometric or serological data.

  20. Bat trait, genetic and pathogen data from large-scale investigations of African fruit bats, Eidolon helvum

    PubMed Central

    Peel, Alison J.; Baker, Kate S.; Hayman, David T. S.; Suu-Ire, Richard; Breed, Andrew C.; Gembu, Guy-Crispin; Lembo, Tiziana; Fernández-Loras, Andrés; Sargan, David R.; Fooks, Anthony R.; Cunningham, Andrew A.; Wood, James L. N.

    2016-01-01

    Bats, including African straw-coloured fruit bats (Eidolon helvum), have been highlighted as reservoirs of many recently emerged zoonotic viruses. This common, widespread and ecologically important species was the focus of longitudinal and continent-wide studies of the epidemiological and ecology of Lagos bat virus, henipaviruses and Achimota viruses. Here we present a spatial, morphological, demographic, genetic and serological dataset encompassing 2827 bats from nine countries over an 8-year period. Genetic data comprises cytochrome b mitochondrial sequences (n=608) and microsatellite genotypes from 18 loci (n=544). Tooth-cementum analyses (n=316) allowed derivation of rare age-specific serologic data for a lyssavirus, a henipavirus and two rubulaviruses. This dataset contributes a substantial volume of data on the ecology of E. helvum and its viruses and will be valuable for a wide range of studies, including viral transmission dynamic modelling in age-structured populations, investigation of seasonal reproductive asynchrony in wide-ranging species, ecological niche modelling, inference of island colonisation history, exploration of relationships between island and body size, and various spatial analyses of demographic, morphometric or serological data. PMID:27479120

  1. A 454 multiplex sequencing method for rapid and reliable genotyping of highly polymorphic genes in large-scale studies

    PubMed Central

    2010-01-01

    Background High-throughput sequencing technologies offer new perspectives for biomedical, agronomical and evolutionary research. Promising progresses now concern the application of these technologies to large-scale studies of genetic variation. Such studies require the genotyping of high numbers of samples. This is theoretically possible using 454 pyrosequencing, which generates billions of base pairs of sequence data. However several challenges arise: first in the attribution of each read produced to its original sample, and second, in bioinformatic analyses to distinguish true from artifactual sequence variation. This pilot study proposes a new application for the 454 GS FLX platform, allowing the individual genotyping of thousands of samples in one run. A probabilistic model has been developed to demonstrate the reliability of this method. Results DNA amplicons from 1,710 rodent samples were individually barcoded using a combination of tags located in forward and reverse primers. Amplicons consisted in 222 bp fragments corresponding to DRB exon 2, a highly polymorphic gene in mammals. A total of 221,789 reads were obtained, of which 153,349 were finally assigned to original samples. Rules based on a probabilistic model and a four-step procedure, were developed to validate sequences and provide a confidence level for each genotype. The method gave promising results, with the genotyping of DRB exon 2 sequences for 1,407 samples from 24 different rodent species and the sequencing of 392 variants in one half of a 454 run. Using replicates, we estimated that the reproducibility of genotyping reached 95%. Conclusions This new approach is a promising alternative to classical methods involving electrophoresis-based techniques for variant separation and cloning-sequencing for sequence determination. The 454 system is less costly and time consuming and may enhance the reliability of genotypes obtained when high numbers of samples are studied. It opens up new perspectives

  2. Conditional Random Fields for Fast, Large-Scale Genome-Wide Association Studies

    PubMed Central

    Huang, Jim C.; Meek, Christopher; Kadie, Carl; Heckerman, David

    2011-01-01

    Understanding the role of genetic variation in human diseases remains an important problem to be solved in genomics. An important component of such variation consist of variations at single sites in DNA, or single nucleotide polymorphisms (SNPs). Typically, the problem of associating particular SNPs to phenotypes has been confounded by hidden factors such as the presence of population structure, family structure or cryptic relatedness in the sample of individuals being analyzed. Such confounding factors lead to a large number of spurious associations and missed associations. Various statistical methods have been proposed to account for such confounding factors such as linear mixed-effect models (LMMs) or methods that adjust data based on a principal components analysis (PCA), but these methods either suffer from low power or cease to be tractable for larger numbers of individuals in the sample. Here we present a statistical model for conducting genome-wide association studies (GWAS) that accounts for such confounding factors. Our method scales in runtime quadratic in the number of individuals being studied with only a modest loss in statistical power as compared to LMM-based and PCA-based methods when testing on synthetic data that was generated from a generalized LMM. Applying our method to both real and synthetic human genotype/phenotype data, we demonstrate the ability of our model to correct for confounding factors while requiring significantly less runtime relative to LMMs. We have implemented methods for fitting these models, which are available at http://www.microsoft.com/science. PMID:21765897

  3. Performance study of Lagrangian methods: reconstruction of large scale peculiar velocities and baryonic acoustic oscillations

    NASA Astrophysics Data System (ADS)

    Keselman, J. A.; Nusser, A.

    2017-05-01

    No Action Method (NoAM) is a framework for reconstructing the past orbits of observed tracers of the large-scale mass density field. It seeks exact solutions of the equations of motion (EoM), satisfying initial homogeneity and the final observed particle (tracer) positions. The solutions are found iteratively reaching a specified tolerance defined as the RMS of the distance between reconstructed and observed positions. Starting from a guess for the initial conditions, NoAM advances particles using standard N-body techniques for solving the EoM. Alternatively, the EoM can be replaced by any approximation such as Zel'dovich and second-order perturbation theory (2LPT). NoAM is suitable for billions of particles and can easily handle non-regular volumes, redshift space and other constraints. We implement NoAM to systematically compare Zel'dovich, 2LPT, and N-body dynamics over diverse configurations ranging from an idealized high-res periodic simulation box to realistic galaxy mocks. Our findings are: (i) non-linear reconstructions with Zel'dovich, 2LPT, and full dynamics perform better than linear theory only for idealized catalogues in real space. For realistic catalogues, linear theory is the optimal choice for reconstructing velocity fields smoothed on scales ≳ 5 h- 1 Mpc; (ii) all non-linear back-in-time reconstructions tested here produce comparable enhancement of the baryonic oscillation signal in the correlation function.

  4. Study of wavelength-shifting chemicals for use in large-scale water Cherenkov detectors

    SciTech Connect

    Sweany, M; Bernstein, A; Dazeley, S; Dunmore, J; Felde, J; Svoboda, R; Tripathi, S M

    2011-09-21

    Cherenkov detectors employ various methods to maximize light collection at the photomultiplier tubes (PMTs). These generally involve the use of highly reflective materials lining the interior of the detector, reflective materials around the PMTs, or wavelength-shifting sheets around the PMTs. Recently, the use of water-soluble wavelength-shifters has been explored to increase the measurable light yield of Cherenkov radiation in water. These wave-shifting chemicals are capable of absorbing light in the ultravoilet and re-emitting the light in a range detectable by PMTs. Using a 250 L water Cherenkov detector, we have characterized the increase in light yield from three compounds in water: 4-Methylumbelliferone, Carbostyril-124, and Amino-G Salt. We report the gain in PMT response at a concentration of 1 ppm as: 1.88 {+-} 0.02 for 4-Methylumbelliferone, stable to within 0.5% over 50 days, 1.37 {+-} 0.03 for Carbostyril-124, and 1.20 {+-} 0.02 for Amino-G Salt. The response of 4-Methylumbelliferone was modeled, resulting in a simulated gain within 9% of the experimental gain at 1 ppm concentration. Finally, we report an increase in neutron detection performance of a large-scale (3.5 kL) gadolinium-doped water Cherenkov detector at a 4-Methylumbelliferone concentration of 1 ppm.

  5. Performance study of Lagrangian methods: reconstruction of large scale peculiar velocities and baryonic acoustic oscillations

    NASA Astrophysics Data System (ADS)

    Keselman, J. A.; Nusser, A.

    2017-01-01

    NoAM for "No Action Method" is a framework for reconstructing the past orbits of observed tracers of the large scale mass density field. It seeks exact solutions of the equations of motion (EoM), satisfying initial homogeneity and the final observed particle (tracer) positions. The solutions are found iteratively reaching a specified tolerance defined as the RMS of the distance between reconstructed and observed positions. Starting from a guess for the initial conditions, NoAM advances particles using standard N-body techniques for solving the EoM. Alternatively, the EoM can be replaced by any approximation such as Zel'dovich and second order perturbation theory (2LPT). NoAM is suitable for billions of particles and can easily handle non-regular volumes, redshift space, and other constraints. We implement NoAM to systematically compare Zel'dovich, 2LPT, and N-body dynamics over diverse configurations ranging from idealized high-res periodic simulation box to realistic galaxy mocks. Our findings are (i) Non-linear reconstructions with Zel'dovich, 2LPT, and full dynamics perform better than linear theory only for idealized catalogs in real space. For realistic catalogs, linear theory is the optimal choice for reconstructing velocity fields smoothed on scales {buildrel > over {˜}} 5 h^{-1}{Mpc}.(ii) all non-linear back-in-time reconstructions tested here, produce comparable enhancement of the baryonic oscillation signal in the correlation function.

  6. Catching the `Bullet' with Parkes: A Pilot Study for large-scale galaxy cluster observations

    NASA Astrophysics Data System (ADS)

    Malu, Siddharth; Carretti, Ettore; Subrahmanyan, Ravi; Wieringa, Mark; Narasimha, D.

    2011-10-01

    We propose to observe the ‘bullet’ cluster of galaxies - 1E 0657-56 - which consists of two sub-clusters in the process of merging and manifests relatively cold clouds plowing through hot intra-cluster gas, using the Parkes Telescope at 18 GHz. We aim to image the sub-structure in the gas pressure distribution via the inverse-Compton scattering of cosmic microwave background photons (the Sunyaev-Zeldovich Effect; SZE). The observations constitute a probe of fine structure in the physical state of the intra-cluster gas, the physics of propagation and stability of cold fronts in cluster mergers and a measure of cluster magnetic field. The small scale structure has been observed with the ATCA already (Wilson et al. MNRAS 2011; Malu et al. arXiv:1005.1394), but the large scale emission, essential to recover the entire amount of the SZ effects, is missed by those observations because of lack of sensitivity on scales larger than the primary beam. Combining with single dish observations is thus essential to derive cluster physical quantities (like electron density and gas temperature) and we propose here to conduct them with the Parkes telescope.

  7. Study on spatial structure of large scale retail stores based on space syntax: case study in Wuhan

    NASA Astrophysics Data System (ADS)

    Zhan, Qingming; Zhou, Jingnan; Sliuzas, Richard

    2009-10-01

    This research analyzes the spatial pattern of large-scale stores based on space syntax theory and explores the correlation between the variations in syntax accessibility and the spatial pattern of large-scale stores. This research develops a framework of spatial topology analysis based on the space syntax theory, which includes the following modifications: the trail to break the traditional long axial line network of space syntax and apply this partitioned network in the topological analysis; the trail to analyze the bus route network; By taking both the syntax accessibility of road and bus network into consideration, we produce the scopes of urban syntax centers of city level, local level and sub local level respectively. In the analysis of the retail distribution pattern, the city level, local level and sub local level urban retail centers are suggested respectively according to the spatial distributions of the quantity and scale of the retail stores. The spatial distribution pattern of each retail format is studied as spatial correlations between the retail locations and the urban space syntax centers based on a case study in Wuhan, China. The Space Syntax can be a useful tool to explain the allocation logic of urban retail space in large cities. We suggest to apply the partitioned transportation network instead of the traditional long axial line network.

  8. Genetic variation reveals large-scale population expansion and migration during the expansion of Bantu-speaking peoples.

    PubMed

    Li, Sen; Schlebusch, Carina; Jakobsson, Mattias

    2014-10-22

    The majority of sub-Saharan Africans today speak a number of closely related languages collectively referred to as 'Bantu' languages. The current distribution of Bantu-speaking populations has been found to largely be a consequence of the movement of people rather than a diffusion of language alone. Linguistic and single marker genetic studies have generated various hypotheses regarding the timing and the routes of the Bantu expansion, but these hypotheses have not been thoroughly investigated. In this study, we re-analysed microsatellite markers typed for large number of African populations that-owing to their fast mutation rates-capture signatures of recent population history. We confirm the spread of west African people across most of sub-Saharan Africa and estimated the expansion of Bantu-speaking groups, using a Bayesian approach, to around 5600 years ago. We tested four different divergence models for Bantu-speaking populations with a distribution comprising three geographical regions in Africa. We found that the most likely model for the movement of the eastern branch of Bantu-speakers involves migration of Bantu-speaking groups to the east followed by migration to the south. This model, however, is only marginally more likely than other models, which might indicate direct movement from the west and/or significant gene flow with the western Branch of Bantu-speakers. Our study use multi-loci genetic data to explicitly investigate the timing and mode of the Bantu expansion and it demonstrates that west African groups rapidly expanded both in numbers and over a large geographical area, affirming the fact that the Bantu expansion was one of the most dramatic demographic events in human history.

  9. Genetic variation reveals large-scale population expansion and migration during the expansion of Bantu-speaking peoples

    PubMed Central

    Li, Sen; Schlebusch, Carina; Jakobsson, Mattias

    2014-01-01

    The majority of sub-Saharan Africans today speak a number of closely related languages collectively referred to as ‘Bantu’ languages. The current distribution of Bantu-speaking populations has been found to largely be a consequence of the movement of people rather than a diffusion of language alone. Linguistic and single marker genetic studies have generated various hypotheses regarding the timing and the routes of the Bantu expansion, but these hypotheses have not been thoroughly investigated. In this study, we re-analysed microsatellite markers typed for large number of African populations that—owing to their fast mutation rates—capture signatures of recent population history. We confirm the spread of west African people across most of sub-Saharan Africa and estimated the expansion of Bantu-speaking groups, using a Bayesian approach, to around 5600 years ago. We tested four different divergence models for Bantu-speaking populations with a distribution comprising three geographical regions in Africa. We found that the most likely model for the movement of the eastern branch of Bantu-speakers involves migration of Bantu-speaking groups to the east followed by migration to the south. This model, however, is only marginally more likely than other models, which might indicate direct movement from the west and/or significant gene flow with the western Branch of Bantu-speakers. Our study use multi-loci genetic data to explicitly investigate the timing and mode of the Bantu expansion and it demonstrates that west African groups rapidly expanded both in numbers and over a large geographical area, affirming the fact that the Bantu expansion was one of the most dramatic demographic events in human history. PMID:25209939

  10. Indexed PCR Primers Induce Template-Specific Bias in Large-Scale DNA Sequencing Studies.

    PubMed

    O'Donnell, James L; Kelly, Ryan P; Lowell, Natalie C; Port, Jesse A

    2016-01-01

    Massively parallel sequencing is rapidly emerging as an efficient way to quantify biodiversity at all levels, from genetic variation and expression to ecological community assemblage. However, the number of reads produced per sequencing run far exceeds the number required per sample for many applications, compelling researchers to sequence multiple samples per run in order to maximize efficiency. For studies that include a PCR step, this can be accomplished using primers that include an index sequence allowing sample origin to be determined after sequencing. The use of indexed primers assumes they behave no differently than standard primers; however, we found that indexed primers cause substantial template sequence-specific bias, resulting in radically different profiles of the same environmental sample. Likely the outcome of differential amplification efficiency due to primer-template mismatch, two indexed primer sets spuriously change the inferred sequence abundance from the same DNA extraction by up to 77.1%. We demonstrate that a double PCR approach alleviates these effects in applications where indexed primers are necessary.

  11. Large-Scale Statistical Study of Electromigration Early Failure for Cu/low-k Interconnects

    NASA Astrophysics Data System (ADS)

    Hauschildt, M.; Gall, M.; Justison, P.; Hernandez, R.; Herrick, M.

    2007-10-01

    Even after the successful introduction of Cu-based metallization, the electromigration (EM) failure risk has remained one of the important reliability concerns for advanced process technologies. The main factors requiring attention are the activation energy related to the dominating diffusion mechanism, the current exponent as well as the median lifetimes and lognormal standard deviation values of experimentally acquired failure time distributions. In general, the origin and scaling behavior of these parameters are relatively well understood. However, the observation of strong bimodality for the electron up-flow direction in dual-inlaid Cu interconnects is adding complexity. The failure voids can occur both within the via ("early" mode) or within the trench ("late" mode). Very recently, bimodality has been reported also in down-flow EM, leading to very short lifetimes due to small, slit-shaped voids under vias. For a more thorough investigation of these early failure phenomena, specific test structures were designed based on the Wheatstone Bridge technique. The use of these structures enabled an increase of the tested sample size past 350000. Experiments were performed at various current densities and a wide temperature range. This large-scale EM testing method enables the detailed characterization of the very early failure mode allowing a deeper understanding of the bimodality. Results indicate that down-flow EM exhibits bimodality at small percentage levels not readily identifiable with standard testing methods. In contrast, up-flow EM shows clear bimodality easily detectable through regular EM testing. Activation energy and current exponents of the early modes for the down-flow and up-flow interfaces were determined and found to be different. Further analysis indicates that the down-flow early mode possibly controls the chip lifetime at operating conditions.

  12. QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse Transcriptase Inhibitors.

    PubMed

    Tarasova, Olga A; Urusova, Aleksandra F; Filimonov, Dmitry A; Nicklaus, Marc C; Zakharov, Alexey V; Poroikov, Vladimir V

    2015-07-27

    Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources can produce inconsistency in the data, defined as sometimes widely diverging activity results for the same compound against the same target. Because such inconsistency can reduce the accuracy of predictive models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or freely available, databases: Thomson Reuters Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models. We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of result sets at the assay level.

  13. Open-path Fourier transform infrared studies of large-scale laboratory biomass fires

    NASA Astrophysics Data System (ADS)

    Yokelson, Robert J.; Griffith, David W. T.; Ward, Darold E.

    1996-09-01

    A series of nine large-scale, open fires was conducted in the Intermountain Fire Sciences Laboratory (IFSL) controlled-environment combustion facility. The fuels were pure pine needles or sagebrush or mixed fuels simulating forest-floor, ground fires; crown fires; broadcast burns; and slash pile burns. Mid-infrared spectra of the smoke were recorded throughout each fire by open path Fourier transform infrared (FTIR) spectroscopy at 0.12 cm-1 resolution over a 3 m cross-stack pathlength and analyzed to provide pseudocontinuous, simultaneous concentrations of up to 16 compounds. Simultaneous measurements were made of fuel mass loss, stack gas temperature, and total mass flow up the stack. The products detected are classified by the type of process that dominates in producing them. Carbon dioxide is the dominant emission of (and primarily produced by) flaming combustion, from which we also measure nitric oxide, nitrogen dioxide, sulfur dioxide, and most of the water vapor from combustion and fuel moisture. Carbon monoxide is the dominant emission formed primarily by smoldering combustion from which we also measure carbon dioxide, methane, ammonia, and ethane. A significant fraction of the total emissions is unoxidized pyrolysis products; examples are methanol, formaldehyde, acetic and formic acid, ethene (ethylene), ethyne (acetylene), and hydrogen cyanide. Relatively few previous data exist for many of these compounds and they are likely to have an important but as yet poorly understood role in plume chemistry. Large differences in emissions occur from different fire and fuel types, and the observed temporal behavior of the emissions is found to depend strongly on the fuel bed and product type.

  14. Issues and Methodologies in Large-Scale Assessments. Special Issue 2: Measuring Students' Family Background in Large-Scale International Education Studies. IERI Monograph Series

    ERIC Educational Resources Information Center

    Brese, Falk; Mirazchiyski, Plamen

    2013-01-01

    The relationship between students' family background and achievement is often seen as an important topic in regard to equality and equity of educational provision. The results of various education studies show that the family background of students correlates with students' academic achievement at school. This paper focuses on the measurement of…

  15. The Nature of Global Large-scale Sea Level Variability in Relation to Atmospheric Forcing: A Modeling Study

    NASA Technical Reports Server (NTRS)

    Fukumori, I.; Raghunath, R.; Fu, L. L.

    1996-01-01

    The relation between large-scale sea level variability and ocean circulation is studied using a numerical model. A global primitive equaiton model of the ocean is forced by daily winds and climatological heat fluxes corresponding to the period from January 1992 to February 1996. The physical nature of the temporal variability from periods of days to a year, are examined based on spectral analyses of model results and comparisons with satellite altimetry and tide gauge measurements.

  16. [Large-scale population-based genetic screening and prenatal diagnosis for thalassemias in Zhuhai City of Guangdong Province].

    PubMed

    Zhou, Yu-qiu; Shang, Xuan; Yin, Bao-min; Xiong, Fu; Xiao, Qi-zhi; Zhou, Wan-jun; Zhang, Yong-liang; Xu, Xiang-min

    2012-02-01

    were voluntarily terminated. In Zhuhai City, the average annual birth rate of fetuses with severe thalassemia was declined by 32.9% (49/149). This study has reduced effectively birth rate of perinatal infants with severe thalassemias in Zhuhai City by genetic screening and prenatal diagnosis of thalassemia in the large population of 13 years. Our summary comes out of technical proposals for prenatal screening and diagnosis, which could be take example by preventative control of thalassemia in other regions of China where are prevalent.

  17. A large-scale mutant panel in wheat developed using heavy-ion beam mutagenesis and its application to genetic research

    NASA Astrophysics Data System (ADS)

    Murai, Koji; Nishiura, Aiko; Kazama, Yusuke; Abe, Tomoko

    2013-11-01

    Mutation analysis is a powerful tool for studying gene function. Heavy-ion beam mutagenesis is a comparatively new approach to inducing mutations in plants and is particularly efficient because of its high linear energy transfer (LET). High LET radiation induces a higher rate of DNA double-strand breaks than other mutagenic methods. Over the last 12 years, we have constructed a large-scale mutant panel in diploid einkorn wheat (Triticum monococcum) using heavy-ion beam mutagenesis. Einkorn wheat seeds were exposed to a heavy-ion beam and then sown in the field. Selfed seeds from each spike of M1 plants were used to generate M2 lines. Every year, we obtained approximately 1000 M2 lines and eventually developed a mutant panel with 10,000 M2 lines in total. This mutant panel is being systematically screened for mutations affecting reproductive growth, and especially for flowering-time mutants. To date, we have identified several flowering-time mutants of great interest: non-flowering mutants (mvp: maintained vegetative phase), late-flowering mutants, and early-flowering mutants. These novel mutations will be of value for investigations of the genetic mechanism of flowering in wheat.

  18. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

    PubMed Central

    Asselbergs, Folkert W.; Guo, Yiran; van Iperen, Erik P.A.; Sivapalaratnam, Suthesh; Tragante, Vinicius; Lanktree, Matthew B.; Lange, Leslie A.; Almoguera, Berta; Appelman, Yolande E.; Barnard, John; Baumert, Jens; Beitelshees, Amber L.; Bhangale, Tushar R.; Chen, Yii-Der Ida; Gaunt, Tom R.; Gong, Yan; Hopewell, Jemma C.; Johnson, Toby; Kleber, Marcus E.; Langaee, Taimour Y.; Li, Mingyao; Li, Yun R.; Liu, Kiang; McDonough, Caitrin W.; Meijs, Matthijs F.L.; Middelberg, Rita P.S.; Musunuru, Kiran; Nelson, Christopher P.; O’Connell, Jeffery R.; Padmanabhan, Sandosh; Pankow, James S.; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P.R.; Schork, Nicholas J.; Shaffer, Jonathan; Shen, Haiqing; Smith, Erin N.; Tischfield, Sam E.; van der Most, Peter J.; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Volcik, Kelly A.; Zhang, Li; Bailey, Kent R.; Bailey, Kristian M.; Bauer, Florianne; Boer, Jolanda M.A.; Braund, Peter S.; Burt, Amber; Burton, Paul R.; Buxbaum, Sarah G.; Chen, Wei; Cooper-DeHoff, Rhonda M.; Cupples, L. Adrienne; deJong, Jonas S.; Delles, Christian; Duggan, David; Fornage, Myriam; Furlong, Clement E.; Glazer, Nicole; Gums, John G.; Hastie, Claire; Holmes, Michael V.; Illig, Thomas; Kirkland, Susan A.; Kivimaki, Mika; Klein, Ronald; Klein, Barbara E.; Kooperberg, Charles; Kottke-Marchant, Kandice; Kumari, Meena; LaCroix, Andrea Z.; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Ouwehand, Willem H.; Post, Wendy S.; Saxena, Richa; Scharnagl, Hubert; Schreiner, Pamela J.; Shah, Tina; Shields, Denis C.; Shimbo, Daichi; Srinivasan, Sathanur R.; Stolk, Ronald P.; Swerdlow, Daniel I.; Taylor, Herman A.; Topol, Eric J.; Toskala, Elina; van Pelt, Joost L.; van Setten, Jessica; Yusuf, Salim; Whittaker, John C.; Zwinderman, A.H.; Anand, Sonia S.; Balmforth, Anthony J.; Berenson, Gerald S.; Bezzina, Connie R.; Boehm, Bernhard O.; Boerwinkle, Eric; Casas, Juan P.; Caulfield, Mark J.; Clarke, Robert; Connell, John M.; Cruickshanks, Karen J.; Davidson, Karina W.; Day, Ian N.M.; de Bakker, Paul I.W.; Doevendans, Pieter A.; Dominiczak, Anna F.; Hall, Alistair S.; Hartman, Catharina A.; Hengstenberg, Christian; Hillege, Hans L.; Hofker, Marten H.; Humphries, Steve E.; Jarvik, Gail P.; Johnson, Julie A.; Kaess, Bernhard M.; Kathiresan, Sekar; Koenig, Wolfgang; Lawlor, Debbie A.; März, Winfried; Melander, Olle; Mitchell, Braxton D.; Montgomery, Grant W.; Munroe, Patricia B.; Murray, Sarah S.; Newhouse, Stephen J.; Onland-Moret, N. Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Rich, Stephen S.; Rotter, Jerome I.; Schunkert, Heribert; Sever, Peter; Shuldiner, Alan R.; Silverstein, Roy L.; Stanton, Alice; Thorand, Barbara; Trip, Mieke D.; Tsai, Michael Y.; van der Harst, Pim; van der Schoot, Ellen; van der Schouw, Yvonne T.; Verschuren, W.M. Monique; Watkins, Hugh; Wilde, Arthur A.M.; Wolffenbuttel, Bruce H.R.; Whitfield, John B.; Hovingh, G. Kees; Ballantyne, Christie M.; Wijmenga, Cisca; Reilly, Muredach P.; Martin, Nicholas G.; Wilson, James G.; Rader, Daniel J.; Samani, Nilesh J.; Reiner, Alex P.; Hegele, Robert A.; Kastelein, John J.P.; Hingorani, Aroon D.; Talmud, Philippa J.; Hakonarson, Hakon; Elbers, Clara C.; Keating, Brendan J.; Drenos, Fotios

    2012-01-01

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids. PMID:23063622

  19. Crowdsourcing the General Public for Large Scale Molecular Pathology Studies in Cancer

    PubMed Central

    Candido dos Reis, Francisco J.; Lynn, Stuart; Ali, H. Raza; Eccles, Diana; Hanby, Andrew; Provenzano, Elena; Caldas, Carlos; Howat, William J.; McDuffus, Leigh-Anne; Liu, Bin; Daley, Frances; Coulson, Penny; Vyas, Rupesh J.; Harris, Leslie M.; Owens, Joanna M.; Carton, Amy F.M.; McQuillan, Janette P.; Paterson, Andy M.; Hirji, Zohra; Christie, Sarah K.; Holmes, Amber R.; Schmidt, Marjanka K.; Garcia-Closas, Montserrat; Easton, Douglas F.; Bolla, Manjeet K.; Wang, Qin; Benitez, Javier; Milne, Roger L.; Mannermaa, Arto; Couch, Fergus; Devilee, Peter; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Cox, Angela; Cross, Simon S.; Blows, Fiona M.; Sanders, Joyce; de Groot, Renate; Figueroa, Jonine; Sherman, Mark; Hooning, Maartje; Brenner, Hermann; Holleczek, Bernd; Stegmaier, Christa; Lintott, Chris; Pharoah, Paul D.P.

    2015-01-01

    Background Citizen science, scientific research conducted by non-specialists, has the potential to facilitate biomedical research using available large-scale data, however validating the results is challenging. The Cell Slider is a citizen science project that intends to share images from tumors with the general public, enabling them to score tumor markers independently through an internet-based interface. Methods From October 2012 to June 2014, 98,293 Citizen Scientists accessed the Cell Slider web page and scored 180,172 sub-images derived from images of 12,326 tissue microarray cores labeled for estrogen receptor (ER). We evaluated the accuracy of Citizen Scientist's ER classification, and the association between ER status and prognosis by comparing their test performance against trained pathologists. Findings The area under ROC curve was 0.95 (95% CI 0.94 to 0.96) for cancer cell identification and 0.97 (95% CI 0.96 to 0.97) for ER status. ER positive tumors scored by Citizen Scientists were associated with survival in a similar way to that scored by trained pathologists. Survival probability at 15 years were 0.78 (95% CI 0.76 to 0.80) for ER-positive and 0.72 (95% CI 0.68 to 0.77) for ER-negative tumors based on Citizen Scientists classification. Based on pathologist classification, survival probability was 0.79 (95% CI 0.77 to 0.81) for ER-positive and 0.71 (95% CI 0.67 to 0.74) for ER-negative tumors. The hazard ratio for death was 0.26 (95% CI 0.18 to 0.37) at diagnosis and became greater than one after 6.5 years of follow-up for ER scored by Citizen Scientists, and 0.24 (95% CI 0.18 to 0.33) at diagnosis increasing thereafter to one after 6.7 (95% CI 4.1 to 10.9) years of follow-up for ER scored by pathologists. Interpretation Crowdsourcing of the general public to classify cancer pathology data for research is viable, engages the public and provides accurate ER data. Crowdsourced classification of research data may offer a valid solution to problems of

  20. Experimental study of the impact of large-scale wind farms on land-atmosphere exchanges

    NASA Astrophysics Data System (ADS)

    Zhang, wei; Markfort, Corey; Porté-Agel, Fernando

    2013-04-01

    Wind energy is one of the fastest growing sources of renewable energy world-wide, and it is expected that many more large-scale wind farms will be built and cover a significant portion of land and ocean surfaces. By extracting kinetic energy from the atmospheric boundary layer and converting it to electricity, wind farms may affect the transport of momentum, heat, moisture and trace gases (e.g. CO2) between the atmosphere and the land surface locally and globally. Understanding wind farm-atmosphere interactions and subsequent environmental impacts are complicated by the effects of turbine array configuration, wind farm size, land-surface characteristics and atmospheric thermal stability. In particular, surface scalar flux is influenced by wind farms and needs to be appropriately parameterized in meso-scale and/or high-resolution numerical models. Wind-tunnel experiments of model wind farms with perfectly aligned and staggered configurations, having the same turbine distribution density, were conducted in a neutral turbulent boundary layer with a surface heat source. Turbulent flow and fluxes over and through the wind farm were measured using a custom x-wire/cold-wire anemometer; and surface scalar flux was measured with an array of surface-mounted heat flux sensors within the quasi-developed flow regime. Although the overall surface heat flux change produced by the wind farms was found to be small, with a net reduction of 4% for the staggered wind farm and nearly zero for the aligned wind farm, the highly heterogeneous spatial distribution of the surface heat flux, dependent on wind farm layout, is significant. The difference between the minimum and maximum surface heat fluxes could be up to 12% and 7% in aligned and staggered wind farms, respectively. This finding is important for planning intensive agriculture practices and optimizing agricultural land use with regard to wind energy project development. The well-controlled wind-tunnel experiments presented here

  1. Large-scale molecular genetic analysis in plant-pathogenic fungi: a decade of genome-wide functional analysis.

    PubMed

    Motaung, Thabiso E; Saitoh, Hiromasa; Tsilo, Toi J

    2016-10-12

    Plant-pathogenic fungi cause diseases to all major crop plants world-wide and threaten global food security. Underpinning fungal diseases are virulence genes facilitating plant host colonization that often marks pathogenesis and crop failures, as well as an increase in staple food prices. Fungal molecular genetics is therefore the cornerstone to the sustainable prevention of disease outbreaks. Pathogenicity studies using mutant collections provide immense function-based information regarding virulence genes of economically relevant fungi. These collections are rich in potential targets for existing and new biological control agents. They contribute to host resistance breeding against fungal pathogens and are instrumental in searching for novel resistance genes through the identification of fungal effectors. Therefore, functional analyses of mutant collections propel gene discovery and characterization, and may be incorporated into disease management strategies. In the light of these attributes, mutant collections enhance the development of practical solutions to confront modern agricultural constraints. Here, a critical review of mutant collections constructed by various laboratories during the past decade is provided. We used Magnaporthe oryzae and Fusarium graminearum studies to show how mutant screens contribute to bridge existing knowledge gaps in pathogenicity and fungal-host interactions.

  2. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

    PubMed

    McKay, James D; Hung, Rayjean J; Han, Younghun; Zong, Xuchen; Carreras-Torres, Robert; Christiani, David C; Caporaso, Neil E; Johansson, Mattias; Xiao, Xiangjun; Li, Yafang; Byun, Jinyoung; Dunning, Alison; Pooley, Karen A; Qian, David C; Ji, Xuemei; Liu, Geoffrey; Timofeeva, Maria N; Bojesen, Stig E; Wu, Xifeng; Le Marchand, Loic; Albanes, Demetrios; Bickeböller, Heike; Aldrich, Melinda C; Bush, William S; Tardon, Adonina; Rennert, Gad; Teare, M Dawn; Field, John K; Kiemeney, Lambertus A; Lazarus, Philip; Haugen, Aage; Lam, Stephen; Schabath, Matthew B; Andrew, Angeline S; Shen, Hongbing; Hong, Yun-Chul; Yuan, Jian-Min; Bertazzi, Pier Alberto; Pesatori, Angela C; Ye, Yuanqing; Diao, Nancy; Su, Li; Zhang, Ruyang; Brhane, Yonathan; Leighl, Natasha; Johansen, Jakob S; Mellemgaard, Anders; Saliba, Walid; Haiman, Christopher A; Wilkens, Lynne R; Fernandez-Somoano, Ana; Fernandez-Tardon, Guillermo; van der Heijden, Henricus F M; Kim, Jin Hee; Dai, Juncheng; Hu, Zhibin; Davies, Michael P A; Marcus, Michael W; Brunnström, Hans; Manjer, Jonas; Melander, Olle; Muller, David C; Overvad, Kim; Trichopoulou, Antonia; Tumino, Rosario; Doherty, Jennifer A; Barnett, Matt P; Chen, Chu; Goodman, Gary E; Cox, Angela; Taylor, Fiona; Woll, Penella; Brüske, Irene; Wichmann, H-Erich; Manz, Judith; Muley, Thomas R; Risch, Angela; Rosenberger, Albert; Grankvist, Kjell; Johansson, Mikael; Shepherd, Frances A; Tsao, Ming-Sound; Arnold, Susanne M; Haura, Eric B; Bolca, Ciprian; Holcatova, Ivana; Janout, Vladimir; Kontic, Milica; Lissowska, Jolanta; Mukeria, Anush; Ognjanovic, Simona; Orlowski, Tadeusz M; Scelo, Ghislaine; Swiatkowska, Beata; Zaridze, David; Bakke, Per; Skaug, Vidar; Zienolddiny, Shanbeh; Duell, Eric J; Butler, Lesley M; Koh, Woon-Puay; Gao, Yu-Tang; Houlston, Richard S; McLaughlin, John; Stevens, Victoria L; Joubert, Philippe; Lamontagne, Maxime; Nickle, David C; Obeidat, Ma'en; Timens, Wim; Zhu, Bin; Song, Lei; Kachuri, Linda; Artigas, María Soler; Tobin, Martin D; Wain, Louise V; Rafnar, Thorunn; Thorgeirsson, Thorgeir E; Reginsson, Gunnar W; Stefansson, Kari; Hancock, Dana B; Bierut, Laura J; Spitz, Margaret R; Gaddis, Nathan C; Lutz, Sharon M; Gu, Fangyi; Johnson, Eric O; Kamal, Ahsan; Pikielny, Claudio; Zhu, Dakai; Lindströem, Sara; Jiang, Xia; Tyndale, Rachel F; Chenevix-Trench, Georgia; Beesley, Jonathan; Bossé, Yohan; Chanock, Stephen; Brennan, Paul; Landi, Maria Teresa; Amos, Christopher I

    2017-07-01

    Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.

  3. Large-scale longitudinal gradients of genetic diversity: a meta-analysis across six phyla in the Mediterranean basin

    PubMed Central

    Conord, Cyrille; Gurevitch, Jessica; Fady, Bruno

    2012-01-01

    Biodiversity is the diversity of life at all scales, from genes to ecosystems. Predicting its patterns of variation across the globe is a fundamental issue in ecology and evolution. Diversity within species, that is, genetic diversity, is of prime importance for understanding past and present evolutionary patterns, and highlighting areas where conservation might be a priority. Using published data on the genetic diversity of species whose populations occur in the Mediterranean basin, we calculated a coefficient of correlation between within-population genetic diversity indices and longitude. Using a meta-analysis framework, we estimated the role of biological, ecological, biogeographic, and marker type factors on the strength and magnitude of this correlation in six phylla. Overall, genetic diversity increases from west to east in the Mediterranean basin. This correlation is significant for both animals and plants, but is not uniformly expressed for all groups. It is stronger in the southern than in the northern Mediterranean, in true Mediterranean plants than in plants found at higher elevations, in trees than in other plants, and in bi-parentally and paternally than in maternally inherited DNA makers. Overall, this correlation between genetic diversity and longitude, and its patterns across biological and ecological traits, suggests the role of two non-mutually exclusive major processes that shaped the genetic diversity in the Mediterranean during and after the cold periods of the Pleistocene: east-west recolonization during the Holocene and population size contraction under local Last Glacial Maximum climate in resident western and low elevation Mediterranean populations. PMID:23145344

  4. The large-scale blast score ratio (LS-BSR) pipeline: a method to rapidly compare genetic content between bacterial genomes.

    PubMed

    Sahl, Jason W; Caporaso, J Gregory; Rasko, David A; Keim, Paul

    2014-01-01

    Background. As whole genome sequence data from bacterial isolates becomes cheaper to generate, computational methods are needed to correlate sequence data with biological observations. Here we present the large-scale BLAST score ratio (LS-BSR) pipeline, which rapidly compares the genetic content of hundreds to thousands of bacterial genomes, and returns a matrix that describes the relatedness of all coding sequences (CDSs) in all genomes surveyed. This matrix can be easily parsed in order to identify genetic relationships between bacterial genomes. Although pipelines have been published that group peptides by sequence similarity, no other software performs the rapid, large-scale, full-genome comparative analyses carried out by LS-BSR. Results. To demonstrate the utility of the method, the LS-BSR pipeline was tested on 96 Escherichia coli and Shigella genomes; the pipeline ran in 163 min using 16 processors, which is a greater than 7-fold speedup compared to using a single processor. The BSR values for each CDS, which indicate a relative level of relatedness, were then mapped to each genome on an independent core genome single nucleotide polymorphism (SNP) based phylogeny. Comparisons were then used to identify clade specific CDS markers and validate the LS-BSR pipeline based on molecular markers that delineate between classical E. coli pathogenic variant (pathovar) designations. Scalability tests demonstrated that the LS-BSR pipeline can process 1,000 E. coli genomes in 27-57 h, depending upon the alignment method, using 16 processors. Conclusions. LS-BSR is an open-source, parallel implementation of the BSR algorithm, enabling rapid comparison of the genetic content of large numbers of genomes. The results of the pipeline can be used to identify specific markers between user-defined phylogenetic groups, and to identify the loss and/or acquisition of genetic information between bacterial isolates. Taxa-specific genetic markers can then be translated into clinical

  5. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes

    PubMed Central

    Morris, Andrew P; Voight, Benjamin F; Teslovich, Tanya M; Ferreira, Teresa; Segrè, Ayellet V; Steinthorsdottir, Valgerdur; Strawbridge, Rona J; Khan, Hassan; Grallert, Harald; Mahajan, Anubha; Prokopenko, Inga; Kang, Hyun Min; Dina, Christian; Esko, Tonu; Fraser, Ross M; Kanoni, Stavroula; Kumar, Ashish; Lagou, Vasiliki; Langenberg, Claudia; Luan, Jian'an; Lindgren, Cecilia M; Müller-Nurasyid, Martina; Pechlivanis, Sonali; Rayner, N William; Scott, Laura J; Wiltshire, Steven; Yengo, Loic; Kinnunen, Leena; Rossin, Elizabeth J; Raychaudhuri, Soumya; Johnson, Andrew D; Dimas, Antigone S; Loos, Ruth J F; Vedantam, Sailaja; Chen, Han; Florez, Jose C; Fox, Caroline; Liu, Ching-Ti; Rybin, Denis; Couper, David J; Kao, Wen Hong L; Li, Man; Cornelis, Marilyn C; Kraft, Peter; Sun, Qi; van Dam, Rob M; Stringham, Heather M; Chines, Peter S; Fischer, Krista; Fontanillas, Pierre; Holmen, Oddgeir L; Hunt, Sarah E; Jackson, Anne U; Kong, Augustine; Lawrence, Robert; Meyer, Julia; Perry, John RB; Platou, Carl GP; Potter, Simon; Rehnberg, Emil; Robertson, Neil; Sivapalaratnam, Suthesh; Stančáková, Alena; Stirrups, Kathleen; Thorleifsson, Gudmar; Tikkanen, Emmi; Wood, Andrew R; Almgren, Peter; Atalay, Mustafa; Benediktsson, Rafn; Bonnycastle, Lori L; Burtt, Noël; Carey, Jason; Charpentier, Guillaume; Crenshaw, Andrew T; Doney, Alex S F; Dorkhan, Mozhgan; Edkins, Sarah; Emilsson, Valur; Eury, Elodie; Forsen, Tom; Gertow, Karl; Gigante, Bruna; Grant, George B; Groves, Christopher J; Guiducci, Candace; Herder, Christian; Hreidarsson, Astradur B; Hui, Jennie; James, Alan; Jonsson, Anna; Rathmann, Wolfgang; Klopp, Norman; Kravic, Jasmina; Krjutškov, Kaarel; Langford, Cordelia; Leander, Karin; Lindholm, Eero; Lobbens, Stéphane; Männistö, Satu; Mirza, Ghazala; Mühleisen, Thomas W; Musk, Bill; Parkin, Melissa; Rallidis, Loukianos; Saramies, Jouko; Sennblad, Bengt; Shah, Sonia; Sigurðsson, Gunnar; Silveira, Angela; Steinbach, Gerald; Thorand, Barbara; Trakalo, Joseph; Veglia, Fabrizio; Wennauer, Roman; Winckler, Wendy; Zabaneh, Delilah; Campbell, Harry; van Duijn, Cornelia; Uitterlinden89-, Andre G; Hofman, Albert; Sijbrands, Eric; Abecasis, Goncalo R; Owen, Katharine R; Zeggini, Eleftheria; Trip, Mieke D; Forouhi, Nita G; Syvänen, Ann-Christine; Eriksson, Johan G; Peltonen, Leena; Nöthen, Markus M; Balkau, Beverley; Palmer, Colin N A; Lyssenko, Valeriya; Tuomi, Tiinamaija; Isomaa, Bo; Hunter, David J; Qi, Lu; Shuldiner, Alan R; Roden, Michael; Barroso, Ines; Wilsgaard, Tom; Beilby, John; Hovingh, Kees; Price, Jackie F; Wilson, James F; Rauramaa, Rainer; Lakka, Timo A; Lind, Lars; Dedoussis, George; Njølstad, Inger; Pedersen, Nancy L; Khaw, Kay-Tee; Wareham, Nicholas J; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Korpi-Hyövälti, Eeva; Saltevo, Juha; Laakso, Markku; Kuusisto, Johanna; Metspalu, Andres; Collins, Francis S; Mohlke, Karen L; Bergman, Richard N; Tuomilehto, Jaakko; Boehm, Bernhard O; Gieger, Christian; Hveem, Kristian; Cauchi, Stephane; Froguel, Philippe; Baldassarre, Damiano; Tremoli, Elena; Humphries, Steve E; Saleheen, Danish; Danesh, John; Ingelsson, Erik; Ripatti, Samuli; Salomaa, Veikko; Erbel, Raimund; Jöckel, Karl-Heinz; Moebus, Susanne; Peters, Annette; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Morris, Andrew D; Donnelly, Peter J; Frayling, Timothy M; Hattersley, Andrew T; Boerwinkle, Eric; Melander, Olle; Kathiresan, Sekar; Nilsson, Peter M; Deloukas, Panos; Thorsteinsdottir, Unnur; Groop, Leif C; Stefansson, Kari; Hu, Frank; Pankow, James S; Dupuis, Josée; Meigs, James B; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2012-01-01

    To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip involving 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two demonstrating sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of further common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signalling and cell cycle regulation, in diabetes pathogenesis. PMID:22885922

  6. Large scale profiles of galaxies at z=0-2 studied by stacking the HSC SSP survey data

    NASA Astrophysics Data System (ADS)

    Kubo, Mariko; Ouchi, Masami; Shibuya, Takatoshi

    2017-03-01

    We are carrying out the study of the evolution of radial surface brightness profiles of galaxies from z = 0 to 2 by stacking analysis using data corrected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP). This will allow us to constrain the large scale average profiles of various galaxy populations at high redshift. From the stacking analysis of galaxies selected based on their photometric redshifts, we successfully detected the outer components of galaxies at z > 1 extending to at least ~80 kpc, which imply an early formation for the galaxy outskirts.

  7. Constraints on neutrino masses from the study of the nearby large-scale structure and galaxy cluster counts

    NASA Astrophysics Data System (ADS)

    Böhringer, Hans; Chon, Gayoung

    2016-07-01

    The high precision measurements of the cosmic microwave background by the Planck survey yielded tight constraints on cosmological parameters and the statistics of the density fluctuations at the time of recombination. This provides the means for a critical study of structure formation in the Universe by comparing the microwave background results with present epoch measurements of the cosmic large-scale structure. It can reveal subtle effects such as how different forms of Dark Matter may modify structure growth. Currently most interesting is the damping effect of structure growth by massive neutrinos. Different observations of low redshift matter density fluctuations provided evidence for a signature of massive neutrinos. Here we discuss the study of the cosmic large-scale structure with a complete sample of nearby, X-ray luminous clusters from our REFLEX cluster survey. From the observed X-ray luminosity function and its reproduction for different cosmological models, we obtain tight constraints on the cosmological parameters describing the matter density, Ωm, and the density fluctuation amplitude, σ8. A comparison of these constraints with the Planck results shows a discrepancy in the framework of a pure ΛCDM model, but the results can be reconciled, if we allow for a neutrino mass in the range of 0.17 eV to 0.7 eV. Also some others, but not all of the observations of the nearby large-scale structure provide evidence or trends for signatures of massive neutrinos. With further improvement in the systematics and future survey projects, these indications will develop into a definitive measurement of neutrino masses.

  8. Large-scale information flow in conscious and unconscious states: an ECoG study in monkeys.

    PubMed

    Yanagawa, Toru; Chao, Zenas C; Hasegawa, Naomi; Fujii, Naotaka

    2013-01-01

    Consciousness is an emergent property of the complex brain network. In order to understand how consciousness is constructed, neural interactions within this network must be elucidated. Previous studies have shown that specific neural interactions between the thalamus and frontoparietal cortices; frontal and parietal cortices; and parietal and temporal cortices are correlated with levels of consciousness. However, due to technical limitations, the network underlying consciousness has not been investigated in terms of large-scale interactions with high temporal and spectral resolution. In this study, we recorded neural activity with dense electrocorticogram (ECoG) arrays and used the spectral Granger causality to generate a more comprehensive network that relates to consciousness in monkeys. We found that neural interactions were significantly different between conscious and unconscious states in all combinations of cortical region pairs. Furthermore, the difference in neural interactions between conscious and unconscious states could be represented in 4 frequency-specific large-scale networks with unique interaction patterns: 2 networks were related to consciousness and showed peaks in alpha and beta bands, while the other 2 networks were related to unconsciousness and showed peaks in theta and gamma bands. Moreover, networks in the unconscious state were shared amongst 3 different unconscious conditions, which were induced either by ketamine and medetomidine, propofol, or sleep. Our results provide a novel picture that the difference between conscious and unconscious states is characterized by a switch in frequency-specific modes of large-scale communications across the entire cortex, rather than the cessation of interactions between specific cortical regions.

  9. A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility.

    PubMed

    Carmona, F David; Mackie, Sarah L; Martín, Jose-Ezequiel; Taylor, John C; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C; Narváez, Javier; Miranda-Filloy, José A; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J; Hoffman, Gary S; Khalidi, Nader A; Koening, Curry L; Langford, Carol A; McAlear, Carol A; Moreland, Larry; Monach, Paul A; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G; Warrington, Kenneth J; Ytterberg, Steven R; Gregersen, Peter K; Pease, Colin T; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P C; de Bakker, Paul I W; Barrett, Jennifer H; Salvarani, Carlo; Merkel, Peter A; González-Gay, Miguel A; Morgan, Ann W; Martín, Javier

    2015-04-02

    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10(-40), OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1(∗)04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10(-43)) and HLA-DQα1 47 (p = 4.02 × 10(-46)), 56, and 76 (both p = 1.84 × 10(-45)) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10(-6), OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10(-6), OR = 1.20), and REL (rs115674477, p = 1.10 × 10(-5), OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function.

  10. Brush and spray: a high-throughput systemic acquired resistance assay suitable for large-scale genetic screening.

    PubMed

    Jing, Beibei; Xu, Shaohua; Xu, Mo; Li, Yan; Li, Shuxin; Ding, Jinmei; Zhang, Yuelin

    2011-11-01

    Systemic acquired resistance (SAR) is a defense mechanism induced in the distal parts of plants after primary infection. It confers long-lasting protection against a broad spectrum of microbial pathogens. Lack of high-throughput assays has hampered the forward genetic analysis of SAR. Here, we report the development of an easy and efficient assay for SAR and its application in a forward genetic screen for SAR-deficient mutants in Arabidopsis (Arabidopsis thaliana). Using the new assay for SAR, we identified six flavin-dependent monooxygenase1, four AGD2-like defense response protein1, three salicylic acid induction-deficient2, one phytoalexin deficient4, and one avrPphB-susceptible3 alleles as well as a gain-of-function mutant of CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR3 designated camta3-3D. Like transgenic plants overexpressing CAMTA3, camta3-3D mutant plants exhibit compromised SAR and enhanced susceptibility to virulent pathogens, suggesting that CAMTA3 is a critical regulator of both basal resistance and SAR.

  11. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    PubMed

    DiTommaso, Tia; Jones, Lynelle K; Cottle, Denny L; Gerdin, Anna-Karin; Vancollie, Valerie E; Watt, Fiona M; Ramirez-Solis, Ramiro; Bradley, Allan; Steel, Karen P; Sundberg, John P; White, Jacqueline K; Smyth, Ian M

    2014-10-01

    The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  12. Large-Scale Wind Integration Studies in the United States: Preliminary Results; Preprint

    SciTech Connect

    Milligan, M.; Lew, D.; Corbus, D.; Piwko, R.; Miller, N.; Clark, K.; Jordan, G.; Freeman, L.; Zavadil, B.; Schuerger, M.

    2009-09-01

    The National Renewable Energy Laboratory is managing two large regional wind integration studies on behalf of the United States Department of Energy. These two studies are believed to be the largest ever undertaken in the United States.

  13. Large scale dynamic systems

    NASA Technical Reports Server (NTRS)

    Doolin, B. F.

    1975-01-01

    Classes of large scale dynamic systems were discussed in the context of modern control theory. Specific examples discussed were in the technical fields of aeronautics, water resources and electric power.

  14. Multi-stage sampling for large scale natural resources surveys: a case study of rice and waterfowl.

    PubMed

    Stafford, Joshua D; Reinecke, Kenneth J; Kaminski, Richard M; Gerard, Patrick D

    2006-03-01

    Large-scale sample surveys to estimate abundance and distribution of organisms and their habitats are increasingly important in ecological studies. Multi-stage sampling (MSS) is especially suited to large-scale surveys because of the natural clustering of resources. To illustrate an application, we: (1) designed a stratified MSS to estimate late autumn abundance (kg/ha) of rice seeds in harvested fields as food for waterfowl wintering in the Mississippi Alluvial Valley (MAV); (2) investigated options for improving the MSS design; and (3) compared statistical and cost efficiency of MSS to simulated simple random sampling (SRS). During 2000-2002, we sampled 25-35 landowners per year, 1 or 2 fields per landowner per year, and measured seed mass in 10 soil cores collected within each field. Analysis of variance components and costs for each stage of the survey design indicated that collecting 10 soil cores per field was near the optimum of 11-15, whereas sampling >1 field per landowner provided few benefits because data from fields within landowners were highly correlated. Coefficients of variation (CV) of annual estimates of rice abundance ranged from 0.23 to 0.31 and were limited by variation among landowners and the number of landowners sampled. Design effects representing the statistical efficiency of MSS relative to SRS ranged from 3.2 to 9.0, and simulations indicated SRS would cost, on average, 1.4 times more than MSS because clustering of sample units in MSS decreased travel costs. We recommend MSS as a potential sampling strategy for large-scale natural resource surveys and specifically for future surveys of the availability of rice as food for waterfowl in the MAV and similar areas.

  15. A mixed-layer model study of the stratocumulus response to changes in large-scale conditions

    NASA Astrophysics Data System (ADS)

    De Roode, Stephan R.; Siebesma, A. Pier; Gesso, Sara Dal; Jonker, Harm J. J.; Schalkwijk, Jerôme; Sival, Jasper

    2014-12-01

    A mixed-layer model is used to study the response of stratocumulus equilibrium state solutions to perturbations of cloud controlling factors which include the sea surface temperature, the specific humidity and temperature in the free troposphere, as well as the large-scale divergence and horizontal wind speed. In the first set of experiments, we assess the effect of a change in a single forcing condition while keeping the entrainment rate fixed, while in the second set, the entrainment rate is allowed to respond. The role of the entrainment rate is exemplified from an experiment in which the sea surface temperature is increased. An analysis of the budget equation for heat and moisture demonstrates that for a fixed entrainment rate, the stratocumulus liquid water path (LWP) will increase since the moistening from the surface evaporation dominates the warming effect. By contrast, if the response of the entrainment rate to the change in the surface forcing is sufficiently strong, enhanced mixing of dry and warm inversion air will cause a thinning of the cloud layer. If the entrainment warming effect is sufficiently strong, the surface sensible heat flux will decrease, as opposed to an increase which will occur for a fixed entrainment rate. It is argued that the surface evaporation will always increase for an increase in the sea surface temperature, and this change will be enlarged if the entrainment rate increases. These experiments aid the interpretation of results of similar simulations with single-column model versions of climate models carried out in the framework of the CFMIP-GCSS Intercomparison of Large-Eddy and Single-Column Models (CGILS) project. Because in a large-scale models, the entrainment response to changes in the large-scale forcing conditions depends on the details of the parameterization of turbulent and convective transport, intermodel differences in the sign of the LWP response may be well attributable to differences in the entrainment response.

  16. Multi-stage sampling for large scale natural resources surveys: A case study of rice and waterfowl

    USGS Publications Warehouse

    Stafford, J.D.; Reinecke, K.J.; Kaminski, R.M.; Gerard, P.D.

    2005-01-01

    Large-scale sample surveys to estimate abundance and distribution of organisms and their habitats are increasingly important in ecological studies. Multi-stage sampling (MSS) is especially suited to large-scale surveys because of the natural clustering of resources. To illustrate an application, we: (1) designed a stratified MSS to estimate late autumn abundance (kg/ha) of rice seeds in harvested fields as food for waterfowl wintering in the Mississippi Alluvial Valley (MAV); (2) investigated options for improving the MSS design; and (3) compared statistical and cost efficiency of MSS to simulated simple random sampling (SRS). During 2000?2002, we sampled 25?35 landowners per year, 1 or 2 fields per landowner per year, and measured seed mass in 10 soil cores collected within each field. Analysis of variance components and costs for each stage of the survey design indicated that collecting 10 soil cores per field was near the optimum of 11?15, whereas sampling >1 field per landowner provided few benefits because data from fields within landowners were highly correlated. Coefficients of variation (CV) of annual estimates of rice abundance ranged from 0.23 to 0.31 and were limited by variation among landowners and the number of landowners sampled. Design effects representing the statistical efficiency of MSS relative to SRS ranged from 3.2 to 9.0, and simulations indicated SRS would cost, on average, 1.4 times more than MSS because clustering of sample units in MSS decreased travel costs. We recommend MSS as a potential sampling strategy for large-scale natural resource surveys and specifically for future surveys of the availability of rice as food for waterfowl in the MAV and similar areas.

  17. Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

    ERIC Educational Resources Information Center

    Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

    2008-01-01

    Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

  18. Pre- and Postnatal Influences on Preschool Mental Health: A Large-Scale Cohort Study

    ERIC Educational Resources Information Center

    Robinson, Monique; Oddy, Wendy H.; Li, Jianghong; Kendall, Garth E.; de Klerk, Nicholas H.; Silburn, Sven R.; Zubrick, Stephen R.; Newnham, John P.; Stanley, Fiona J.; Mattes, Eugen

    2008-01-01

    Background: Methodological challenges such as confounding have made the study of the early determinants of mental health morbidity problematic. This study aims to address these challenges in investigating antenatal, perinatal and postnatal risk factors for the development of mental health problems in pre-school children in a cohort of Western…

  19. Surface mass balance on Fimbul ice shelf, East Antarctica: Comparison of field measurements and large-scale studies

    NASA Astrophysics Data System (ADS)

    Sinisalo, Anna; Anschütz, Helgard; Aasen, Anne Târând; Langley, Kirsty; Deschwanden, Angela; Kohler, Jack; Matsuoka, Kenichi; Hamran, Svein-Erik; Øyan, Mats-Jørgen; Schlosser, Elisabeth; Hagen, Jon Ove; Nøst, Ole Anders; Isaksson, Elisabeth

    2013-10-01

    challenges remain for estimating the Antarctic ice sheet surface mass balance (SMB), which represents a major uncertainty in predictions of future sea-level rise. Validating continental scale studies is hampered by the sparse distribution of in situ data. Here we present a 26 year mean SMB of the Fimbul ice shelf in East Antarctica between 1983-2009, and recent interannual variability since 2010. We compare these data to the results of large-scale SMB studies for similar time periods, obtained from regional atmospheric modeling and remote sensing. Our in situ data include ground penetrating radar, firn cores, and mass balance stakes and provide information on both temporal and spatial scales. The 26 year mean SMB on the Fimbul ice shelf varies between 170 and 620 kg m-2 a-1 giving a regional average value of 310 ± 70 kg m-2 a-1. Our measurements indicate higher long-term accumulation over large parts of the ice shelf compared to the large-scale studies. We also show that the variability of the mean annual SMB, which can be up to 90%, can be a dominant factor in short-term estimates. The results emphasize the importance of using a combination of ground-based validation data, regional climate models, and remote sensing over a relevant time period in order to achieve a reliable SMB for Antarctica.

  20. What do large scale studies of medication in schizophrenia add to our management strategies?

    PubMed

    Agius, Mark; Davis, Abigail; Gilhooley, Michael; Chapman, Shelley; Zaman, Rashid

    2010-06-01

    A number of large naturalistic trials have reported in recent years comparing second generation antipsychotic drugs with their predecessors. The conclusions they draw have rightly sparked much debate, but are these studies truly comparable? If not, which of them are most methodologically robust and are these the studies most suitable as a foundation for clinical care guidelines with a strong evidence base. We aimed to conduct a review of the current literature to establish the appropriateness of several recent major clinical studies being used as the basis for clinical guidelines. A literature search using the PUBMED database was carried out. Five major studies comparing antipsychotic efficacy were selected as possible candidates and subjected to further analysis. The studies were: * CUTLASS (Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia study); * CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness study); * SOHO (Schizophrenia outpatients Health Outcomes study); * CAFE (Comparison of Atypicals in First Episode study); * EUFEST (European First Episode Schizophrenia Trial). The trials: * CAFE - the trial, although well randomised and blinded, uses discontinuation as a primary endpoint - this is hard to draw conclusions from: patients may discontinue due to side effects, due to lack of efficacy or with against medical advice for a multitude of reasons. As a secondary endpoint, the study does make use of a PANSS scoring system to measure efficacy, adding some weight to the conclusion that olanzapine, quetiaine and risperidone in early psychosis patients have equivalent efficacies. * CATIE - This trial was a comparative study, and so lacked a control arm and used discontinuation of medication an inverse measure of efficacy - an easily quantifiable event, but making for difficult interpretation. However most criticism has been directed at the unusually low (quitiapine, ziprasidone) and high (olanzapine and perphenazine) doses of drug

  1. Design of a protocol for large-scale epidemiological studies in individual sports: the Swedish Athletics injury study.

    PubMed

    Jacobsson, Jenny; Timpka, Toomas; Ekberg, Joakim; Kowalski, Jan; Nilsson, Sverker; Renström, Per

    2010-12-01

    Epidemiological studies have mainly been performed on team sports. The authors set out to develop a protocol for large-scale epidemiological studies of injuries among elite athletics athletes. An argument-based method for investigation of complex design problems was used to structure the collection and analysis of data. Specification of the protocol was preceded by an examination of requirements on injury surveillance in individual sports and iterated drafting of protocol specifications, and followed by formative evaluations. The requirements analysis shows that the central demand on the protocol is to allow for detailed epidemiological analyses of overuse injuries, which subsequently requires regular collection of self-reported data from athletes. The resulting study protocol is centred on a web-based weekly athlete e-diary enabling continual collection of individual-level data on exposure and injuries. To be able to interpret the self-reported data on injury events, collection of a wide range of personal baseline data from the athlete, including a psychological profile, is included in the protocol. The resulting protocol can be employed in intervention programmes that can prevent suffering among both adult elite and youth talent athletes who have made considerable life investments in their sport.

  2. Large-scale production and protein engineering of G protein-coupled receptors for structural studies.

    PubMed

    Milić, Dalibor; Veprintsev, Dmitry B

    2015-01-01

    Structural studies of G protein-coupled receptors (GPCRs) gave insights into molecular mechanisms of their action and contributed significantly to molecular pharmacology. This is primarily due to technical advances in protein engineering, production and crystallization of these important receptor targets. On the other hand, NMR spectroscopy of GPCRs, which can provide information about their dynamics, still remains challenging due to difficulties in preparation of isotopically labeled receptors and their low long-term stabilities. In this review, we discuss methods used for expression and purification of GPCRs for crystallographic and NMR studies. We also summarize protein engineering methods that played a crucial role in obtaining GPCR crystal structures.

  3. Large-scale production and protein engineering of G protein-coupled receptors for structural studies

    PubMed Central

    Milić, Dalibor; Veprintsev, Dmitry B.

    2015-01-01

    Structural studies of G protein-coupled receptors (GPCRs) gave insights into molecular mechanisms of their action and contributed significantly to molecular pharmacology. This is primarily due to technical advances in protein engineering, production and crystallization of these important receptor targets. On the other hand, NMR spectroscopy of GPCRs, which can provide information about their dynamics, still remains challenging due to difficulties in preparation of isotopically labeled receptors and their low long-term stabilities. In this review, we discuss methods used for expression and purification of GPCRs for crystallographic and NMR studies. We also summarize protein engineering methods that played a crucial role in obtaining GPCR crystal structures. PMID:25873898

  4. Including English Language Learners with Disabilities in Large-Scale Assessments: A Case Study of Linguistically-Diverse Populations. ELLs with Disabilities Report 14

    ERIC Educational Resources Information Center

    Minnema, Jane E.; Thurlow, Martha L.; VanGetson, Gretchen R.; Jimenez, Rene

    2006-01-01

    The National Center on Educational Outcomes (NCEO) has for the past four years conducted research on large-scale assessment and instructional issues for English language learners (ELLs) with disabilities, but neither NCEO's research nor any other research study has yet described large-scale assessment experiences at the local school level for…

  5. Large-Scale Assessments and English Language Learners with Disabilities: A Case Study of Participation, Performance, and Perceptions--"Walking the Talk!" ELLs with Disabilities Report 15

    ERIC Educational Resources Information Center

    Minnema, Jane E.; Thurlow, Martha L.; VanGetson, Gretchen R.; Jimenez, Rene

    2006-01-01

    This study was designed, in part, to clarify some of the issues that surround including English language learners in states' large-scale assessment programs. More specifically, the authors gathered practical information at the local school level to understand these students' large-scale assessment experiences from a variety of perspectives, to…

  6. Uncovering Implicit Assumptions: A Large-Scale Study on Students' Mental Models of Diffusion

    ERIC Educational Resources Information Center

    Stains, Marilyne; Sevian, Hannah

    2015-01-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in…

  7. Emotional Competencies in Geriatric Nursing: Empirical Evidence from a Computer Based Large Scale Assessment Calibration Study

    ERIC Educational Resources Information Center

    Kaspar, Roman; Hartig, Johannes

    2016-01-01

    The care of older people was described as involving substantial emotion-related affordances. Scholars in vocational training and nursing disagree whether emotion-related skills could be conceptualized and assessed as a professional competence. Studies on emotion work and empathy regularly neglect the multidimensionality of these phenomena and…

  8. Designing Large-Scale Multisite and Cluster-Randomized Studies of Professional Development

    ERIC Educational Resources Information Center

    Kelcey, Ben; Spybrook, Jessaca; Phelps, Geoffrey; Jones, Nathan; Zhang, Jiaqi

    2017-01-01

    We develop a theoretical and empirical basis for the design of teacher professional development studies. We build on previous work by (a) developing estimates of intraclass correlation coefficients for teacher outcomes using two- and three-level data structures, (b) developing estimates of the variance explained by covariates, and (c) modifying…

  9. Comparing Achievement between K-8 and Middle Schools: A Large-Scale Empirical Study

    ERIC Educational Resources Information Center

    Byrnes, Vaughan; Ruby, Allen

    2007-01-01

    This study compares middle schools to K-8 schools, as well as to newly formed K-8 schools that are part of a K-8 conversion policy. The outcome is student achievement, and our sample includes 40,883 eighth-grade students from 95 schools across five cohorts. The analysis uses multilevel modeling to account for student, cohort, and school-level…

  10. The first large scale molecular study of Cryptosporidium and Giardia in horses

    USDA-ARS?s Scientific Manuscript database

    The prevalence of species and genotypes of Giardia and Cryptosporidium in horses is poorly known. The present study examined feces from 195 horses, 1 month to 17 years of age, in 4 locations in Colombia. Prevalence and age distribution of Giardia and Cryptosporidium were determined by PCR. All PCR p...

  11. Uncovering Implicit Assumptions: A Large-Scale Study on Students' Mental Models of Diffusion

    ERIC Educational Resources Information Center

    Stains, Marilyne; Sevian, Hannah

    2015-01-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in…

  12. Emotional Competencies in Geriatric Nursing: Empirical Evidence from a Computer Based Large Scale Assessment Calibration Study

    ERIC Educational Resources Information Center

    Kaspar, Roman; Hartig, Johannes

    2016-01-01

    The care of older people was described as involving substantial emotion-related affordances. Scholars in vocational training and nursing disagree whether emotion-related skills could be conceptualized and assessed as a professional competence. Studies on emotion work and empathy regularly neglect the multidimensionality of these phenomena and…

  13. Aquifer thermal energy storage - a feasibility study for large scale demonstration

    SciTech Connect

    Skinner, W.V.; Supkow, D.J.

    1981-01-01

    An aquifer thermal energy storage (ATES) feasibility study was conducted to evaluate the feasibility of using a portion of the Magothy Aquifer underlying the Stony Brook University Campus on Long Island, New York, for storing water that is chilled during the winter and then recovering this water during the following summer months for air conditioning purposes.

  14. A large scale molecular study of Giardia duodenalis in horses in Colombia

    USDA-ARS?s Scientific Manuscript database

    The prevalence of Giardia duodenalis genotypes in horses is poorly known. The present study examined feces from 195 horses, 1 month to 17 years of age, in 4 locations in Colombia. Prevalence of infection was determined by PCR and all positives were sequenced to determine the genotypes. Thirty four (...

  15. Segmentation of Object Outlines into Parts: A Large-Scale Integrative Study

    ERIC Educational Resources Information Center

    De Winter, Joeri; Wagemans, Johan

    2006-01-01

    In this study, a large number of observers (N=201) were asked to segment a collection of outlines derived from line drawings of everyday objects (N=88). This data set was then used as a benchmark to evaluate current models of object segmentation. All of the previously proposed rules of segmentation were found supported in our results. For example,…

  16. Chronic Physical Illness and Mental Health in Children. Results from a Large-Scale Population Study

    ERIC Educational Resources Information Center

    Hysing, Mari; Elgen, Irene; Gillberg, Christopher; Lie, Stein Atle; Lundervold, Astri J.

    2007-01-01

    Background: The aim of the present study was to evaluate the sensitivity and specificity of the Strengths and Difficulties Questionnaire (SDQ) in detecting emotional and behavioural problems among children with chronic illness (CI). Methods: Parents and teachers of a population of primary school children in Norway (n = 9430) completed a…

  17. Comparing Achievement between K-8 and Middle Schools: A Large-Scale Empirical Study

    ERIC Educational Resources Information Center

    Byrnes, Vaughan; Ruby, Allen

    2007-01-01

    This study compares middle schools to K-8 schools, as well as to newly formed K-8 schools that are part of a K-8 conversion policy. The outcome is student achievement, and our sample includes 40,883 eighth-grade students from 95 schools across five cohorts. The analysis uses multilevel modeling to account for student, cohort, and school-level…

  18. Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci

    USDA-ARS?s Scientific Manuscript database

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholest...

  19. Methods used for successful follow-up in a large scale national cohort study in Thailand

    PubMed Central

    2011-01-01

    Background Ensuring successful follow-up is essential when conducting a prospective cohort study. Most existing literature reviewing methods to ensure a high response rate is based on experience in developed nations. Findings We report our 4-year follow-up success for a national cohort study examining the health transition underway in Thailand. We began the cohort study in 2005 with a baseline postal questionnaire sent to all 200,000 Thais enrolled as distance learning students at Sukhothai Thammathirat Open University and residing all over Thailand; 87,134 or 44% of the students responded. Subsequently we used University and national media to inform cohort members of study progress. Also, we prepared a health book with study results and health advice which was distributed to all cohort members. After 4 years we repeated the survey and achieved a 71% response rate. In this paper we report the methods used to achieve this response The initial follow-up mail-out generated a response rate of about 48% reflecting the extensive preparatory work between baseline and follow-up. After 4 rounds of telephone contact (more than 100,000 phone calls) and 4 related mail-out rounds progressively over 16 months an overall response rate was achieved of just over 71% (n = 60,774). The total cost was US$4.06/respondent - 19% for printing, 21% for postage, 14% for tape measures (included in mail-out), 18% for data processing 22% for prizes and 6% for telephone. Conclusions Many of the methods reported as effective for mail questionnaire and cohort response rates held true for Thailand. These included being associated with a university, incentivating cooperation, follow-up contact, providing a second copy of questionnaire where necessary, and assurance of confidentiality. Telephone contact with the cohort and the small prizes given to responders were particularly important in the Thai context as was Thai leadership of the research team. PMID:21615963

  20. Large-scale feature selection from imaging spectrometer data using a genetic algorithm for invasive species mapping and monitoring

    NASA Astrophysics Data System (ADS)

    Huth, John F.

    Invasive species pose the single greatest threat of natural disaster in this century. With rare exceptions, the estimated annual cost of invasive species to the U.S. exceeds all other natural disasters combined. Invasive plant species can rapidly displace native vegetation and upset the balance in an ecosystem. Accurate and rapid identification and monitoring of effected areas are critical to maintaining control in environments where invasive species have or could develop. The goal of this research is to develop a method for selecting the near-optimal spectral band subset from hyperspectral imagery (HSI) data to improve classification accuracy and feature transparency. The research presented in this dissertation is focused on the implementation and testing of a genetic algorithm (GA) to reduce the number of spectral bands that are needed to produce an accurate and rapid classification map using HSI data. This algorithm was applied to the invasive species mapping and monitoring problem and can be used for similar "needle in a haystack" problems. This research has also provided a sensitivity analysis for a number of the parameters used by a GA including: the chromosome population size; the number of generations required achieve an optimal feature set; the crossover and mutation rates; and the size of the feature subset. This research should provide a base for additional research into the application GA's for feature selection and extraction in high dimensional remote sensing data. Statistics of the time it takes to run the algorithm have also been captured in order to give users a sense of how this algorithm compares to the runtime for other feature extraction methods such as the Minimum Noise Fraction (MNF) algorithm. The contribution of this research is a demonstrated method to provide a high accuracy feature selection technique to identify invasive species that provides direct feature traceability to class spectra, through the development of a genetic algorithm

  1. Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

    SciTech Connect

    Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

    2016-07-26

    It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, used for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.

  2. Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

    DOE PAGES

    Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

    2016-07-26

    It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, usedmore » for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.« less

  3. Large-scale optimization-based non-negative computational framework for diffusion equations: Parallel implementation and performance studies

    SciTech Connect

    Chang, Justin; Karra, Satish; Nakshatrala, Kalyana B.

    2016-07-26

    It is well-known that the standard Galerkin formulation, which is often the formulation of choice under the finite element method for solving self-adjoint diffusion equations, does not meet maximum principles and the non-negative constraint for anisotropic diffusion equations. Recently, optimization-based methodologies that satisfy maximum principles and the non-negative constraint for steady-state and transient diffusion-type equations have been proposed. To date, these methodologies have been tested only on small-scale academic problems. The purpose of this paper is to systematically study the performance of the non-negative methodology in the context of high performance computing (HPC). PETSc and TAO libraries are, respectively, used for the parallel environment and optimization solvers. For large-scale problems, it is important for computational scientists to understand the computational performance of current algorithms available in these scientific libraries. The numerical experiments are conducted on the state-of-the-art HPC systems, and a single-core performance model is used to better characterize the efficiency of the solvers. Furthermore, our studies indicate that the proposed non-negative computational framework for diffusion-type equations exhibits excellent strong scaling for real-world large-scale problems.

  4. Development of Residential Prototype Building Models and Analysis System for Large-Scale Energy Efficiency Studies Using EnergyPlus

    SciTech Connect

    Mendon, Vrushali V.; Taylor, Zachary T.

    2014-09-10

    ABSTRACT: Recent advances in residential building energy efficiency and codes have resulted in increased interest in detailed residential building energy models using the latest energy simulation software. One of the challenges of developing residential building models to characterize new residential building stock is to allow for flexibility to address variability in house features like geometry, configuration, HVAC systems etc. Researchers solved this problem in a novel way by creating a simulation structure capable of creating fully-functional EnergyPlus batch runs using a completely scalable residential EnergyPlus template system. This system was used to create a set of thirty-two residential prototype building models covering single- and multifamily buildings, four common foundation types and four common heating system types found in the United States (US). A weighting scheme with detailed state-wise and national weighting factors was designed to supplement the residential prototype models. The complete set is designed to represent a majority of new residential construction stock. The entire structure consists of a system of utility programs developed around the core EnergyPlus simulation engine to automate the creation and management of large-scale simulation studies with minimal human effort. The simulation structure and the residential prototype building models have been used for numerous large-scale studies, one of which is briefly discussed in this paper.

  5. Stormbow: A Cloud-Based Tool for Reads Mapping and Expression Quantification in Large-Scale RNA-Seq Studies

    PubMed Central

    Zhao, Shanrong; Prenger, Kurt; Smith, Lance

    2013-01-01

    RNA-Seq is becoming a promising replacement to microarrays in transcriptome profiling and differential gene expression study. Technical improvements have decreased sequencing costs and, as a result, the size and number of RNA-Seq datasets have increased rapidly. However, the increasing volume of data from large-scale RNA-Seq studies poses a practical challenge for data analysis in a local environment. To meet this challenge, we developed Stormbow, a cloud-based software package, to process large volumes of RNA-Seq data in parallel. The performance of Stormbow has been tested by practically applying it to analyse 178 RNA-Seq samples in the cloud. In our test, it took 6 to 8 hours to process an RNA-Seq sample with 100 million reads, and the average cost was $3.50 per sample. Utilizing Amazon Web Services as the infrastructure for Stormbow allows us to easily scale up to handle large datasets with on-demand computational resources. Stormbow is a scalable, cost effective, and open-source based tool for large-scale RNA-Seq data analysis. Stormbow can be freely downloaded and can be used out of box to process Illumina RNA-Seq datasets. PMID:25937948

  6. A 6-month large-scale study into the safety of tamsulosin

    PubMed Central

    Michel, M C; Bressel, H-U; Goepel, M; Rübben, H

    2001-01-01

    Aims Tamsulosin is an α1-adrenoceptor antagonist for the treatment of symptomatic benign prostatic hyperplasia with a tolerability similar to that of placebo in short-term, placebo-controlled studies with limited patient numbers. The present study was designed to test the safety of tamsulosin treatment in a large cohort of men during a prolonged period of time, particularly with regard to comedications. Methods A multicentre, open-label phase IIIb study with 1784 patients receiving 0.4 mg o.d. tamsulosin for 6 months was performed according to good clinical practice guidelines. The analysis was performed on an intention-to-treat basis and powered to detect adverse events (AE) occurring in 0.15% of patients with 95% confidence. Results During a total drug exposure time of 811 patient years, 386 AE were recorded in 253 patients (14.2%; 95% confidence intervals [CI] 12.0–15.2%). Twenty-nine patients suffered 44 serious AE including five fatal events (CI 0.12–0.73%) due to myocardial infarction (n = 3) and to pneumonia and a car accident (one each), but all deaths were judged to be unlikely to be related to study medication. The frequency of AE in patients without any comedication (n = 1095) was 13.0% (CI 11.3–14.9%). In a logistic regression analysis β-adrenoceptor blockers, converting enzyme inhibitors, antidiabetics and diuretics did not significantly affect the odds ratio for having AE. However, concomitant α-adrenoceptor antagonists (a protocol violation) and treatment with verapamil (which also has α-adrenoceptor antagonist activity) significantly enhanced the odds ratio for having AE to 3.87 (CI 1.52–9.85) and 3.17 (CI 1.52–6.58), respectively. Minor increases in the odds ratio, which did not reach statistical significance, were also observed for Ca2+ antagonists other than verapamil and for nitrates. Conclusions We conclude that tamsulosin has a good safety profile relative to AE rates in the placebo arms of previous studies on tamsulosin even in

  7. Aquifer thermal energy storage - A feasibility study for large scale demonstration

    NASA Astrophysics Data System (ADS)

    Skinner, W. V.; Supkow, D. J.

    Engineering procedures necessary for aquifer thermal energy storage (ATES), based on studies of the Magothy Aquifer on Long Island, NY, are presented, with chilled winter water pumped into the aquifer and reclaimed in summer months for air conditioning. The choice of aquifer involves necessary volume, flow rate, efficiency of thermal recovery, and avoidance of conflict with other users; utilization depends on choice of appropriate piping, heat exchangers, and well construction to prevent degradation of the aquifer. The methods employed to probe the Magothy for suitability are described, including drilling an asymmetric well cluster for observation, and 48 hr pumping and 8 hr recovery. Transmissivity was found to vary from 8,000 to 29,000 sq ft/day. A doublet well was then drilled and water withdrawn, chilled, and returned. Later withdrawal indicated a 46% thermal recovery, with computer models projecting 80% with additional cycling. The study verified the feasibility of ATES, which can be expanded with additional demand.

  8. A large scale finite element study of a cementless osseointegrated tibial tray.

    PubMed

    Galloway, Francis; Kahnt, Max; Ramm, Heiko; Worsley, Peter; Zachow, Stefan; Nair, Prasanth; Taylor, Mark

    2013-07-26

    The aim of this study was to investigate the performance of a cementless osseointegrated tibial tray (P.F.C. ® Sigma®, Depuy® Inc, USA) in a general population using finite element (FE) analysis. Computational testing of total knee replacements (TKRs) typically only use a model of a single patient and assume the results can be extrapolated to the general population. In this study, two statistical models (SMs) were used; one of the shape and elastic modulus of the tibia, and one of the tibiofemoral joint loads over a gait cycle, to generate a population of FE models. A method was developed to automatically size, position and implant the tibial tray in each tibia, and 328 models were successfully implanted and analysed. The peak strain in the bone of the resected surface was examined and the percentage surface area of bone above yield strain (PSAY) was used to determine the risk of failure of a model. Using an arbitrary threshold of 10% PSAY, the models were divided into two groups ('higher risk' and 'lower risk') in order to explore factors that may influence potential failure. In this study, 17% of models were in the 'higher risk' group and it was found that these models had a lower elastic modulus (mean 275.7MPa), a higher weight (mean 85.3kg), and larger peak loads, of which the axial force was the most significant. This study showed the mean peak strain of the resected surface and PSAY were not significantly different between implant sizes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Study of an engine flow diverter system for a large scale ejector powered aircraft model

    NASA Technical Reports Server (NTRS)

    Springer, R. J.; Langley, B.; Plant, T.; Hunter, L.; Brock, O.

    1981-01-01

    Requirements were established for a conceptual design study to analyze and design an engine flow diverter system and to include accommodations for an ejector system in an existing 3/4 scale fighter model equipped with YJ-79 engines. Model constraints were identified and cost-effective limited modification was proposed to accept the ejectors, ducting and flow diverter valves. Complete system performance was calculated and a versatile computer program capable of analyzing any ejector system was developed.

  10. Association between weight gain, obesity, and sleep duration: a large-scale 3-year cohort study.

    PubMed

    Kobayashi, Daiki; Takahashi, Osamu; Deshpande, Gautam A; Shimbo, Takuro; Fukui, Tsuguya

    2012-09-01

    Previous research suggests that sleep duration is associated with obesity and weight gain. However, the majority of these studies are of cross-sectional design, with only a few cohort studies. In order to validate previous findings in a more real-world context, we evaluated the association between sleep duration, obesity, and weight gain in a large, 3-year cohort study. A retrospective cohort study was conducted involving 21,469 apparently healthy individuals aged 20 years or older who underwent annual health check-ups at the Center for Preventive Medicine, St. Luke's International Hospital, between 2005 and 2008. The participants were divided into four groups according to their self-reported average nightly sleep duration (≤5, 6, 7, and ≥8 h). We identified individuals with obesity (body mass index ≥25 kg/m(2)) and weight gain. Multivariate linear regression analysis and logistic regression analysis were used to explore the association between these variables and sleep duration, adjusting for age, gender, alcohol consumption, current smoking, past medical history, and level of physical activity. Compared with those who slept 7 h, the individuals who slept ≤5 h night were more likely to experience weight gain (β coefficient = 0.03; 95% CI = 0.03-1.1) and to become obese (OR = 1.5; 95% CI = 1.1-2.0). No significant difference was seen between subjects who slept more than 8 h and those sleeping 7 h (OR = 1.3; 95% CI = 0.9-1.8). Short sleep (≤5 h) is significantly associated with weight gain and obesity in both male and female adults.

  11. Inter- and intra-individual variability in human skin barrier function: a large scale retrospective study.

    PubMed

    Meidan, Victor M; Roper, Clive S

    2008-06-01

    In vitro transepidermal tritiated water flux measurements are frequently used to evaluate skin barrier integrity for quality control purposes. However, research in this area to date has been largely based upon small-scale studies, each involving relatively few skin permeation measurements. In order to enhance our understanding in this area, we have conducted a much larger scale retrospective statistical analysis of tritiated water kp values. These values reflected the permeability of 2400 skin samples that were derived from 112 female volunteers over a 4 year period. It was found that the population of tritiated water kp values constituted a positively skewed, non-Normal distribution. Mean kp was 2.04 x 10(-3)cm/h while the 95th percentile was 4.50 x 10(-3)cm/h. Both values are higher than those reported in previous smaller studies. Hence, our study indicates that previously suggested upper limits for tritiated water flux are too low and that they be revised upwards to a value of 4.5 x 10(-3)cm/h. Analysis was also performed on smaller data subsets allowing inter-individual and intra-individual comparisons. For intra-individual kp variability, site-related differences yielded a non-Normal, positively skewed pattern in most individuals. Inter-individual variability was Normally-distributed and showed scatter that was much smaller in magnitude.

  12. Placental pathology measures: Can they be rapidly and reliably integrated into large-scale perinatal studies?

    PubMed

    Catov, J M; Peng, Y; Scifres, C M; Parks, W T

    2015-06-01

    Normal placental function is critical to optimize fetal growth and development, but few perinatal studies incorporate placental measures. Our objectives were to link clinical placental pathology records to birth records, and validate an automated abstraction strategy. Of the 47,329 deliveries at our hospital from 2008 to 2012, we retrieved electronic copies of pathology reports (n = 21,585, 45.4%). Pathology data were extracted with Extensible Markup Language (XML) script using Java and structured query language (SQL) transformed the text information into variables that were linked to delivery data. A subgroup of records was selected for a validation study that compared automated to manual abstraction (n = 144). Linked birth-placental records included 93% of all preterm (<37 weeks, n = 5108) and 37.1% of term births (n = 14,019). Over 90% of deliveries complicated by preeclampsia, chronic hypertension, or gestational diabetes included pathology data. The validation study indicated excellent agreement, sensitivity and specificity between the two abstraction strategies. We demonstrate a reliable approach to electronically integrate placental pathology and delivery data. These linked data provide a platform to identify risk factors and sequelae associated with placental lesions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Liver enzymes and metabolic syndrome: a large-scale case-control study.

    PubMed

    Zhang, Lu; Ma, Xiangyu; Jiang, Zhi; Zhang, Kejun; Zhang, Mengxuan; Li, Yafei; Zhao, Xiaolan; Xiong, Hongyan

    2015-09-29

    Previous studies suggested that elevated liver enzymes could be used as potential novel biomarkers of Metabolic syndrome (MetS) and its clinical outcomes, although the results were inconsistent and the conclusions were underpowered. A case-control study with 6,268 MetS subjects and 6,330 frequency-matched healthy controls was conducted to systematically evaluated levels of four liver enzymes (ALT, AST, GGT and ALP), both in overall populations and in subjects with normal liver enzymes, with MetS risk using both quartiles and continuous unit of liver enzymes. We found significant associations were detected for all above analyses. Compared with quartile 1 (Q1), other quartiles have significant higher MetS risk, with ORs ranging from 1.15 to 18.15. The highest effected was detected for GGT, for which the OR value for the highest versus lowest quartile was 18.15 (95% CI: 15.7-20.9). Mutual adjustment proved the independence of the relations for all four liver enzymes. Sensitivity analyses didn't materially changed the trend. To the best of our knowledge, this study should be the largest, which aimed at evaluating the association between liver enzymes measures and MetS risk. The results can better support that liver enzyme levels could be used as clinical predictors of MetS.

  14. Weather and headache onset: a large-scale study of headache medicine purchases

    NASA Astrophysics Data System (ADS)

    Ozeki, Kayoko; Noda, Tatsuya; Nakamura, Mieko; Ojima, Toshiyuki

    2015-04-01

    It is widely recognized that weather changes can trigger headache onset. Most people who develop headaches choose to self-medicate rather than visit a hospital or clinic. We investigated the association between weather and headache onset using large-sample sales of the headache medicine, loxoprofen. We collected daily sales figures of loxoprofen and over-the-counter drugs over a 1-year period from a drugstore chain in western Shizuoka prefecture, Japan. To adjust for changes in daily sales of loxoprofen due to social environmental factors, we calculated a proportion of loxoprofen daily sales to over-the-counter drug daily sales. At the same time, we obtained weather data for the study region from the website of the Japan Meteorological Agency. We performed linear regression analysis to ascertain the association between weather conditions and the loxoprofen daily sales proportion. We also conducted a separate questionnaire survey at the same drugstores to determine the reason why people purchased loxoprofen. Over the study period, we surveyed the sale of hundreds of thousands of loxoprofen tablets. Most people purchased loxoprofen because they had a headache. We found that the sales proportion of loxoprofen increased when average barometric pressure decreased, and that precipitation, average humidity, and minimum humidity increased on loxoprofen purchase days compared to the previous day of purchases. This study, performed using a large dataset that was easy-to-collect and representative of the general population, revealed that sales of loxoprofen, which can represent the onset and aggravation of headache, significantly increased with worsening weather conditions.

  15. Weather and headache onset: a large-scale study of headache medicine purchases.

    PubMed

    Ozeki, Kayoko; Noda, Tatsuya; Nakamura, Mieko; Ojima, Toshiyuki

    2015-04-01

    It is widely recognized that weather changes can trigger headache onset. Most people who develop headaches choose to self-medicate rather than visit a hospital or clinic. We investigated the association between weather and headache onset using large-sample sales of the headache medicine, loxoprofen. We collected daily sales figures of loxoprofen and over-the-counter drugs over a 1-year period from a drugstore chain in western Shizuoka prefecture, Japan. To adjust for changes in daily sales of loxoprofen due to social environmental factors, we calculated a proportion of loxoprofen daily sales to over-the-counter drug daily sales. At the same time, we obtained weather data for the study region from the website of the Japan Meteorological Agency. We performed linear regression analysis to ascertain the association between weather conditions and the loxoprofen daily sales proportion. We also conducted a separate questionnaire survey at the same drugstores to determine the reason why people purchased loxoprofen. Over the study period, we surveyed the sale of hundreds of thousands of loxoprofen tablets. Most people purchased loxoprofen because they had a headache. We found that the sales proportion of loxoprofen increased when average barometric pressure decreased, and that precipitation, average humidity, and minimum humidity increased on loxoprofen purchase days compared to the previous day of purchases. This study, performed using a large dataset that was easy-to-collect and representative of the general population, revealed that sales of loxoprofen, which can represent the onset and aggravation of headache, significantly increased with worsening weather conditions.

  16. Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies.

    PubMed

    West, Janne; Dahlqvist Leinhard, Olof; Romu, Thobias; Collins, Rory; Garratt, Steve; Bell, Jimmy D; Borga, Magnus; Thomas, Louise

    Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource.

  17. How brain asymmetry relates to performance - a large-scale dichotic listening study.

    PubMed

    Hirnstein, Marco; Hugdahl, Kenneth; Hausmann, Markus

    2014-01-01

    All major mental functions including language, spatial and emotional processing are lateralized but how strongly and to which hemisphere is subject to inter- and intraindividual variation. Relatively little, however, is known about how the degree and direction of lateralization affect how well the functions are carried out, i.e., how lateralization and task performance are related. The present study therefore examined the relationship between lateralization and performance in a dichotic listening task for which we had data available from 1839 participants. In this task, consonant-vowel syllables are presented simultaneously to the left and right ear, such that each ear receives a different syllable. When asked which of the two they heard best, participants typically report more syllables from the right ear, which is a marker of left-hemispheric speech dominance. We calculated the degree of lateralization (based on the difference between correct left and right ear reports) and correlated it with overall response accuracy (left plus right ear reports). In addition, we used reference models to control for statistical interdependency between left and right ear reports. The results revealed a u-shaped relationship between degree of lateralization and overall accuracy: the stronger the left or right ear advantage, the better the overall accuracy. This u-shaped asymmetry-performance relationship consistently emerged in males, females, right-/non-right-handers, and different age groups. Taken together, the present study demonstrates that performance on lateralized language functions depends on how strongly these functions are lateralized. The present study further stresses the importance of controlling for statistical interdependency when examining asymmetry-performance relationships in general.

  18. New Insights about Enzyme Evolution from Large Scale Studies of Sequence and Structure Relationships*

    PubMed Central

    Brown, Shoshana D.; Babbitt, Patricia C.

    2014-01-01

    Understanding how enzymes have evolved offers clues about their structure-function relationships and mechanisms. Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites. Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily. The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes. PMID:25210038

  19. New insights about enzyme evolution from large scale studies of sequence and structure relationships.

    PubMed

    Brown, Shoshana D; Babbitt, Patricia C

    2014-10-31

    Understanding how enzymes have evolved offers clues about their structure-function relationships and mechanisms. Here, we describe evolution of functionally diverse enzyme superfamilies, each representing a large set of sequences that evolved from a common ancestor and that retain conserved features of their structures and active sites. Using several examples, we describe the different structural strategies nature has used to evolve new reaction and substrate specificities in each unique superfamily. The results provide insight about enzyme evolution that is not easily obtained from studies of one or only a few enzymes.

  20. Large scale prop-fan structural design study. Volume 1: Initial concepts

    NASA Technical Reports Server (NTRS)

    Billman, L. C.; Gruska, C. J.; Ladden, R. M.; Leishman, D. K.; Turnberg, J. E.

    1988-01-01

    In recent years, considerable attention has been directed toward improving aircraft fuel consumption. Studies have shown that the inherent efficiency advantage that turboprop propulsion systems have demonstrated at lower cruise speeds may now be extended to the higher speeds of today's turbofan and turbojet-powered aircraft. To achieve this goal, new propeller designs will require features such as thin, high speed airfoils and aerodynamic sweep, features currently found only in wing designs for high speed aircraft. This is Volume 1 of a 2 volume study to establish structural concepts for such advanced propeller blades, to define their structural properties, to identify any new design, analysis, or fabrication techniques which were required, and to determine the structural tradeoffs involved with several blade shapes selected primarily on the basis of aero/acoustic design considerations. The feasibility of fabricating and testing dynamically scaled models of these blades for aeroelastic testing was also established. The preliminary design of a blade suitable for flight use in a testbed advanced turboprop was conducted and is described in Volume 2.

  1. Large scale prop-fan structural design study. Volume 2: Preliminary design of SR-7

    NASA Technical Reports Server (NTRS)

    Billman, L. C.; Gruska, C. J.; Ladden, R. M.; Leishman, D. K.; Turnberg, J. E.

    1988-01-01

    In recent years, considerable attention has been directed toward improving aircraft fuel consumption. Studies have shown that the inherent efficiency advantage that turboprop propulsion systems have demonstrated at lower cruise speeds may now be extended to the higher speeds of today's turbofan and turbojet-powered aircraft. To achieve this goal, new propeller designs will require features such as thin, high speed airfoils and aerodynamic sweep, features currently found only in wing designs for high speed aircraft. This is Volume 2 of a 2 volume study to establish structural concepts for such advanced propeller blades, to define their structural properties, to identify any new design, analysis, or fabrication techniques which were required, and to determine the structural tradeoffs involved with several blade shapes selected primarily on the basis of aero/acoustic design considerations. The feasibility of fabricating and testing dynamically scaled models of these blades for aeroelastic testing was also established. The preliminary design of a blade suitable for flight use in a testbed advanced turboprop was conducted and is described.

  2. Uncovering Implicit Assumptions: a Large-Scale Study on Students' Mental Models of Diffusion

    NASA Astrophysics Data System (ADS)

    Stains, Marilyne; Sevian, Hannah

    2015-12-01

    Students' mental models of diffusion in a gas phase solution were studied through the use of the Structure and Motion of Matter (SAMM) survey. This survey permits identification of categories of ways students think about the structure of the gaseous solute and solvent, the origin of motion of gas particles, and trajectories of solute particles in the gaseous medium. A large sample of data ( N = 423) from students across grade 8 (age 13) through upper-level undergraduate was subjected to a cluster analysis to determine the main mental models present. The cluster analysis resulted in a reduced data set ( N = 308), and then, mental models were ascertained from robust clusters. The mental models that emerged from analysis were triangulated through interview data and characterised according to underlying implicit assumptions that guide and constrain thinking about diffusion of a solute in a gaseous medium. Impacts of students' level of preparation in science and relationships of mental models to science disciplines studied by students were examined. Implications are discussed for the value of this approach to identify typical mental models and the sets of implicit assumptions that constrain them.

  3. User Friendly Open GIS Tool for Large Scale Data Assimilation - a Case Study of Hydrological Modelling

    NASA Astrophysics Data System (ADS)

    Gupta, P. K.

    2012-08-01

    Open source software (OSS) coding has tremendous advantages over proprietary software. These are primarily fuelled by high level programming languages (JAVA, C++, Python etc...) and open source geospatial libraries (GDAL/OGR, GEOS, GeoTools etc.). Quantum GIS (QGIS) is a popular open source GIS package, which is licensed under GNU GPL and is written in C++. It allows users to perform specialised tasks by creating plugins in C++ and Python. This research article emphasises on exploiting this capability of QGIS to build and implement plugins across multiple platforms using the easy to learn - Python programming language. In the present study, a tool has been developed to assimilate large spatio-temporal datasets such as national level gridded rainfall, temperature, topographic (digital elevation model, slope, aspect), landuse/landcover and multi-layer soil data for input into hydrological models. At present this tool has been developed for Indian sub-continent. An attempt is also made to use popular scientific and numerical libraries to create custom applications for digital inclusion. In the hydrological modelling calibration and validation are important steps which are repetitively carried out for the same study region. As such the developed tool will be user friendly and used efficiently for these repetitive processes by reducing the time required for data management and handling. Moreover, it was found that the developed tool can easily assimilate large dataset in an organised manner.

  4. Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study

    PubMed Central

    Jackson, Dan; Hammerla, Nils; Granat, Malcolm H.; van Hees, Vincent T.; Trenell, Michael I.; Owen, Christoper G.; Preece, Stephen J.; Peakman, Tim; Brage, Soren

    2017-01-01

    Background Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. Methods Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. Results 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5–7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen’s d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. Conclusions It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as

  5. Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study.

    PubMed

    Doherty, Aiden; Jackson, Dan; Hammerla, Nils; Plötz, Thomas; Olivier, Patrick; Granat, Malcolm H; White, Tom; van Hees, Vincent T; Trenell, Michael I; Owen, Christoper G; Preece, Stephen J; Gillions, Rob; Sheard, Simon; Peakman, Tim; Brage, Soren; Wareham, Nicholas J

    2017-01-01

    Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5-7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen's d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as exposures, confounding factors or outcome

  6. Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies

    PubMed Central

    West, Janne; Dahlqvist Leinhard, Olof; Romu, Thobias; Collins, Rory; Garratt, Steve; Bell, Jimmy D.; Borga, Magnus; Thomas, Louise

    2016-01-01

    Introduction Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. Materials and Methods 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. Results Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. Discussion and Conclusions In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource. PMID:27662190

  7. Hydrolysis and large scale ultrafiltration study of alfalfa protein concentrate enzymatic hydrolysate.

    PubMed

    D'Alvise; Lesueur-Lambert; Fertin; Dhulster; Guillochon

    2000-08-01

    Batch enzymatic hydrolysis of insoluble Alfalfa Protein Concentrate by Delvolase was carried out at laboratory and at pilot-plant scale coupled to an ultrafiltration reactor with a mineral tubular membrane. Parametric studies were carried out on the batch system to determine the biochemical and hydrodynamical optimum conditions. The hydrolysis conditions selected were 40 degrees C, pH 9.5, initial substrate level 3 g protein/100 g and the enzyme substrate ratio 152 U/g protein. After 5 h of hydrolysis, 96% of the total amount of initial nitrogen was solubilized. The ultrafiltration conditions selected were a 10 000 Nominal Molecular Weight Cut-Off, a transmembrane pressure of 1.5 bar, a flux velocity of 0.8 m/s. Fifty percent of the initial nitrogen appeared in the permeate.

  8. Efficient and large scale synthesis of graphene from coal and its film electrical properties studies.

    PubMed

    Wu, Yingpeng; Ma, Yanfeng; Wang, Yan; Huang, Lu; Li, Na; Zhang, Tengfei; Zhang, Yi; Wan, Xiangjian; Huang, Yi; Chen, Yongsheng

    2013-02-01

    Coal, which is abundant and has an incompact structure, is a good candidate to replace graphite as the raw material for the production of graphene. Here, a new solution phase technique for the preparation of graphene from coal has been developed. The precursor: graphene oxide got from coal was examined by atomic force microscopy, dynamic light scattering and X-ray diffraction, the results showed the GO was a small and single layer sheet. The graphene was examined by X-ray photoelectron spectroscopy, and Raman spectroscopy. Furthermore, graphene films have been prepared using direct solution process and the electrical conductivity and Hall effect have been studied. The results showed the conductivity of the films could reach as high as 2.5 x 10(5) Sm(-1) and exhibited an n-type behavior.

  9. Environmental determinants of outdoor play in children: a large-scale cross-sectional study.

    PubMed

    Aarts, Marie-Jeanne; Wendel-Vos, Wanda; van Oers, Hans A M; van de Goor, Ien A M; Schuit, Albertine J

    2010-09-01

    Outdoor play is a cheap and natural way for children to be physically active. This study aims to identify physical as well as social correlates of outdoor play in the home and neighborhood environment among children of different age groups. Cross-sectional data were derived from 6470 parents of children from 42 primary schools in four Dutch cities by means of questionnaires (2007-2008). Multivariate sequential Poisson GEE analyses were conducted (2010) to quantify the correlation between physical and social home and neighborhood characteristics and outdoor play among boys and girls aged 4-6 years, 7-9 years, and 10-12 years. This study showed that next to proximal (home) environmental characteristics such as parental education (RR=0.93-0.97); the importance parents pay to outdoor play (RR=1.32-1.75); and the presence of electronic devices in the child's own room (RR=1.04-1.15), several neighborhood characteristics were significantly associated with children's outdoor play. Neighborhood social cohesion was related to outdoor play in five of six subgroups (RR=1.01-1.02), whereas physical neighborhood characteristics (e.g., green neighborhood type, presence of water, diversity of routes) were associated with outdoor play in specific subgroups only. Neighborhood social cohesion was related to outdoor play among children of different age and gender, which makes it a promising point of action for policy development. Policies aimed at improving physical neighborhood characteristics in relation to outdoor play should take into account age and gender of the target population. 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Sodium-chloride Difference and Metabolic Syndrome: A Population-based Large-scale Cohort Study.

    PubMed

    Kimura, Toshihiro; Hashimoto, Yoshitaka; Tanaka, Muhei; Asano, Mai; Yamazaki, Masahiro; Oda, Yohei; Toda, Hitoshi; Marunaka, Yoshinori; Nakamura, Naoto; Fukui, Michiaki

    Objective Metabolic syndrome (MetS) is associated with cardiovascular disease, which is the leading cause of mortality and morbidity. Hypernatremia and hypochloremia are also associated with an increased mortality. Thus, the aim of this study was to evaluate the association between the sodium-chloride difference (Na(+)-Cl(-)) and MetS. Methods In this cross-sectional and retrospective cohort study, we enrolled 3,875 subjects and evaluated the relationship between Na(+)-Cl(-) and MetS using logistic regression analyses. MetS was diagnosed according to the joint interim statement when a subject had three or more of the following criteria: hypertension; hyperglycemia; hypertriglyceridemia; low high-density lipoprotein (HDL) cholesterol; and abdominal obesity. Results There were 3,354 subjects without MetS and 521 subjects with MetS at baseline. The highest Na(+)-Cl(-) quartile (≥43 mmol/L) was associated with an increased risk of the presence of MetS compared to the lowest Na(+)-Cl(-) quartile (≤38 mmol/L) after adjusting for covariates, including age, sex, the body mass index, systolic blood pressure, fasting plasma glucose, triglycerides, HDL cholesterol, creatinine, uric acid and lifestyle factors [multivariate odds ratio (OR) 1.81, 95% confidence interval (CI) 1.17-2.84, p=0.0078]. After an 8-year follow-up, 658 out of 3,352 subjects were newly diagnosed with MetS. The highest Na(+)-Cl(-) quartile (≥43 mmol/L) was associated with an increased risk of the development of MetS compared to the lowest Na(+)-Cl(-) quartiles (≤38 mmol/L) after adjusting for covariates (multivariate OR 1.76, 95% CI 1.27-2.45, p=0.0007). Conclusion The sodium and chloride difference is associated with MetS.

  11. Studies supporting the use of mechanical mixing in large scale beer fermentations.

    PubMed

    Nienow, Alvin W; McLeod, Georgina; Hewitt, Christopher J

    2010-05-01

    Brewing fermentations have traditionally been undertaken without the use of mechanical agitation, with mixing being provided only by the fluid motion induced by the CO(2) evolved during the batch process. This approach has largely been maintained because of the belief in industry that rotating agitators would damage the yeast. Recent studies have questioned this view. At the bench scale, brewer's yeast is very robust and withstands intense mechanical agitation under aerobic conditions without observable damage as measured by flow cytometry and other parameters. Much less intense mechanical agitation also decreases batch fermentation time for anaerobic beer production by about 25% compared to mixing by CO(2) evolution alone with a small change in the concentration of the different flavour compounds. These changes probably arise for two reasons. Firstly, the agitation increases the relative velocity and the area of contact between the cells and the wort, thereby enhancing the rate of mass transfer to and from the cells. Secondly, the agitation eliminates spatial variations in both yeast concentration and temperature, thus ensuring that the cells are maintained close to the optimum temperature profile during the whole of the fermentation time. These bench scale studies have recently been supported by results at the commercial scale from mixing by an impeller or by a rotary jet head, giving more consistent production without changes in final flavour. It is suggested that this reluctance of the brewing industry to use (adequate) mechanical agitation is another example where the myth of shear damage has had a detrimental effect on the optimal operation of commercial bioprocessing.

  12. Association Between Smoking and Problematic Internet Use Among Japanese Adolescents: Large-Scale Nationwide Epidemiological Study.

    PubMed

    Morioka, Hisayoshi; Itani, Osamu; Osaki, Yoneatsu; Higuchi, Susumu; Jike, Maki; Kaneita, Yoshitaka; Kanda, Hideyuki; Nakagome, Sachi; Ohida, Takashi

    2016-09-01

    The aim of this study was to clarify the association between smoking and problematic Internet use (PIU), such as Internet addiction (IA) and excessive Internet use (EIU), among Japanese adolescents. A self-administered questionnaire was administered to students enrolled in randomly selected junior and senior high schools throughout Japan. Responses were obtained from 100,050 students (0.94:1 ratio of boys to girls). The prevalence of IA (as indicated by a Young Diagnostic Questionnaire for Internet Addiction score ≥5) in all participants, boys, and girls was 8.1%, 6.4%, and 9.9%, respectively. The prevalence of EIU (≥5 hours/day) in all participants, boys, and girls was 12.6%, 12.3%, and 13.0%, respectively. The results of multiple logistic regression analyses indicated that the adjusted odds ratios (AORs) for IA and EIU were significantly higher among students who smoked (including those who previously smoked) than among those who never smoked (p < 0.01 for all comparisons). In addition, the AORs were the highest for students who smoked ≥21 cigarettes per day. The prevalence and AORs of IA and EIU tended to increase with smoking frequency and number of cigarettes smoked per day, indicating a dose-dependent relationship. Thus, IA and EIU have strong associations with smoking. This study revealed that adolescents who routinely smoked or those who smoked more cigarettes per day had a higher risk of PIU than adolescents who did not. These findings suggest that there is a close association between smoking and PIU among Japanese adolescents.

  13. Data management in large-scale collaborative toxicity studies: how to file experimental data for automated statistical analysis.

    PubMed

    Stanzel, Sven; Weimer, Marc; Kopp-Schneider, Annette

    2013-06-01

    High-throughput screening approaches are carried out for the toxicity assessment of a large number of chemical compounds. In such large-scale in vitro toxicity studies several hundred or thousand concentration-response experiments are conducted. The automated evaluation of concentration-response data using statistical analysis scripts saves time and yields more consistent results in comparison to data analysis performed by the use of menu-driven statistical software. Automated statistical analysis requires that concentration-response data are available in a standardised data format across all compounds. To obtain consistent data formats, a standardised data management workflow must be established, including guidelines for data storage, data handling and data extraction. In this paper two procedures for data management within large-scale toxicological projects are proposed. Both procedures are based on Microsoft Excel files as the researcher's primary data format and use a computer programme to automate the handling of data files. The first procedure assumes that data collection has not yet started whereas the second procedure can be used when data files already exist. Successful implementation of the two approaches into the European project ACuteTox is illustrated. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. A comparative study of all-vanadium and iron-chromium redox flow batteries for large-scale energy storage

    NASA Astrophysics Data System (ADS)

    Zeng, Y. K.; Zhao, T. S.; An, L.; Zhou, X. L.; Wei, L.

    2015-12-01

    The promise of redox flow batteries (RFBs) utilizing soluble redox couples, such as all vanadium ions as well as iron and chromium ions, is becoming increasingly recognized for large-scale energy storage of renewables such as wind and solar, owing to their unique advantages including scalability, intrinsic safety, and long cycle life. An ongoing question associated with these two RFBs is determining whether the vanadium redox flow battery (VRFB) or iron-chromium redox flow battery (ICRFB) is more suitable and competitive for large-scale energy storage. To address this concern, a comparative study has been conducted for the two types of battery based on their charge-discharge performance, cycle performance, and capital cost. It is found that: i) the two batteries have similar energy efficiencies at high current densities; ii) the ICRFB exhibits a higher capacity decay rate than does the VRFB; and iii) the ICRFB is much less expensive in capital costs when operated at high power densities or at large capacities.

  15. Splitting failure in side walls of a large-scale underground cavern group: a numerical modelling and a field study.

    PubMed

    Wang, Zhishen; Li, Yong; Zhu, Weishen; Xue, Yiguo; Yu, Song

    2016-01-01

    Vertical splitting cracks often appear in side walls of large-scale underground caverns during excavations owing to the brittle characteristics of surrounding rock mass, especially under the conditions of high in situ stress and great overburden depth. This phenomenon greatly affects the integral safety and stability of the underground caverns. In this paper, a transverse isotropic constitutive model and a splitting failure criterion are simultaneously proposed and secondly programmed in FLAC3D to numerically simulate the integral stability of the underground caverns during excavations in Dagangshan hydropower station in Sichuan province, China. Meanwhile, an in situ monitoring study on the displacement of the key points of the underground caverns has also been carried out, and the monitoring results are compared with the numerical results. From the comparative analysis, it can be concluded that the depths of splitting relaxation area obtained by numerical simulation are almost consistent with the actual in situ monitoring values, as well as the trend of the displacement curves, which shows that the transverse isotropic constitutive model combining with the splitting failure criterion is appropriate for investigating the splitting failure in side walls of large-scale underground caverns and it will be a helpful guidance of predicting the depths of splitting relaxation area in surrounding rock mass.

  16. A new technique for landslide mapping from a large-scale remote sensed image: A case study of Central Nepal

    NASA Astrophysics Data System (ADS)

    Yu, Bo; Chen, Fang

    2017-03-01

    This paper presents a new technique for landslide mapping from large-scale Landsat8 images. The method introduces saliency enhancement to enhance the landslide regions, making the landslides salient objects in the image. Morphological operations are applied to the enhanced image to remove most background objects. Afterwards, digital elevation model is applied to further remove the ground objects of plain areas according to the height of landscape, since most landslides occur in mountainous areas. Final landslides are extracted by the proposal regions from selective search. The study area covers 2°x2°, making it more similar with practical cases, such as emergency response and landslide inventory mappings. The proposed method performs satisfactorily by detecting 99.1% of the landslides in the image, and obtains an overall accuracy of 99.8% in the landslides/background classification problem, which gets further validated in another Landsat8 image of a different site. The experiment shows that the proposed method is feasible for landslide detection from large-scale area, which may contribute to the further landslide-related research.

  17. Large-scale overexpression and purification of ADARs from Saccharomyces cerevisiae for biophysical and biochemical studies.

    PubMed

    Macbeth, Mark R; Bass, Brenda L

    2007-01-01

    Many biochemical and biophysical analyses of enzymes require quantities of protein that are difficult to obtain from expression in an endogenous system. To further complicate matters, native adenosine deaminases that act on RNA (ADARs) are expressed at very low levels, and overexpression of active protein has been unsuccessful in common bacterial systems. Here we describe the plasmid construction, expression, and purification procedures for ADARs overexpressed in the yeast Saccharomyces cerevisiae. ADAR expression is controlled by the Gal promoter, which allows for rapid induction of transcription when the yeast are grown in media containing galactose. The ADAR is translated with an N-terminal histidine tag that is cleaved by the tobacco etch virus protease, generating one nonnative glycine residue at the N-terminus of the ADAR protein. ADARs expressed using this system can be purified to homogeneity, are highly active in deaminating RNA, and are produced in quantities (from 3 to 10mg of pure protein per liter of yeast culture) that are sufficient for most biophysical studies.

  18. Emotional competencies in geriatric nursing: empirical evidence from a computer based large scale assessment calibration study.

    PubMed

    Kaspar, Roman; Hartig, Johannes

    2016-03-01

    The care of older people was described as involving substantial emotion-related affordances. Scholars in vocational training and nursing disagree whether emotion-related skills could be conceptualized and assessed as a professional competence. Studies on emotion work and empathy regularly neglect the multidimensionality of these phenomena and their relation to the care process, and are rarely conclusive with respect to nursing behavior in practice. To test the status of emotion-related skills as a facet of client-directed geriatric nursing competence, 402 final-year nursing students from 24 German schools responded to a 62-item computer-based test. 14 items were developed to represent emotion-related affordances. Multi-dimensional IRT modeling was employed to assess a potential subdomain structure. Emotion-related test items did not form a separate subdomain, and were found to be discriminating across the whole competence continuum. Tasks concerning emotion work and empathy are reliable indicators for various levels of client-directed nursing competence. Claims for a distinct emotion-related competence in geriatric nursing, however, appear excessive with a process-oriented perspective.

  19. Nasopharyngeal biopsy in adults: a large-scale study in a non endemic area.

    PubMed

    Abu-Ghanem, Sara; Carmel, Narin-Nard; Horowitz, Gilad; Yehuda, Moshe; Leshno, Moshe; Abu-Ghanem, Yasmin; Fliss, Dan M; Abergel, Avraham

    2015-06-01

    Limited data exist on the referral criteria for endoscopic-guided nasopharyngeal biopsy to rule out nasopharyngeal malignancy among adults in a non-endemic area. Retrospective study of all adult patients that had been referred to our outpatient clinic to undergo endoscopic-guided nasopharyngeal biopsy to exclude nasopharyngeal malignancy between 1/2006-10/2013. All medical consultation referral letters were reviewed, and statistical analyses were conducted to evaluate clinically significant predictors (demographics, clinical manife- stations, nasopharyngeal endoscopic findings) for nasopharyngeal malignancy. A total of 470 patients (470 nasopharyngeal biopsies, 54.9% males and 66% smokers) were included. The most common pathological result was adenoid/lymphoid hyperplasia (76.2%). The overall negative rate of all biopsies for malignancy was 94.2%. Twenty-seven patients had nasopharyngeal malignancy: 22 had squamous cell carcinoma and 5 had non-Hodgkin`s lymphoma. Advanced age, cervical mass, and suspicious nasopharyngeal mass were independent risk factors for nasopharyngeal malignancy on univariate and multivariate analyses. Nasopharyngeal biopsy may safely be avoided in adults living in a non-endemic area for NPC who are free of the risk factors of advanced age, the presence of a cervical mass, and suspicious nasopharyngeal mass.

  20. Clinical prediction from structural brain MRI scans: a large-scale empirical study.

    PubMed

    Sabuncu, Mert R; Konukoglu, Ender

    2015-01-01

    Multivariate pattern analysis (MVPA) methods have become an important tool in neuroimaging, revealing complex associations and yielding powerful prediction models. Despite methodological developments and novel application domains, there has been little effort to compile benchmark results that researchers can reference and compare against. This study takes a significant step in this direction. We employed three classes of state-of-the-art MVPA algorithms and common types of structural measurements from brain Magnetic Resonance Imaging (MRI) scans to predict an array of clinically relevant variables (diagnosis of Alzheimer's, schizophrenia, autism, and attention deficit and hyperactivity disorder; age, cerebrospinal fluid derived amyloid-β levels and mini-mental state exam score). We analyzed data from over 2,800 subjects, compiled from six publicly available datasets. The employed data and computational tools are freely distributed ( https://www.nmr.mgh.harvard.edu/lab/mripredict), making this the largest, most comprehensive, reproducible benchmark image-based prediction experiment to date in structural neuroimaging. Finally, we make several observations regarding the factors that influence prediction performance and point to future research directions. Unsurprisingly, our results suggest that the biological footprint (effect size) has a dramatic influence on prediction performance. Though the choice of image measurement and MVPA algorithm can impact the result, there was no universally optimal selection. Intriguingly, the choice of algorithm seemed to be less critical than the choice of measurement type. Finally, our results showed that cross-validation estimates of performance, while generally optimistic, correlate well with generalization accuracy on a new dataset.

  1. Large scale study of HPV genotypes in cervical cancer and different cytological cervical specimens in Thailand.

    PubMed

    Chansaenroj, Jira; Junyangdikul, Pairoj; Chinchai, Teeraporn; Swangvaree, Sukumarn; Karalak, Anant; Gemma, Nobuhiro; Poovorawan, Yong

    2014-04-01

    Identification of high-risk HPV genotypes in patients is essential for vaccination and prevention programs while the geographic distribution of cervical cancer varies widely. HPV 16 is the major cause of cervical cancer followed by HPV 18, HPV 31, HPV 52, or HPV 58 depending on geographic area. In this study, the distribution of HPV genotypes in cervical specimens from women living in Thailand was analyzed by HPV testing with electrochemical DNA chip and PCR direct sequencing. The 716 specimens were grouped according to their cytological grades; 100 normal, 100 low-grade squamous intraepithelial lesions, 100 high grade squamous intraepithelial lesions, and 416 specimens of cervical cancer. The results showed that HPV 16, HPV 18, HPV 52, and HPV 58 are the most common HPV genotypes in Thailand, respectively. With respect to age, women below the age of 26 years were almost negative for high-risk HPV DNA exclusively. Conversely, high prevalence of high-risk HPV DNA and abnormal cytology were usually found in women between 26 and 45 years while cervical cancer was detected mainly in women above the age of 45 years. To increase protection efficiency, a vaccine including HPV 52 and HPV 58 should be offered to Asian women, and primary HPV screening should start at 26-30 years of age. © 2013 Wiley Periodicals, Inc.

  2. Toxoplasma gondii seroprevalence in dairy and beef cattle: Large-scale epidemiological study in Estonia.

    PubMed

    Jokelainen, Pikka; Tagel, Maarja; Mõtus, Kerli; Viltrop, Arvo; Lassen, Brian

    2017-03-15

    Toxoplasma gondii is a zoonotic protozoan parasite that thrives in Estonia. In this nationwide cross-sectional study, we tested sera from 3991 cattle, collected from 228 farms in 2012-2013, for anti-T. gondii immunoglobulin G antibodies using a commercial direct agglutination test. Titer of 100 was set as cut-off: samples that tested positive at the dilution 1:100 were defined as positive. The apparent animal-level seroprevalence was 18.62%. At least one seropositive animal was found on 68.86% of the farms, and seropositive cattle were detected in all counties. The seroprevalence appeared to increase with age until five years (60-71 months) of age, but had no obvious pattern in the older animals. Animals of the local Estonian Red breed had higher odds to test seropositive than did animals of the Estonian Holstein breed. Whether the farm focused on dairy or beef cattle was not associated with an animal testing T. gondii seropositive nor with finding at least one T. gondii seropositive animal on the farm. The odds of finding at least one T. gondii seropositive animal on the farm were higher if the herd size was above median (105 in dairy and mixed dairy farms; 35 in beef and mixed beef farms). The results indicate that T. gondii is endemic within the agricultural setting in Estonia and present on the majority of cattle farms.

  3. AN HST PROPER-MOTION STUDY OF THE LARGE-SCALE JET OF 3C273

    SciTech Connect

    Meyer, Eileen T.; Georganopoulos, Markos; Sparks, William B.; Anderson, Jay; Marel, Roeland van der; Biretta, John; Chiaberge, Marco; Norman, Colin; Tony Sohn, Sangmo; Perlman, Eric

    2016-02-20

    The radio galaxy 3C 273 hosts one of the nearest and best-studied powerful quasar jets. Having been imaged repeatedly by the Hubble Space Telescope (HST) over the past twenty years, it was chosen for an HST program to measure proper motions in the kiloparsec-scale resolved jets of nearby radio-loud active galaxies. The jet in 3C 273 is highly relativistic on sub-parsec scales, with apparent proper motions up to 15c observed by very long baseline interferometry. In contrast, we find that the kiloparsec-scale knots are compatible with being stationary, with a mean speed of −0.2 ± 0.5c over the whole jet. Assuming the knots are packets of moving plasma, an upper limit of 1c implies a bulk Lorentz factor Γ < 2.9. This suggests that the jet has either decelerated significantly by the time it reaches the kiloparsec scale, or that the knots in the jet are standing shock features. The second scenario is incompatible with the inverse Compton off the Cosmic Microwave Background (IC/CMB) model for the X-ray emission of these knots, which requires the knots to be in motion, but IC/CMB is also disfavored in the first scenario due to energetic considerations, in agreement with the recent finding of Meyer and Georganopoulos which ruled out the IC/CMB model for the X-ray emission of 3C 273 via gamma-ray upper limits.

  4. SU-E-T-531: Large--Scale DVH Quality Study: Correlated Aims Lead Relaxations

    SciTech Connect

    Nohadani, O; Roy, A; Das, I

    2015-06-15

    Purpose: Intensity modulated radiation therapy plans are designed to optimally target a tumor while sparing surrounding tissue. Desired dose distributions are iteratively approached via inverse planning. This leads to tradeoffs between clinical objectives for the planning target volume (PTV), organs at risk, and normal tissues. Dose volume histogram (DVHs) related aims are followed that are either institutional or internationally recommended. We analyze common goals and identify potential reasons that often lead to tradeoffs. Methods: 524 IMRT plans for various tumor sites were analyzed based on the main institutional DVH goal for PTV (D95) and the recommendations by ICRU-83 (D2, D50, and D98). Robust statistical tools are developed and applied to ensure that the results are immune to data uncertainties. The probability of violation was measured for each of the DVH goals based on the frequency of not meeting recommended doses. Conditional probabilities for satisfying and/or violating DVH aims were computed to test the hypothesized pair-wise relations between DVH aims. For example, for plans that satisfied D50, the probability of violating D98 was computed via P(D98 < 95% | 98% ≤ D50 ≤ 102%). The equality constraint D50 = 100% was relaxed to encompass the range [98,102]%. Results: A large majority of cases (88%) satisfied the institutional goal for PTV of D95 ≤ 95%. Similar consensus existed for D98. 51% of cases satisfied D2 ≥ 107%. However, only 18% of cases satisfied D50. The conditional probability showed correlations amongst the studied DVH goals. In fact, a negative correlation was revealed between D50 and D95 (and D98), suggesting that these competing goals cannot be satisfied concurrently. Conclusion: The majority of plans followed the institutional guidelines. The reason for their deviation from international recommendations seems to be that the latter goals are competing and cannot be satisfied concurrently in clinical practice.

  5. Maternal Smoking during Pregnancy and Neonatal Behavior: A Large-Scale Community Study

    PubMed Central

    Stroud, Laura R.; Paster, Rachel L.; Goodwin, Matthew S.; Shenassa, Edmond; Buka, Stephen; Niaura, Raymond; Rosenblith, Judy F.; Lipsitt, Lewis P.

    2009-01-01

    Objective To investigate the influence of prospectively-measured smoking during pregnancy on aspects of neonatal behavior in a large, community sample. Patients and Methods Participants were mothers and infants from the Providence Cohort of the National Collaborative Perinatal Project enrolled between 1960 and 1966. Mothers with pregnancy/medical complications and infants with medical complications and/or born premature or low birthweight were excluded. The final sample included 962 mother-infant pairs, of whom 23% were African-American. Maternal smoking was measured prospectively at each prenatal visit. Neonatal behavior was assessed using the Graham-Rosenblith Behavioral Examination of the Neonate. Items from the examination were reduced to three subscales: irritability, muscle tone, response to respiratory challenge. Results Sixty-two percent of the sample reported smoking during pregnancy with 24% of smokers reporting smoking a pack per day or more. We found a significant influence of maternal smoking exposure (none, moderate/less than a pack per day, heavy/pack a day or more) on irritability and muscle tone in the neonate (p's<.005), with exposed infants showing greater irritability and hypertonicity. Effects remained significant after controlling for significant covariates: maternal socioeconomic status, age and race, and infant birthweight and age (p's<.001). Post hoc tests suggested particular effects of heavy smoking on increased infant irritability, but both moderate and heavy smoking exposure on increased muscle tone. Conclusions In a large, community sample, exposure to maternal smoking was associated with increased irritability and hypertonicity in neonates. Exposure to maternal smoking did not influence neonatal response to respiratory challenge. This study is the largest-scale investigation to date of effects of maternal smoking (heavy and moderate) on examiner-assessed neonatal behavior. Given associations between both maternal smoking and infant

  6. Music Proficiency and Quantification of Absolute Pitch: A Large-Scale Study among Brazilian Musicians.

    PubMed

    Leite, Raphael B C; Mota-Rolim, Sergio A; Queiroz, Claudio M T

    2016-01-01

    Absolute pitch (AP) is the ability to identify and name the pitch of a sound without external reference. Often, accuracy and speed at naming isolated musical pitches are correlated with demographic, biological, and acoustical parameters to gain insight into the genesis and evolution of this ability in specific cohorts. However, the majority of those studies were conducted in North America, Europe, or Asia. To fill this gap, here we investigated the pitch-naming performance in a large population of Brazilian conservatory musicians (N = 200). As previously shown, we found that the population performance was rather a continuum than an "all-or-none" ability. By comparing the observed distribution of correct responses to a theoretical binomial distribution, we estimated the prevalence of AP as being 18% amongst regular music students. High accuracy thresholds (e.g., 85% of correct responses) yielded a prevalence of 4%, suggesting that AP might have been underestimated in previous reports. Irrespective of the threshold used, AP prevalence was higher in musicians who started their musical practice and formal musical education early in life. Finally, we compared the performance of those music students (average proficiency group) with another group of students selected to take part in the conservatory orchestra (high proficiency group, N = 30). Interestingly, the prevalence of AP was higher in the latter in comparison to the former group. In addition, even when the response was incorrect, the mean absolute deviation from the correct response was smaller in the high proficiency group compared to the average proficiency group (Glass's Δ: 0.5). Taken together, our results show that the prevalence of AP in Brazilian students is similar to other non-tonal language populations, although this measure is highly dependent on the scoring threshold used. Despite corroborating that early involvement with musical practice and formal education can foster AP ability, the present data

  7. Music Proficiency and Quantification of Absolute Pitch: A Large-Scale Study among Brazilian Musicians

    PubMed Central

    Leite, Raphael B. C.; Mota-Rolim, Sergio A.; Queiroz, Claudio M. T.

    2016-01-01

    Absolute pitch (AP) is the ability to identify and name the pitch of a sound without external reference. Often, accuracy and speed at naming isolated musical pitches are correlated with demographic, biological, and acoustical parameters to gain insight into the genesis and evolution of this ability in specific cohorts. However, the majority of those studies were conducted in North America, Europe, or Asia. To fill this gap, here we investigated the pitch-naming performance in a large population of Brazilian conservatory musicians (N = 200). As previously shown, we found that the population performance was rather a continuum than an “all-or-none” ability. By comparing the observed distribution of correct responses to a theoretical binomial distribution, we estimated the prevalence of AP as being 18% amongst regular music students. High accuracy thresholds (e.g., 85% of correct responses) yielded a prevalence of 4%, suggesting that AP might have been underestimated in previous reports. Irrespective of the threshold used, AP prevalence was higher in musicians who started their musical practice and formal musical education early in life. Finally, we compared the performance of those music students (average proficiency group) with another group of students selected to take part in the conservatory orchestra (high proficiency group, N = 30). Interestingly, the prevalence of AP was higher in the latter in comparison to the former group. In addition, even when the response was incorrect, the mean absolute deviation from the correct response was smaller in the high proficiency group compared to the average proficiency group (Glass's Δ: 0.5). Taken together, our results show that the prevalence of AP in Brazilian students is similar to other non-tonal language populations, although this measure is highly dependent on the scoring threshold used. Despite corroborating that early involvement with musical practice and formal education can foster AP ability, the present data

  8. Utilisation of ISA Reverse Genetics and Large-Scale Random Codon Re-Encoding to Produce Attenuated Strains of Tick-Borne Encephalitis Virus within Days

    PubMed Central

    Aubry, Fabien; Gould, Ernest A.; de Lamballerie, Xavier

    2016-01-01

    Large-scale codon re-encoding is a new method of attenuating RNA viruses. However, the use of infectious clones to generate attenuated viruses has inherent technical problems. We previously developed a bacterium-free reverse genetics protocol, designated ISA, and now combined it with large-scale random codon-re-encoding method to produce attenuated tick-borne encephalitis virus (TBEV), a pathogenic flavivirus which causes febrile illness and encephalitis in humans. We produced wild-type (WT) and two re-encoded TBEVs, containing 273 or 273+284 synonymous mutations in the NS5 and NS5+NS3 coding regions respectively. Both re-encoded viruses were attenuated when compared with WT virus using a laboratory mouse model and the relative level of attenuation increased with the degree of re-encoding. Moreover, all infected animals produced neutralizing antibodies. This novel, rapid and efficient approach to engineering attenuated viruses could potentially expedite the development of safe and effective new-generation live attenuated vaccines. PMID:27548676

  9. A New Model for Conducting Large-Scale Aerogeophysical Studies in Antarctica Through International Collaboration

    NASA Astrophysics Data System (ADS)

    Holt, J. W.; Blankenship, D. D.; Peters, M. E.; Vaughan, D. G.; Corr, H. F.

    2006-12-01

    The aerogeophysical surveys of the 1970's conducted by the Scott Polar Research Institute (SPRI), the National Science Foundation (NSF), and the Technical University of Denmark (TUD) were the successful result of an international collaboration to implement geophysical capabilities, primarily ice penetrating radar, onto a long-range aircraft and operate that system in Antarctica for multiple field seasons in a reconnaissance mode. This produced the first continental-scale insights into the Antarctic ice sheet and subglacial geomorphology, and this context made it possible to plan more detailed studies with new geophysical systems. The University of Texas Institute for Geophysics (UTIG) led such an effort through the successful implementation of a multi-instrumented Twin Otter aerogeophysical platform. UTIG, in collaboration with others, modified the 60 MHz TUD radar used in the SPRI/NSF/TUD survey and integrated it with a gravity meter, towed magnetometer, and laser altimeter. First used in 1991, this system later became the basis for the Support Office for Aerogeophysical Research (SOAR), an NSF facility operated by UTIG from 1994 2001. SOAR acquired over 200,000 line-km of data in both East and West Antarctica during seven field seasons. Subsequent to this, UTIG further modified the system, combining components of a coherent, chirped radar built by NASA's Jet Propulsion Laboratory with the TUD high power transmitter. Meanwhile, the British Antarctic Survey (BAS) designed and built a 150 MHz coherent radar system and integrated it into their Twin Otter aerogeophysical platform with gravity meter and wingtip magnetometers. In 2004-05, UTIG and BAS joined forces to conduct the largest single aerogeophysical survey undertaken in Antarctica to date. The target was the Amundsen Sea Embayment, a largely unexplored and scientifically critical area located far from the logistical centers of the US and UK. Both aerogeophysical systems were deployed using two temporary field

  10. Genetic Diversity and Ecological Niche Modelling of Wild Barley: Refugia, Large-Scale Post-LGM Range Expansion and Limited Mid-Future Climate Threats?

    PubMed Central

    Russell, Joanne; van Zonneveld, Maarten; Dawson, Ian K.; Booth, Allan; Waugh, Robbie; Steffenson, Brian

    2014-01-01

    Describing genetic diversity in wild barley (Hordeum vulgare ssp. spontaneum) in geographic and environmental space in the context of current, past and potential future climates is important for conservation and for breeding the domesticated crop (Hordeum vulgare ssp. vulgare). Spatial genetic diversity in wild barley was revealed by both nuclear- (2,505 SNP, 24 nSSR) and chloroplast-derived (5 cpSSR) markers in 256 widely-sampled geo-referenced accessions. Results were compared with MaxEnt-modelled geographic distributions under current, past (Last Glacial Maximum, LGM) and mid-term future (anthropogenic scenario A2, the 2080s) climates. Comparisons suggest large-scale post-LGM range expansion in Central Asia and relatively small, but statistically significant, reductions in range-wide genetic diversity under future climate. Our analyses support the utility of ecological niche modelling for locating genetic diversity hotspots and determine priority geographic areas for wild barley conservation under anthropogenic climate change. Similar research on other cereal crop progenitors could play an important role in tailoring conservation and crop improvement strategies to support future human food security. PMID:24505252

  11. Large-scale clinical endodontic research in the National Dental Practice-Based Research Network: study overview and methods.

    PubMed

    Nixdorf, Donald R; Law, Alan S; Look, John O; Rindal, D Brad; Durand, Emily U; Kang, Wenjun; Agee, Bonita S; Fellows, Jeffrey L; Gordan, Valeria V; Gilbert, Gregg H

    2012-11-01

    This article reports on the feasibility of conducting a large-scale endodontic prospective cohort study in The National Dental Practice-Based Research Network. This study was designed to measure pain and burden associated with initial orthograde root canal therapy (RCT) and to explore potential prognostic factors for pain outcomes. The main objectives of this first report in a series are to describe the project's feasibility and methods and the demographics of the sample obtained. Sixty-two dentist practitioner-investigators (ie, 46 generalists and 16 endodontists) in 5 geographic areas were certified within the network and trained regarding the standardized study protocol. Enrollment and baseline data collection occurred over 6 months with postobturation follow-up for another 6 months. Patients and dentists completed questionnaires before and immediately after treatment visits. Patients also completed questionnaires at 1 week, 3 months, and 6 months after obturation. Enrollment exceeded target expectations, with 708 eligible patient-participants. Questionnaire return rates were good, ranging between 90% and 100%. Patient demographics were typical of persons who receive RCT in the United States (ie, mean age = 48 years [standard deviation = 13 years], with most being female [59%], college educated [81%], white non-Hispanic [86%], and having dental insurance [81%]). The tooth types being treated were also typical (ie, 61% molars, 28% premolars, and 11% anteriors, with maxillary teeth being predominant [59%]). This study shows the feasibility of conducting large-scale endodontic prospective cohort studies in the network. Patients were rapidly recruited with high levels of compliance in data collection. Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  12. Large-scale Clinical Endodontic Research in The National Dental Practice-Based Research Network: Study Overview and Methods

    PubMed Central

    Nixdorf, Donald R.; Law, Alan S.; Look, John O.; Rindal, D. Brad; Durand, Emily U.; Kang, Wenjun; Agee, Bonita S.; Fellows, Jeffrey L.; Gordan, Valeria V.; Gilbert, Gregg H.

    2013-01-01

    Introduction This paper reports on the feasibility of conducting a large-scale endodontic prospective cohort study in The National Dental Practice-Based Research Network. This study was designed to measure pain and burden associated with initial orthograde root canal therapy (RCT) and to explore potential prognostic factors for pain outcomes. The main objectives of this first report in a series are to describe the project’s feasibility and methods and the demographics of the sample obtained. Methods Sixty-two dentist practitioner-investigators (46 generalists, 16 endodontists) in five geographical areas were certified within the network and trained regarding the standardized study protocol. Enrollment and baseline data collection occurred over 6 months, with post-obturation follow-up for another 6 months. Patients and dentists completed questionnaires before and immediately after treatment visits. Patients also completed questionnaires at 1 week, 3 months, and 6 months after obturation. Results Enrollment exceeded target expectations, with 708 eligible patient-participants. Questionnaire return rates were good, ranging between 90% to 100%. Patient demographics were typical of persons who receive RCT in the United States: mean age 48 years (SD 13 years), with most being female (59%), college-educated (81%), white non-Hispanic (86%), and having dental insurance (81%). The tooth types being treated were also typical: 61% molars, 28% premolars, and 11% anteriors, with maxillary teeth being predominant (59%). Conclusions This study demonstrates the feasibility of conducting large-scale endodontic prospective cohort studies in the network. Patients were rapidly recruited, with high levels of compliance in data collection. PMID:23063220

  13. Large Scale Functional Brain Networks Underlying Temporal Integration of Audio-Visual Speech Perception: An EEG Study

    PubMed Central

    Kumar, G. Vinodh; Halder, Tamesh; Jaiswal, Amit K.; Mukherjee, Abhishek; Roy, Dipanjan; Banerjee, Arpan

    2016-01-01

    Observable lip movements of the speaker influence perception of auditory speech. A classical example of this influence is reported by listeners who perceive an illusory (cross-modal) speech sound (McGurk-effect) when presented with incongruent audio-visual (AV) speech stimuli. Recent neuroimaging studies of AV speech perception accentuate the role of frontal, parietal, and the integrative brain sites in the vicinity of the superior temporal sulcus (STS) for multisensory speech perception. However, if and how does the network across the whole brain participates during multisensory perception processing remains an open question. We posit that a large-scale functional connectivity among the neural population situated in distributed brain sites may provide valuable insights involved in processing and fusing of AV speech. Varying the psychophysical parameters in tandem with electroencephalogram (EEG) recordings, we exploited the trial-by-trial perceptual variability of incongruent audio-visual (AV) speech stimuli to identify the characteristics of the large-scale cortical network that facilitates multisensory perception during synchronous and asynchronous AV speech. We evaluated the spectral landscape of EEG signals during multisensory speech perception at varying AV lags. Functional connectivity dynamics for all sensor pairs was computed using the time-frequency global coherence, the vector sum of pairwise coherence changes over time. During synchronous AV speech, we observed enhanced global gamma-band coherence and decreased alpha and beta-band coherence underlying cross-modal (illusory) perception compared to unisensory perception around a temporal window of 300–600 ms following onset of stimuli. During asynchronous speech stimuli, a global broadband coherence was observed during cross-modal perception at earlier times along with pre-stimulus decreases of lower frequency power, e.g., alpha rhythms for positive AV lags and theta rhythms for negative AV lags. Thus

  14. Large Scale Functional Brain Networks Underlying Temporal Integration of Audio-Visual Speech Perception: An EEG Study.

    PubMed

    Kumar, G Vinodh; Halder, Tamesh; Jaiswal, Amit K; Mukherjee, Abhishek; Roy, Dipanjan; Banerjee, Arpan

    2016-01-01

    Observable lip movements of the speaker influence perception of auditory speech. A classical example of this influence is reported by listeners who perceive an illusory (cross-modal) speech sound (McGurk-effect) when presented with incongruent audio-visual (AV) speech stimuli. Recent neuroimaging studies of AV speech perception accentuate the role of frontal, parietal, and the integrative brain sites in the vicinity of the superior temporal sulcus (STS) for multisensory speech perception. However, if and how does the network across the whole brain participates during multisensory perception processing remains an open question. We posit that a large-scale functional connectivity among the neural population situated in distributed brain sites may provide valuable insights involved in processing and fusing of AV speech. Varying the psychophysical parameters in tandem with electroencephalogram (EEG) recordings, we exploited the trial-by-trial perceptual variability of incongruent audio-visual (AV) speech stimuli to identify the characteristics of the large-scale cortical network that facilitates multisensory perception during synchronous and asynchronous AV speech. We evaluated the spectral landscape of EEG signals during multisensory speech perception at varying AV lags. Functional connectivity dynamics for all sensor pairs was computed using the time-frequency global coherence, the vector sum of pairwise coherence changes over time. During synchronous AV speech, we observed enhanced global gamma-band coherence and decreased alpha and beta-band coherence underlying cross-modal (illusory) perception compared to unisensory perception around a temporal window of 300-600 ms following onset of stimuli. During asynchronous speech stimuli, a global broadband coherence was observed during cross-modal perception at earlier times along with pre-stimulus decreases of lower frequency power, e.g., alpha rhythms for positive AV lags and theta rhythms for negative AV lags. Thus, our

  15. Self-sampling for analysis of respiratory viruses in a large-scale epidemiological study in Sweden.

    PubMed

    Plymoth, A; Rotzen-Ostlund, M; Zweygberg-Wirgart, B; Sundin, C G; Ploner, A; Nyren, O; Linde, A

    2015-03-19

    Viral diagnosis of respiratory tract infections has so far required sampling by health professionals,hampering large-scale epidemiological studies of virus-specific disease outcomes. As part of a population-based, prospective study of work-related risk factors for transmission of viral infections (SWEDE-I), we developed a scheme for self-sampling with nasal swabs. Random selection from the gainfully employed population of a medium-sized town in central Sweden resulted in a study cohort of 2,237 men and women aged 25 to 63 years. From September 2011 through May 2012, the cohort reported all instances of respiratory tract infection or gastroenteritis and participants concomitantly sent self-sampled nasal swabs for analysis using regular mail. Diagnosis of 14 viruses was performed. A total of 1,843 samples were received. The week-wise average delay between disease on set and arrival of the specimens at the laboratory varied between four and six days, and the corresponding median delay was between 3.5 and six days. In line with previous community-based studies, picorna- and coronaviruses dominated in specimens obtained from the self-sampling scheme. The results of self-sampling were contrasted to those from contemporaneous routine clinical sampling, on the same age group, in the adjacent Stockholm county. Although higher proportions of positive samples for respiratory syncytial virus and influenza were observed in the clinical sampling scheme, estimations of seasonality for influenza A and picornaviruses derived from both schemes were similar. Our findings show that nasal self-sampling is feasible in large-scale surveillance of respiratory infections and opens new prospects for population based,virologically verified research on virus spread,burden of disease, and effects of environmental factors or interventions.

  16. A topological analysis of large-scale structure, studied using the CMASS sample of SDSS-III

    SciTech Connect

    Parihar, Prachi; Gott, J. Richard III; Vogeley, Michael S.; Choi, Yun-Young; Kim, Juhan; Kim, Sungsoo S.; Speare, Robert; Brownstein, Joel R.; Brinkmann, J. E-mail: yy.choi@khu.ac.kr

    2014-12-01

    We study the three-dimensional genus topology of large-scale structure using the northern region of the CMASS Data Release 10 (DR10) sample of the SDSS-III Baryon Oscillation Spectroscopic Survey. We select galaxies with redshift 0.452 < z < 0.625 and with a stellar mass M {sub stellar} > 10{sup 11.56} M {sub ☉}. We study the topology at two smoothing lengths: R {sub G} = 21 h {sup –1} Mpc and R {sub G} = 34 h {sup –1} Mpc. The genus topology studied at the R {sub G} = 21 h {sup –1} Mpc scale results in the highest genus amplitude observed to date. The CMASS sample yields a genus curve that is characteristic of one produced by Gaussian random phase initial conditions. The data thus support the standard model of inflation where random quantum fluctuations in the early universe produced Gaussian random phase initial conditions. Modest deviations in the observed genus from random phase are as expected from shot noise effects and the nonlinear evolution of structure. We suggest the use of a fitting formula motivated by perturbation theory to characterize the shift and asymmetries in the observed genus curve with a single parameter. We construct 54 mock SDSS CMASS surveys along the past light cone from the Horizon Run 3 (HR3) N-body simulations, where gravitationally bound dark matter subhalos are identified as the sites of galaxy formation. We study the genus topology of the HR3 mock surveys with the same geometry and sampling density as the observational sample and find the observed genus topology to be consistent with ΛCDM as simulated by the HR3 mock samples. We conclude that the topology of the large-scale structure in the SDSS CMASS sample is consistent with cosmological models having primordial Gaussian density fluctuations growing in accordance with general relativity to form galaxies in massive dark matter halos.

  17. High-throughput genotyping assay for the large-scale genetic characterization of Cryptosporidium parasites from human and bovine samples.

    PubMed

    Abal-Fabeiro, J L; Maside, X; Llovo, J; Bello, X; Torres, M; Treviño, M; Moldes, L; Muñoz, A; Carracedo, A; Bartolomé, C

    2014-04-01

    The epidemiological study of human cryptosporidiosis requires the characterization of species and subtypes involved in human disease in large sample collections. Molecular genotyping is costly and time-consuming, making the implementation of low-cost, highly efficient technologies increasingly necessary. Here, we designed a protocol based on MALDI-TOF mass spectrometry for the high-throughput genotyping of a panel of 55 single nucleotide variants (SNVs) selected as markers for the identification of common gp60 subtypes of four Cryptosporidium species that infect humans. The method was applied to a panel of 608 human and 63 bovine isolates and the results were compared with control samples typed by Sanger sequencing. The method allowed the identification of species in 610 specimens (90·9%) and gp60 subtype in 605 (90·2%). It displayed excellent performance, with sensitivity and specificity values of 87·3 and 98·0%, respectively. Up to nine genotypes from four different Cryptosporidium species (C. hominis, C. parvum, C. meleagridis and C. felis) were detected in humans; the most common ones were C. hominis subtype Ib, and C. parvum IIa (61·3 and 28·3%, respectively). 96·5% of the bovine samples were typed as IIa. The method performs as well as the widely used Sanger sequencing and is more cost-effective and less time consuming.

  18. Parents' perceived vulnerability and perceived control in preventing Meningococcal C infection: a large-scale interview study about vaccination

    PubMed Central

    Timmermans, Danielle RM; Henneman, Lidewij; Hirasing, Remy A; van der Wal, Gerrit

    2008-01-01

    Background Parents' reported ambivalence toward large-scale vaccination programs for childhood diseases may be related to their perception of the risks of side-effects or safety of vaccination and the risk of contracting the disease. The aim of this study is to evaluate parents' perceptions of their child's risk contracting a Meningococcal C infection and parents' perceived control in preventing infection in relation to their evaluation of the safety, effectiveness and usefulness of vaccination. Methods In a large-scale interview study, a random sample of parents was interviewed after their children had received vaccination against Meningococcal C in a catch-up campaign. Questions were asked about the perceived relative vulnerability of their child contracting an infection, perceived control in preventing an infection, and parents' evaluation of the safety, usefulness and effectiveness of vaccination. Results 61% of 2910 (N = 1763) parents who were approached participated. A higher perceived relative vulnerability of their own child contracting the disease was related to a more positive evaluation of the vaccination campaign, while a lower perceived vulnerability did not result in a more negative evaluation. A higher perceived control in being able to prevent an infection was, however, related to a more critical attitude toward the safety, usefulness and effectiveness of vaccination. Conclusion Perceived relative vulnerability contracting an infection and parents' perceived control in preventing an infection seem to influence parents' evaluation of the vaccination programme. Future studies should determine if, and under which circumstances, these perceptions also affect parents' vaccination behaviour and would be relevant to be taken into account when educating parents about vaccination. PMID:18241345

  19. Experimental study on seismic responses of piping systems with friction. Part 1: Large-scale shaking table vibration test

    SciTech Connect

    Suzuki, K.; Watanabe, T.; Mitsumori, T.; Shimizu, N.; Kobayashi, H.; Ogawa, N.

    1995-08-01

    This report deals with the experimental study of seismic response behavior of piping systems in industrial facilities such as petrochemical, oil refinery, and nuclear plants. Special attention is focused on the nonlinear dynamic response of piping systems due to frictional vibration appearing in piping and supporting devices. A three-dimensional mock-up piping and supporting structure model wherein piping is of 30-m length and 200-mm diameter is excited by a large-scale (15 m x 15 m) shaking table belong to the National Research Institute for Earth Science and Disaster Prevention in Tsukuba, Ibaraki. Power spectra of the response vibration and the loading-response relationship in the form of a hysteresis loop under several loading conditions are obtained. The response reduction effect caused by frictional vibration is evaluated and demonstrated in terms of response reduction factor.

  20. Examining Agencies' Satisfaction with Electronic Record Management Systems in e-Government: A Large-Scale Survey Study

    NASA Astrophysics Data System (ADS)

    Hsu, Fang-Ming; Hu, Paul Jen-Hwa; Chen, Hsinchun; Hu, Han-Fen

    While e-government is propelling and maturing steadily, advanced technological capabilities alone cannot guarantee agencies’ realizing the full benefits of the enabling computer-based systems. This study analyzes information systems in e-government settings by examining agencies’ satisfaction with an electronic record management system (ERMS). Specifically, we investigate key satisfaction determinants that include regulatory compliance, job relevance, and satisfaction with support services for using the ERMS. We test our model and the hypotheses in it, using a large-scale survey that involves a total of 1,652 government agencies in Taiwan. Our results show significant effects of regulatory compliance on job relevance and satisfaction with support services, which in turn determine government agencies’ satisfaction with an ERMS. Our data exhibit a reasonably good fit to our model, which can explain a significant portion of the variance in agencies’ satisfaction with an ERMS. Our findings have several important implications to research and practice, which are also discussed.

  1. Large scale scientific computing

    SciTech Connect

    Deuflhard, P. ); Engquist, B. )

    1987-01-01

    This book presents papers on large scale scientific computing. It includes: Initial value problems of ODE's and parabolic PDE's; Boundary value problems of ODE's and elliptic PDE's; Hyperbolic PDE's; Inverse problems; Optimization and optimal control problems; and Algorithm adaptation on supercomputers.

  2. Study of stress-strain and volume change behavior of emplaced municipal solid waste using large-scale triaxial testing.

    PubMed

    Ramaiah, B J; Ramana, G V

    2017-01-27

    The article presents the stress-strain and volume change behavior, shear strength and stiffness parameters of landfilled municipal solid waste (MSW) collected from two dump sites located in Delhi, India. Over 30 drained triaxial compression (TXC) tests were conducted on reconstituted large-scale specimens of 150mm diameter to study the influence of fiber content, age, density and confining pressure on the shear strength of MSW. In addition, a few TXC tests were also conducted on 70mm diameter specimen to examine the effect of specimen size on the mobilized shear strength. It is observed that the fibrous materials such as textiles and plastics, and their percentage by weight have a significant effect on the stress-strain-volume change behavior, shear strength and stiffness of solid waste. The stress-strain-volume change behavior of MSW at Delhi is qualitatively in agreement with the behavior reported for MSW from different countries. Results of large-scale direct shear tests conducted on MSW with an identical composition used for TXC tests revealed the cross-anisotropic behavior as reported by previous researchers. Effective shear strength parameters of solid waste evaluated from this study is best characterized by ϕ'=39° and c'=0kPa for the limiting strain-based failure criteria of K0=0.3+5% axial strain and are in the range of the data reported for MSW from different countries. Data presented in this article is useful for the stress-deformation and stability analysis of the dump sites during their operation as well as closure plans.

  3. High-Throughput Microbore UPLC-MS Metabolic Phenotyping of Urine for Large-Scale Epidemiology Studies.

    PubMed

    Gray, Nicola; Lewis, Matthew R; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2015-06-05

    A new generation of metabolic phenotyping centers are being created to meet the increasing demands of personalized healthcare, and this has resulted in a major requirement for economical, high-throughput metabonomic analysis by liquid chromatography-mass spectrometry (LC-MS). Meeting these new demands represents an emerging bioanalytical problem that must be solved if metabolic phenotyping is to be successfully applied to large clinical and epidemiological sample sets. Ultraperformance (UP)LC-MS-based metabolic phenotyping, based on 2.1 mm i.d. LC columns, enables comprehensive metabolic phenotyping but, when employed for the analysis of thousands of samples, results in high solvent usage. The use of UPLC-MS employing 1 mm i.d. columns for metabolic phenotyping rather than the conventional 2.1 mm i.d. methodology shows that the resulting optimized microbore method provided equivalent or superior performance in terms of peak capacity, sensitivity, and robustness. On average, we also observed, when using the microbore scale separation, an increase in response of 2-3 fold over that obtained with the standard 2.1 mm scale method. When applied to the analysis of human urine, the 1 mm scale method showed no decline in performance over the course of 1000 analyses, illustrating that microbore UPLC-MS represents a viable alternative to conventional 2.1 mm i.d. formats for routine large-scale metabolic profiling studies while also resulting in a 75% reduction in solvent usage. The modest increase in sensitivity provided by this methodology also offers the potential to either reduce sample consumption or increase the number of metabolite features detected with confidence due to the increased signal-to-noise ratios obtained. Implementation of this miniaturized UPLC-MS method of metabolic phenotyping results in clear analytical, economic, and environmental benefits for large-scale metabolic profiling studies with similar or improved analytical performance compared to

  4. A Large-Scale Genetic Analysis Reveals a Strong Contribution of the HLA Class II Region to Giant Cell Arteritis Susceptibility

    PubMed Central

    Carmona, F. David; Mackie, Sarah L.; Martín, Jose-Ezequiel; Taylor, John C.; Vaglio, Augusto; Eyre, Stephen; Bossini-Castillo, Lara; Castañeda, Santos; Cid, Maria C.; Hernández-Rodríguez, José; Prieto-González, Sergio; Solans, Roser; Ramentol-Sintas, Marc; González-Escribano, M. Francisca; Ortiz-Fernández, Lourdes; Morado, Inmaculada C.; Narváez, Javier; Miranda-Filloy, José A.; Martínez-Berriochoa, Agustín; Unzurrunzaga, Ainhoa; Hidalgo-Conde, Ana; Madroñero-Vuelta, Ana B.; Fernández-Nebro, Antonio; Ordóñez-Cañizares, M. Carmen; Escalante, Begoña; Marí-Alfonso, Begoña; Sopeña, Bernardo; Magro, César; Raya, Enrique; Grau, Elena; Román, José A.; de Miguel, Eugenio; López-Longo, F. Javier; Martínez, Lina; Gómez-Vaquero, Carmen; Fernández-Gutiérrez, Benjamín; Rodríguez-Rodríguez, Luis; Díaz-López, J. Bernardino; Caminal-Montero, Luis; Martínez-Zapico, Aleida; Monfort, Jordi; Tío, Laura; Sánchez-Martín, Julio; Alegre-Sancho, Juan J.; Sáez-Comet, Luis; Pérez-Conesa, Mercedes; Corbera-Bellalta, Marc; García-Villanueva, M. Jesús; Fernández-Contreras, M. Encarnación; Sanchez-Pernaute, Olga; Blanco, Ricardo; Ortego-Centeno, Norberto; Ríos-Fernández, Raquel; Callejas, José L.; Fanlo-Mateo, Patricia; Martínez-Taboada, Víctor M.; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Gianfreda, Davide; Santilli, Daniele; Ramirez, Giuseppe A.; Soriano, Alessandra; Muratore, Francesco; Pazzola, Giulia; Addimanda, Olga; Wijmenga, Cisca; Witte, Torsten; Schirmer, Jan H.; Moosig, Frank; Schönau, Verena; Franke, Andre; Palm, Øyvind; Molberg, Øyvind; Diamantopoulos, Andreas P.; Carette, Simon; Cuthbertson, David; Forbess, Lindsy J.; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; McAlear, Carol A.; Moreland, Larry; Monach, Paul A.; Pagnoux, Christian; Seo, Philip; Spiera, Robert; Sreih, Antoine G.; Warrington, Kenneth J.; Ytterberg, Steven R.; Gregersen, Peter K.; Pease, Colin T.; Gough, Andrew; Green, Michael; Hordon, Lesley; Jarrett, Stephen; Watts, Richard; Levy, Sarah; Patel, Yusuf; Kamath, Sanjeet; Dasgupta, Bhaskar; Worthington, Jane; Koeleman, Bobby P.C.; de Bakker, Paul I.W.; Barrett, Jennifer H.; Salvarani, Carlo; Merkel, Peter A.; González-Gay, Miguel A.; Morgan, Ann W.; Martín, Javier

    2015-01-01

    We conducted a large-scale genetic analysis on giant cell arteritis (GCA), a polygenic immune-mediated vasculitis. A case-control cohort, comprising 1,651 case subjects with GCA and 15,306 unrelated control subjects from six different countries of European ancestry, was genotyped by the Immunochip array. We also imputed HLA data with a previously validated imputation method to perform a more comprehensive analysis of this genomic region. The strongest association signals were observed in the HLA region, with rs477515 representing the highest peak (p = 4.05 × 10−40, OR = 1.73). A multivariate model including class II amino acids of HLA-DRβ1 and HLA-DQα1 and one class I amino acid of HLA-B explained most of the HLA association with GCA, consistent with previously reported associations of classical HLA alleles like HLA-DRB1∗04. An omnibus test on polymorphic amino acid positions highlighted DRβ1 13 (p = 4.08 × 10−43) and HLA-DQα1 47 (p = 4.02 × 10−46), 56, and 76 (both p = 1.84 × 10−45) as relevant positions for disease susceptibility. Outside the HLA region, the most significant loci included PTPN22 (rs2476601, p = 1.73 × 10−6, OR = 1.38), LRRC32 (rs10160518, p = 4.39 × 10−6, OR = 1.20), and REL (rs115674477, p = 1.10 × 10−5, OR = 1.63). Our study provides evidence of a strong contribution of HLA class I and II molecules to susceptibility to GCA. In the non-HLA region, we confirmed a key role for the functional PTPN22 rs2476601 variant and proposed other putative risk loci for GCA involved in Th1, Th17, and Treg cell function. PMID:25817017

  5. Large-scale production and study of a synthetic G protein-coupled receptor: human olfactory receptor 17-4.

    PubMed

    Cook, Brian L; Steuerwald, Dirk; Kaiser, Liselotte; Graveland-Bikker, Johanna; Vanberghem, Melanie; Berke, Allison P; Herlihy, Kara; Pick, Horst; Vogel, Horst; Zhang, Shuguang

    2009-07-21

    Although understanding of the olfactory system has progressed at the level of downstream receptor signaling and the wiring of olfactory neurons, the system remains poorly understood at the molecular level of the receptors and their interaction with and recognition of odorant ligands. The structure and functional mechanisms of these receptors still remain a tantalizing enigma, because numerous previous attempts at the large-scale production of functional olfactory receptors (ORs) have not been successful to date. To investigate the elusive biochemistry and molecular mechanisms of olfaction, we have developed a mammalian expression system for the large-scale production and purification of a functional OR protein in milligram quantities. Here, we report the study of human OR17-4 (hOR17-4) purified from a HEK293S tetracycline-inducible system. Scale-up of production yield was achieved through suspension culture in a bioreactor, which enabled the preparation of >10 mg of monomeric hOR17-4 receptor after immunoaffinity and size exclusion chromatography, with expression yields reaching 3 mg/L of culture medium. Several key post-translational modifications were identified using MS, and CD spectroscopy showed the receptor to be approximately 50% alpha-helix, similar to other recently determined G protein-coupled receptor structures. Detergent-solubilized hOR17-4 specifically bound its known activating odorants lilial and floralozone in vitro, as measured by surface plasmon resonance. The hOR17-4 also recognized specific odorants in heterologous cells as determined by calcium ion mobilization. Our system is feasible for the production of large quantities of OR necessary for structural and functional analyses and research into OR biosensor devices.

  6. Assessing the impact of hydrodynamics on large-scale flood wave propagation - a case study for the Amazon Basin

    NASA Astrophysics Data System (ADS)

    Hoch, Jannis M.; Haag, Arjen V.; van Dam, Arthur; Winsemius, Hessel C.; van Beek, Ludovicus P. H.; Bierkens, Marc F. P.

    2017-01-01

    Large-scale flood events often show spatial correlation in neighbouring basins, and thus can affect adjacent basins simultaneously, as well as result in superposition of different flood peaks. Such flood events therefore need to be addressed with large-scale modelling approaches to capture these processes. Many approaches currently in place are based on either a hydrologic or a hydrodynamic model. However, the resulting lack of interaction between hydrology and hydrodynamics, for instance, by implementing groundwater infiltration on inundated floodplains, can hamper modelled inundation and discharge results where such interactions are important. In this study, the global hydrologic model PCR-GLOBWB at 30 arcmin spatial resolution was one-directionally and spatially coupled with the hydrodynamic model Delft 3D Flexible Mesh (FM) for the Amazon River basin at a grid-by-grid basis and at a daily time step. The use of a flexible unstructured mesh allows for fine-scale representation of channels and floodplains, while preserving a coarser spatial resolution for less flood-prone areas, thus not unnecessarily increasing computational costs. In addition, we assessed the difference between a 1-D channel/2-D floodplain and a 2-D schematization in Delft 3D FM. Validating modelled discharge results shows that coupling PCR-GLOBWB to a hydrodynamic routing scheme generally increases model performance compared to using a hydrodynamic or hydrologic model only for all validation parameters applied. Closer examination shows that the 1-D/2-D schematization outperforms 2-D for r2 and root mean square error (RMSE) whilst having a lower Kling-Gupta efficiency (KGE). We also found that spatial coupling has the significant advantage of a better representation of inundation at smaller streams throughout the model domain. A validation of simulated inundation extent revealed that only those set-ups incorporating 1-D channels are capable of representing inundations for reaches below the

  7. Large-scale circuit simulation

    NASA Astrophysics Data System (ADS)

    Wei, Y. P.

    1982-12-01

    The simulation of VLSI (Very Large Scale Integration) circuits falls beyond the capabilities of conventional circuit simulators like SPICE. On the other hand, conventional logic simulators can only give the results of logic levels 1 and 0 with the attendent loss of detail in the waveforms. The aim of developing large-scale circuit simulation is to bridge the gap between conventional circuit simulation and logic simulation. This research is to investigate new approaches for fast and relatively accurate time-domain simulation of MOS (Metal Oxide Semiconductors), LSI (Large Scale Integration) and VLSI circuits. New techniques and new algorithms are studied in the following areas: (1) analysis sequencing (2) nonlinear iteration (3) modified Gauss-Seidel method (4) latency criteria and timestep control scheme. The developed methods have been implemented into a simulation program PREMOS which could be used as a design verification tool for MOS circuits.

  8. Study of Large-Scale Wave Structure and Development of Equatorial Plasma Bubbles Using the C/NOFS Satellite

    DTIC Science & Technology

    2012-10-31

    R.T., Multi-reflected echoes : Another ionogram signature of large-scale wave structure, Geophys. Res. Lett., 36, L01102, doi:10.1029/2008GL036221...model to relate multi-reflected echoes and satellite traces to large-scale wave structure, Geophys. Res. Lett., in press, 2012a. Tsunoda, R.T., On...Ram et al. [2011]). (a) Satellite tracks at the ionospheric penetration points (IPP) from each of the three stations. (b) Absolute TEC as a function

  9. Large-Scale Disasters

    NASA Astrophysics Data System (ADS)

    Gad-El-Hak, Mohamed

    "Extreme" events - including climatic events, such as hurricanes, tornadoes, and drought - can cause massive disruption to society, including large death tolls and property damage in the billions of dollars. Events in recent years have shown the importance of being prepared and that countries need to work together to help alleviate the resulting pain and suffering. This volume presents a review of the broad research field of large-scale disasters. It establishes a common framework for predicting, controlling and managing both manmade and natural disasters. There is a particular focus on events caused by weather and climate change. Other topics include air pollution, tsunamis, disaster modeling, the use of remote sensing and the logistics of disaster management. It will appeal to scientists, engineers, first responders and health-care professionals, in addition to graduate students and researchers who have an interest in the prediction, prevention or mitigation of large-scale disasters.

  10. Using Social Media to Measure Student Wellbeing: A Large-Scale Study of Emotional Response in Academic Discourse

    SciTech Connect

    Volkova, Svitlana; Han, Kyungsik; Corley, Courtney D.

    2016-11-15

    Student resilience and emotional well-being are essential for both academic and social development. Earlier studies on tracking students' happiness in academia showed that many of them struggle with mental health issues. For example, a 2015 study at the University of California Berkeley found that 47% of graduate students suffer from depression, following a 2005 study that showed 10% had considered suicide. This is the first large-scale study that uses signals from social media to evaluate students' emotional well-being in academia. This work presents fine-grained emotion and opinion analysis of 79,329 tweets produced by students from 44 universities. The goal of this study is to qualitatively evaluate and compare emotions and sentiments emanating from students' communications across different academic discourse types and across universities in the U.S. We first build novel predictive models to categorize academic discourse types generated by students into personal, social, and general categories. We then apply emotion and sentiment classification models to annotate each tweet with six Ekman's emotions -- joy, fear, sadness, disgust, anger, and surprise and three opinion types -- positive, negative, and neutral. We found that emotions and opinions expressed by students vary across discourse types and universities, and correlate with survey-based data on student satisfaction, happiness and stress. Moreover, our results provide novel insights on how students use social media to share academic information, emotions, and opinions that would pertain to students academic performance and emotional well-being.

  11. Prospective and Retrospective Studies of Substance Abuse Treatment Outcomes: Methods and Results of Four Large-Scale Follow-Up Studies.

    ERIC Educational Resources Information Center

    Gerstein, Dean R.; Johnson, Robert A.

    This report compares the research methods, provider and patient characteristics, and outcome results from four large-scale followup studies of drug treatment during the 1990s: (1) the California Drug and Alcohol Treatment Assessment (CALDATA); (2) Services Research Outcomes Study (SROS); (3) National Treatment Improvement Evaluation Study (NTIES);…

  12. A large-scale study of the world wide web: network correlation functions with scale-invariant boundaries

    NASA Astrophysics Data System (ADS)

    Ludueña, Guillermo A.; Meixner, Harald; Kaczor, Gregor; Gros, Claudius

    2013-08-01

    We performed a large-scale crawl of the world wide web, covering 6.9 million domains and 57 million subdomains, including all high-traffic sites of the internet. We present a study of the correlations found between quantities measuring the structural relevance of each node in the network (the in- and out-degree, the local clustering coefficient, the first-neighbor in-degree and the Alexa rank). We find that some of these properties show strong correlation effects and that the dependencies occurring out of these correlations follow power laws not only for the averages, but also for the boundaries of the respective density distributions. In addition, these scale-free limits do not follow the same exponents as the corresponding averages. In our study we retain the directionality of the hyperlinks and develop a statistical estimate for the clustering coefficient of directed graphs. We include in our study the correlations between the in-degree and the Alexa traffic rank, a popular index for the traffic volume, finding non-trivial power-law correlations. We find that sites with more/less than about 103 links from different domains have remarkably different statistical properties, for all correlation functions studied, indicating towards an underlying hierarchical structure of the world wide web.

  13. Study of materials and machines for 3D printed large-scale, flexible electronic structures using fused deposition modeling

    NASA Astrophysics Data System (ADS)

    Hwang, Seyeon

    The 3 dimensional printing (3DP), called to additive manufacturing (AM) or rapid prototyping (RP), is emerged to revolutionize manufacturing and completely transform how products are designed and fabricated. A great deal of research activities have been carried out to apply this new technology to a variety of fields. In spite of many endeavors, much more research is still required to perfect the processes of the 3D printing techniques especially in the area of the large-scale additive manufacturing and flexible printed electronics. The principles of various 3D printing processes are briefly outlined in the Introduction Section. New types of thermoplastic polymer composites aiming to specified functional applications are also introduced in this section. Chapter 2 shows studies about the metal/polymer composite filaments for fused deposition modeling (FDM) process. Various metal particles, copper and iron particles, are added into thermoplastics polymer matrices as the reinforcement filler. The thermo-mechanical properties, such as thermal conductivity, hardness, tensile strength, and fracture mechanism, of composites are tested to figure out the effects of metal fillers on 3D printed composite structures for the large-scale printing process. In Chapter 3, carbon/polymer composite filaments are developed by a simple mechanical blending process with an aim of fabricating the flexible 3D printed electronics as a single structure. Various types of carbon particles consisting of multi-wall carbon nanotube (MWCNT), conductive carbon black (CCB), and graphite are used as the conductive fillers to provide the thermoplastic polyurethane (TPU) with improved electrical conductivity. The mechanical behavior and conduction mechanisms of the developed composite materials are observed in terms of the loading amount of carbon fillers in this section. Finally, the prototype flexible electronics are modeled and manufactured by the FDM process using Carbon/TPU composite filaments and

  14. Functional connectivity of large-scale brain networks in patients with anti-NMDA receptor encephalitis: an observational study.

    PubMed

    Peer, Michael; Prüss, Harald; Ben-Dayan, Inbal; Paul, Friedemann; Arzy, Shahar; Finke, Carsten

    2017-10-01

    In anti-NMDA receptor (NMDAR) encephalitis, antibody-mediated dysfunction of NMDARs causes severe neuropsychiatric symptoms, including psychosis, memory deficits, and movement disorders. However, it remains elusive how antibody-mediated NMDAR dysfunction leads to these symptoms, and whether the symptoms arise from impairment in specific brain regions and the interactions between impaired regions. In this observational study, we recruited 43 patients with anti-NMDAR encephalitis from a tertiary university hospital and 43 age-matched and sex-matched healthy controls without a history of neurological or psychiatric disorders, who were recruited from the general population of Berlin. We used structural and resting-state functional MRI to investigate alterations in connectivity in all participants. We did functional connectivity analyses, including large-scale network analysis, whole-brain pair-wise connectivity, and machine-learning classification, and compared the results with patients' functional impairment. Although structural MRI was normal in 31 (72%) of the 43 patients, we observed widespread alterations of functional connectivity that correlated with clinical measures. These alterations included impaired hippocampal functional connectivity, decoupling of the medial temporal and the default-mode networks, and an overall impairment of frontotemporal connections. Furthermore, functional connectivity was impaired within distributed large-scale networks, including sensorimotor, frontoparietal, lateral-temporal, and visual networks. Memory impairment correlated with hippocampal and medial-temporal-lobe network connectivity, whereas schizophrenia-like symptoms were associated with functional connectivity changes in frontoparietal networks. Machine-learning analyses corroborated these findings and identified frontoparietal and frontotemporal connections as reliably discriminating features between patients and controls, yielding an overall accuracy of 81%. This study

  15. Effect of taxanes-based induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: A large scale propensity-matched study.

    PubMed

    Zhang, Lu-Ning; Gao, Yuan-Hong; Lan, Xiao-Wen; Tang, Jie; OuYang, Pu-Yun; Xie, Fang-Yun

    2015-10-01

    The effect of taxanes-based induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) was quite contradictory in two phase II randomized controlled trials with small sample size. We aimed to investigate it in this large scale propensity-matched study. Totally, 779 LA-NPC patients who underwent intensity-modulated radiotherapy (IMRT) plus concurrent chemotherapy with or without taxanes-based IC were included. Patients in both treatment arms were matched using propensity score matching method at the ratio of 1:1. Failure-free survival (FFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression analysis. After matching, 534 patients were identified for analysis. In univariate analysis, both treatment arms resulted in parallel survival (4-years FFS 78.0% vs 74.1%, P = 0.304; OS 87.5% vs 87.3%, P = 0.595; DMFS 88.2% vs 84.4%, P = 0.154; and LRFS 91.2% vs 90.1%, P = 0.960). In multivariate analysis, taxanes-based IC did not improve any survival (P ⩾ 0.139). And this association remained unchanged in subgroup analysis by age, sex and histology, and among patients with stage III and T4N0M0. But among patients with T4N1-2M0 and stage IVb, taxanes-based IC significantly prolonged the 4-year DMFS by 11.2% (86.1% vs 74.9%, P = 0.034), and marginally improved FFS (P = 0.133) and OS (P = 0.215) in both univariate and multivariate analysis. In this large scale propensity-matched study, LA-NPC patients could not benefit from taxanes-based IC on the whole. But the risk of distant metastasis significantly decreased by above 10% for patients with T4N1-2M0 and stage IVb. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  16. Large-scale biofilm cultivation of Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 for physiologic studies and drug discovery.

    PubMed

    Parrilli, Ermenegilda; Ricciardelli, Annarita; Casillo, Angela; Sannino, Filomena; Papa, Rosanna; Tilotta, Marco; Artini, Marco; Selan, Laura; Corsaro, Maria Michela; Tutino, Maria Luisa

    2016-03-01

    Microbial biofilms are mainly studied due to detrimental effects on human health but they are also well established in industrial biotechnology for the production of chemicals. Moreover, biofilm can be considered as a source of novel drugs since the conditions prevailing within biofilm can allow the production of specific metabolites. Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 when grown in biofilm condition produces an anti-biofilm molecule able to inhibit the biofilm of the opportunistic pathogen Staphylococcus epidermidis. In this paper we set up a P. haloplanktis TAC125 biofilm cultivation methodology in automatic bioreactor. The biofilm cultivation was designated to obtain two goals: (1) the scale up of cell-free supernatant production in an amount necessary for the anti-biofilm molecule/s purification; (2) the recovery of P. haloplanktis TAC125 cells grown in biofilm for physiological studies. We set up a fluidized-bed reactor fermentation in which floating polystyrene supports were homogeneously mixed, exposing an optimal air-liquid interface to let bacterium biofilm formation. The proposed methodology allowed a large-scale production of anti-biofilm molecule and paved the way to study differences between P. haloplanktis TAC125 cells grown in biofilm and in planktonic conditions. In particular, the modifications occurring in the lipopolysaccharide of cells grown in biofilm were investigated.

  17. Characterizing Coherent Wind Structures using Large-Scale Particle Tracking Velocimetry: A Proof-of-Principle Study

    NASA Astrophysics Data System (ADS)

    Rosi, G. A.; la Bastide, B.; Gaebler, J.; Kinzel, M.; Rival, D. E.

    2014-12-01

    The following study proposes a two-dimensional large-scale particle tracking velocimetry (LS-PTV) system to characterize coherent wind structures. Seven minutes of LS-PTV data is collected via an apparatus that seeds fog-filled soap bubbles into the wind at a height of 6m from the ground. The LS-PTV data is compared to 20 minutes of data collected concurrently from a wind mast at the same site. The LS-PTV system recorded a mean streamwise velocity of 1.35m/s with a standard deviation of 0.23m/s at a mean height of 2.50m with a standard deviation of 0.7m, which agrees well with the velocity profile measured by the wind mast. Furthermore, the Reynolds stresses measured by the LS-PTV system are found to compare to those measured by the wind mast and by Klebanoff [1] for a canonical turbulent boundary layer. The current study assumes that the centre-of-curvature trajectories of the particle pathlines are representative of the trajectories followed by the spanwise vortices. As a proof-of-principle study, this work has been successful in accurately describing the vortex distribution very near to the ground. However, the trajectories followed by the centres-of- curvat.ure belonging to pathlines concurrently passing through the field-of-view were sporadic and uncorrelated.

  18. A follow-up study of hygiene in catering premises at large-scale events in the United Kingdom.

    PubMed

    Willis, C; Elviss, N; McLauchlin, J

    2015-01-01

    To investigate food hygiene practices at large events by assessing the microbiological quality of ready-to-eat food, drinking water, food preparation surfaces, cleaning cloths and wristbands worn by food handlers for event security purposes. Over a 7-month period, 1662 samples were collected at 153 events and examined for microbiological contamination. Eight per cent of food samples were of an unsatisfactory quality. A further one per cent contained potentially hazardous levels of human pathogenic bacteria. 27% of water samples, 32% of swabs and 56% of cloths were also unsatisfactory. These results represented an improvement in hygiene compared to a previous study carried out 12 months previously. A fifth of food handler wristbands were contaminated with Enterobacteriaceae, Escherichia coli and/or coagulase-positive staphylococci, with those bands made from fabric being more frequently contaminated than those made from plastic or other materials. This study provides evidence that the food hygiene at large-scale events may have improved. However, there is still a need for continued efforts to maintain an ongoing improvement in cleaning regimes and food hygiene management. This study was part of an ongoing focus on large events in the lead-up to the London 2012 Olympics. Lessons learnt here will be important in the planning of future large events. © 2014 Crown copyright. © 2014 Society for Applied Microbiology This article is Published with the permission of the Controller of HMSO and Queen's Printer for Scotland.

  19. Concurrent Validity and Feasibility of Short Tests Currently Used to Measure Early Childhood Development in Large Scale Studies

    PubMed Central

    Rubio-Codina, Marta; Araujo, M. Caridad; Attanasio, Orazio; Muñoz, Pablo; Grantham-McGregor, Sally

    2016-01-01

    below 19 months, and language above. Predictive validity investigation is needed to further guide the choice of instruments for large scale studies. PMID:27548634

  20. Calibration of a large-scale groundwater flow model using GRACE data: a case study in the Qaidam Basin, China

    NASA Astrophysics Data System (ADS)

    Hu, Litang; Jiao, Jiu Jimmy

    2015-11-01

    Traditional numerical models usually use extensive observed hydraulic-head data as calibration targets. However, this calibration process is not applicable in remote areas with limited or no monitoring data. This study presents an approach to calibrate a large-scale groundwater flow model using the monthly Gravity Recovery and Climate Experiment (GRACE) satellite data, which have been available globally on a spatial grid of 1° in the geographic coordinate system since 2002. A groundwater storage anomaly isolated from the terrestrial water storage (TWS) anomaly is converted into hydraulic head at the center of the grid, which is then used as observed data to calibrate a numerical model to estimate aquifer hydraulic conductivity. The aquifer system in the remote and hyperarid Qaidam Basin, China, is used as a case study to demonstrate the applicability of this approach. A groundwater model using FEFLOW is constructed for the Qaidam Basin and the GRACE-derived groundwater storage anomaly over the period 2003-2012 is included to calibrate the model, which is done using an automatic estimation method (PEST). The calibrated model is then run to output hydraulic heads at three sites where long-term hydraulic head data are available. The reasonably good fit between the calculated and observed hydraulic heads, together with the very similar groundwater storage anomalies from the numerical model and GRACE data, demonstrate that this approach is generally applicable in regions of groundwater data scarcity.

  1. Identifiability of large-scale non-linear dynamic network models applied to the ADM1-case study.

    PubMed

    Nimmegeers, Philippe; Lauwers, Joost; Telen, Dries; Logist, Filip; Impe, Jan Van

    2017-06-01

    In this work, both the structural and practical identifiability of the Anaerobic Digestion Model no. 1 (ADM1) is investigated, which serves as a relevant case study of large non-linear dynamic network models. The structural identifiability is investigated using the probabilistic algorithm, adapted to deal with the specifics of the case study (i.e., a large-scale non-linear dynamic system of differential and algebraic equations). The practical identifiability is analyzed using a Monte Carlo parameter estimation procedure for a 'non-informative' and 'informative' experiment, which are heuristically designed. The model structure of ADM1 has been modified by replacing parameters by parameter combinations, to provide a generally locally structurally identifiable version of ADM1. This means that in an idealized theoretical situation, the parameters can be estimated accurately. Furthermore, the generally positive structural identifiability results can be explained from the large number of interconnections between the states in the network structure. This interconnectivity, however, is also observed in the parameter estimates, making uncorrelated parameter estimations in practice difficult. Copyright © 2017. Published by Elsevier Inc.

  2. Final Results from a Large-Scale National Study of General Education Astronomy Students’ Learning Difficulties with Cosmology

    NASA Astrophysics Data System (ADS)

    Wallace, Colin Scott; Prather, E. E.; Duncan, D. K.; Collaboration of Astronomy Teaching Scholars CATS

    2012-01-01

    We recently completed a large-scale, systematic study of general education introductory astronomy students’ conceptual and reasoning difficulties related to cosmology. As part of this study, we analyzed a total of 4359 surveys (pre- and post-instruction) containing students’ responses to questions about the Big Bang, the evolution and expansion of the universe, using Hubble plots to reason about the age and expansion rate of the universe, and using galaxy rotation curves to infer the presence of dark matter. We also designed, piloted, and validated a new suite of five cosmology Lecture-Tutorials. We found that students who use the new Lecture-Tutorials can achieve larger learning gains than their peers who did not. This material is based in part upon work supported by the National Science Foundation under Grant Nos. 0833364 and 0715517, a CCLI Phase III Grant for the Collaboration of Astronomy Teaching Scholars (CATS). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

  3. Final Results from a Large-Scale National Study of General Education Astronomy Students' Learning Difficulties with Cosmology

    NASA Astrophysics Data System (ADS)

    Wallace, Colin; Prather, Edward; Duncan, Douglas

    2011-10-01

    We recently completed a large-scale, systematic study of general education introductory astronomy students' conceptual and reasoning difficulties related to cosmology. As part of this study, we analyzed a total of 4359 surveys (pre- and post-instruction) containing students' responses to questions about the Big Bang, the evolution and expansion of the universe, using Hubble plots to reason about the age and expansion rate of the universe, and using galaxy rotation curves to infer the presence of dark matter. We also designed, piloted, and validated a new suite of five cosmology Lecture-Tutorials. We found that students who use the new Lecture-Tutorials can achieve larger learning gains than their peers who did not. This material is based in part upon work supported by the National Science Foundation under Grant Nos. 0833364 and 0715517, a CCLI Phase III Grant for the Collaboration of Astronomy Teaching Scholars (CATS). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation.

  4. High Intake of Manganese During Second Trimester, Increases the Risk of Preterm Delivery: A Large Scale Cohort Study

    PubMed Central

    Bakouei, Sare; Reisian, Fatemeh; Lamyian, Minoor; Zadeh, Ebrahim Haji; Zamanian, Hadi; Kharameh, Zahra Taheri

    2015-01-01

    Evidence indicates that nutrients and minerals might play an important role in preterm delivery (PTD). The aim of this study was to determine maternal nutritional status during second trimester of pregnancy and its association with preterm delivery (< 34 weeks gestation) in Iranian women. In a large scale longitudinal study, 1033 pregnant women were recruited from prenatal clinics since December 2012 to June 2013. Dietary intake was assessed by Food Frequency Questionnaire (FFQ) in pregnant women of 14 to 20 weeks gestational age. The participants were followed up until delivery. Dietary intake of women with preterm delivery was compared with women who had term delivery. The results show that 61.2% of women were primiparous and that the incidence of preterm delivery was 7%. Manganese dietary intake was significantly higher in mothers with preterm delivery than those with term delivery (P = .03). Manganese was the only micronutrient correlated with preterm delivery after adjustment for maternal characteristics during second trimesters of pregnancy (OR = 1.12; P = .01). These results suggest that high maternal manganese dietary intake during the second trimester of pregnancy may be associated with the risk of preterm delivery in Iranian pregnant women. PMID:26156900

  5. Galaxy clustering on large scales.

    PubMed Central

    Efstathiou, G

    1993-01-01

    I describe some recent observations of large-scale structure in the galaxy distribution. The best constraints come from two-dimensional galaxy surveys and studies of angular correlation functions. Results from galaxy redshift surveys are much less precise but are consistent with the angular correlations, provided the distortions in mapping between real-space and redshift-space are relatively weak. The galaxy two-point correlation function, rich-cluster two-point correlation function, and galaxy-cluster cross-correlation function are all well described on large scales ( greater, similar 20h-1 Mpc, where the Hubble constant, H0 = 100h km.s-1.Mpc; 1 pc = 3.09 x 10(16) m) by the power spectrum of an initially scale-invariant, adiabatic, cold-dark-matter Universe with Gamma = Omegah approximately 0.2. I discuss how this fits in with the Cosmic Background Explorer (COBE) satellite detection of large-scale anisotropies in the microwave background radiation and other measures of large-scale structure in the Universe. PMID:11607400

  6. Large Scale Nonlinear Programming.

    DTIC Science & Technology

    1978-06-15

    KEY WORDS (Conhinu. as, t.n.t.. aid. if nic••iary aid ld.ntify by block n,a,b.r) L. In,~~~ IP!CIE LARGE SCALE OPTIMIZATION APPLICATIONS OF NONLINEAR ... NONLINEAR PROGRAMMING by Garth P. McCormick 1. Introduction The general mathematical programming ( optimization ) problem can be stated in the following form...because the difficulty in solving a general nonlinear optimization problem has a~ much to do with the nature of the functions involved as it does with the

  7. Absolute pitch among students at the Shanghai Conservatory of Music: a large-scale direct-test study.

    PubMed

    Deutsch, Diana; Li, Xiaonuo; Shen, Jing

    2013-11-01

    This paper reports a large-scale direct-test study of absolute pitch (AP) in students at the Shanghai Conservatory of Music. Overall note-naming scores were very high, with high scores correlating positively with early onset of musical training. Students who had begun training at age ≤5 yr scored 83% correct not allowing for semitone errors and 90% correct allowing for semitone errors. Performance levels were higher for white key pitches than for black key pitches. This effect was greater for orchestral performers than for pianists, indicating that it cannot be attributed to early training on the piano. Rather, accuracy in identifying notes of different names (C, C#, D, etc.) correlated with their frequency of occurrence in a large sample of music taken from the Western tonal repertoire. There was also an effect of pitch range, so that performance on tones in the two-octave range beginning on Middle C was higher than on tones in the octave below Middle C. In addition, semitone errors tended to be on the sharp side. The evidence also ran counter to the hypothesis, previously advanced by others, that the note A plays a special role in pitch identification judgments.

  8. Evaluation of human response to blasting vibration from excavation of a large scale rock slope: A case study

    NASA Astrophysics Data System (ADS)

    Yan, Peng; Lu, Wenbo; Zhang, Jing; Zou, Yujun; Chen, Ming

    2017-04-01

    Ground vibration, as the most critical public hazard of blasting, has received much attention from the community. Many countries established national standards to suppress vibration impact on structures, but a world-accepted blasting vibration criterion on human safety is still missing. In order to evaluate human response to the vibration from blasting excavation of a large-scale rock slope in China, this study aims to suggest a revised criterion. The vibration frequency was introduced to improve the existing single-factor (peak particle velocity) standard recommended by the United States Bureau of Mines (USBM). The feasibility of the new criterion was checked based on field vibration monitoring and investigation of human reactions. Moreover, the air overpressure or blast effects on human beings have also been discussed. The result indicates that the entire zone of influence can be divided into three subzones: severe-annoyance, light-annoyance and perception zone according to the revised safety standard. Both the construction company and local residents have provided positive comments on this influence degree assessment, which indicates that the presented criterion is suitable for evaluating human response to nearby blasts. Nevertheless, this specific criterion needs more field tests and verifications before it can be

  9. Nanochannel Platform for Single-DNA Studies; From DNA-Protein Interaction to Large Scale Genome Sequencing

    NASA Astrophysics Data System (ADS)

    van der Maarel, Johan; van Kan, Jeroen; Zhang, Ce

    2014-03-01

    The study of nanochannel-confined DNA molecules is of importance from both biotechnological and biophysical points of view. We produce nanochannels in elastomer-based biochips with soft lithography using proton beam writing technology. The cross-sectional diameter of the channels is in the range of 50 to 300 nm. Single DNA molecules confined inside these channels can be visualized with fluorescence microscopy. Two related issues concerning DNA confined in such a nanospace will be discussed. For the first issue, the dynamic effects of nucleoid associated proteins (H-NS and HU) and protamine on the conformation and condensation of DNA will be presented. We use a novel, cross-channel device, which allows the monitoring of the conformational response after a change in environmental solution conditions in situ. The second issue concerns bottlebrush-coated DNA. The bottlebrush has an increased bending rigidity and thickness, which results in an amplified stretch once it is confined inside a nanochannel. It will be demonstrated that large-scale genomic organization can be sequenced using single DNA molecules on an array of elastomeric nanochannels with cross-sectional diameters of 200 nm. Overall, our results show that the effects of proteins on the conformation and folding of DNA are not only related to protein binding, osmolarity, and charge, but that the interplay with confinement in a nanospace is of paramount importance.

  10. A field study of large-scale oscillation ripples in a very coarse-grained, high-energy marine environment

    USGS Publications Warehouse

    Hirschaut, D.W.; Dingler, J.R.

    1982-01-01

    Monastery Beach, Carmel, California is a pocket beach that sits within 200 m of the head of Carmel Submarine Canyon. Coarse to very coarse sand covers both the beach and adjacent shelf; in the latter area incoming waves have shaped the sand into large oscillation ripples. The accessibility of this area and a variable wave climate produce a unique opportunity to study large-scale coarse-grained ripples in a high-energy environment. These ripples, which only occur in very coarse sand, form under the intense, wave-generated currents that exist during storm conditions. Once formed, these ripples do not significantly change under lower energy waves. On three separate occasions scuba divers measured ripples and collected sand samples from ripple crests near fixed reference stakes along three transects. Ripple wavelength and grain size decreased with an increase in water depth. Sediment sorting was best closest to the surf zone and poorest at the rim of Carmel Canyon. Cobbles and gravel observed in ripple troughs represent lag deposits. Carmel Canyon refracts waves approaching Monastery Beach such that wave energy is focused towards the northern and southern portions of the beach, leaving the central part of the beach lower in energy. This energy distribution causes spatial variations in the ripples and grain sizes with the shortest wavelengths and smallest grain sizes being in the central part of the shelf.

  11. Serotonin reuptake inhibitor-induced sexual dysfunction and its treatment: a large-scale retrospective study of 596 psychiatric outpatients.

    PubMed

    Keller Ashton, A; Hamer, R; Rosen, R C

    1997-01-01

    In the present study, a large-scale retrospective case review was undertaken to assess the incidence and type of sexual dysfunctions associated with serotonin reuptake inhibitor (SRI) therapy, in addition to the effects of three pharmacological antidotes (yohimbine, amantadine, cyproheptadine) on SRI-induced sexual dysfunctions. A retrospective chart review was conducted on 596 patients treated with SRIs in an outpatient psychiatric practice between July 1991 and September 1994. Patients who reported new-onset sexual dysfunction during this time were categorized as having SRI-induced sexual dysfunctions. Sexual difficulties were characterized by type and duration, and the background characteristics and psychiatric diagnoses of all patients were recorded. Psychiatric outcome and sexual functioning at follow-up were independently assessed by a single psychiatrist by means of a 4-point rating scale. Sexual dysfunction symptoms were clearly associated with SRI administration in 97 (16.3%) cases. The most common problems reported were orgasmic delay or anorgasmia and hypoactive sexual desire. Sexual difficulties were more frequent among men (23.4%) and married patients of both sexes (22.3%), whereas psychiatric diagnosis and type of SRI were unrelated to the occurrence of sexual problems. Of the patients with sexual dysfunction, 45 (46.4%) opted for a trial of antidote therapy with yohimbine, amantadine, or cyproheptadine. All three antidotes were found to be safe and relatively effective, although yohimbine was significantly more effective than amantadine or cyproheptadine in reversing SRI-induced sexual dysfunction.

  12. A Triple Network Connectivity Study of Large-Scale Brain Systems in Cognitively Normal APOE4 Carriers

    PubMed Central

    Wu, Xia; Li, Qing; Yu, Xinyu; Chen, Kewei; Fleisher, Adam S.; Guo, Xiaojuan; Zhang, Jiacai; Reiman, Eric M.; Yao, Li; Li, Rui

    2016-01-01

    The triple network model, consisting of the central executive network (CEN), salience network (SN) and default mode network (DMN), has been recently employed to understand dysfunction in core networks across various disorders. Here we used the triple network model to investigate the large-scale brain networks in cognitively normal apolipoprotein e4 (APOE4) carriers who are at risk of Alzheimer’s disease (AD). To explore the functional connectivity for each of the three networks and the effective connectivity among them, we evaluated 17 cognitively normal individuals with a family history of AD and at least one copy of the APOE4 allele and compared the findings to those of 12 individuals who did not carry the APOE4 gene or have a family history of AD, using independent component analysis (ICA) and Bayesian network (BN) approach. Our findings indicated altered within-network connectivity that suggests future cognitive decline risk, and preserved between-network connectivity that may support their current preserved cognition in the cognitively normal APOE4 allele carriers. The study provides novel sights into our understanding of the risk factors for AD and their influence on the triple network model of major psychopathology. PMID:27733827

  13. Large-scale traveling ionospheric disturbances using ionospheric imaging at storm time: A case study on 17 march 2013

    NASA Astrophysics Data System (ADS)

    Tang, Jun; Yao, Yibin; Kong, Jian; Zhang, Liang

    2016-07-01

    A moderate geomagnetic storm occurred on March 17, 2013, during which large-scale traveling ionospheric disturbances (LSTIDs) are observed over China by ionosondes and GPS from Crustal Movement Observation Network of China (CMONOC) and the International GNSS Service (IGS). Ionosonde data and computerized ionospheric tomography (CIT) technique are employed to analyze the disturbances in our study. The maximum entropy cross spectral analysis (MECSA) method is used to obtain the propagation parameters of the LSTIDs. Spatio-temporal variations of ionospheric electron density (IED) and total electron content (TEC) during this geomagnetic storm over China are investigated. Disturbance images of IED and TEC are also presented in the paper. The results show two LSTID events at about 12:00 UT and 15:00 UT during the main phase of the storm. Besides, the LSTIDs with a duration of 40 min are detected over China. It is confirmed that the LSTIDs travel from north to south with a horizontal velocity of 400-500 m/s, and moved southwestwards with a horizontal velocity of 250-300 m/s, respectively.

  14. The importance of combining MRI and large-scale digital histology in neuroimaging studies of brain connectivity and disease

    PubMed Central

    Annese, Jacopo

    2012-01-01

    One of the major issues hindering a comprehensive connectivity model for the human brain is the difficulty in linking Magnetic Resonance Imaging (MRI) measurements to anatomical evidence produced by histological methods. In vivo and postmortem neuroimaging methodologies are still largely incompatible in terms of sample size, scale, and resolution. To help bridge the hiatus between different approaches we have established a program that characterizes the brain of individual subjects, combining MRI with postmortem neuroanatomy. The direct correlation of MRI and histological features is possible, because registered images from different modalities represent the same regions in the same brain. Comparisons are also facilitated by large-scale, digital microscopy techniques that afford images of the whole-brain sections at cellular resolution. The goal is to create a neuroimaging catalog representative of discrete age groups and specific neurological conditions. Individually, the datasets allow for investigating the relationship between different modalities; combined, they provide sufficient predictive power to inform analyses and interpretations made in the context of non-invasive studies of brain connectivity and disease. PMID:22536182

  15. Large-scale introduction of the Indo-Pacific damselfish Abudefduf vaigiensis into Hawai'i promotes genetic swamping of the endemic congener A. abdominalis.

    PubMed

    Coleman, Richard R; Gaither, Michelle R; Kimokeo, Bethany; Stanton, Frank G; Bowen, Brian W; Toonen, Robert J

    2014-11-01

    Hybridization in the ocean was once considered rare, a process prohibited by the rapid evolution of intrinsic reproductive barriers in a high-dispersal medium. However, recent genetic surveys have prompted a reappraisal of marine hybridization as an important demographic and evolutionary process. The Hawaiian Archipelago offers an unusual case history in this arena, due to the recent arrival of the widely distributed Indo-Pacific sergeant (Abudefduf vaigiensis), which is hybridizing with the endemic congener, A. abdominalis. Surveys of mtDNA and three nuclear loci across Hawai'i (N = 396, Abudefduf abdominalis and N = 314, A. vaigiensis) reveal that hybridization is significantly higher in the human-perturbed southeast archipelago (19.8%), tapering off to 5.9% in the pristine northwest archipelago. While densities of the two species varied throughout Hawai'i, hybridization was highest in regions with similar species densities, contradicting the generalization that the rarity of one species promotes interspecific mating. Our finding of later generation hybrids throughout the archipelago invokes the possibility of genetic swamping of the endemic species. Exaptation, an adaptation with unintended consequences, may explain these findings: the endemic species has transient yellow coloration during reproduction, whereas the introduced species has yellow coloration continuously as adults, in effect a permanent signal of reproductive receptivity. Haplotype diversity is higher in Hawaiian A. vaigiensis than in our samples from the native range, indicating large-scale colonization almost certainly facilitated by the historically recent surge of marine debris. In this chain of events, marine debris promotes colonization, exaptation promotes hybridization, and introgression invokes the possible collapse of an endemic species.

  16. Programmed Nanomaterial Assemblies in Large Scales: Applications of Synthetic and Genetically- Engineered Peptides to Bridge Nano-Assemblies and Macro-Assemblies

    SciTech Connect

    Matsui, Hiroshi

    2014-09-09

    Work is reported in these areas: Large-scale & reconfigurable 3D structures of precise nanoparticle assemblies in self-assembled collagen peptide grids; Binary QD-Au NP 3D superlattices assembled with collagen-like peptides and energy transfer between QD and Au NP in 3D peptide frameworks; Catalytic peptides discovered by new hydrogel-based combinatorial phage display approach and their enzyme-mimicking 2D assembly; New autonomous motors of metal-organic frameworks (MOFs) powered by reorganization of self-assembled peptides at interfaces; Biomimetic assembly of proteins into microcapsules on oil-in-water droplets with structural reinforcement via biomolecular recognition-based cross-linking of surface peptides; and Biomimetic fabrication of strong freestanding genetically-engineered collagen peptide films reinforced by quantum dot joints. We gained the broad knowledge about biomimetic material assembly from nanoscale to microscale ranges by coassembling peptides and NPs via biomolecular recognition. We discovered: Genetically-engineered collagen-like peptides can be self-assembled with Au NPs to generate 3D superlattices in large volumes (> μm{sup 3}); The assembly of the 3D peptide-Au NP superstructures is dynamic and the interparticle distance changes with assembly time as the reconfiguration of structure is triggered by pH change; QDs/NPs can be assembled with the peptide frameworks to generate 3D superlattices and these QDs/NPs can be electronically coupled for the efficient energy transfer; The controlled assembly of catalytic peptides mimicking the catalytic pocket of enzymes can catalyze chemical reactions with high selectivity; and, For the bacteria-mimicking swimmer fabrication, peptide-MOF superlattices can power translational and propellant motions by the reconfiguration of peptide assembly at the MOF-liquid interface.

  17. A large-scale complex haploinsufficiency-based genetic interaction screen in Candida albicans: analysis of the RAM network during morphogenesis.

    PubMed

    Bharucha, Nike; Chabrier-Rosello, Yeissa; Xu, Tao; Johnson, Cole; Sobczynski, Sarah; Song, Qingxuan; Dobry, Craig J; Eckwahl, Matthew J; Anderson, Christopher P; Benjamin, Andrew J; Kumar, Anju; Krysan, Damian J

    2011-04-01

    The morphogenetic transition between yeast and filamentous forms of the human fungal pathogen Candida albicans is regulated by a variety of signaling pathways. How these pathways interact to orchestrate morphogenesis, however, has not been as well characterized. To address this question and to identify genes that interact with the Regulation of Ace2 and Morphogenesis (RAM) pathway during filamentation, we report the first large-scale genetic interaction screen in C. albicans.Our strategy for this screen was based on the concept of complex haploinsufficiency (CHI). A heterozygous mutant of CBK1(cbk1Δ/CBK1), a key RAM pathway protein kinase, was subjected to transposon-mediated, insertional mutagenesis. The resulting double heterozygous mutants (6,528 independent strains) were screened for decreased filamentation on SpiderMedium (SM). From the 441 mutants showing altered filamentation, 139 transposon insertion sites were sequenced,yielding 41 unique CBK1-interacting genes. This gene set was enriched in transcriptional targets of Ace2 and, strikingly, the cAMP-dependent protein kinase A (PKA) pathway, suggesting an interaction between these two pathways. Further analysis indicates that the RAM and PKA pathways co-regulate a common set of genes during morphogenesis and that hyperactivation of the PKA pathway may compensate for loss of RAM pathway function. Our data also indicate that the PKA–regulated transcription factor Efg1 primarily localizes to yeast phase cells while the RAM–pathway regulated transcription factor Ace2 localizes to daughter nuclei of filamentous cells, suggesting that Efg1 and Ace2 regulate a common set of genes at separate stages of morphogenesis. Taken together, our observations indicate that CHI–based screening is a useful approach to genetic interaction analysis in C. albicans and support a model in which these two pathways regulate a common set of genes at different stages of filamentation.

  18. Development of the first marmoset-specific DNA microarray (EUMAMA): a new genetic tool for large-scale expression profiling in a non-human primate

    PubMed Central

    Datson, Nicole A; Morsink, Maarten C; Atanasova, Srebrena; Armstrong, Victor W; Zischler, Hans; Schlumbohm, Christina; Dutilh, Bas E; Huynen, Martijn A; Waegele, Brigitte; Ruepp, Andreas; de Kloet, E Ronald; Fuchs, Eberhard

    2007-01-01

    Background The common marmoset monkey (Callithrix jacchus), a small non-endangered New World primate native to eastern Brazil, is becoming increasingly used as a non-human primate model in biomedical research, drug development and safety assessment. In contrast to the growing interest for the marmoset as an animal model, the molecular tools for genetic analysis are extremely limited. Results Here we report the development of the first marmoset-specific oligonucleotide microarray (EUMAMA) containing probe sets targeting 1541 different marmoset transcripts expressed in hippocampus. These 1541 transcripts represent a wide variety of different functional gene classes. Hybridisation of the marmoset microarray with labelled RNA from hippocampus, cortex and a panel of 7 different peripheral tissues resulted in high detection rates of 85% in the neuronal tissues and on average 70% in the non-neuronal tissues. The expression profiles of the 2 neuronal tissues, hippocampus and cortex, were highly similar, as indicated by a correlation coefficient of 0.96. Several transcripts with a tissue-specific pattern of expression were identified. Besides the marmoset microarray we have generated 3215 ESTs derived from marmoset hippocampus, which have been annotated and submitted to GenBank [GenBank: EF214838 – EF215447, EH380242 – EH382846]. Conclusion We have generated the first marmoset-specific DNA microarray and demonstrated its use to characterise large-scale gene expression profiles of hippocampus but also of other neuronal and non-neuronal tissues. In addition, we have generated a large collection of ESTs of marmoset origin, which are now available in the public domain. These new tools will facilitate molecular genetic research into this non-human primate animal model. PMID:17592630

  19. RACORO continental boundary layer cloud investigations. Part I: Case study development and ensemble large-scale forcings

    DOE PAGES

    Vogelmann, Andrew M.; Fridlind, Ann M.; Toto, Tami; ...

    2015-06-19

    Observation-based modeling case studies of continental boundary layer clouds have been developed to study cloudy boundary layers, aerosol influences upon them, and their representation in cloud- and global-scale models. Three 60-hour case study periods span the temporal evolution of cumulus, stratiform, and drizzling boundary layer cloud systems, representing mixed and transitional states rather than idealized or canonical cases. Based on in-situ measurements from the RACORO field campaign and remote-sensing observations, the cases are designed with a modular configuration to simplify use in large-eddy simulations (LES) and single-column models. Aircraft measurements of aerosol number size distribution are fit to lognormal functionsmore » for concise representation in models. Values of the aerosol hygroscopicity parameter, κ, are derived from observations to be ~0.10, which are lower than the 0.3 typical over continents and suggestive of a large aerosol organic fraction. Ensemble large-scale forcing datasets are derived from the ARM variational analysis, ECMWF forecasts, and a multi-scale data assimilation system. The forcings are assessed through comparison of measured bulk atmospheric and cloud properties to those computed in 'trial' large-eddy simulations, where more efficient run times are enabled through modest reductions in grid resolution and domain size compared to the full-sized LES grid. Simulations capture many of the general features observed, but the state-of-the-art forcings were limited at representing details of cloud onset, and tight gradients and high-resolution transients of importance. Methods for improving the initial conditions and forcings are discussed. The cases developed are available to the general modeling community for studying continental boundary clouds.« less

  20. RACORO continental boundary layer cloud investigations. Part I: Case study development and ensemble large-scale forcings

    SciTech Connect

    Vogelmann, Andrew M.; Fridlind, Ann M.; Toto, Tami; Endo, Satoshi; Lin, Wuyin; Wang, Jian; Feng, Sha; Zhang, Yunyan; Turner, David D.; Liu, Yangang; Li, Zhijin; Xie, Shaocheng; Ackerman, Andrew S.; Zhang, Minghua; Khairoutdinov, Marat

    2015-06-19

    Observation-based modeling case studies of continental boundary layer clouds have been developed to study cloudy boundary layers, aerosol influences upon them, and their representation in cloud- and global-scale models. Three 60-hour case study periods span the temporal evolution of cumulus, stratiform, and drizzling boundary layer cloud systems, representing mixed and transitional states rather than idealized or canonical cases. Based on in-situ measurements from the RACORO field campaign and remote-sensing observations, the cases are designed with a modular configuration to simplify use in large-eddy simulations (LES) and single-column models. Aircraft measurements of aerosol number size distribution are fit to lognormal functions for concise representation in models. Values of the aerosol hygroscopicity parameter, κ, are derived from observations to be ~0.10, which are lower than the 0.3 typical over continents and suggestive of a large aerosol organic fraction. Ensemble large-scale forcing datasets are derived from the ARM variational analysis, ECMWF forecasts, and a multi-scale data assimilation system. The forcings are assessed through comparison of measured bulk atmospheric and cloud properties to those computed in 'trial' large-eddy simulations, where more efficient run times are enabled through modest reductions in grid resolution and domain size compared to the full-sized LES grid. Simulations capture many of the general features observed, but the state-of-the-art forcings were limited at representing details of cloud onset, and tight gradients and high-resolution transients of importance. Methods for improving the initial conditions and forcings are discussed. The cases developed are available to the general modeling community for studying continental boundary clouds.

  1. Linking Errors in Trend Estimation in Large-Scale Surveys: A Case Study. Research Report. ETS RR-10-10

    ERIC Educational Resources Information Center

    Xu, Xueli; von Davier, Matthias

    2010-01-01

    One of the major objectives of large-scale educational surveys is reporting trends in academic achievement. For this purpose, a substantial number of items are carried from one assessment cycle to the next. The linking process that places academic abilities measured in different assessments on a common scale is usually based on a concurrent…

  2. Self-Beliefs Mediate Math Performance between Primary and Lower Secondary School: A Large-Scale Longitudinal Cohort Study

    ERIC Educational Resources Information Center

    Reed, Helen C.; Kirschner, Paul A.; Jolles, Jelle

    2015-01-01

    It is often argued that enhancement of self-beliefs should be one of the key goals of education. However, very little is known about the relation between self-beliefs and performance when students move from primary to secondary school in highly differentiated educational systems with early tracking. This large-scale longitudinal cohort study…

  3. NAEP Validity Studies: Improving the Information Value of Performance Items in Large Scale Assessments. Working Paper No. 2003-08

    ERIC Educational Resources Information Center

    Pearson, P. David; Garavaglia, Diane R.

    2003-01-01

    The purpose of this essay is to explore both what is known and what needs to be learned about the information value of performance items "when they are used in large scale assessments." Within the context of the National Assessment of Educational Progress (NAEP), there is substantial motivation for answering these questions. Over the…

  4. The Relationships between Workaholism and Symptoms of Psychiatric Disorders: A Large-Scale Cross-Sectional Study

    PubMed Central

    Griffiths, Mark D.; Sinha, Rajita; Hetland, Jørn

    2016-01-01

    Despite the many number of studies examining workaholism, large-scale studies have been lacking. The present study utilized an open web-based cross-sectional survey assessing symptoms of psychiatric disorders and workaholism among 16,426 workers (Mage = 37.3 years, SD = 11.4, range = 16–75 years). Participants were administered the Adult ADHD Self-Report Scale, the Obsession-Compulsive Inventory-Revised, the Hospital Anxiety and Depression Scale, and the Bergen Work Addiction Scale, along with additional questions examining demographic and work-related variables. Correlations between workaholism and all psychiatric disorder symptoms were positive and significant. Workaholism comprised the dependent variable in a three-step linear multiple hierarchical regression analysis. Basic demographics (age, gender, relationship status, and education) explained 1.2% of the variance in workaholism, whereas work demographics (work status, position, sector, and annual income) explained an additional 5.4% of the variance. Age (inversely) and managerial positions (positively) were of most importance. The psychiatric symptoms (ADHD, OCD, anxiety, and depression) explained 17.0% of the variance. ADHD and anxiety contributed considerably. The prevalence rate of workaholism status was 7.8% of the present sample. In an adjusted logistic regression analysis, all psychiatric symptoms were positively associated with being a workaholic. The independent variables explained between 6.1% and 14.4% in total of the variance in workaholism cases. Although most effect sizes were relatively small, the study’s findings expand our understanding of possible psychiatric predictors of workaholism, and particularly shed new insight into the reality of adult ADHD in work life. The study’s implications, strengths, and shortcomings are also discussed. PMID:27192149

  5. A MBD-seq protocol for large-scale methylome-wide studies with (very) low amounts of DNA.

    PubMed

    Aberg, Karolina A; Chan, Robin F; Shabalin, Andrey A; Zhao, Min; Turecki, Gustavo; Heine Staunstrup, Nicklas; Starnawska, Anna; Mors, Ole; Xie, Lin Y; van den Oord, Edwin J C G

    2017-07-13

    We recently showed that, after optimization, our methyl-CpG binding domain sequencing (MBD-seq) application approximates the methylome-wide coverage obtained with whole-genome bisulfite sequencing (WGB-seq), but at a cost that enables adequately powered large-scale association studies. A prior drawback of MBD-seq is the relatively large amount of genomic DNA (ideally >1 μg) required to obtain high-quality data. Biomaterials are typically expensive to collect, provide a finite amount of DNA, and may simply not yield sufficient starting material. The ability to use low amounts of DNA will increase the breadth and number of studies that can be conducted. Therefore, we further optimized the enrichment step. With this low starting material protocol, MBD-seq performed equally well, or better, than the protocol requiring ample starting material (>1 μg). Using only 15 ng of DNA as input, there is minimal loss in data quality, achieving 93% of the coverage of WGB-seq (with standard amounts of input DNA) at similar false/positive rates. Furthermore, across a large number of genomic features, the MBD-seq methylation profiles closely tracked those observed for WGB-seq with even slightly larger effect sizes. This suggests that MBD-seq provides similar information about the methylome and classifies methylation status somewhat more accurately. Performance decreases with <15 ng DNA as starting material but, even with as little as 5 ng, MBD-seq still achieves 90% of the coverage of WGB-seq with comparable genome-wide methylation profiles. Thus, the proposed protocol is an attractive option for adequately powered and cost-effective methylome-wide investigations using (very) low amounts of DNA.

  6. A Case Study for Large-Scale Human Microbiome Analysis Using JCVI’s Metagenomics Reports (METAREP)

    PubMed Central

    Goll, Johannes; Thiagarajan, Mathangi; Abubucker, Sahar; Huttenhower, Curtis; Yooseph, Shibu; Methé, Barbara A.

    2012-01-01

    As metagenomic studies continue to increase in their number, sequence volume and complexity, the scalability of biological analysis frameworks has become a rate-limiting factor to meaningful data interpretation. To address this issue, we have developed JCVI Metagenomics Reports (METAREP) as an open source tool to query, browse, and compare extremely large volumes of metagenomic annotations. Here we present improvements to this software including the implementation of a dynamic weighting of taxonomic and functional annotation, support for distributed searches, advanced clustering routines, and integration of additional annotation input formats. The utility of these improvements to data interpretation are demonstrated through the application of multiple comparative analysis strategies to shotgun metagenomic data produced by the National Institutes of Health Roadmap for Biomedical Research Human Microbiome Project (HMP) (http://nihroadmap.nih.gov). Specifically, the scalability of the dynamic weighting feature is evaluated and established by its application to the analysis of over 400 million weighted gene annotations derived from 14 billion short reads as predicted by the HMP Unified Metabolic Analysis Network (HUMAnN) pipeline. Further, the capacity of METAREP to facilitate the identification and simultaneous comparison of taxonomic and functional annotations including biological pathway and individual enzyme abundances from hundreds of community samples is demonstrated by providing scenarios that describe how these data can be mined to answer biological questions related to the human microbiome. These strategies provide users with a reference of how to conduct similar large-scale metagenomic analyses using METAREP with their own sequence data, while in this study they reveal insights into the nature and extent of variation in taxonomic and functional profiles across body habitats and individuals. Over one thousand HMP WGS datasets and the latest open source code

  7. Large scale human metabolic phenotyping and molecular epidemiological studies via 1H NMR spectroscopy of urine: Investigation of borate preservation

    PubMed Central

    Smith, Leon M.; Maher, Anthony D.; Want, Elizabeth J.; Elliott, Paul; Stamler, Jeremiah; Hawkes, Geoffrey E.; Holmes, Elaine; Lindon, John C.; Nicholson, Jeremy K.

    2009-01-01

    Borate is an antibacterial preservative widely used in clinical and large scale epidemiological studies involving urine sample analysis. Since it readily forms covalent adducts and reversible complexes with hydroxyl and carboxylate groups, the effects of borate preservation in 1H NMR spectroscopy-based metabolic profiling of human urine samples have been assessed. Effects of various concentrations of borate (range 0–30 mM) on 1H NMR spectra of urine were observed at sequential time points over a 12 month period. Consistent with known borate chemistry, the principal alterations in the 1H resonance metabolite patterns were observed for compounds such as mannitol, citrate and α-hydroxyisobutyrate and confirmed by ESI-MS analysis. These included line-broadening, T1 and T2 relaxation and chemical shift changes consistent with complex formation and chemical exchange processes. To further investigate complexation behavior in the urinary metabolite profiles, a new tool for visualization of multi-component relaxation variations in which the spectra were color-coded according to the T1 and T2 proton relaxation times respectively (T1 or T2 Ordered Projection SpectroscopY, TOPSY) was also developed and applied. Addition of borate caused a general decrease in 1H T1 values consistent with non-specific effects such as solution viscosity changes. Minor changes in proton T2 relaxation rates were observed for the most strongly complexing metabolites. From a molecular phenotyping and epidemiologic viewpoint, typical interpersonal biological variation was shown to be vastly greater than any variation introduced by the borate complexation which had a negligible effect on the metabolic mapping and classification of samples. Whilst caution is indicated in the assignment of biomarker signals where metabolites have diol groupings or where there are adjacent hydroxyl and carboxylate functions, it is concluded that borate preservation is “fit-forpurpose” for 1H NMR

  8. Association between toothbrushing and risk factors for cardiovascular disease: a large-scale, cross-sectional Japanese study

    PubMed Central

    Kuwabara, Masanari; Motoki, Yoko; Ichiura, Kayoko; Fujii, Mizue; Inomata, Chisato; Sato, Hiroki; Morisawa, Taichiro; Morita, Yoshinori; Kuwabara, Kazumichi; Nakamura, Yosikazu

    2016-01-01

    Objectives To clarify the association between toothbrushing and risk factors for cardiovascular disease—namely, hypertension (HT), diabetes mellitus (DM), dyslipidaemia (DL), hyperuricaemia (HUA) and chronic kidney disease (CKD). Design A large-scale, single-centre, cross-sectional study. Setting St Luke's International Hospital, Center for Preventive Medicine, Tokyo, Japan, between January 2004 and June 2010. Participants This study examined the toothbrushing practices of 85 866 individuals according to the 3-category frequency criterion: ‘after every meal’, ‘at least once a day’ and ‘less than once a day’. The ORs by frequency were calculated for the prevalences of HT, DM, DL, HUA and CKD according to binominal logistic regression analyses adjusted for age, gender, body mass index and lifestyle habits—smoking, drinking, walk time and sleep time. Results The prevalences of the risk factors were as follows: HT (‘after every meal’: 13.3%, ‘at least once a day’: 17.9% and ‘less than once a day’: 31.0%), DM (3.1%, 5.3% and 17.4%, respectively), DL (29.0%, 42.1% and 60.3%, respectively), HUA (8.6%, 17.5% and 27.2%, respectively) and CKD (3.8%, 3.1% and 8.3%, respectively). The prevalences were significantly higher in the ‘less than once a day’ group than in the ‘after every meal’ group for DM (OR=2.03; 95% CI 1.29 to 3.21) and DL (OR=1.50; 95% CI 1.06 to 2.14), but not for HT, HUA and CKD. Conclusions Even taking into account lifestyle habits, a lower frequency of toothbrushing was associated with high prevalences of DM and DL. Toothbrushing practices may be beneficial for oral health improvement and also for prevention of certain systemic diseases. PMID:26769787

  9. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry.

    PubMed

    Ueland, Per Magne; Midttun, Oivind; Windelberg, Amrei; Svardal, Asbjørn; Skålevik, Rita; Hustad, Steinar

    2007-01-01

    of one-carbon metabolism in large-scale epidemiological studies.

  10. Large-scale high-resolution seismic study in the western end of the Nankai seismogenic zone

    NASA Astrophysics Data System (ADS)

    Nakanishi, A.; Kodaira, S.; Fujie, G.; Obana, K.; Takizawa, K.; Kashiwase, K.; Kaneda, Y.

    2009-12-01

    In the Nankai Trough subduction seismogenic zone, M8-class great earthquake area can be divided into three segments; they are source regions of the Nankai, Tonankai and presumed Tokai earthquakes. The Nankai and Tonankai earthquakes had often occurred simultaneously, and caused a great event. Possibility of a megathrust earthquake along the Nankai Trough from Tokai to the Hyuga-nada, east off the Kyushu Island, Japan, is recently pointed out. To understand rupture synchronization and segmentation of the Nankai megathrust earthquake, it is important to know the deep seismic image and activity in the Hyuga-nada, the western end of the Nankai seismogenic zone. To obtain the deep structure related to the rupture synchronization and segmentation in this region, the large-scale high-resolution wide-angle seismic study was conducted in Dec. 2008. In this study, 160 ocean bottom seismographs are deployed with a spacing of 5km along four seismic profiles, 830km in a total length. A tuned airgun system (7800 cu. in.) was shot every 200m along these profiles (Fig. 1). This research is part of ‘Research concerning Interaction Between the Tokai, Tonankai and Nankai Earthquakes’ funded by Ministry of Education, Culture, Sports, Science and Technology, Japan. The subducting plate interface beneath coseismic slip zone of the 1968 event (Mw7.5) is the top of the oceanic crust contacting with the old accreted sediments. The young accretionary sediments (Vp<5km/s) above the subducting Philippine Sea plate reaches a maximum thickness of ~10km, and is widely distributed landward. In the northwestern half of the slip zone of the 1968 event, the young Accretionary sediments become thin abruptly. Figure 1: Location map of seismic survey

  11. The SRG/eROSITA All-Sky Survey: A new era of large-scale structure studies with AGN

    NASA Astrophysics Data System (ADS)

    Kolodzig, Alexander; Gilfanov, Marat; Hütsi, Gert; Sunyaev, Rashid

    2015-08-01

    The four-year X-ray All-Sky Survey (eRASS) of the eROSITA telescope aboard the Spektrum-Roentgen-Gamma (SRG) satellite will detect about 3 million active galactic nuclei (AGN) with a median redshift of z~1 and typical luminosity of L0.5-2.0keV ~ 1044 erg/s. We demonstrate that this unprecedented AGN sample, complemented with redshift information, will supply us with outstanding opportunities for large-scale structure (LSS) studies.We show that with this sample of X-ray selected AGN, it will become possible for the first time to perform detailed redshift- and luminosity-resolved studies of the AGN clustering. This enable us to put strong constraints on different AGN triggering/fueling models as a function of AGN environment, which will dramatically improve our understanding of super-massive black hole growth and its correlation with the co-evolving LSS.Further, the eRASS AGN sample will become a powerful cosmological probe. We demonstrate for the first time that, given the breadth and depth of eRASS, it will become possible to convincingly detect baryonic acoustic oscillations (BAOs) with ~8σ confidence in the 0.8 < z < 2.0 range, currently uncovered by any existing BAO survey.Finally, we discuss the requirements for follow-up missions and demonstrate that in order to fully exploit the potential of the eRASS AGN sample, photometric and spectroscopic surveys of large areas and a sufficient depth will be needed.

  12. Comparative study of large scale simulation of underground explosions inalluvium and in fractured granite using stochastic characterization

    NASA Astrophysics Data System (ADS)

    Vorobiev, O.; Ezzedine, S. M.; Antoun, T.; Glenn, L.

    2014-12-01

    This work describes a methodology used for large scale modeling of wave propagation fromunderground explosions conducted at the Nevada Test Site (NTS) in two different geological settings:fractured granitic rock mass and in alluvium deposition. We show that the discrete nature of rockmasses as well as the spatial variability of the fabric of alluvium is very important to understand groundmotions induced by underground explosions. In order to build a credible conceptual model of thesubsurface we integrated the geological, geomechanical and geophysical characterizations conductedduring recent test at the NTS as well as historical data from the characterization during the undergroundnuclear test conducted at the NTS. Because detailed site characterization is limited, expensive and, insome instances, impossible we have numerically investigated the effects of the characterization gaps onthe overall response of the system. We performed several computational studies to identify the keyimportant geologic features specific to fractured media mainly the joints; and those specific foralluvium porous media mainly the spatial variability of geological alluvium facies characterized bytheir variances and their integral scales. We have also explored common key features to both geologicalenvironments such as saturation and topography and assess which characteristics affect the most theground motion in the near-field and in the far-field. Stochastic representation of these features based onthe field characterizations have been implemented in Geodyn and GeodynL hydrocodes. Both codeswere used to guide site characterization efforts in order to provide the essential data to the modelingcommunity. We validate our computational results by comparing the measured and computed groundmotion at various ranges. This work performed under the auspices of the U.S. Department of Energy by Lawrence LivermoreNational Laboratory under Contract DE-AC52-07NA27344.

  13. Embarking on large-scale qualitative research: reaping the benefits of mixed methods in studying youth, clubs and drugs

    PubMed Central

    Hunt, Geoffrey; Moloney, Molly; Fazio, Adam

    2012-01-01

    Qualitative research is often conceptualized as inherently small-scale research, primarily conducted by a lone researcher enmeshed in extensive and long-term fieldwork or involving in-depth interviews with a small sample of 20 to 30 participants. In the study of illicit drugs, traditionally this has often been in the form of ethnographies of drug-using subcultures. Such small-scale projects have produced important interpretive scholarship that focuses on the culture and meaning of drug use in situated, embodied contexts. Larger-scale projects are often assumed to be solely the domain of quantitative researchers, using formalistic survey methods and descriptive or explanatory models. In this paper, however, we will discuss qualitative research done on a comparatively larger scale—with in-depth qualitative interviews with hundreds of young drug users. Although this work incorporates some quantitative elements into the design, data collection, and analysis, the qualitative dimension and approach has nevertheless remained central. Larger-scale qualitative research shares some of the challenges and promises of smaller-scale qualitative work including understanding drug consumption from an emic perspective, locating hard-to-reach populations, developing rapport with respondents, generating thick descriptions and a rich analysis, and examining the wider socio-cultural context as a central feature. However, there are additional challenges specific to the scale of qualitative research, which include data management, data overload and problems of handling large-scale data sets, time constraints in coding and analyzing data, and personnel issues including training, organizing and mentoring large research teams. Yet large samples can prove to be essential for enabling researchers to conduct comparative research, whether that be cross-national research within a wider European perspective undertaken by different teams or cross-cultural research looking at internal divisions

  14. Embarking on large-scale qualitative research: reaping the benefits of mixed methods in studying youth, clubs and drugs.

    PubMed

    Hunt, Geoffrey; Moloney, Molly; Fazio, Adam

    2011-12-21

    Qualitative research is often conceptualized as inherently small-scale research, primarily conducted by a lone researcher enmeshed in extensive and long-term fieldwork or involving in-depth interviews with a small sample of 20 to 30 participants. In the study of illicit drugs, traditionally this has often been in the form of ethnographies of drug-using subcultures. Such small-scale projects have produced important interpretive scholarship that focuses on the culture and meaning of drug use in situated, embodied contexts. Larger-scale projects are often assumed to be solely the domain of quantitative researchers, using formalistic survey methods and descriptive or explanatory models.In this paper, however, we will discuss qualitative research done on a comparatively larger scale-with in-depth qualitative interviews with hundreds of young drug users. Although this work incorporates some quantitative elements into the design, data collection, and analysis, the qualitative dimension and approach has nevertheless remained central. Larger-scale qualitative research shares some of the challenges and promises of smaller-scale qualitative work including understanding drug consumption from an emic perspective, locating hard-to-reach populations, developing rapport with respondents, generating thick descriptions and a rich analysis, and examining the wider socio-cultural context as a central feature. However, there are additional challenges specific to the scale of qualitative research, which include data management, data overload and problems of handling large-scale data sets, time constraints in coding and analyzing data, and personnel issues including training, organizing and mentoring large research teams. Yet large samples can prove to be essential for enabling researchers to conduct comparative research, whether that be cross-national research within a wider European perspective undertaken by different teams or cross-cultural research looking at internal divisions and

  15. SEQSpark: A Complete Analysis Tool for Large-Scale Rare Variant Association Studies Using Whole-Genome and Exome Sequence Data.

    PubMed

    Zhang, Di; Zhao, Linhai; Li, Biao; He, Zongxiao; Wang, Gao T; Liu, Dajiang J; Leal, Suzanne M

    2017-07-06

    Massively parallel sequencing technologies provide great opportunities for discovering rare susceptibility variants involved in complex disease etiology via large-scale imputation and exome and whole-genome sequence-based association studies. Due to modest effect sizes, large sample sizes of tens to hundreds of thousands of individuals are required for adequately powered studies. Current analytical tools are obsolete when it comes to handling these large datasets. To facilitate the analysis of large-scale sequence-based studies, we developed SEQSpark which implements parallel processing based on Spark to increase the speed and efficiency of performing data quality control, annotation, and association analysis. To demonstrate the versatility and speed of SEQSpark, we analyzed whole-genome sequence data from the UK10K, testing for associations with waist-to-hip ratios. The analysis, which was completed in 1.5 hr, included loading data, annotation, principal component analysis, and single variant and rare variant aggregate association analysis of >9 million variants. For rare variant aggregate analysis, an exome-wide significant association (p < 2.5 × 10(-6)) was observed with CCDC62 (SKAT-O [p = 6.89 × 10(-7)], combined multivariate collapsing [p = 1.48 × 10(-6)], and burden of rare variants [p = 1.48 × 10(-6)]). SEQSpark was also used to analyze 50,000 simulated exomes and it required 1.75 hr for the analysis of a quantitative trait using several rare variant aggregate association methods. Additionally, the performance of SEQSpark was compared to Variant Association Tools and PLINK/SEQ. SEQSpark was always faster and in some situations computation was reduced to a hundredth of the time. SEQSpark will empower large sequence-based epidemiological studies to quickly elucidate genetic variation involved in the etiology of complex traits. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  16. A unified quantitative framework for studying large-scale disturbances and their dynamic impact on terrestrial ecosystems

    NASA Astrophysics Data System (ADS)

    Gu, L.; Sun, Y.

    2011-12-01

    Disturbances have long been recognized as a fundamental force in shaping the structure, function and evolution of terrestrial ecosystems. However progress in disturbance research remains frustratingly slow. This slow progress has multiple causes. Disturbances are tough to study due to the high diversity in agent types, large scope, intensity and unpredictability of individual occurrences, huge spatial and temporal heterogeneity in the impact, and exceptional complexity in ecosystem recovery in the aftermath. But progress has also been hindered by the lack of a proper model of disturbances and by the unavailability of quantitative methods to study them. Here we propose a conceptual model that not only unifies large-scale natural disturbances over their idiosyncrasies but also facilitates the development of quantitative methods that have broad applicability in the study of the dynamic impact on terrestrial ecosystems. We take an ecosystem-centric approach which measures a disturbance based on its impact. We consider a disturbance as a spatial set of life cycle phenomena each of which can be characterized with five spatially-varying parameters: start time, impact growing rate, impact severity, recovery rate, and recovered (back-to-normal) time. The spatial heterogeneity of the disturbance is represented by the statistical properties of the fields of these five parameters. We further group natural disturbances into two types. Type I occurs suddenly with the start time clearly definable and a destructive forcing that lasts a relatively short (hours to days) period, which corresponds to an infinitive impact growing rate. Examples of Type I disturbances include fires, hurricanes, and ice storms. Type II starts gradually with a forcing that builds up over time. Examples of this type include droughts and insect infestation. We present remote sensing-based indices and mathematical models that can be used to infer these parameters and estimate their spatial variability. We

  17. A study of interhemispheric magnetic conjugacy and large scale magnetosphere-ionosphere coupling using SuperDARN radars

    NASA Astrophysics Data System (ADS)

    Kunduri, Bharat Simha Reddy

    Ionospheric convection dynamics is an important window for understanding the coupling of the solar wind and interplanetary magnetic field to the Earth's ionosphere and upper atmosphere. In this study, we use measurements of ionospheric convection made by the SuperDARN radars to investigate the role of interhemispheric magnetic conjugacy in magnetosphere-ionosphere coupling and study the large-scale interactions between the magnetosphere and ionosphere. SuperDARN radars cover large geographic regions in both hemispheres and have a dataset spanning more than a decade, making them ideal for such studies. We begin in chapter 2 with an analysis of the degree of interhemispheric conjugacy exhibited in a Sub-Auroral Polarization Stream (SAPS). We present simultaneous observations of a SAPS event in both hemispheres made by mid-latitude SuperDARN radars with magnetically conjugate fields-of-view. An interhemispheric comparison of the characteristics of the SAPS channel reveals that the channel was conjugate in terms of potential variations across the channel even though substantial differences in latitudinal width and electric fields were observed in the channel. In chapter 3, we use interhemispheric SuperDARN observations of high latitude ionospheric convection in the noon-dusk sector to investigate the effects of IMF B Y penetrating into the closed magnetic field line region. The observations support the existence of an IMF BY associated interhemispheric potential difference and field-aligned current system resulting in the generation of the interhemispheric asymmetries in ionospheric convection. Four events are analyzed in this study and the strength of interhemispheric currents associated with IMF BY are estimated. Moreover, the strength of the interhemispheric currents is found to depend on the magnitude of IMF BY, proximity of the currents to open-closed field line boundary, ionospheric conductivity and magnetic local time. In chapter 4, we use data from the mid

  18. Emergence of Sex Differences in Insomnia Symptoms in Adolescents: A Large-Scale School-Based Study

    PubMed Central

    Zhang, Jihui; Chan, Ngan Yin; Lam, Siu Ping; Li, Shirley Xin; Liu, Yaping; Chan, Joey W.Y.; Kong, Alice Pik Shan; Ma, Ronald C.W.; Chan, Kate C.C.; Li, Albert Martin; Wing, Yun-Kwok

    2016-01-01

    Study Objectives: This study aimed to explore the moderation of pubertal status on the onset of sex differences in the prevalence of insomnia symptoms and their health correlates. Methods: A total of 7,507 children and adolescents (weighted percentage of female: 48.5%) aged between 6–17 y were recruited from thirty-one primary and secondary schools. Participants with difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and/or early morning awakening (EMA) ≥ 3 times/week in the past month were considered as having insomnia symptoms. The severity of insomnia was measured by the Insomnia Severity Index (ISI). Results: The prevalence of insomnia symptoms increased from 3.4% to 12.2% in girls (3.6-fold) and from 4.3% to 9.1% in boys (2.1-fold) from Tanner stage 1 to 5. There was a significant interaction between sex and Tanner stage in the prevalence of insomnia (P < 0.001) with an emergence of female preponderance at Tanner stage 4 even after controlling for age, family income, and school start time. Similar sex-Tanner stage interactions were found in DIS, DMS, and ISI total score but not EMA. Insomnia symptoms were strongly associated with behavioral problems, poor mental health, and poor general health in both sexes. Boys with insomnia would report more maladaptive lifestyles (smoking, alcohol, and energy drinks) whereas girls with insomnia were more susceptible to emotional and relationship difficulties. Conclusions: Pubertal maturation was associated with a progressive increase in the prevalence of insomnia symptoms with the emergence of female preponderance in both the prevalence and severity of insomnia symptoms at late puberty. Clinical Trials Registration: Chinese Clinical Trial Register, http://www.chictr.org.cn, ID: ChiCTR-TRC-12002798 Citation: Zhang J, Chan NY, Lam SP, Li SX, Liu Y, Chan JW, Kong AP, Ma RC, Chan KC, Li AM, Wing YK. Emergence of sex differences in insomnia symptoms in adolescents: a large-scale school-based study. SLEEP

  19. Gene, Environment and Methylation (GEM): a tool suite to efficiently navigate large scale epigenome wide association studies and integrate genotype and interaction between genotype and environment.

    PubMed

    Pan, Hong; Holbrook, Joanna D; Karnani, Neerja; Kwoh, Chee Keong

    2016-08-02

    The interplay among genetic, environment and epigenetic variation is not fully understood. Advances in high-throughput genotyping methods, high-density DNA methylation detection and well-characterized sample collections, enable epigenetic association studies at the genomic and population levels (EWAS). The field has extended to interrogate the interaction of environmental and genetic (GxE) influences on epigenetic variation. Also, the detection of methylation quantitative trait loci (methQTLs) and their association with health status has enhanced our knowledge of epigenetic mechanisms in disease trajectory. However analysis of this type of data brings computational challenges and there are few practical solutions to enable large scale studies in standard computational environments. GEM is a highly efficient R tool suite for performing epigenome wide association studies (EWAS). GEM provides three major functions named GEM_Emodel, GEM_Gmodel and GEM_GxEmodel to study the interplay of Gene, Environment and Methylation (GEM). Within GEM, the pre-existing "Matrix eQTL" package is utilized and extended to study methylation quantitative trait loci (methQTL) and the interaction of genotype and environment (GxE) to determine DNA methylation variation, using matrix based iterative correlation and memory-efficient data analysis. Benchmarking presented here on a publicly available dataset, demonstrated that GEM can facilitate reliable genome-wide methQTL and GxE analysis on a standard laptop computer within minutes. The GEM package facilitates efficient EWAS study in large cohorts. It is written in R code and can be freely downloaded from Bioconductor at https://www.bioconductor.org/packages/GEM/ .

  20. Large scale tracking algorithms

    SciTech Connect

    Hansen, Ross L.; Love, Joshua Alan; Melgaard, David Kennett; Karelitz, David B.; Pitts, Todd Alan; Zollweg, Joshua David; Anderson, Dylan Z.; Nandy, Prabal; Whitlow, Gary L.; Bender, Daniel A.; Byrne, Raymond Harry

    2015-01-01

    Low signal-to-noise data processing algorithms for improved detection, tracking, discrimination and situational threat assessment are a key research challenge. As sensor technologies progress, the number of pixels will increase signi cantly. This will result in increased resolution, which could improve object discrimination, but unfortunately, will also result in a significant increase in the number of potential targets to track. Many tracking techniques, like multi-hypothesis trackers, suffer from a combinatorial explosion as the number of potential targets increase. As the resolution increases, the phenomenology applied towards detection algorithms also changes. For low resolution sensors, "blob" tracking is the norm. For higher resolution data, additional information may be employed in the detection and classfication steps. The most challenging scenarios are those where the targets cannot be fully resolved, yet must be tracked and distinguished for neighboring closely spaced objects. Tracking vehicles in an urban environment is an example of such a challenging scenario. This report evaluates several potential tracking algorithms for large-scale tracking in an urban environment.

  1. Large scale traffic simulations

    SciTech Connect

    Nagel, K.; Barrett, C.L. |; Rickert, M. |

    1997-04-01

    Large scale microscopic (i.e. vehicle-based) traffic simulations pose high demands on computational speed in at least two application areas: (i) real-time traffic forecasting, and (ii) long-term planning applications (where repeated {open_quotes}looping{close_quotes} between the microsimulation and the simulated planning of individual person`s behavior is necessary). As a rough number, a real-time simulation of an area such as Los Angeles (ca. 1 million travellers) will need a computational speed of much higher than 1 million {open_quotes}particle{close_quotes} (= vehicle) updates per second. This paper reviews how this problem is approached in different projects and how these approaches are dependent both on the specific questions and on the prospective user community. The approaches reach from highly parallel and vectorizable, single-bit implementations on parallel supercomputers for Statistical Physics questions, via more realistic implementations on coupled workstations, to more complicated driving dynamics implemented again on parallel supercomputers. 45 refs., 9 figs., 1 tab.

  2. The invasive bighead goby Ponticola kessleri displays large-scale genetic similarities and small-scale genetic differentiation in relation to shipping patterns.

    PubMed

    Adrian-Kalchhauser, I; Hirsch, P E; Behrmann-Godel, J; N'Guyen, A; Watzlawczyk, S; Gertzen, S; Borcherding, J; Burkhardt-Holm, P

    2016-05-01

    Colonization events, range expansions and species invasions leave genetic signatures in the genomes of invasive organisms and produce intricate special patterns. Predictions have been made as to how those patterns arise, but only very rarely, genetic processes can be monitored in real time during range expansions. In an attempt to change that, we track a very recently established invasive population of a fish species, the bighead goby Ponticola kessleri, with high temporal and spatial resolution through 2 years to identify patterns over time. We then compare Swiss and German samples of bighead goby along the river Rhine using microsatellites, mitochondrial D-loop sequences and geometric morphometrics to investigate geographic patterns. We detect weak temporal and strong geographic patterns in the data, which are inconsistent with isolation by distance and indicate long range transport. In search of an explanation for our observations, we analyse the vector properties and travel patterns of commercial vessels on the river Rhine. We present evidence that freshwater cargo ships and tankers are plausible vectors for larvae of invasive goby species. We also present indications that cargo ships and tankers act as differential vectors for this species. In summary, we present genetic data at unique temporal resolution from a vertebrate invasion front and substantiate the paramount role of commercial shipping in freshwater fish translocations. © 2016 John Wiley & Sons Ltd.

  3. A large-scale study of bacterial contamination of drinking water and its public health impact in Nepal.

    PubMed

    Rai, S K; Ono, K; Yanagida, J I; Ishiyama-Imura, S; Kurokawa, M; Rai, C K

    2012-09-01

    Bacterial contamination of drinking water is a major public health in Nepal. A large scale study on contamination of drinking water was done covering all three ecological belts (mountain, hill and Terai) in all five (eastern, central, western, mid-western and far-western) development regions of Nepal during 2009-2011. Of the total 506 water samples studied, one-forth (25.1%; 127/506) were visually turbid. Bacteriologically, 88.5% (448/506) samples were positive for total coliform (TC) whereas 56.5% (286/506) were positive for fecal coliform (FC) (Esch. coli). The TC positive rate ranged from 53.8% in Damak (Jhapa) to 100.0% in different districts. The FC positive rate varied more widely ranging from 10.0% in Bharatpur City (Chitawan) to 100.0% in Baglung Township (Baglung) with over 50.0% in most of the districts (over 75.0% in eight districts). Both TC and FC positive rate were highest in Far-western Development Region (DR). High TC positive rate (96.7%) in Far-western DR was followed by Western DR (93.9%), Eastern DR (89.2%), Central DR (87.0%) and Mid-western DR (74.6%). Highest FC positive rate (65.5%) in Far-western DR was followed by Med-western DR (63.5%), Western DR (55.9%), Central DR (53.2%) and Eastern DR (52.0%). TC positive was highest (90.7%) in hills followed by mountain (89.7%) and Terai (plain) (84.1%) belt. In contrast, FC positive rate was highest (66.2%) in mountain, followed by hills (58.0%) and Terai (49.7%). Of the total 506, 335 were piped tap water, 129 were boring water, 16 natural tap (spout), 16 were well (sallow/deep well) and 10 were mineral/uroguard treated water. TC positive rate was very high (81.2% to 100.0%) in different type water samples (piped tap: 90.1%; boring water: 85.2%; natural spout/tap: 81.2%; well water 100.0% and mineral water/uroguard treated water: 80.0%). FC positive rate ranged from 0.0% in mineral water/uroguard treated water to 93.7% in well water samples. These findings are of serious public health concern with

  4. A large-scale study of the Trichinella genus in the golden jackal (Canis aureus) population in Serbia.

    PubMed

    Ćirović, Duško; Teodorović, Vlado; Vasilev, Dragan; Marković, Marija; Ćosić, Nada; Dimitrijević, Mirjana; Klun, Ivana; Djurković-Djaković, Olgica

    2015-09-15

    Over the last decades the golden jackal (Canis aureus) has significantly expanded its range throughout Southeast and Central Europe, and the Balkan Peninsula is considered to be a core area of the species distribution in this part of the range. Due to its increasing number, ability of long distance movement through a wide range of landscapes and opportunistic feeding habits, the golden jackal may represent an important reservoir and transmitter of a variety of zoonotic agents, including parasites. The Balkans, Serbia included, remain an endemic area for various zoonotic parasites including Trichinella spp. Trichinella has recently been recorded in jackals in Serbia, which prompted us to carry out a large-scale survey of its prevalence, distribution and species identification in this host. In cooperation with local hunters, carcasses of a total of 738 legally hunted golden jackals were collected at 24 localities over an 11-year period (2003-2013). Analysis of tongue base tissue revealed Trichinella larvae in 122, indicating a prevalence of infection of 16.5%. No difference in the prevalence of infection was found between genders [16.2% in males and 16.9% in females (χ(2)=0.05, p=0.821)], or among the study years (G=7.22, p=0.705). Trichinella larvae were found in 13 out of the 24 examined localities. Molecular identification was performed for 90 isolates, and 64 (71.1%) larvae were identified as Trichinella spiralis and 25 (27.9%) as Trichinella britovi. Mixed infection (T. spiralis and T. britovi) was recorded in a single case. Although T. spiralis was more prevalent, T. britovi had a wider distribution, and was the only recorded species in jackal populations from the mountainous region of eastern Serbia. On the other hand, T. spiralis was dominant in jackals in the lowlands of central and northern Serbia, where domestic pigs are mostly reared. These results show that the golden jackal is involved in both the domestic and sylvatic cycle, and that it has emerged as

  5. Large-Scale Fluorescence Calcium-Imaging Methods for Studies of Long-Term Memory in Behaving Mammals.

    PubMed

    Jercog, Pablo; Rogerson, Thomas; Schnitzer, Mark J

    2016-05-02

    During long-term memory formation, cellular and molecular processes reshape how individual neurons respond to specific patterns of synaptic input. It remains poorly understood how such changes impact information processing across networks of mammalian neurons. To observe how networks encode, store, and retrieve information, neuroscientists must track the dynamics of large ensembles of individual cells in behaving animals, over timescales commensurate with long-term memory. Fluorescence Ca(2+)-imaging techniques can monitor hundreds of neurons in behaving mice, opening exciting avenues for studies of learning and memory at the network level. Genetically encoded Ca(2+) indicators allow neurons to be targeted by genetic type or connectivity. Chronic animal preparations permit repeated imaging of neural Ca(2+) dynamics over multiple weeks. Together, these capabilities should enable unprecedented analyses of how ensemble neural codes evolve throughout memory processing and provide new insights into how memories are organized in the brain. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function.

    PubMed

    Varshney, Gaurav K; Lu, Jing; Gildea, Derek E; Huang, Haigen; Pei, Wuhong; Yang, Zhongan; Huang, Sunny C; Schoenfeld, David; Pho, Nam H; Casero, David; Hirase, Takashi; Mosbrook-Davis, Deborah; Zhang, Suiyuan; Jao, Li-En; Zhang, Bo; Woods, Ian G; Zimmerman, Steven; Schier, Alexander F; Wolfsberg, Tyra G; Pellegrini, Matteo; Burgess, Shawn M; Lin, Shuo

    2013-04-01

    With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1's predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ~0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome.

  7. What Large-Scale, Survey Research Tells Us about Teacher Effects on Student Achievement: Insights from the "Prospects" Study of Elementary Schools. CPRE Research Report Series.

    ERIC Educational Resources Information Center

    Rowan, Brian; Correnti, Richard; Miller, Robert J.

    This report is about the conceptual and methodological issues that arise when educational researchers use data from large-scale survey research studies to investigate teacher effects on student achievement. The report illustrates these issues by reporting on a series of analyses of data from "Prospects: The Congressionally Mandated Study of…

  8. Gaining Ground in the Middle Grades: Why Some Schools Do Better. A Large-Scale Study of Middle Grades Practices and Student Outcomes. Technical Appendix B

    ERIC Educational Resources Information Center

    EdSource, 2010

    2010-01-01

    This appendix focuses on the descriptive statistics of the middle study schools that participated in the "Gaining Ground in the Middle Grades: Why Some Schools Do Better. A Large-Scale Study of Middle Grades Practices and Student Outcomes. Initial Research." This appendix contains the following figures: (1) Student…

  9. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans

    PubMed Central

    Fowler, Sharon P.G.

    2016-01-01

    For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators’ work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs – including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol + aspartame – have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or – in many cases – even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed ‘Western’ diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet

  10. Low-calorie sweetener use and energy balance: Results from experimental studies in animals, and large-scale prospective studies in humans.

    PubMed

    Fowler, Sharon P G

    2016-10-01

    For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators' work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs - including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol+aspartame - have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or - in many cases - even to calorically-sweetened foods or liquids. Adverse impacts of LCS have appeared diminished in animals on dietary restriction, but were pronounced among males, animals genetically predisposed to obesity, and animals with diet-induced obesity. Impacts have been especially striking in animals on high-energy diets: diets high in fats and sugars, and diets which resemble a highly-processed 'Western' diet, including trans-fatty acids and monosodium glutamate. These studies have offered both support for, and biologically plausible mechanisms to explain, the results from a series of large-scale, long-term prospective observational studies conducted in humans, in which longitudinal increases in weight, abdominal adiposity, and incidence of overweight and obesity have been observed among study participants who reported using diet sodas and other

  11. Genetic manipulation of sex ratio for the large-scale breeding of YY super-male and XY all-male yellow catfish (Pelteobagrus fulvidraco (Richardson)).

    PubMed

    Liu, Hanqin; Guan, Bo; Xu, Jiang; Hou, Changchun; Tian, Hua; Chen, Hongxi

    2013-06-01

    Yellow catfish has become one of the most important freshwater aquaculture species in China. The mono-sex male yellow catfish has important application value in aquaculture because the male grows generally faster than the sibling females under the same conditions. This study has screened YY super-male and YY physiological female yellow catfish by sex reversal, gynogenesis, and progeny testing, which can help to achieve the large-scale production of YY super-male and XY all-male. From 2008 to 2010, about 123,000 YY super-male were produced, and about 81 million XY all-male fry were produced with 100% male rate by random sampling. Therefore, these results indicate that YY super-male and YY physiological female yellow catfish can be viable and fertile. We conclude that the mono-sex breeding technique by YY super-male yellow catfish is stable and reliable, which has great potential for application in yellow catfish aquaculture.

  12. Assimilation of satellite data to optimize large scale hydrological model parameters: a case study for the SWOT mission

    NASA Astrophysics Data System (ADS)

    Pedinotti, V.; Boone, A.; Ricci, S.; Biancamaria, S.; Mognard, N.

    2014-04-01

    During the last few decades, satellite measurements have been widely used to study the continental water cycle, especially in regions where in situ measurements are not readily available. The future Surface Water and Ocean Topography (SWOT) satellite mission will deliver maps of water surface elevation (WSE) with an unprecedented resolution and provide observation of rivers wider than 100 m and water surface areas greater than approximately 250 m × 250 m over continental surfaces between 78° S and 78° N. This study aims to investigate the potential of SWOT data for parameter optimization for large scale river routing models which are typically employed in Land Surface Models (LSM) for global scale applications. The method consists in applying a data assimilation approach, the Extended Kalman Filter (EKF) algorithm, to correct the Manning roughness coefficients of the ISBA-TRIP Continental Hydrologic System. Indeed, parameters such as the Manning coefficient, used within such models to describe water basin characteristics, are generally derived from geomorphological relationships, which might have locally significant errors. The current study focuses on the Niger basin, a trans-boundary river, which is the main source of fresh water for all the riparian countries. In addition, geopolitical issues in this region can restrict the exchange of hydrological data, so that SWOT should help improve this situation by making hydrological data freely available. In a previous study, the model was first evaluated against in-situ and satellite derived data sets within the framework of the international African Monsoon Multi-disciplinary Analysis (AMMA) project. Since the SWOT observations are not available yet and also to assess the proposed assimilation method, the study is carried out under the framework of an Observing System Simulation Experiment (OSSE). It is assumed that modeling errors are only due to uncertainties in the Manning coefficient. The true Manning

  13. Validation of a two-step quality control approach for a large-scale human urine metabolomic study conducted in seven experimental batches with LC/QTOF-MS.

    PubMed

    Demetrowitsch, Tobias J; Petersen, Beate; Keppler, Julia K; Koch, Andreas; Schreiber, Stefan; Laudes, Matthias; Schwarz, Karin

    2015-01-01

    After his study of food science at the Rheinische Friedrich-Wilhelms University of Bonn, Tobias J Demetrowitsch obtained his doctoral degree in the research field of metabolomics at the Christian-Albrechts-University of Kiel. The present paper is part of his doctoral thesis and describes an extended strategy to evaluate and verify complex or large-scale experiments and data sets. Large-scale studies result in high sample numbers, requiring the analysis of samples in different batches. So far, the verification of such LC-MS-based metabolomics studies is difficult. Common approaches have not provided a reliable validation procedure to date. This article shows a novel verification process for a large-scale human urine study (analyzed by a LC/QToF-MS system) using a two-step validation procedure. The first step comprises a targeted approach that aims to examine and exclude statistical outliers. The second step consists of a principle component analysis, with the aim of a tight cluster of all quality controls and a second for all volunteer samples. The applied study design provides a reliable two-step validation procedure for large-scale studies and additionally contains an inhouse verification procedure.

  14. Reconstruction and visualization of large-scale volumetric models of neocortical circuits for physically-plausible in silico optical studies.

    PubMed

    Abdellah, Marwan; Hernando, Juan; Antille, Nicolas; Eilemann, Stefan; Markram, Henry; Schürmann, Felix

    2017-09-13

    We present a software workflow capable of building large scale, highly detailed and realistic volumetric models of neocortical circuits from the morphological skeletons of their digitally reconstructed neurons. The limitations of the existing approaches for creating those models are explained, and then, a multi-stage pipeline is discussed to overcome those limitations. Starting from the neuronal morphologies, we create smooth piecewise watertight polygonal models that can be efficiently utilized to synthesize continuous and plausible volumetric models of the neurons with solid voxelization. The somata of the neurons are reconstructed on a physically-plausible basis relying on the physics engine in Blender. Our pipeline is applied to create 55 exemplar neurons representing the various morphological types that are reconstructed from the somatsensory cortex of a juvenile rat. The pipeline is then used to reconstruct a volumetric slice of a cortical circuit model that contains ∼210,000 neurons. The applicability of our pipeline to create highly realistic volumetric models of neocortical circuits is demonstrated with an in silico imaging experiment that simulates tissue visualization with brightfield microscopy. The results were evaluated with a group of domain experts to address their demands and also to extend the workflow based on their feedback. A systematic workflow is presented to create large scale synthetic tissue models of the neocortical circuitry. This workflow is fundamental to enlarge the scale of in silico neuroscientific optical experiments from several tens of cubic micrometers to a few cubic millimeters. Modelling and Simulation.

  15. Designing Topology-Aware Collective Communication Algorithms for Large Scale InfiniBand Clusters: Case Studies with Scatter and Gather

    SciTech Connect

    Kandalla, Krishna; Subramoni, Hari; Vishnu, Abhinav; Panda, Dhabaleswar K.

    2010-04-01

    Modern high performance computing systems are being increasingly deployed in a hierarchical fashion with multi-core computing platforms forming the base of the hierarchy. These systems are usually comprised of multiple racks, with each rack consisting of a finite number of chassis, with each chassis having multiple compute nodes or blades, based on multi-core architectures. The networks are also hierarchical with multiple levels of switches. Message exchange operations between processes that belong to different racks involve multiple hops across different switches and this directly affects the performance of collective operations. In this paper, we take on the challenges involved in detecting the topology of large scale InfiniBand clusters and leveraging this knowledge to design efficient topology-aware algorithms for collective operations. We also propose a communication model to analyze the communication costs involved in collective operations on large scale supercomputing systems. We have analyzed the performance characteristics of two collectives, MPI_Gather and MPI_Scatter on such systems and we have proposed topology-aware algorithms for these operations. Our experimental results have shown that the proposed algorithms can improve the performance of these collective operations by almost 54% at the micro-benchmark level.

  16. First Large-Scale Proteogenomic Study of Breast Cancer Provides Insight into Potential Therapeutic Targets | Office of Cancer Clinical Proteomics Research

    Cancer.gov

    News Release: May 25, 2016 — Building on data from The Cancer Genome Atlas (TCGA) project, a multi-institutional team of scientists has completed the first large-scale “proteogenomic” study of breast cancer, linking DNA mutations to protein signaling and helping pinpoint the genes that drive cancer.

  17. Issues in Estimating Program Effects and Studying Implementation in Large-Scale Educational Experiments: The Case of a Connected Classroom Technology Program

    ERIC Educational Resources Information Center

    Shin, Hye Sook

    2009-01-01

    Using data from a nationwide, large-scale experimental study of the effects of a connected classroom technology on student learning in algebra (Owens et al., 2004), this dissertation focuses on challenges that can arise in estimating treatment effects in educational field experiments when samples are highly heterogeneous in terms of various…

  18. Issues in Estimating Program Effects and Studying Implementation in Large-Scale Educational Experiments: The Case of a Connected Classroom Technology Program

    ERIC Educational Resources Information Center

    Shin, Hye Sook

    2009-01-01

    Using data from a nationwide, large-scale experimental study of the effects of a connected classroom technology on student learning in algebra (Owens et al., 2004), this dissertation focuses on challenges that can arise in estimating treatment effects in educational field experiments when samples are highly heterogeneous in terms of various…

  19. Gender Differences in Reading Impairment and in the Identification of Impaired Readers: Results from a Large-Scale Study of At-Risk Readers

    ERIC Educational Resources Information Center

    Quinn, Jamie M.; Wagner, Richard K.

    2015-01-01

    Reading impairment is more common in males, but the magnitude and origin of this gender difference are debated. In a large-scale study of reading impairment among 491,103 beginning second-graders, gender differences increased with greater severity of reading impairment, peaking at a ratio of 2.4:1 for a broad measure of fluency and a ratio of…

  20. Gaining Ground in the Middle Grades: Why Some Schools Do Better. A Large-Scale Study of Middle Grades. Practices and Student Outcomes. Narrative Summary of Findings

    ERIC Educational Resources Information Center

    EdSource, 2010

    2010-01-01

    In the 2008-09 school year researchers from EdSource and Stanford University conducted a large-scale study of 303 middle grades schools in California. The team surveyed 303 principals, 3,752 English Language Arts (ELA) and math teachers in grades 6-8, and 157 superintendents of the districts and charter management organizations that oversee the…

  1. A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

    PubMed Central

    Chu, Minjie; Mehta, Amar; Wei, Yongyue; Liu, Yao; Xun, Pengcheng; Bai, Jianling; Yu, Hao; Su, Li; Zhang, Hongxi; Hu, Zhibin; Shen, Hongbing; Chen, Feng; Christiani, David C.

    2013-01-01

    Background Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood. Objective We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV1) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers. Methods DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV1 was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively. Results Two SNPs were found to be significant (P<6.29×10−5), including rs1910047 (P = 3.07×10−5, FDR = 0.0778) and rs9469089 (P = 6.19×10−5, FDR = 0.0967), as well as other eight suggestive (P<5×10−4) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV1 decline occurred (Ptrend = 3.01×10−18). However, the association was different among age subgroups (P = 7.11×10−6) and endotoxin subgroups (P = 1.08×10−2). Functional network analysis illustrates potential biological connections of all interacted genes. Conclusions Genetic variants together with environmental factors interact to affect the rate of FEV1 decline in cotton textile workers. PMID:23527081

  2. A large-scale zebrafish gene knockout resource for the genome-wide study of gene function

    PubMed Central

    Varshney, Gaurav K.; Lu, Jing; Gildea, Derek E.; Huang, Haigen; Pei, Wuhong; Yang, Zhongan; Huang, Sunny C.; Schoenfeld, David; Pho, Nam H.; Casero, David; Hirase, Takashi; Mosbrook-Davis, Deborah; Zhang, Suiyuan; Jao, Li-En; Zhang, Bo; Woods, Ian G.; Zimmerman, Steven; Schier, Alexander F.; Wolfsberg, Tyra G.; Pellegrini, Matteo; Burgess, Shawn M.; Lin, Shuo

    2013-01-01

    With the completion of the zebrafish genome sequencing project, it becomes possible to analyze the function of zebrafish genes in a systematic way. The first step in such an analysis is to inactivate each protein-coding gene by targeted or random mutation. Here we describe a streamlined pipeline using proviral insertions coupled with high-throughput sequencing and mapping technologies to widely mutagenize genes in the zebrafish genome. We also report the first 6144 mutagenized and archived F1's predicted to carry up to 3776 mutations in annotated genes. Using in vitro fertilization, we have rescued and characterized ∼0.5% of the predicted mutations, showing mutation efficacy and a variety of phenotypes relevant to both developmental processes and human genetic diseases. Mutagenized fish lines are being made freely available to the public through the Zebrafish International Resource Center. These fish lines establish an important milestone for zebrafish genetics research and should greatly facilitate systematic functional studies of the vertebrate genome. PMID:23382537

  3. Bisphenol-A and phthalates contamination of urine samples by catheters in the Elfe pilot study: implications for large-scale biomonitoring studies.

    PubMed

    Vandentorren, Stephanie; Zeman, Florence; Morin, Lise; Sarter, Hélène; Bidondo, Marie-Laure; Oleko, Amivi; Leridon, Henri

    2011-08-01

    Exposure to phthalates and Bisphenol A could cause developmental and reproductive toxicity. This study provides a first assessment of these exposures for more than 250 French pregnant women. The median concentrations of total and free Bisphenol A in urine were similar to those in other studies except the highest concentrations (5% of women had total and free Bisphenol A >50μg/L). Our study highlights high levels of Di-(2-ethylhexyl)-phthalate metabolites in pregnant women, suggesting recent exposure, probably in hospital. Differences between types of delivery (caesarean vs. natural) support this hypothesis. This is a significant implication for large-scale biomonitoring studies among this population.

  4. Streakline flow visualization study of a horseshoe vortex in a large-scale, two-dimensional turbine stator cascade

    NASA Technical Reports Server (NTRS)

    Gaugler, R. E.; Russell, L. M.

    1979-01-01

    Neutrally bouyant helium-filled bubbles were observed as they followed the streamlines in a horseshoe vortex system around the vane leading edge in a large scale, two dimensional, turbine stator cascade. Inlet Reynolds number, based on true chord, ranged between 100,000 to 300,000. Bubbles were introduced into the endwall boundary layer through a slot upstream of the vane leading edge. The paths of the bubbles were recorded photographically as streaklines on 16 mm movie film. Individual frames from the film were selected, and overlayed to show the details of the horseshoe vortex around the leading edge. The transport of the vortex across the passage near the leading edge is clearly seen when compared to the streaks formed by bubbles carried in the main stream. Limiting streamlines on the endwall surface were traced by the flow of oil drops.

  5. Mechanism of Arachidonic Acid Accumulation during Aging in Mortierella alpina: A Large-Scale Label-Free Comparative Proteomics Study.

    PubMed

    Yu, Yadong; Li, Tao; Wu, Na; Ren, Lujing; Jiang, Ling; Ji, Xiaojun; Huang, He

    2016-11-30

    Arachidonic acid (ARA) is an important polyunsaturated fatty acid having various beneficial physiological effects on the human body. The aging of Mortierella alpina has long been known to significantly improve ARA yield, but the exact mechanism is still elusive. Herein, multiple approaches including large-scale label-free comparative proteomics were employed to systematically investigate the mechanism mentioned above. Upon ultrastructural observation, abnormal mitochondria were found to aggregate around shrunken lipid droplets. Proteomics analysis revealed a total of 171 proteins with significant alterations of expression during aging. Pathway analysis suggested that reactive oxygen species (ROS) were accumulated and stimulated the activation of the malate/pyruvate cycle and isocitrate dehydrogenase, which might provide additional NADPH for ARA synthesis. EC 4.2.1.17-hydratase might be a key player in ARA accumulation during aging. These findings provide a valuable resource for efforts to further improve the ARA content in the oil produced by aging M. alpina.

  6. A case study of the intraseasonal oscillation traversing the TOGA-COARE LSD. [large-scale domain

    NASA Technical Reports Server (NTRS)

    Vincent, Dayton G.; Schrage, Jon M.; Sliwinski, L. D.

    1993-01-01

    The paper presents examination of tree intraseasonal (30-60 day) oscillations (ISOs) that occurred during the southern summer season (December 1, 1985 - February 28, 1986) traversing the Large-Scale Domain (LSD) TOGA-COARE, the region which also plays an important role in ENSO, Australian monsoon, and extratropical circulations. Data presented include Hovmoeller diagrams of 5-day running means of 250-mb velocity potential anomalies and OLR anomalies; graphs of five-day running means of OLR in precipitable water (W) per sq m, averaged over 10 x 10 deg boxes centered on 5 S and (1) 145 E, (2) 155 E, (3) 165 E, and (4) 165 D, indicating the midpoint of each ISO; and vertical profiles of zonal wind in m/s averaged over the time period that each ISO spends in the 10 x 10 deg box centered at 5 S, and 175 E and 145 E.

  7. A Preliminary Model Study of the Large-Scale Seasonal Cycle in Bottom Pressure Over the Global Ocean

    NASA Technical Reports Server (NTRS)

    Ponte, Rui M.

    1998-01-01

    Output from the primitive equation model of Semtner and Chervin is used to examine the seasonal cycle in bottom pressure (Pb) over the global ocean. Effects of the volume-conserving formulation of the model on the calculation Of Pb are considered. The estimated seasonal, large-scale Pb signals have amplitudes ranging from less than 1 cm over most of the deep ocean to several centimeters over s